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Sample records for renal glycosuria induced

  1. Pregnancy-associated polyuria in familial renal glycosuria.

    Science.gov (United States)

    Toka, Hakan R; Yang, Jun; Zera, Chloe A; Duffield, Jeremy S; Pollak, Martin R; Mount, David B

    2013-12-01

    A pregnant woman presented at gestational week 28 with loss of consciousness and profound polyuria. Further characterization revealed osmotic diuresis due to massive glycosuria without hyperglycemia. Glycosuria reduced substantially postpartum, from approximately 100 to approximately 30 g/1.73 m2 per day. DNA sequencing analysis of the SLC5A2 gene encoding the renal glucose transporter SGLT2 showed a homozygous frame-shift mutation (occurring after the glutamine at amino acid 168 and leading to premature termination of the protein at amino acid 186) diagnostic of familial renal glycosuria. Pregnant women with familial renal glycosuria can be at risk of profound polyuria during pregnancy due to the associated increase in glycosuria. These findings also have implications for the use of SGLT2 inhibitors in clinical practice. Published by Elsevier Inc.

  2. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria

    Science.gov (United States)

    Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

    2014-01-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UEUA) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UEUA, suggesting that SUA decreased as a result of the increase in the UEUA. The increase in UEUA was correlated with an increase in urinary d-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UEUA is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and d-glucose. It was observed that the efflux of [14C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm d-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [14C]UA by oocytes was cis-inhibited by 100 mm d-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UEUA could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose. PMID:25044127

  3. [Sodium-glucose co-transporter-2 inhibitors: from the bark of apple trees and familial renal glycosuria to the treatment of type 2 diabetes mellitus].

    Science.gov (United States)

    Mauricio, Dídac

    2013-09-01

    The therapeutic armamentarium for the treatment of hyperglycemia in type 2 diabetes mellitus is still inadequate. We are currently witnessing the introduction of a new mode of hypoglycemic treatment through induction of glycosuria to decrease the availability of the metabolic substrate, i.e. glucose. Clinical trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors are as efficacious as other oral hypoglycemic drugs. This article discusses the basic features of this new treatment concept and the efficacy and safety of this new drug group. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  4. A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in type 2 diabetes mellitus.

    Science.gov (United States)

    Hohendorff, J; Szopa, M; Skupien, J; Kapusta, M; Zapala, B; Platek, T; Mrozinska, S; Parpan, T; Glodzik, W; Ludwig-Galezowska, A; Kiec-Wilk, B; Klupa, T; Malecki, M T

    2017-08-01

    SGLT2 inhibitors are a new class of oral hypoglycemic agents used in type 2 diabetes (T2DM). Their effectiveness in maturity onset diabetes of the young (MODY) is unknown. We aimed to assess the response to a single dose of 10 mg dapagliflozin in patients with Hepatocyte Nuclear Factor 1 Alpha (HNF1A)-MODY, Glucokinase (GCK)-MODY, and type 2 diabetes. We examined 14 HNF1A-MODY, 19 GCK-MODY, and 12 type 2 diabetes patients. All studied individuals received a single morning dose of 10 mg of dapagliflozin added to their current therapy of diabetes. To assess the response to dapagliflozin we analyzed change in urinary glucose to creatinine ratio and serum 1,5-Anhydroglucitol (1,5-AG) level. There were only four patients with positive urine glucose before dapagliflozin administration (one with HNF1A-MODY, two with GCK-MODY, and one with T2DM), whereas after SGLT-2 inhibitor use, glycosuria occurred in all studied participants. Considerable changes in mean glucose to creatinine ratio after dapagliflozin administration were observed in all three groups (20.51 ± 12.08, 23.19 ± 8.10, and 9.84 ± 6.68 mmol/mmol for HNF1A-MODY, GCK-MODY, and T2DM, respectively, p MODY, respectively), but not between the two MODY forms (p = 0.7231). Significant change in serum 1,5-AG was noticed only in T2DM and it was -6.57 ± 7.34 mg/ml (p = 0.04). A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in T2DM. Whether flozins are a valid therapeutic option in these forms of MODY requires long-term clinical studies.

  5. Peripheral vascular disease is associated with reduced glycosuria in newly diagnosed type 2 diabetic patients

    DEFF Research Database (Denmark)

    Olivarius, Niels de Fine; Holstein-Rathlou, N H; Siersma, V

    2004-01-01

    was 65.2 years. Urinary glucose concentration (UGC) was determined quantitatively in a freshly voided morning urine specimen. RESULTS: The over-all prevalence of peripheral vascular disease (PVD) was 16.5%. Bivariately, high values of UGC were associated with low prevalence of PVD (p...). The predictive value of PVD--together with HbA1c, glomerular filtration rate (GFR) and 10 other possible predictors--was confirmed in a logistic regression analysis with glycosuria (Y/N) as outcome variable (p=0.0004). CONCLUSION: Surprisingly, type 2 diabetic patients with PVD tend not to have glycosuria...... as compared to patients without PVD. PVD may be indicative of generalized atherosclerotic lesions in the major vessels, including the renal arteries. This could lead to a lowering of GFR and thereby of the amount of glucose filtered. Assuming no, or only a minor direct effect of PVD on tubular function...

  6. Drug-induced renal injury

    African Journals Online (AJOL)

    The kidney receives a rich blood flow of 25% of resting cardiac output ... Drugs can cause acute renal failure by causing pre-renal, intrinsic or .... tubular epithelial cells causing cell swelling ... the dose as required or prescribe alternative drugs.

  7. Renal replacement therapy in sepsis-induced acute renal failure

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    Rajapakse Senaka

    2009-01-01

    Full Text Available Acute renal failure (ARF is a common complication of sepsis and carries a high mortality. Renal replacement therapy (RRT during the acute stage is the mainstay of therapy. Va-rious modalities of RRT are available. Continuous RRT using convective methods are preferred in sepsis-induced ARF, especially in hemodynamically unstable patients, although clear evidence of benefit over intermittent hemodialysis is still not available. Peritoneal dialysis is clearly inferior, and is not recommended. Early initiation of RRT is probably advantageous, although the optimal timing of dialysis is yet unknown. Higher doses of RRT are more likely to be beneficial. Use of bio-compatible membranes and bicarbonate buffer in the dialysate are preferred. Anticoagulation during dialysis must be carefully adjusted and monitored.

  8. Ketamine induced renal fibrosis in a ketamine addition rat model

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    Mei-Yu Jang

    2017-09-01

    Conclusion: Ketamine treatment not only induced cystitis-like syndrome, but also renal fibrosis. These renal interstitial fibrosis changes may be induced by the TGF-β pathway. These preliminary results can provide valuable information from a clinical perspective.

  9. Soyfood consumption and risk of glycosuria in post-menopausal women

    Directory of Open Access Journals (Sweden)

    Nurmillah

    2010-12-01

    Full Text Available Menopause is a natural event to be experienced by every woman and appears to be associated with increased risk for developing type 2 diabetes mellitus. It has been postulated that a diet high in legumes may be beneficial for the prevention of glycosuria. These unique components of soy have been shown to have beneficial effects on glucose and insulin homeostasis. The objective of the present study was to examine the possibility of an association between soy food consumption and risk of glycosuria in postmenopausal women. A cross-sectional study was conducted among 94 postmenopausal women attending Mampang Prapatan Health Center, Mampang Prapatan subdistrict, South Jakarta. Anthropometric measurements were taken using standard instruments and dietary intake was assessed with a validated food-frequency questionnaire. A dipstick semiquantitative assay for urinary glucose was used to define glycosuria (positive. The results showed that 12.8% of postmenopausal women had glycosuria and mean isoflavone intake was 69.5 ± 61.4 g/d. Intake of isoflavone was inversely associated with risk of glycosuria. Compared to women in the lowest quintile of isoflavone intake (Q1, postmenopausal women in the highest quintile (Q5 had a lower risk for glycosuria of 0.30 times that of Q1, which risk was however statistically not significant (OR = 0.30; 95% CI = 0.02 – 3.14. In conclusion, isoflavone may play a role in the prevention of glycosuria (an important indicator of diabetes among postmenopausal women.

  10. Soyfood consumption and risk of glycosuria in post-menopausal women

    Directory of Open Access Journals (Sweden)

    Nurmillah Nurmillah

    2016-02-01

    Full Text Available Menopause is a natural event to be experienced by every woman and appears to be associated with increased risk for developing type 2 diabetes mellitus. It has been postulated that a diet high in legumes may be beneficial for the prevention of glycosuria. These unique components of soy have been shown to have beneficial effects on glucose and insulin homeostasis. The objective of the present study was to examine the possibility of an association between soy food consumption and risk of glycosuria in postmenopausal women. A cross-sectional study was conducted among 94 postmenopausal women attending Mampang Prapatan Health Center, Mampang Prapatan subdistrict, South Jakarta. Anthropometric measurements were taken using standard instruments and dietary intake was assessed with a validated food-frequency questionnaire. A dipstick semiquantitative assay for urinary glucose was used to define glycosuria (positive. The results showed that 12.8% of postmenopausal women had glycosuria and mean isoflavone intake was 69.5 ± 61.4 g/d. Intake of isoflavone was inversely associated with risk of glycosuria. Compared to women in the lowest quintile of isoflavone intake (Q1, postmenopausal women in the highest quintile (Q5 had a lower risk for glycosuria of 0.30 times that of Q1, which risk was however statistically not significant (OR = 0.30; 95% CI = 0.02 – 3.14. In conclusion, isoflavone may play a role in the prevention of glycosuria (an important indicator of diabetes among postmenopausal women.

  11. Renal effects of renal x irradiation and induced autoallergic glomerulonephritis

    International Nuclear Information System (INIS)

    Rappaport, D.S.; Casarett, G.W.

    1979-01-01

    This study was conducted to determine what influence a single large x-ray exposure of kidney has on the development and course of an experimental autoallergic glomerulonephritis (EAG) in rats. EAG was induced in female Sprague-Dawley rats by immunization with Bordetella pertussis vaccine and homogenate of homologous kidney tissue and Freund's complete adjuvant. Progressive arteriolonephrosclerosis (ANS) was observed in right (irradiated) kidneys following unilateral renal irradiation (1500 rad). Rats were either immunized, sham-immunized, irradiated, sham-irradiated, or both immunized and irradiated. Light and immunofluorescent microscopic observation, urine protein content, and kidney weights were evaluated. In immunized-irradiated animals the effects of irradiation and immunization were largely additive. Immunization did not considerably influence the development and course of ANS and irradiation did not considerably influence the development and course of EAG

  12. Lipopolysaccharide-induced acute renal failure in conscious rats

    DEFF Research Database (Denmark)

    Jonassen, Thomas E N; Graebe, Martin; Promeneur, Dominique

    2002-01-01

    In conscious, chronically instrumented rats we examined 1) renal tubular functional changes involved in lipopolysaccharide (LPS)-induced acute renal failure; 2) the effects of LPS on the expression of selected renal tubular water and sodium transporters; and 3) effects of milrinone......-alpha and lactate, inhibited the LPS-induced tachycardia, and exacerbated the acute LPS-induced fall in GFR. Furthermore, Ro-20-1724-treated rats were unable to maintain MAP. We conclude 1) PDE3 or PDE4 inhibition exacerbates LPS-induced renal failure in conscious rats; and 2) LPS treated rats develop an escape......, a phosphodiesterase type 3 (PDE3) inhibitor, and Ro-20-1724, a PDE4 inhibitor, on LPS-induced changes in renal function. Intravenous infusion of LPS (4 mg/kg b.wt. over 1 h) caused an immediate decrease in glomerular filtration rate (GFR) and proximal tubular outflow without changes in mean arterial pressure (MAP...

  13. Serum uric acid and disorders of glucose metabolism: the role of glycosuria

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, J.A.M. [Divisão de Nefrologia, Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, RJ (Brazil); Kang, H.C. [Departamento de Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, RJ (Brazil); Greffin, S. [Divisão de Nefrologia, Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, RJ (Brazil); Garcia Rosa, M.L. [Departamento de Epidemiologia e Bioestatística, Universidade Federal Fluminense, Niterói, RJ (Brazil); Lugon, J.R. [Divisão de Nefrologia, Departamento de Medicina Clínica, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, RJ (Brazil)

    2014-08-22

    Hyperuricemia has been associated with hypertension, diabetes mellitus, and metabolic syndrome. We studied the association between hyperuricemia and glycemic status in a nonrandomized sample of primary care patients. This was a cross-sectional study of adults ≥20 years old who were members of a community-based health care program. Hyperuricemia was defined as a value >7.0 mg/dL for men and >6.0 mg/dL for women. The sample comprised 720 participants including controls (n=257) and patients who were hypertensive and euglycemic (n=118), prediabetic (n=222), or diabetic (n=123). The mean age was 42.4±12.5 years, 45% were male, and 30% were white. The prevalence of hyperuricemia increased from controls (3.9%) to euglycemic hypertension (7.6%) and prediabetic state (14.0%), with values in prediabetic patients being statistically different from controls. Overall, diabetic patients had an 11.4% prevalence of hyperuricemia, which was also statistically different from controls. Of note, diabetic subjects with glycosuria, who represented 24% of the diabetic participants, had a null prevalence of hyperuricemia, and statistically higher values for fractional excretion of uric acid, Na excretion index, and prevalence of microalbuminuria than those without glycosuria. Participants who were prediabetic or diabetic but without glycosuria had a similarly elevated prevalence of hyperuricemia. In contrast, diabetic patients with glycosuria had a null prevalence of hyperuricemia and excreted more uric acid and Na than diabetic subjects without glycosuria. The findings can be explained by enhanced proximal tubule reabsorption early in the course of dysglycemia that decreases with the ensuing glycosuria at the late stage of the disorder.

  14. Serum uric acid and disorders of glucose metabolism: the role of glycosuria

    International Nuclear Information System (INIS)

    Andrade, J.A.M.; Kang, H.C.; Greffin, S.; Garcia Rosa, M.L.; Lugon, J.R.

    2014-01-01

    Hyperuricemia has been associated with hypertension, diabetes mellitus, and metabolic syndrome. We studied the association between hyperuricemia and glycemic status in a nonrandomized sample of primary care patients. This was a cross-sectional study of adults ≥20 years old who were members of a community-based health care program. Hyperuricemia was defined as a value >7.0 mg/dL for men and >6.0 mg/dL for women. The sample comprised 720 participants including controls (n=257) and patients who were hypertensive and euglycemic (n=118), prediabetic (n=222), or diabetic (n=123). The mean age was 42.4±12.5 years, 45% were male, and 30% were white. The prevalence of hyperuricemia increased from controls (3.9%) to euglycemic hypertension (7.6%) and prediabetic state (14.0%), with values in prediabetic patients being statistically different from controls. Overall, diabetic patients had an 11.4% prevalence of hyperuricemia, which was also statistically different from controls. Of note, diabetic subjects with glycosuria, who represented 24% of the diabetic participants, had a null prevalence of hyperuricemia, and statistically higher values for fractional excretion of uric acid, Na excretion index, and prevalence of microalbuminuria than those without glycosuria. Participants who were prediabetic or diabetic but without glycosuria had a similarly elevated prevalence of hyperuricemia. In contrast, diabetic patients with glycosuria had a null prevalence of hyperuricemia and excreted more uric acid and Na than diabetic subjects without glycosuria. The findings can be explained by enhanced proximal tubule reabsorption early in the course of dysglycemia that decreases with the ensuing glycosuria at the late stage of the disorder

  15. Fructokinase activity mediates dehydration-induced renal injury.

    Science.gov (United States)

    Roncal Jimenez, Carlos A; Ishimoto, Takuji; Lanaspa, Miguel A; Rivard, Christopher J; Nakagawa, Takahiko; Ejaz, A Ahsan; Cicerchi, Christina; Inaba, Shinichiro; Le, MyPhuong; Miyazaki, Makoto; Glaser, Jason; Correa-Rotter, Ricardo; González, Marvin A; Aragón, Aurora; Wesseling, Catharina; Sánchez-Lozada, Laura G; Johnson, Richard J

    2014-08-01

    The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy) has been linked with recurrent dehydration. Here we tested whether recurrent dehydration may cause renal injury by activation of the polyol pathway, resulting in the generation of endogenous fructose in the kidney that might subsequently induce renal injury via metabolism by fructokinase. Wild-type and fructokinase-deficient mice were subjected to recurrent heat-induced dehydration. One group of each genotype was provided water throughout the day and the other group was hydrated at night, after the dehydration. Both groups received the same total hydration in 24 h. Wild-type mice that received delayed hydration developed renal injury, with elevated serum creatinine, increased urinary NGAL, proximal tubular injury, and renal inflammation and fibrosis. This was associated with activation of the polyol pathway, with increased renal cortical sorbitol and fructose levels. Fructokinase-knockout mice with delayed hydration were protected from renal injury. Thus, recurrent dehydration can induce renal injury via a fructokinase-dependent mechanism, likely from the generation of endogenous fructose via the polyol pathway. Access to sufficient water during the dehydration period can protect mice from developing renal injury. These studies provide a potential mechanism for Mesoamerican nephropathy.

  16. Malaria induced acute renal failure: A single center experience

    International Nuclear Information System (INIS)

    KV Kanodia; AV Vanikar

    2010-01-01

    Malaria has protean clinical manifestations and renal complications, particularly acute renal failure that could be life threatening. To evaluate the incidence, clinical profile, ou come and predictors of mortality in patients with malarial acute renal failure, we retrospectively studied the last two years records of malaria induced acute renal failure in patients with peripheral smear positive for malarial parasites. One hundred (10.4%) (63 males, 37 females) malaria induced acute renal failure amongst 958 cases of acute renal failure were evaluated. Plasmodium (P). falciparum was reported in 85%, P. vivax in 2%, and both in 13% patients. The mean serum creatinine was 9.2 ± 4.2 mg%, and oligo/anuria was present in 82%; 78% of the patients required hemodialysis. Sixty four percent of the patients recovered completely, 10% incompletely, and 5% developed chronic kidney failure; mortality occurred in 21% of the patients. Low hemoglobin, oligo/anuria on admission, hyperbilirubinemia, cerebral malaria, disseminated intravascular coagulation, and high serum creatinine were the main predictors of mortality. We conclude that malaria is associated with acute renal failure, which occurs most commonly in plasmodium falciparum infected patients. Early diagnosis and prompt dialysis with supportive management can reduce morality and enhance recovery of renal function (Author).

  17. Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

    Science.gov (United States)

    Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

    2011-01-01

    The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

  18. Allopurinol-induced Severe Hypersensitivity with Acute Renal Failure

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    I-Hung Chen

    2005-05-01

    Full Text Available A 62-year-old male was sent to the emergency room due to a high fever and generalized skin rash after taking allopurinol for 9 days. Physical examination was normal except for the generalized skin rash presenting with erythematous macules. Complete blood count showed leukocytosis with eosinophilia. Blood biochemistry showed impaired renal and hepatic function. Pathologic examination concluded that the skin rash was erythema multiforme. These findings met the diagnostic criteria for allopurinol-induced hypersensitivity syndrome (AHS. Our patient not only had the most common skin lesion but soon developed acute renal failure that required intermittent hemodialysis, despite rapid discontinuation of allopurinol and adequate hydration and steroid therapy. No other causes of acute renal failure were found. Renal impairment was the worst part of the patient's condition and he never completely recovered. AHS should be considered in the differential diagnosis of acute renal and hepatic failure in patients with evidence of allergy and recent use of allopurinol.

  19. How Kidney Cell Death Induces Renal Necroinflammation.

    Science.gov (United States)

    Mulay, Shrikant R; Kumar, Santhosh V; Lech, Maciej; Desai, Jyaysi; Anders, Hans-Joachim

    2016-05-01

    The nephrons of the kidney are independent functional units harboring cells of a low turnover during homeostasis. As such, physiological renal cell death is a rather rare event and dead cells are flushed away rapidly with the urinary flow. Renal cell necrosis occurs in acute kidney injuries such as thrombotic microangiopathies, necrotizing glomerulonephritis, or tubular necrosis. All of these are associated with intense intrarenal inflammation, which contributes to further renal cell loss, an autoamplifying process referred to as necroinflammation. But how does renal cell necrosis trigger inflammation? Here, we discuss the role of danger-associated molecular patterns (DAMPs), mitochondrial (mito)-DAMPs, and alarmins, as well as their respective pattern recognition receptors. The capacity of DAMPs and alarmins to trigger cytokine and chemokine release initiates the recruitment of leukocytes into the kidney that further amplify necroinflammation. Infiltrating neutrophils often undergo neutrophil extracellular trap formation associated with neutrophil death or necroptosis, which implies a release of histones, which act not only as DAMPs but also elicit direct cytotoxic effects on renal cells, namely endothelial cells. Proinflammatory macrophages and eventually cytotoxic T cells further drive kidney cell death and inflammation. Dissecting the molecular mechanisms of necroinflammation may help to identify the best therapeutic targets to limit nephron loss in kidney injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Renal hemodynamics in uranyl acetate-induced acute renal failure of rabbits

    International Nuclear Information System (INIS)

    Sudo, M.; Honda, N.; Hishida, A.; Nagase, M.

    1977-01-01

    The role of renal hemodynamic alterations in the curtailment of renal function was studied in rabbits with uranyl acetate-induced acute renal failure. The day following the i.v. injection of uranyl acetate (2 mg/kg of body wt), renal blood flow (RBF) and clearance of creatinine (Ccr) decreased to approximately 60 and 20% of controls, respectively. Intracortical fractional flow distribution, estimated by radioactive microsphere method, did not change. The extraction ratio of para-aminohippurate (EPAH) decreased and the renal extraction of sodium (CNa/Ccr) increased, with minimal structural change in the kidney. Urine output increased two to three times that of the control. After three days oliguria appeared despite complete recovery of RBF. The zonal flow redistributed toward the deep cortex. CCr and EPAH reached their minimums, concomitantly with tubular necrosis and intratubular casts. After seven days animals could be divided into the oliguric and diuretic groups. CCr and EPAH were higher in the diuretic group, while there was no significant difference in RBF and the flow distribution between groups. Regeneration of damaged tubular cells was found in the diuretic group but not in the oliguric group. The findings suggest the minor roles of RBF and the intracortical flow distribution, and a fundamental role of back leakage of filtrate across damaged tubular epithelium in the maintenance of reduced CCR and urine output during the oliguric stage in rabbits with uranyl acetate-induced renal failure

  1. Diabetes, glycosuria, and proteinuria in a Japanese cohort followed for 20 years

    International Nuclear Information System (INIS)

    Brodsky, J.B.; Moore, D.F.; Hamilton, H.B.; Kawate, Ryoso.

    1988-07-01

    An analysis of noninsulin-dependent diabetes mellitus, glycosuria, and proteinuria in a Japanese cohort, which has been followed for 20 years, is presented. For the last 14 years of follow-up in Hiroshima, the sex-specific incidence rates of diabetes were approximately constant at 1.2 - 1.4 cases/100 per 2-year interval for males (p > .50) and at 0.5 - 0.6 cases/100 per 2-year interval for females (p > .20). The diagnosis of diabetes depended on first screening for glycosuria and then administering an oral glucose tolerance test only to those with glycosuria. The relatively greater prevalence of glycosuria and diabetes among males has also been noted by others using similar methods. It has been reported elsewhere that if the glucose tolerance test were used to screen for diabetes, the sex difference may not be apparent. The prevalence of diabetes increased over the course of study (p < .001), and the increase was attributed to aging of the cohort. The size of the undiagnosed diabetic population was estimated and the observed prevalence rate was determined to be about 75 % of the actual prevalence rate at the end of 8 years of follow-up and to be about 89 % of the actual prevalence rate at the end of 20 years of follow-up. Proteinuria prevalence was 4.3 % in nondiabetics, 23.5 % in Hiroshima diabetics, and 18.7 % in Nagasaki diabetics. The differences in prevalence rates between nondiabetics and diabetics were highly significant (p < .001). (author)

  2. Methotrexate-induced Pancytopenia in Two Patients with Renal Dysfunction

    OpenAIRE

    Yusuf OĞUZ; Tayfun EYİLETEN; Murat KARAMAN; Seyid Ahmet AY; Mahmut İlker YILMAZ

    2011-01-01

    Methotrexate (MTX) is cleared primarily by renal excretion. The excretion of MTX is delayed in subjects with renal dysfunction and elevated plasma MTX concentrations develop which lead to bone marrow toxicities and possible pancytopenia. In this case report, we presented two advanced age patients with MTX-induced pancytopenia. The first patient on hemodialysis was diagnosed with seronegative arthritis while the second patient with congestive heart failure was diagnosed with rheumatoid arthrit...

  3. Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats

    NARCIS (Netherlands)

    L. Zafrani (Lara); B. Ergin (Bulent); Kapucu, A. (Aysegul); C. Ince (Can)

    2016-01-01

    textabstractBackground: The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Methods: Twenty-seven Wistar

  4. Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats

    NARCIS (Netherlands)

    Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

    2016-01-01

    The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into

  5. Renal effects of renal x irradiation and induced autoallergic glomerulonephritis

    International Nuclear Information System (INIS)

    Rappaport, D.S.

    1977-01-01

    This study was conducted to determine what, if any, influence a single large x-ray exposure of kidney has on the development and course of an experimental autoallergic glomerulonephritis (EAG) in rats. The EAG was induced by immunization with B. pertussis vaccine and homogenate of homologous kidney tissue and Freund's complete adjuvant. Rats were either immunized, sham-immunized, irradiated (1500 R to right kidney temporarily exteriorized), sham-irradiated, or both immunized and irradiated. Immunized-irradiated animals were irradiated either 4 or 2 weeks prior to, concurrently with, or 1 or 2 weeks after immunization, and were sacrificed at 2, 4, 6, 10, or 14 weeks post-immunization. Immunized-only and sham-immunized-only animals were sacrificed at corresponding post-immunization times, and irradiated-only and sham-irradiated-only animals were sacrificed at corresponding post-irradiation times. Progressive arteriolonephrosclerosis (ANA) was observed in right (irradiated) kidneys following x irradiation. The experimental autoallergic glomerulonephritis (EAG) was observed in both kidneys following immunization. The histopathological changes associated with EAG were distinct from those associated with ANS

  6. Contrast media induced acute renal failure in diabetics

    International Nuclear Information System (INIS)

    Rambausek, M.

    1985-01-01

    Dehydration, preexisting renal insufficiency, multiple myeloma and insulin-dependent diabetes mellitus are known risk factors for a radiocontrast medium induced acute renal failure. In 90% of patients with insulin-dependent diabetes mellitus, renal insufficiency and proteinuria, a further detoriation of renal function can be expected after i.v. administration of radiocontrast medium. Recent concepts on the genesis of acute renal failure after radiocontrast medium in multiple myeloma emphasize the role of tubular blocade (tubular precipitation of myeloma protein with contrast medium). In insulin-dependent diabetic patients we found altered carbohydrate composition of urinary Tamm Horsfall Protein (THP), with increased glucose and diminished N-acetyl-neuraminicacid content. This was paralleled by a difference in an in-vitro system of coprecipitation where THP of diabetes triggered more pronounced calcium dependent coprecipitation of contrast medium and albumin. These in-vitro findings might be important for the explanation of the genesis of radiocontrast medium-induced acute renal failure in insulin-dependent diabetes mellitus. (orig.) [de

  7. Renal glucose handling in diabetes and sodium glucose cotransporter 2 inhibition

    Directory of Open Access Journals (Sweden)

    Resham Raj Poudel

    2013-01-01

    Full Text Available The kidneys play a major role in glucose homeostasis through its utilization, gluconeogenesis, and reabsorption via sodium glucose cotransporters (SGLTs. The defective renal glucose handling from upregulation of SGLTs, mainly the SGLT2, plays a fundamental role in the pathogenesis of type 2 diabetes mellitus. Genetic mutations in a SGLT2 isoform that results in benign renal glycosuria, as well as clinical studies with SGLT2 inhibitors in type 2 diabetes support the potential of this approach. These studies indicate that inducing glycosuria by suppressing SGLT2 can reduce plasma glucose and A1c levels, as well as decrease weight, resulting in improved β-cell function and enhanced insulin sensitivity in liver and muscle. Because the mechanism of SGLT2 inhibition is independent of insulin secretion and sensitivity, these agents can be combined with other antidiabetic agents, including exogenous insulin. This class represents a novel therapeutic approach with potential for the treatment of both type 2 and type 1 diabetes.

  8. Nephrolithiasis-induced end stage renal disease

    Directory of Open Access Journals (Sweden)

    M Ounissi

    2010-03-01

    Full Text Available M Ounissi¹, T Gargueh², M Mahfoudhi¹, K Boubaker¹, H Hedri¹, R Goucha¹, E Abderrahim¹, F Ben Hamida¹, T Ben Abdallah¹, F El Younsi¹, H Ben Maiz³, A Kheder¹1Internal Medicine Department, 2Pediatric Department, 3Laboratory of Kidney Diseases, Charles Nicolle Hospital, Tunis, TunisiaIntroduction: Nephrolithiasis still remains a too frequent and underappreciated cause of end stage renal disease (ESRD.Methods and patients: Of the entire cohort of 7128 consecutive patients who started maintenance dialysis in our nephrology department between January 1992 and December 2006, a total of 45 patients (26 women, 19 men had renal stone disease as the cause of ESRD. The type of nephrolithiasis was determined in 45 cases and etiology in 42. The treatment and evolution of stone disease and patient’s survival were studied.Results: The overall proportion of nephrolithiasis related ESRD was 0.63%. The mean age was 48.4 years. Infection stones (struvite accounted for 40%, calcium stones, 26.67% (primary hyperparathyroidism:15.56%; familial hypercalciuria: 4.44%, unknown etiology: 6.66%, primary hyperoxaluria type 1, 17.78% and uric acid lithiasis in 15.56% of cases. The mean delay of the evolution of the stone renal disease to chronic renal failure was 85.8 months. The feminine gender, obesity and elevated alkaline phosphatases >128 IU/L were significantly correlated with fast evolution of ESRD. The median evolution to ESRD was 12 months. The normal body mass index (BMI, medical treatment of stone and primary hyperoxaluria type 1 were correlated with fast evolution to ESRD. All patients were treated by hemodialysis during a mean evolution of 60 months. Sixteen patients died. The patient's survival rate at 1, 3 and 5 years was 97.6, 92.8 and 69% respectively. Hypocalcemia, cardiopathy and normal calcium-phosphate product were significantly correlated with lower survival rate.Conclusion: Severe forms of nephrolithiasis remain an underestimated cause of

  9. Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy

    Science.gov (United States)

    Liu, Qian; Zhang, Qi; Wang, Kai; Wang, Shengchan; Lu, Dasheng; Li, Zhenzhen; Geng, Jie; Fang, Ping; Wang, Ying; Shan, Qijun

    2015-12-01

    Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced cardiomyopathy rats were randomized to RDN (n = 15) and Sham group (n = 16). Compared with Control group, ejection fraction was decreased, diastolic interventricular septal thickness and left atrial dimension were increased in ISO-induced cardiomyopathy group at 5 week. After 10 weeks, cardio-renal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the pro-fibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-α), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin II type-1 receptor (AT1R) axis was downregulated. Meanwhile, angiotensin-converting enzyme 2 (ACE2)/angiotensin-1-7 (Ang-(1-7))/mas receptor (Mas-R) axis was upregulated. RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis.

  10. Protection of Chinese herbs against Adenine-induced chronic renal ...

    African Journals Online (AJOL)

    The aim of the study is to evaluate the efficacy of Chinese herbs (Angelica sinensis, Ligusticum wallichii, Salvia miltiorrhiza, Rhizoma dioscoreae, Rhodiola crenilata, Astragalus membranaceus and Angelica sinensis) on adenine-induced chronic renal failure in rats. 30 age-matched male Wistar rats were divided into three ...

  11. Effect of selective inhibition of renal inducible nitric oxide synthase on renal blood flow and function in experimental hyperdynamic sepsis.

    Science.gov (United States)

    Ishikawa, Ken; Calzavacca, Paolo; Bellomo, Rinaldo; Bailey, Michael; May, Clive N

    2012-08-01

    Nitric oxide plays an important role in the control of renal blood flow and renal function. In sepsis, increased levels of inducible nitric oxide synthase produce excessive nitric oxide, which may contribute to the development of acute kidney injury. We, therefore, examined the effects of intrarenal infusion of selective inducible nitric oxide synthase inhibitors in a large animal model of hyperdynamic sepsis in which acute kidney injury occurs in the presence of increased renal blood flow. Prospective crossover randomized controlled interventional studies. University-affiliated research institute. Twelve unilaterally nephrectomized Merino ewes. Infusion of a selective (1400W) and a partially selective inducible nitric oxide synthase inhibitor (aminoguanidine) into the renal artery for 2 hrs after the induction of sepsis, and comparison with a nonselective inhibitor (Nω-nitro-L-arginine methyl ester). In sheep with nonhypotensive hyperdynamic sepsis, creatinine clearance halved (32 to 16 mL/min, ratio [95% confidence interval] 0.51 [0.28-0.92]) despite increased renal blood flow (241 to 343 mL/min, difference [95% confidence interval] 102 [78-126]). Infusion of 1400W did not change renal blood flow, urine output, or creatinine clearance, whereas infusion of Nω-nitro-L-arginine methyl ester and a high dose of aminoguanidine normalized renal blood flow, but did not alter creatinine clearance. In hyperdynamic sepsis, intrarenal infusion of a highly selective inducible nitric oxide synthase inhibitor did not reduce the elevated renal blood flow or improve renal function. In contrast, renal blood flow was reduced by infusion of a nonselective NOS inhibitor or a high dose of a partially selective inducible nitric oxide synthase inhibitor. The renal vasodilatation in septic acute kidney injury may be due to nitric oxide derived from the endothelial and neural isoforms of nitric oxide synthase, but their blockade did not restore renal function.

  12. A review of dietary supplement-induced renal dysfunction.

    Science.gov (United States)

    Gabardi, Steven; Munz, Kristin; Ulbricht, Catherine

    2007-07-01

    Complementary and alternative medicine (CAM) is a multibillion-dollar industry. Almost half of the American population uses some form of CAM, with many using them in addition to prescription medications. Most patients fail to inform their health care providers of their CAM use, and physicians rarely inquire. Annually, thousands of dietary supplement-induced adverse events are reported to Poison Control Centers nationwide. CAM manufacturers are not responsible for proving safety and efficacy, because the Food and Drug Administration does not regulate them. However, concern exists surrounding the safety of CAM. A literature search using MEDLINE and EMBASE was undertaken to explore the impact of CAM on renal function. English-language studies and case reports were selected for inclusion but were limited to those that consisted of human subjects, both adult and pediatric. This review provides details on dietary supplements that have been associated with renal dysfunction and focuses on 17 dietary supplements that have been associated with direct renal injury, CAM-induced immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, and hepatorenal syndrome. It is concluded that it is imperative that use of dietary supplements be monitored closely in all patients. Health care practitioners must take an active role in identifying patients who are using CAM and provide appropriate patient education.

  13. Alteration of renal excretion pathways in gentamicin-induced renal injury in rats.

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    Ma, Yan-Rong; Luo, Xuan; Wu, Yan-Fang; Zhang, Tiffany; Zhang, Fan; Zhang, Guo-Qiang; Wu, Xin-An

    2018-02-20

    The kidney plays a major part in the elimination of many drugs and their metabolites, and drug-induced kidney injury commonly alters either glomerular filtration or tubular transport, or both. However, the renal excretion pathway of drugs has not been fully elucidated at different stages of renal injury. This study aimed to evaluate the alteration of renal excretion pathways in gentamicin (GEN)-induced renal injury in rats. Results showed that serum cystatin C, creatinine and urea nitrogen levels were greatly increased by the exposure of GEN (100 mg kg -1 ), and creatinine concentration was increased by 39.7% by GEN (50 mg kg -1 ). GEN dose-dependently upregulated the protein expression of rOCT1, downregulated rOCT2 and rOAT1, but not affected rOAT2. Efflux transporters, rMRP2, rMRP4 and rBCRP expressions were significantly increased by GEN(100), and the rMATE1 level was markedly increased by GEN(50) but decreased by GEN(100). GEN(50) did not alter the urinary excretion of inulin, but increased metformin and furosemide excretion. However, GEN(100) resulted in a significant decrease of the urinary excretion of inulin, metformin and p-aminohippurate. In addition, urinary metformin excretions in vivo were significantly decreased by GEN(100), but slightly increased by GEN(50). These results suggested that GEN(50) resulted in the induction of rOCTs-rMATE1 and rOAT3-rMRPs pathway, but not changed the glomerular filtration rate, and GEN(100)-induced acute kidney injury caused the downregulated function of glomerular filtration -rOCTs-rMATE1 and -rOAT1-rMRPs pathway. Copyright © 2018 John Wiley & Sons, Ltd.

  14. Renal Nerve Stimulation-Induced Blood Pressure Changes Predict Ambulatory Blood Pressure Response After Renal Denervation.

    Science.gov (United States)

    de Jong, Mark R; Adiyaman, Ahmet; Gal, Pim; Smit, Jaap Jan J; Delnoy, Peter Paul H M; Heeg, Jan-Evert; van Hasselt, Boudewijn A A M; Lau, Elizabeth O Y; Persu, Alexandre; Staessen, Jan A; Ramdat Misier, Anand R; Steinberg, Jonathan S; Elvan, Arif

    2016-09-01

    Blood pressure (BP) response to renal denervation (RDN) is highly variable and its effectiveness debated. A procedural end point for RDN may improve consistency of response. The objective of the current analysis was to look for the association between renal nerve stimulation (RNS)-induced BP increase before and after RDN and changes in ambulatory BP monitoring (ABPM) after RDN. Fourteen patients with drug-resistant hypertension referred for RDN were included. RNS was performed under general anesthesia at 4 sites in the right and left renal arteries, both before and immediately after RDN. RNS-induced BP changes were monitored and correlated to changes in ambulatory BP at a follow-up of 3 to 6 months after RDN. RNS resulted in a systolic BP increase of 50±27 mm Hg before RDN and systolic BP increase of 13±16 mm Hg after RDN (Pefficacy of RDN and predict BP response to RDN. © 2016 American Heart Association, Inc.

  15. Renal tissue damage induced by focused shock waves

    Science.gov (United States)

    Ioritani, N.; Kuwahara, M.; Kambe, K.; Taguchi, K.; Saitoh, T.; Shirai, S.; Orikasa, S.; Takayama, K.; Lush, P. A.

    1990-07-01

    Biological evidence of renal arterial wall damage induced by the microjet due to shock wave-cavitation bubble interaction was demonstrated in living dog kidneys. We also intended to clarify the mechanism of renal tissue damage and the effects of different conditions of shock wave exposure (peak pressure of focused area, number of shots, exposure rate) on the renal tissue damage in comparison to stone disintegration. Disruption of arterial wall was the most remarkable histological change in the focused area of the kidneys. This lesion appeared as if the wall had been punctured by a needle. Large hematoma formation in the renal parenchym, and interstitial hemorrhage seemed to be the results of the arterial lesion. This arterial disorder also led to ischemic necrosis of the tubules surrounding the hematoma. Micro-angiographic examination of extracted kidneys also proved such arterial puncture lesions and ischemic lesions. The number of shots required for model stone disintegration was not inversely proportional to peak pressure. It decreased markedly when peak pressure was above 700 bar. Similarly thenumber of shots for hematoma formation was not inversely proportional to peak pressure, however, this decreased markedly above 500 bar. These results suggested that a hematoma could be formed under a lower peak pressure than that required for stone disintegration.

  16. Nephrotic Syndrome and Acute Renal Failure Apparently Induced by Sunitinib

    Directory of Open Access Journals (Sweden)

    Ying-Shou Chen

    2009-10-01

    Full Text Available We report a case of nephrotic syndrome and acute renal failure apparently induced by sunitinib. A 67-year-old man with a history of metastatic renal cell carcinoma presented with progressive kidney dysfunction with proteinuria, general edema, and body weight gain of 21 kg after undergoing 3 weeks of sunitinib therapy. The patient had taken no other over-the-counter medications, and all other possible causes of nephrotic syndrome were excluded. The Naranjo Adverse Drug Reaction Probability Scale score for this event was 6, indicating a high probability that the observed presentations were associated with use of the drug. However, despite the discontinuation of sunitinib, his condition deteriorated, and hemodialysis was initiated for respiratory distress. A renal biopsy was performed, which revealed ischemic acute tubular necrosis with minimal change nephropathy. In conclusion, nephrologists and oncologists should be aware that nephrotic syndrome with ischemic acute tubular necrosis is a possible adverse effect of sunitinib. For early diagnosis of this condition and to avoid renal damage, we recommend differential diagnosis of serum creatinine and proteinuria in patients undergoing sunitinib therapy.

  17. Mechanisms of bee venom-induced acute renal failure.

    Science.gov (United States)

    Grisotto, Luciana S D; Mendes, Glória E; Castro, Isac; Baptista, Maria A S F; Alves, Venancio A; Yu, Luis; Burdmann, Emmanuel A

    2006-07-01

    The spread of Africanized bees in the American continent has increased the number of severe envenomation after swarm attacks. Acute renal failure (ARF) is one of the major hazards in surviving patients. To assess the mechanisms of bee venom-induced ARF, rats were evaluated before, up to 70 min and 24h after 0.5mg/kg of venom injection. Control rats received saline. Bee venom caused an early and significant reduction in glomerular filtration rate (GFR, inulin clearance, 0.84+/-0.05 to 0.40+/-0.08 ml/min/100g, pbee venom-induced ARF that may occur even without hemolysis or hypotension.

  18. Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats.

    Science.gov (United States)

    Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

    2016-12-20

    The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured. Fluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups. Blood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in renal microvascular oxygenation and sepsis-induced endothelial dysfunction via the restoration of eNOS expression within the kidney.

  19. Manifestations of Renal Impairment in Fructose-induced Metabolic Syndrome.

    Science.gov (United States)

    Bratoeva, Kameliya; Stoyanov, George S; Merdzhanova, Albena; Radanova, Mariya

    2017-11-07

    Introduction International studies show an increased incidence of chronic kidney disease (CKD) in patients with metabolic syndrome (MS). It is assumed that the major components of MS - obesity, insulin resistance, dyslipidemia, and hypertension - are linked to renal damage through the systemic release of several pro-inflammatory mediators, such as uric acid (UA), C-reactive protein (CRP), and generalized oxidative stress. The aim of the present study was to investigate the extent of kidney impairment and manifestations of dysfunction in rats with fructose-induced MS. Methods We used a model of high-fructose diet in male Wistar rats with 35% glucose-fructose corn syrup in drinking water over a duration of 16 weeks. The experimental animals were divided into two groups: control and high-fructose drinking (HFD). Serum samples were obtained from both groups for laboratory study, and the kidneys were extracted for observation via light microscopy examination. Results All HFD rats developed obesity, hyperglycemia, hypertriglyceridemia, increased levels of CRP and UA (when compared to the control group), and oxidative stress with high levels of malondialdehyde and low levels of reduced glutathione. The kidneys of the HFD group revealed a significant increase in kidney weight in the absence of evidence of renal dysfunction and electrolyte disturbances. Under light microscopy, the kidneys of the HFD group revealed amyloid deposits in Kimmelstiel-Wilson-like nodules and the walls of the large caliber blood vessels, early-stage atherosclerosis with visible ruptures and scarring, hydropic change (vacuolar degeneration) in the epithelial cells covering the proximal tubules, and increased eosinophilia in the distant tubules when compared to the control group. Conclusion Under the conditions of a fructose-induced metabolic syndrome, high serum UA and CRP correlate to the development of early renal disorders without a clinical manifestation of renal dysfunction. These

  20. Renal transplantation induces mitochondrial uncoupling, increased kidney oxygen consumption, and decreased kidney oxygen tension

    NARCIS (Netherlands)

    Papazova, Diana A.; Friederich-Persson, Malou; Joles, Jaap A.; Verhaar, Marianne C.

    2015-01-01

    Hypoxia is an acknowledged pathway to renal injury and ischemia-reperfusion (I/R) and is known to reduce renal oxygen tension (PO2). We hypothesized that renal I/R increases oxidative damage and induces mitochondrial uncoupling, resulting in increased oxygen consumption and hence kidney

  1. Renal endothelial function and blood flow predict the individual susceptibility to adriamycin-induced renal damage

    NARCIS (Netherlands)

    Ochodnicky, Peter; Henning, Robert H.; Buikema, Hendrik; Kluppel, Alex C. A.; van Wattum, Marjolein; de Zeeuw, Dick; van Dokkum, Richard P. E.

    2009-01-01

    Susceptibility to renal injury varies among individuals. Previously, we found that individual endothelial function of healthy renal arteries in vitro predicted severity of renal damage after 5/6 nephrectomy. Here we hypothesized that individual differences in endothelial function in vitro and renal

  2. CIRRHOSIS INDUCES APOPTOSIS IN RENAL TISSUE THROUGH INTRACELLULAR OXIDATIVE STRESS

    Directory of Open Access Journals (Sweden)

    Keli Cristina Simões da SILVEIRA

    2015-03-01

    Full Text Available Background Renal failure is a frequent and serious complication in patients with decompensated cirrhosis. Objectives We aimed to evaluate the renal oxidative stress, cell damage and impaired cell function in animal model of cirrhosis. Methods Secondary biliary cirrhosis was induced in rats by ligation of the common bile duct. We measured TBARS, ROS and mitochondrial membrane potential in kidney as markers of oxidative stress, and activities of the antioxidant enzymes. Relative cell viability was determined by trypan blue dye-exclusion assay. Annexin V-PE was used with a vital dye, 7-AAD, to distinguish apoptotic from necrotic cells and comet assay was used for determined DNA integrity in single cells. Results In bile duct ligation animals there was significant increase in the kidney lipoperoxidation and an increase of the level of intracellular ROS. There was too an increase in the activity of all antioxidant enzymes evaluated in the kidney. The percentage viability was above 90% in the control group and in bile duct ligation was 64.66% and the dominant cell death type was apoptosis. DNA damage was observed in the bile duct ligation. There was a decreased in the mitochondrial membrane potential from 71.40% ± 6.35% to 34.48% ± 11.40% in bile duct ligation. Conclusions These results indicate that intracellular increase of ROS cause damage in the DNA and apoptosis getting worse the renal function in cirrhosis.

  3. Efferent pathways in sodium overload-induced renal vasodilation in rats.

    Directory of Open Access Journals (Sweden)

    Nathalia O Amaral

    Full Text Available Hypernatremia stimulates the secretion of oxytocin (OT, but the physiological role of OT remains unclear. The present study sought to determine the involvement of OT and renal nerves in the renal responses to an intravenous infusion of hypertonic saline. Male Wistar rats (280-350 g were anesthetized with sodium thiopental (40 mg. kg(-1, i.v.. A bladder cannula was implanted for collection of urine. Animals were also instrumented for measurement of mean arterial pressure (MAP and renal blood flow (RBF. Renal vascular conductance (RVC was calculated as the ratio of RBF by MAP. In anesthetized rats (n = 6, OT infusion (0.03 µg • kg(-1, i.v. induced renal vasodilation. Consistent with this result, ex vivo experiments demonstrated that OT caused renal artery relaxation. Blockade of OT receptors (OXTR reduced these responses to OT, indicating a direct effect of this peptide on OXTR on this artery. Hypertonic saline (3 M NaCl, 1.8 ml • kg(-1 b.wt., i.v. was infused over 60 s. In sham rats (n = 6, hypertonic saline induced renal vasodilation. The OXTR antagonist (AT; atosiban, 40 µg • kg(-1 • h(-1, i.v.; n = 7 and renal denervation (RX reduced the renal vasodilation induced by hypernatremia. The combination of atosiban and renal denervation (RX+AT; n = 7 completely abolished the renal vasodilation induced by sodium overload. Intact rats excreted 51% of the injected sodium within 90 min. Natriuresis was slightly blunted by atosiban and renal denervation (42% and 39% of load, respectively, whereas atosiban with renal denervation reduced sodium excretion to 16% of the load. These results suggest that OT and renal nerves are involved in renal vasodilation and natriuresis induced by acute plasma hypernatremia.

  4. Bradykinin receptor blockade restores the baroreflex control of renal sympathetic nerve activity in cisplatin-induced renal failure rats.

    Science.gov (United States)

    Abdulla, M H; Duff, M; Swanton, H; Johns, E J

    2016-11-01

    This study investigated the effect of renal bradykinin B1 and B2 receptor blockade on the high- and low-pressure baroreceptor reflex regulation of renal sympathetic nerve activity (RSNA) in rats with cisplatin-induced renal failure. Cisplatin (5 mg/kg) or saline was given intraperitoneally 4 days prior to study. Following chloralose/urethane anaesthesia, rats were prepared for measurement of mean arterial pressure (MAP), heart rate and RSNA and received intrarenal infusions of either Lys-[des-Arg 9 , Leu 8 ]-bradykinin (LBK), a bradykinin B1 receptor blocker, or bradyzide (BZ), a bradykinin B2 receptor blocker. RSNA baroreflex gain curves and renal sympatho-inhibitory responses to volume expansion (VE) were obtained. In the control and renal failure groups, basal MAP (89 ± 3 vs. 80 ± 8 mmHg) and RSNA (2.0 ± 0.3 vs. 1.7 ± 0.6 μV.s) were similar but HR was lower in the latter group (331 ± 8 vs. 396 ± 9 beats/min). The baroreflex gain for RSNA in the renal failure rats was 39% (P renal failure rats. Intrarenal LBK infusion in the renal failure rats normalized the VE induced renal sympatho-inhibition whereas BZ only partially restored the response. These findings suggest that pro-inflammatory bradykinin acting at different receptors within the kidney generates afferent neural signals which impact differentially within the central nervous system on high- and low-pressure regulation of RSNA. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  5. Two cases of cisplatin-induced permanent renal failure following neoadjuvant chemotherapy for esophageal cancer.

    Science.gov (United States)

    Sasaki, Tomohiko; Motoyama, Satoru; Komatsuda, Atsushi; Shibata, Hiroyuki; Sato, Yusuke; Yoshino, Kei; Wakita, Akiyuki; Saito, Hajime; Anbai, Akira; Jin, Mario; Minamiya, Yoshihiro

    2016-01-01

    We experienced two esophageal cancer patients who developed severe acute renal failure after neoadjuvant chemotherapy with cisplatin and 5-fluorourasil. After administration of cisplatin, their serum creatinine increased gradually until they required hemodialysis and their renal failure was permanent. In both cases, renal biopsy examination indicated partial recovery of the proximal tubule, but renal function did not recover. After these events, one patient underwent definitive radiotherapy and the other underwent esophagectomy for their esophageal cancers, while continuing dialysis. Both patients are alive without cancer recurrence. In these two cases of cisplatin-induced renal failure, renal biopsy examination showed only slight disorder of proximal tubules and tendency to recover. Although cisplatin-related nephrotoxicity is a well-recognized complication, there have been few reports of renal failure requiring hemodialysis in cancer patients. In this report, we present their clinical courses and the pathological findings of cisplatin-related renal failure. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Renal endothelial function and blood flow predict the individual susceptibility to adriamycin-induced renal damage

    NARCIS (Netherlands)

    Ochodnicky, Peter; Henning, Robert H.; Buikema, Hendrik; Kluppel, Alex C. A.; van Wattum, Marjolein; de Zeeuw, Dick; van Dokkum, Richard P. E.

    Background. Susceptibility to renal injury varies among individuals. Previously, we found that individual endothelial function of healthy renal arteries in vitro predicted severity of renal damage after 5/6 nephrectomy. Here we hypothesized that individual differences in endothelial function in

  7. Nutritional status, hypertension, proteinuria and glycosuria amongst the women of rural Bangladesh

    Directory of Open Access Journals (Sweden)

    Shaila Ahmed

    2008-01-01

    Full Text Available Methods and materials – A rural community was purposively selected in Sreepur thana of which four villages were selected randomly. The total population of all age groups was 14,165 and the eligible reproductive aged females were 3,820 based on age between 15 and 45 years. Sample size was estimated at 573 (15% of the eligible participants depending on the availability of time and logistic support. The study design was to use a questionnaire related to age, education, family income, housing and sanitation. Height (ht, weight (wt and blood pressure (BP were measured. Urine protein was estimated. Clinical examinations noted the presence of anemia, jaundice, edema, ring-worm, scabies, goiter, xerophthalmia and gum bleeding. Body mass index (BMI was calculated to determine their obesity or wasting. Results – Overall, 501 volunteered and the response rate was 87.4%. Of these participants, 30.3% were illiterate. Almost all of them had supply of tube-well water and 68% had sanitary latrines. Their mean (±SD age was 30.2 (±2.9y, wt was 46 (±8.5kg, ht was 149 (±5cm and BMI was 20.5 (±3.5. The poor women had significantly lower BMI than the rich [20.0 (2.93 vs. 21.2 (4.1, (p<0.05]. Their mean (±SD systolic and diastolic blood pressure were 116 (±17 and 73 (±12 mmHg, respectively. The prevalence of hypertension, proteinuria and glycosuria were 16.6, 10.4 and 2.6%, respectively. The frequencies of proteinuria and ring-worm were significantly higher among the poor than among the rich social class (both cases p<0.05. Regarding nutritional deficiency, about half of the rural women (52% had some form of signs relating to Vit-A deficiency and 65% had signs of Vit-B complex deficiency either in the form of glossitis or of angular stomatitis or both. Conclusions – Despite time and logistic constraint, the study revealed that most of the rural women had a poor nutritional status (80% had BMI<23.0. The prevalence of hypertension and glycosuria were also

  8. High-NaCl diet impairs dynamic renal blood flow autoregulation in rats with adenine-induced chronic renal failure

    DEFF Research Database (Denmark)

    Saeed, Aso; DiBona, Gerald F; Grimberg, Elisabeth

    2014-01-01

    This study examined the effects of 2 wk of high-NaCl diet on kidney function and dynamic renal blood flow autoregulation (RBFA) in rats with adenine-induced chronic renal failure (ACRF). Male Sprague-Dawley rats received either chow containing adenine or were pair-fed an identical diet without...... arterial pressure variability (SAPV), and heart rate variability were assessed by spectral analytical techniques. Rats with ACRF showed marked reductions in glomerular filtration rate and renal blood flow (RBF), whereas mean arterial pressure and SAPV were significantly elevated. In addition, spontaneous...... adenine (controls). After 10 wk, rats were randomized to either remain on the same diet (0.6% NaCl) or to be switched to high 4% NaCl chow. Two weeks after randomization, renal clearance experiments were performed under isoflurane anesthesia and dynamic RBFA, baroreflex sensitivity (BRS), systolic...

  9. Neural regulation of the kidney function in rats with cisplatin induced renal failure

    Science.gov (United States)

    Goulding, Niamh E.; Johns, Edward J.

    2015-01-01

    Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

  10. Cyclosporine A induces senescence in renal tubular epithelial cells

    NARCIS (Netherlands)

    Jennings, Paul; Koppelstaetter, Christian; Aydin, Sonia; Abberger, Thomas; Wolf, Anna Maria; Mayer, Gert; Pfaller, Walter

    The nephrotoxic potential of the widely used immunosuppressive agent cyclosporine A (CsA) is well recognized. However, the mechanism of renal tubular toxicity is not yet fully elucidated. Chronic CsA nephropathy and renal organ aging share some clinical features, such as renal fibrosis and tubular

  11. Effects of renal denervation on tubular sodium handling in rats with CBL-induced liver cirrhosis

    DEFF Research Database (Denmark)

    Jonassen, T.E.; Brond, L.; Torp, M.

    2003-01-01

    This study was designed to examine the effect of bilateral renal denervation (DNX) on thick ascending limb of Henle's loop (TAL) function in rats with liver cirrhosis induced by common bile duct ligation (CBL). The CBL rats had, as previously shown, sodium retention associated with hypertrophy...... renal sympathetic nerve activity known to be present in CBL rats plays a significant role in the formation of sodium retention by stimulating sodium reabsorption in the TAL via increased renal abundance of NKCC2....

  12. Antithymocyte antibody-induced coagulopathy in renal transplant recipients.

    Science.gov (United States)

    Siparsky, N F; Klein, R; Kushnir, L F; Gallichio, M H; Conti, D J

    2013-05-01

    Antithymocyte antibody (ATA) remains the most commonly used induction immunosuppressive agent in renal transplantation (RT). To date, few case reports of ATA-induced coagulopathy exist. We performed a single-center, retrospective analysis of renal transplant recipients (RTRs) who underwent RT followed by ATA therapy between 2007 and 2011. The protocol used for deceased donor and unrelated living donor recipient immunosuppression was Thymoglobulin (TMG), methylprednisolone, Cellcept, Prograf, and Rapamune. In related living donor recipients, Simulect (SIM) was substituted for TMG. The international normalized ratio (INR) was routinely checked on days 0 and 2, and thereafter at the discretion of the surgeon. RTRs were transfused packed red blood cells (PRBCs) or fresh frozen plasma (FFP) at the discretion of the surgeon. During the study period, 257 RTs were performed at our institution. The following 18 RTR were excluded: simultaneous kidney and pancreas transplant recipients (4), RTRs on warfarin at the time of admission (2), RTRs who received OKT3 (2), and RTRs with INR ≥ 1.2 at the time of admission (10). Of the remaining 239 RTR, 208 (87%) underwent TMG induction therapy; 31 RTR (13%) underwent SIM induction therapy. The mean INR peaked in both groups on day 4 but was higher in TMG recipients (TMG 1.35, SIM 1.20). FFP was transfused in 65 TMG (31%) and 3 SIM (10%) recipients (P = .01); PRBCs were transfused in 88 TMG (44%) and 6 SIM (19%) recipients (P = .02). No patients returned to the operating room for bleeding complications within 7 days of RT. Patient age, gender, ethnicity, and diabetes status were not statistically significant factors in the development of coagulopathy. TMG administration is associated with coagulopathy. Using an INR screening protocol and an aggressive transfusion protocol, bleeding complications associated with coagulopathy can be avoided in this higher-risk group. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

    Directory of Open Access Journals (Sweden)

    Magdalena Cristóbal-García

    2015-01-01

    Full Text Available We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks and short-term (3 weeks effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW, OA+Allopurinol (AP, 150 mg/L drinking water, OA+Tempol (T, 15 mg/kg BW, or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase and oxidative stress markers (lipid and protein oxidation along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

  14. Role of pressure in angiotensin II-induced renal injury: chronic servo-control of renal perfusion pressure in rats.

    Science.gov (United States)

    Mori, Takefumi; Cowley, Allen W

    2004-04-01

    Renal perfusion pressure was servo-controlled chronically in rats to quantify the relative contribution of elevated arterial pressure versus angiotensin II (Ang II) on the induction of renal injury in Ang II-induced hypertension. Sprague-Dawley rats fed a 4% salt diet were administered Ang II for 14 days (25 ng/kg per minute IV; saline only for sham rats), and the renal perfusion pressure to the left kidney was continuously servo-controlled to maintain a normal pressure in that kidney throughout the period of hypertension. An aortic occluder was implanted around the aorta between the two renal arteries and carotid and femoral arterial pressure were measured continuously throughout the experiment to determine uncontrolled and controlled renal perfusion pressure, respectively. Renal perfusion pressure of uncontrolled, controlled, and sham kidneys over the period of Ang II or saline infusion averaged 152.6+/-7.0, 117.4+/-3.5, and 110.7+/-2.2 mm Hg, respectively. The high-pressure uncontrolled kidneys exhibited tubular necrosis and interstitial fibrosis, especially prominent in the outer medullary region. Regional glomerular sclerosis and interlobular artery injury were also pronounced. Controlled kidneys were significantly protected from interlobular artery injury, juxtamedullary glomeruli injury, tubular necrosis, and interstitial fibrosis as determined by comparing the level of injury. Glomerular injury was not prevented in the outer cortex. Transforming growth factor (TGF)-beta and active NF-kappaB proteins determined by immunohistochemistry were colocalized in the uncontrolled kidney in regions of interstitial fibrosis. We conclude that the preferential juxtamedullary injury found in Ang II hypertension is largely induced by pressure and is probably mediated through the TGF-beta and NF-kappaB pathway.

  15. High-NaCl diet impairs dynamic renal blood flow autoregulation in rats with adenine-induced chronic renal failure.

    Science.gov (United States)

    Saeed, Aso; DiBona, Gerald F; Grimberg, Elisabeth; Nguy, Lisa; Mikkelsen, Minne Line Nedergaard; Marcussen, Niels; Guron, Gregor

    2014-03-15

    This study examined the effects of 2 wk of high-NaCl diet on kidney function and dynamic renal blood flow autoregulation (RBFA) in rats with adenine-induced chronic renal failure (ACRF). Male Sprague-Dawley rats received either chow containing adenine or were pair-fed an identical diet without adenine (controls). After 10 wk, rats were randomized to either remain on the same diet (0.6% NaCl) or to be switched to high 4% NaCl chow. Two weeks after randomization, renal clearance experiments were performed under isoflurane anesthesia and dynamic RBFA, baroreflex sensitivity (BRS), systolic arterial pressure variability (SAPV), and heart rate variability were assessed by spectral analytical techniques. Rats with ACRF showed marked reductions in glomerular filtration rate and renal blood flow (RBF), whereas mean arterial pressure and SAPV were significantly elevated. In addition, spontaneous BRS was reduced by ∼50% in ACRF animals. High-NaCl diet significantly increased transfer function fractional gain values between arterial pressure and RBF in the frequency range of the myogenic response (0.06-0.09 Hz) only in ACRF animals (0.3 ± 4.0 vs. -4.4 ± 3.8 dB; P renal failure by facilitating pressure transmission to the microvasculature.

  16. Renal damage induced by dosorubicin-lipiodol emulsion infused into rabbit renal artery : comparison with CT and histologic findings

    International Nuclear Information System (INIS)

    Kim, Jin Gyoo; Moon, Tae Young; Lee, Suck Hong; Kim, Byung Soo; Choi, Sang Yul; Park, Choong Hoon

    1998-01-01

    The purpose of this study is to evaluate the utility of renal CT scanning and to histologically correlate renal damage induced by renal arterial infusion of 0.2 ml/kg of doxorubicin-lipiodol emulsion. Renal CT scans of 20 rabbit kidneys were obtained 15 days after transcatheter arterial chemoembolization and were classified into four grades, as follows: grade 0 - no fleck, grade 1 - one to three nodular flecks; grade 2 - four or more nodular flecks, or one semilunar fleck; and grade 3 - two or more semilunar flecks. The percentage of histological section occupied by lesion was determined using squared paper, and compared with the grades determined on the basis of CT. The histologic findings were interstitial inflammatory cell infiltration, intratubular lipiodol droplets, dystrophic calcification, and and cellular necrosis. The mean sizes of grade 0, 1, 2 and 3 histological lesions were 2.2 % (n=5), 4.5 % (n=4), 21.9 % (n=7), and 24% (n=4), respectively. Grades 0 and 1 accounted for nine cases (3.2%), while grades 2 and 3 accounted for 11 (22.6%); this difference was statistically significant (p<0.01). CT findings showing nodular or semilunar flecks 15 days after infusion into the renal artery of doxorubicin-lipiodol emulsion correlate with the size of the damaged kidney, as seen on histological specimens. (author). 19 refs., 3 tabs., 5 figs

  17. Erhuang Formula ameliorates renal damage in adenine-induced chronic renal failure rats via inhibiting inflammatory and fibrotic responses.

    Science.gov (United States)

    Zhang, Chun-Yan; Zhu, Jian-Yong; Ye, Ying; Zhang, Miao; Zhang, Li-Jun; Wang, Su-Juan; Song, Ya-Nan; Zhang, Hong

    2017-11-01

    The present study aimed to evaluate the protective effects of Erhuang Formula (EHF) and explore its pharmacological mechanisms on adenine-induced chronic renal failure (CRF). The compounds in EHF were analyzed by HPLC/MS. Adenine-induced CRF rats were administrated by EHF. The effects were evaluated by renal function examination and histology staining. Immunostaining of some proteins related cell adhesion was performedin renal tissues, including E-cadherin, β-catenin, fibronectin and laminin. The qRT-PCR was carried out determination of gene expression related inflammation and fibrosis including NF-κB, TNF-α, TGF-β1, α-SMA and osteopontin (OPN). Ten compounds in EHF were identified including liquiritigenin, farnesene, vaccarin, pachymic acid, cycloastragenol, astilbin, 3,5,6,7,8,3',4'-heptemthoxyflavone, physcion, emodin and curzerene. Abnormal renal function and histology had significant improvements by EHF treatment. The protein expression of β-catenin, fibronectin and laminin were significantly increased and the protein expression of E-cadherin significantly decreased in CRF groups. However, these protein expressions were restored to normal levels in EHF group. Furthermore, low expression of PPARγ and high expression of NF-κB, TNF-α, TGF-β1, α-SMA and OPN were substantially restored by EHF treatment in a dose-dependent manner. EHF ameliorated renal damage in adenine-induced CRF rats, and the mechanisms might involve in the inhibition of inflammatory and fibrotic responses and the regulation of PPARγ, NF-κB and TGF-β signaling pathways. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Perinatal radiation-induced renal damage in the beagle

    International Nuclear Information System (INIS)

    Jaenke, R.S.; Angleton, G.M.

    1990-01-01

    The developing perinatal kidney is particularly sensitive to radiation. The pathogenesis of the radiation-induced lesion is related to the destruction of outer cortical developing nephrons and direct radiation injury with secondary hemodynamic alterations in remnant nephrons. In this study, which is part of a life span investigation of the effects of whole-body gamma radiation during prenatal and early postnatal life, dogs were given 0, 0.16, 0.83, or 1.25 Gy irradiation at either 55 days postcoitus or 2 days postpartum and were examined morphometrically and histopathologically at 70 days of age. Although irradiated dogs showed no reduction in the total number of nephrons per kidney, there was a significant increase in the total number and relative percentage of immature, dysplastic glomeruli. In addition, deeper cortical glomeruli of irradiated kidneys exhibited mesangial sclerosis similar to that associated with progressive renal failure in our previous studies. These findings are in accord with those reported at doses of 2.24 to 3.57 Gy and demonstrate that the perinatal kidney is affected by radiation doses much lower than previously demonstrated

  19. Heat-processed ginseng saponin ameliorates the adenine-induced renal failure in rats

    OpenAIRE

    Kim, Eun Jin; Oh, Hyun-A; Choi, Hyuck Jai; Park, Jeong Hill; Kim, Dong-Hyun; Kim, Nam Jae

    2013-01-01

    To evaluate the effect of the saponin of heat-processed ginseng (Sun ginseng, SG), we investigated the protective effect of SG total saponin fraction against adenine-induced chronic renal failure in rats. SG saponin significantly decreased the levels of urea nitrogen and creatinine in the serum, but increased the urinary excretion of urea nitrogen and creatinine, indicating an improvement of renal function. SG saponin also inhibited adenine-induced kidney hypertrophy and edema. SG saponin red...

  20. Tubular overexpression of gremlin induces renal damage susceptibility in mice.

    Directory of Open Access Journals (Sweden)

    Alejandra Droguett

    Full Text Available A growing number of patients are recognized worldwide to have chronic kidney disease. Glomerular and interstitial fibrosis are hallmarks of renal progression. However, fibrosis of the kidney remains an unresolved challenge, and its molecular mechanisms are still not fully understood. Gremlin is an embryogenic gene that has been shown to play a key role in nephrogenesis, and its expression is generally low in the normal adult kidney. However, gremlin expression is elevated in many human renal diseases, including diabetic nephropathy, pauci-immune glomerulonephritis and chronic allograft nephropathy. Several studies have proposed that gremlin may be involved in renal damage by acting as a downstream mediator of TGF-β. To examine the in vivo role of gremlin in kidney pathophysiology, we generated seven viable transgenic mouse lines expressing human gremlin (GREM1 specifically in renal proximal tubular epithelial cells under the control of an androgen-regulated promoter. These lines demonstrated 1.2- to 200-fold increased GREM1 expression. GREM1 transgenic mice presented a normal phenotype and were without proteinuria and renal function involvement. In response to the acute renal damage cause by folic acid nephrotoxicity, tubule-specific GREM1 transgenic mice developed increased proteinuria after 7 and 14 days compared with wild-type treated mice. At 14 days tubular lesions, such as dilatation, epithelium flattening and hyaline casts, with interstitial cell infiltration and mild fibrosis were significantly more prominent in transgenic mice than wild-type mice. Tubular GREM1 overexpression was correlated with the renal upregulation of profibrotic factors, such as TGF-β and αSMA, and with increased numbers of monocytes/macrophages and lymphocytes compared to wild-type mice. Taken together, our results suggest that GREM1-overexpressing mice have an increased susceptibility to renal damage, supporting the involvement of gremlin in renal damage

  1. Mixed organic solvents induce renal injury in rats.

    Directory of Open Access Journals (Sweden)

    Weisong Qin

    Full Text Available To investigate the injury effects of organic solvents on kidney, an animal model of Sprague-Dawley (SD rats treated with mixed organic solvents via inhalation was generated and characterized. The mixed organic solvents consisted of gasoline, dimethylbenzene and formaldehyde (GDF in the ratio of 2:2:1, and were used at 12,000 PPM to treat the rats twice a day, each for 3 hours. Proteinuria appeared in the rats after exposure for 5-6 weeks. The incidences of proteinuria in male and female rats after exposure for 12 weeks were 43.8% (7/16 and 25% (4/16, respectively. Urinary N-Acetyl-β-(D-Glucosaminidase (NAG activity was increased significantly after exposure for 4 weeks. Histological examination revealed remarkable injuries in the proximal renal tubules, including tubular epithelial cell detachment, cloud swelling and vacuole formation in the proximal tubular cells, as well as proliferation of parietal epithelium and tubular reflux in glomeruli. Ultrastructural examination found that brush border and cytoplasm of tubular epithelial cell were dropped, that tubular epithelial cells were partially disintegrated, and that the mitochondria of tubular epithelial cells were degenerated and lost. In addition to tubular lesions, glomerular damages were also observed, including segmental foot process fusion and loss of foot process covering on glomerular basement membrane (GBM. Immunofluorescence staining indicated that the expression of nephrin and podocin were both decreased after exposure of GDF. In contrast, increased expression of desmin, a marker of podocyte injury, was found in some areas of a glomerulus. TUNEL staining showed that GDF induced apoptosis in tubular cells and glomerular cells. These studies demonstrate that GDF can induce both severe proximal tubular damage and podocyte injury in rats, and the tubular lesions appear earlier than that of glomeruli.

  2. Mixed organic solvents induce renal injury in rats.

    Science.gov (United States)

    Qin, Weisong; Xu, Zhongxiu; Lu, Yizhou; Zeng, Caihong; Zheng, Chunxia; Wang, Shengyu; Liu, Zhihong

    2012-01-01

    To investigate the injury effects of organic solvents on kidney, an animal model of Sprague-Dawley (SD) rats treated with mixed organic solvents via inhalation was generated and characterized. The mixed organic solvents consisted of gasoline, dimethylbenzene and formaldehyde (GDF) in the ratio of 2:2:1, and were used at 12,000 PPM to treat the rats twice a day, each for 3 hours. Proteinuria appeared in the rats after exposure for 5-6 weeks. The incidences of proteinuria in male and female rats after exposure for 12 weeks were 43.8% (7/16) and 25% (4/16), respectively. Urinary N-Acetyl-β-(D)-Glucosaminidase (NAG) activity was increased significantly after exposure for 4 weeks. Histological examination revealed remarkable injuries in the proximal renal tubules, including tubular epithelial cell detachment, cloud swelling and vacuole formation in the proximal tubular cells, as well as proliferation of parietal epithelium and tubular reflux in glomeruli. Ultrastructural examination found that brush border and cytoplasm of tubular epithelial cell were dropped, that tubular epithelial cells were partially disintegrated, and that the mitochondria of tubular epithelial cells were degenerated and lost. In addition to tubular lesions, glomerular damages were also observed, including segmental foot process fusion and loss of foot process covering on glomerular basement membrane (GBM). Immunofluorescence staining indicated that the expression of nephrin and podocin were both decreased after exposure of GDF. In contrast, increased expression of desmin, a marker of podocyte injury, was found in some areas of a glomerulus. TUNEL staining showed that GDF induced apoptosis in tubular cells and glomerular cells. These studies demonstrate that GDF can induce both severe proximal tubular damage and podocyte injury in rats, and the tubular lesions appear earlier than that of glomeruli.

  3. Sida rhomboidea.Roxb leaf extract ameliorates gentamicin induced nephrotoxicity and renal dysfunction in rats.

    Science.gov (United States)

    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Devkar, Ranjitsinh V; Ramachandran, A V

    2010-10-28

    Sida rhomboidea.Roxb (SR) known as "Mahabala" in Ayurveda and marketed as "Shahadeyi" is used in ethnomedicine to treat ailments such as dysuria and urinary disorders. To evaluate nephroprotective potential of SR against gentamicin (GM) induced nephrotoxicity and renal dysfunction. Nephrotoxicity was induced in rats with GM (100 mg/kg bodyweight (i.p.) for 8 days) and were treated with SR extract (200 and 400 mg/kg bodyweight (p.o.) for 8 days) or 0.5% carboxymethyl cellulose (vehicle). Plasma and urine urea and creatinine, renal enzymatic and non-enzymatic antioxidants along with lipid peroxidation were evaluated in various experimental groups. GM treatment induced significant elevation (p<0.05) in plasma and urine urea, creatinine, renal lipid peroxidation along with significant decrement (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR treatment to GM treated rats (GM+SR) recorded significant decrement (p<0.05) in plasma and urine urea and creatinine, renal lipid peroxidation along with significant increment (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR leaf extract ameliorates GM induced nephrotoxicity and renal dysfunction and thus validates its ethnomedicinal use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Amlodipine-induced gingival hyperplasia in chronic renal

    African Journals Online (AJOL)

    Administrator

    Keywords: Amlodipine, gingival hyperplasia, chronic renal failure. African Health ... for the treatment of hypertension and angina. Pharmacokinetic ... patient appealed to the dentist at first. ... Am Heart J. 1989 Nov; 118(5 Pt 2):. 1100-1103. 2.

  5. Exercise Induced Rhabdomyolysis with Compartment Syndrome and Renal Failure

    Directory of Open Access Journals (Sweden)

    Mary Colleen Bhalla

    2014-01-01

    Full Text Available Exertional rhabdomyolysis is sequela that is occasionally seen after strenuous exercise. The progression to compartment syndrome or renal failure is a rare complication that requires prompt recognition and treatment to prevent morbidity (Giannoglou et al. 2007. We present a case of a 22-year-old college football player who presented to the emergency department (ED after a typical leg workout as part of his weight conditioning. He was found to have rhabdomyolysis with evidence of renal insufficiency. His condition progressed to bilateral compartment syndrome and renal failure requiring dialysis. After bilateral fasciotomies were performed he had resolution of his compartment syndrome. He continued to be dialysis dependent and had no return of his renal function at discharge 12 days after admission.

  6. Renal handling of drugs in renal failure. I: Differential effects of uranyl nitrate- and glycerol-induced acute renal failure on renal excretion of TEAB and PAH in rats

    International Nuclear Information System (INIS)

    Lin, J.H.; Lin, T.H.

    1988-01-01

    Two etiologically different models of experimental acute renal failure were induced in rats by administration of either glycerol or uranyl nitrate. Both compounds caused a substantial decrease in the glomerular filtration rate (GFR) and the net tubular secretion of tetraethylammonium bromide (TEAB) and para-aminohippuric acid (PAH). The degree of renal impairment induced by uranyl nitrate and glycerol appeared to be dose related. Deprivation of drinking water 24 hr before the administration of glycerol potentiated the renal damage. In uranyl nitrate-induced renal failure, the decline of the net tubular secretion for TEAB and PAH was not proportional to the decrease in GFR; the secretion process deteriorated faster than the GFR. For example, when 0.5 mg/kg uranyl nitrate was administered, GFR fell to approximately 65% of normal, whereas the net tubular secretion was decreased to 30% of normal. These results suggest that the tubular transport was preferentially affected by uranyl nitrate. In contrast, in glycerol-induced renal failure, the decline of TEAB secretion fell in a parallel fashion with the GFR, suggesting that the glomeruli and the proximal tubules were equally damaged by glycerol. However, in this latter model, the decline of PAH secretion did not parallel the decrease in GFR, contradicting the proposal that glycerol affects equally the glomeruli and the proximal tubules. This discrepancy may be due to the selective competitive inhibition of PAH secretion by the accumulation of naturally occurring organic acids

  7. Nephrolithiasis and Osteomalacia associated with adefovir-induced Fanconi syndrome in a patient with hepatitis B.

    Science.gov (United States)

    Lin, Jueying; Zhuo, Yufeng; Zhang, Dongdong

    2017-08-29

    An increasing number of case reports suggest that acquired renal Fanconi syndrome may be associated with prolonged use of adefovir against hepatitis B virus. Renal Fanconi syndrome is an uncommon disease, and its complication with nephrolithiasis is quite rare. Herein, we report a rare coexistence of nephrolithiasis and acquired renal Fanconi syndrome in a chronic hepatitis B-positive patient with prolonged adefovir therapy. The patient presented with osteomalacia and nephrolithiasis. Consequently, extracorporeal shock-wave lithotripsy and left double-J ureteral stent insertion were considered for obstructive nephropathy, which was caused by nephrolithiasis. However, osteomalacia had been misdiagnosed as osteoporosis before admission to our hospital. On admission, a complexity of multiple fractures, hypophosphataemia, glycosuria without hyperglycaemia and non-anion-gap metabolic acidosis indicated a diagnosis of acquired renal Fanconi syndrome induced by adefovir. After switching from adefovir to entecavir, the patient's symptoms and laboratory findings improved significantly. The mechanism responsible for nephrolithiasis in renal Fanconi syndrome is still unclear. We recommend regularly monitoring renal function and serum calcium and serum phosphate to prevent renal Fanconi syndrome during the prolonged use of adefovir for hepatitis B virus.

  8. Rhabdomyolysis induced acute renal failure secondary to statins

    Directory of Open Access Journals (Sweden)

    R Ram

    2013-01-01

    Full Text Available Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle contents into the systemic circulation. We report a patient with chronic kidney disease who had deterioration of renal function due to combination of risk factors like hypothyroidism and interaction of amlodipine and clopidogrel with statins.

  9. OBESITY-INDUCED HYPERTENSION: INTERACTION OF NEUROHUMORAL AND RENAL MECHANISMS

    Science.gov (United States)

    Hall, John E.; do Carmo, Jussara M.; da Silva, Alexandre A.; Wang, Zhen; Hall, Michael E.

    2015-01-01

    Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65–75% of the risk for human primary (essential) hypertension. Increased renal tubular sodium reabsorption impairs pressure natriuresis and plays an important role in initiating obesity hypertension. The mediators of abnormal kidney function and increased blood pressure during development of obesity hypertension include 1) physical compression of the kidneys by fat in and around the kidneys, 2) activation of the renin-angiotensin-aldosterone system (RAAS), and 3) increased sympathetic nervous system (SNS) activity. Activation of the RAAS system is likely due, in part, to renal compression as well as SNS activation. However, obesity also causes mineralocorticoid receptor activation independent of aldosterone or angiotensin II. The mechanisms for SNS activation in obesity have not been fully elucidated but appear to require leptin and activation of the brain melanocortin system. With prolonged obesity and development of target organ injury, especially renal injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes, and inflammation. Unless effective anti-obesity drugs are developed, the impact of obesity on hypertension and related cardiovascular, renal and metabolic disorders is likely to become even more important in the future as the prevalence of obesity continues to increase. PMID:25767285

  10. Tobacco Induced Renal Function Alterations in Wistar Rats: An 8 ...

    African Journals Online (AJOL)

    ... pattern was observed for urea and uric acid levels. Over all, the significant increase (P<0.05) in renal function parameters of the test rats (as compared to the control values), suggests that the ingestion of tobacco snuff has harmful effects on kidney functions. Keywords: Tobacco, Snuff, Kidney function, Nicotine substitute.

  11. Acute Renal Failure Induced by Chinese Herbal Medication in Nigeria

    Directory of Open Access Journals (Sweden)

    Effiong Ekong Akpan

    2015-01-01

    Full Text Available Traditional herbal medicine is a global phenomenon especially in the resource poor economy where only the very rich can access orthodox care. These herbal products are associated with complications such as acute renal failure and liver damage with a high incidence of mortalities and morbidities. Acute renal failure from the use of herbal remedies is said to account for about 30–35% of all cases of acute renal failure in Africa. Most of the herbal medications are not usually identified, but some common preparation often used in Nigeria includes “holy water” green water leaves, bark of Mangifera indica (mango, shoot of Anacardium occidentale (cashew, Carica papaya (paw-paw leaves, lime water, Solanum erianthum (Potato tree, and Azadirachta indica (Neem trees. We report a rare case of a young man who developed acute renal failure two days after ingestion of Chinese herb for “body cleansing” and general wellbeing. He had 4 sessions of haemodialysis and recovered kidney function fully after 18 days of admission.

  12. Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats.

    Science.gov (United States)

    Tsai, Jen-Pi; Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Hsu, Bang-Gee

    2017-01-01

    Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects.

  13. Chinese herbal medicine Shenqi Detoxification Granule inhibits fibrosis in adenine induced chronic renal failure rats.

    Science.gov (United States)

    Peng, Min; Cai, Pingping; Ma, Hongbo; Meng, Hongyan; Xu, Yuan; Zhang, Xiaoyi; Si, Guomin

    2014-01-01

    Progressive fibrosis accompanies all chronic renal disease, connective tissue growth factor (CTGF,) and platelet-derived growth factor-B, (PDGF-B,) play important roles in extra-cellular matrix abnormal accumulation, while endothelin-1 (ET-1) nitric oxide (NO,) are related to endothelial dysfunction, which mediates the progression of renal fibrosis. Shenqi Detoxification Granule (SDG), a traditional Chinese herbal formula, has been used for treatment of chronic renal failure in clinic for many years. In order to evaluate the efficacy, and explore the mechanism of SDG to inhibit the progression of renal fibrosis, study was carried out using the adenine-induced Wister rats as the CRF model, and losartan as postive control drug. Levels of serum creatinine [Scr], and blood urea nitrogen (BUN), albumin (ALB), 24hrs, urine protein (24hUP), triacylglycerol (TG), and cholesterol (CHO), together with ET-1, and NO were detected. Pathological changes of renal tissues were observed by HE, staining. In addition, CTGF and PDGF-B expression were analyzed by immuno-histo-chemistry. The results indicated that SDG can effectively reduce Scr, BUN, 24hUP, TG, and CHO levels, increase ALB levels, inhibit renal tissue damage in CRF rats, and the mechanism maybe reduce PDGF-B, CTGF expression and ET-1/NO. Shenqi Detoxification Granule is a beneficial treatment for chronic renal failure.

  14. Drug-interaction-induced hemodynamically mediated acute renal failure in postsurgical patient

    Directory of Open Access Journals (Sweden)

    Arup K Misra

    2014-01-01

    Full Text Available Acute renal failure is a life threatening condition. Nonsteroidal antiinflammatory drugs (NSAIDs and cephalosporins are widely used postoperative drugs. NSAID-induced acute renal failure has been reported in the past. In this case, drug interaction and decompensated state of the patient precipitate the condition. NSAIDs inhibit prostaglandins synthesis and thus aggravate ischemia to the kidney that is already facing volume crisis due to surgery. Due to renal dysfunction, plasma ceftriaxone level increases due to decrease clearance and it also acts as nephrotoxic by unknown mechanism. On the other hand, ceftriaxone on its interaction with diclofenac for renal tubular clearance also increases the level of diclofenac and thus further aggravate the ischemia. It is a reversible condition with excluding diclofenac from the treatment regimen and giving adequate hydration to the patient. This highlights the importance of hydration and knowledge of drugs interactions in a postsurgical patient.

  15. Comparison of the in vitro and in vivo dissolution rates of two diuranates and research on an early urinary indicator of renal failure in humans and animals poisoned with uranium

    International Nuclear Information System (INIS)

    Henge-Napoli, M.H.; Rongier, E.; Ansoborlo, E.; Chalabreysse, J.

    1989-01-01

    The objective of this study was to investigate the solubility of industrial calcined diuranate in various in vitro systems and to test the sensitivity of biological parameters in detecting renal alterations after intoxication in animals and in human subjects. The dissolution rates in in vitro static and dynamic tests are consistent for each solution for both types of test. The in vivo results are comparable to the in vitro results obtained with Gamble solution for both compounds. The excretion kinetics observed are compared with the values calculated from ICRP standards. Urinary GGT excretion measurements are found to be a satisfactory indicator of uranium-induced kidney alterations. GGT excretion increases for injected doses exceeding 50 μg.kg -1 . Initial results in human subjects suggest that following accidental exposure to uranium, GGT is a more sensitive indicator of kidney damage than glycosuria. (author)

  16. Linezolid-induced thrombocytopenia in two patients with renal dysfunction

    Directory of Open Access Journals (Sweden)

    Engin Melek

    2016-12-01

    Full Text Available Linezolid is an oxazolidinone antibiotic, active against gram positive bacteria that are resistant to other antibiotics including glycopeptides. Thrombocytopenia is an adverse effect of linezolid. Although various risk factors have been suggested, the mechanisms behind this side effect are largely unknown. Here, we report two adolescents with the diagnosis of chronic kidney disease who developed thrombocytopenia following treatment with linezolid. Our purpose in highlighting these cases is to increase the clinical awareness concerning this side effect of linezolid. While it is well known that thrombocytopenia may develop during linezolid treatment, it is relatively unknown that patients with renal dysfunction have an increased risk for the development of thrombocytopenia compared to patients without renal dysfunction. [Cukurova Med J 2016; 41(4.000: 808-810

  17. Cocaine-induced renal infarction: report of a case and review of the literature

    Directory of Open Access Journals (Sweden)

    Nosrati Saeid M

    2005-09-01

    Full Text Available Abstract Background Cocaine abuse has been known to have detrimental effects on the cardiovascular system. Its toxicity has been associated with myocardial ischemia, cerebrovascular accidents and mesenteric ischemia. The pathophysiology of cocaine-related renal injury is multifactorial and involves renal hemodynamic changes, alterations in glomerular matrix synthesis, degradation and oxidative stress, and possibly induction of renal atherogenesis. Renal infarction as a result of cocaine exposure, however, is rarely reported in the literature. Case presentation A 48 year-old male presented with a four-day history of severe right flank pain following cocaine use. On presentation, he was tachycardic, febrile and had severe right costovertebral angle tenderness. He had significant proteinuria, leukocytosis and elevated serum creatinine and lactate dehydrogenase. Radiographic imaging studies as well as other screening tests for thromboembolic events, hypercoagulability states, collagen vascular diseases and lipid disorders were suggestive of Cocaine-Induced Renal Infarction (CIRI by exclusion. Conclusion In a patient with a history of cocaine abuse presenting with fevers and flank pain suggestive of urinary tract infection or nephrolithiasis, cocaine-induced renal infarction must be considered in the differential diagnosis. In this article, we discuss the prior reported cases of CIRI and thoroughly review the literature available on this disorder. This is important for several reasons. First, it will allow us to discuss and elaborate on the mechanism of renal injury caused by cocaine. In addition, this review will demonstrate the importance of considering the diagnosis of CIRI in a patient with documented cocaine use and an atypical presentation of acute renal injury. Finally, we will emphasize the need for a consensus on optimal treatment of this disease, for which therapy is not yet standardized.

  18. The potential anti-inflammatory effect of tetrahydrobiopterin administration in renal mass reduction-induced chronic renal failure in rats

    International Nuclear Information System (INIS)

    Korish, Aida A.; Arafah, Maha M.

    2007-01-01

    Objective was to investigate the impact of tetrahydrobiopterin (BH4) supplementation on the markers of inflammation and on the histological picture of the kidney in chronic renal failure C-reactive protein (CRF) induced in rats by subtotal nephrectomy (SNx). This study was performed at the Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia during the period from December 2005 to January 2007. Chronic renal failure was induced by 5/6 SNx in 20 male Wister rats and another 10 rats were sham operated by flank incision and served as controls. Ten SNx rats received 10 mg/kg-1 BH4 intraperitoneally daily for 4 weeks. Plasma C-reactive protein (CRP), interlukin-6 (IL-6), malondialdehyde (MDA) and kidney functions were measured in all rats. Histopathological examination of kidney tissues was also performed. Untreated CRF rats showed significant elevation of plasma CRP, IL-6 and MDA levels and significant decrease in plasma albumin and total protein levels, tubuloglomerular fibrosis and interstitial tubular infiltration with inflammatory cells in comparison with the sham-operated rats. Tetrahydrobiopterin treatment decreased CRP, IL-6, MDA levels and decreased tubuloglomerular fibrosis and interstitial inflammation in treated CRF rats. Supplementation with exogenous BH4 decreased markers of inflammation and protected the kidney against post-renal mass reduction histological damage. Restoration of intracellular BH4 balance could normalize nitrous oxide production. Therefore, BH4 might be a promising strategy in attenuating inflammation in CRF. This may decrease endothelial dysfunction and limit the associated cardiovascular morbidity and mortality of this disease. (author)

  19. Pharmacological investigations of Punica granatum in glycerol-induced acute renal failure in rats.

    Science.gov (United States)

    Singh, Amrit Pal; Singh, Amteshwar Jaggi; Singh, Nirmal

    2011-09-01

    The present study was designed to investigate the ameliorative potential and possible mechanism of hydroalcoholic extract of flowers of P. granatum in glycerol-induced acute renal failure (ARF) in rats. The rats were subjected to rhabdomyolytic ARF by single intramuscular injection of hypertonic glycerol (50% v/v; 8 ml/kg) and the animals were sacrificed after 24 hours of glycerol injection. The plasma creatinine, blood urea nitrogen, creatinine clearance, and histopathological studies were performed to assess the degree of renal injury. Pretreatment with hydroalcoholic extract of flowers of P. granatum (125 and 250 mg/kg p.o. twice daily for 3 days) significantly attenuated hypertonic glycerol-induced renal dysfunction in a dose-dependent manner. BADGE (Bisphenol-A-diglycidyl ether) (30 mg/kg), a peroxisome proliferator-activated receptor (PPAR)-γ antagonist, and N(omega)-nitro-l-arginine-methyl ester (L-NAME) (10, 20, and 40 mg/kg), nitric oxide synthase inhibitor, were employed to explore the mechanism of renoprotective effects of Punica granatum. Administration of BADGE (30 mg/kg) and L-NAME (40 mg/kg) abolished the beneficial effects of P. granatum in glycerol-induced renal dysfunction. Hydroalcoholic extract of flowers of P. granatum has ameliorative potential in attenuating myoglobinuric renal failure and its renoprotective effects involve activation of PPAR-γ and nitric oxide-dependent signaling pathway.

  20. Usefulness of zebrafish larvae to evaluate drug-induced functional and morphological renal tubular alterations.

    Science.gov (United States)

    Gorgulho, Rita; Jacinto, Raquel; Lopes, Susana S; Pereira, Sofia A; Tranfield, Erin M; Martins, Gabriel G; Gualda, Emilio J; Derks, Rico J E; Correia, Ana C; Steenvoorden, Evelyne; Pintado, Petra; Mayboroda, Oleg A; Monteiro, Emilia C; Morello, Judit

    2018-01-01

    Prediction and management of drug-induced renal injury (DIRI) rely on the knowledge of the mechanisms of drug insult and on the availability of appropriate animal models to explore it. Zebrafish (Danio rerio) offers unique advantages for assessing DIRI because the larval pronephric kidney has a high homology with its human counterpart and it is fully mature at 3.5 days post-fertilization. Herein, we aimed to evaluate the usefulness of zebrafish larvae as a model of renal tubular toxicity through a comprehensive analysis of the renal alterations induced by the lethal concentrations for 10% of the larvae for gentamicin, paracetamol and tenofovir. We evaluated drug metabolic profile by mass spectrometry, renal function with the inulin clearance assay, the 3D morphology of the proximal convoluted tubule by two-photon microscopy and the ultrastructure of proximal convoluted tubule mitochondria by transmission electron microscopy. Paracetamol was metabolized by conjugation and oxidation with further detoxification with glutathione. Renal clearance was reduced with gentamicin and paracetamol. Proximal tubules were enlarged with paracetamol and tenofovir. All drugs induced mitochondrial alterations including dysmorphic shapes ("donuts", "pancakes" and "rods"), mitochondrial swelling, cristae disruption and/or loss of matrix granules. These results are in agreement with the tubular effects of gentamicin, paracetamol and tenofovir in man and demonstrate that zebrafish larvae might be a good model to assess functional and structural damage associated with DIRI.

  1. Lacking Ketohexokinase-A Exacerbates Renal Injury in Streptozotocin-induced Diabetic Mice.

    Science.gov (United States)

    Doke, Tomohito; Ishimoto, Takuji; Hayasaki, Takahiro; Ikeda, Satsuki; Hasebe, Masako; Hirayama, Akiyoshi; Soga, Tomoyoshi; Kato, Noritoshi; Kosugi, Tomoki; Tsuboi, Naotake; Lanaspa, Miguel A; Johnson, Richard J; Kadomatsu, Kenji; Maruyama, Shoichi

    2018-03-28

    Ketohexokinase (KHK), a primary enzyme in fructose metabolism, has two isoforms, namely, KHK-A and KHK-C. Previously, we reported that renal injury was reduced in streptozotocin-induced diabetic mice which lacked both isoforms. Although both isoforms express in kidney, it has not been elucidated whether each isoform plays distinct roles in the development of diabetic kidney disease (DKD). The aim of the study is to elucidate the role of KHK-A for DKD progression. Diabetes was induced by five consecutive daily intraperitoneal injections of streptozotocin (50 mg/kg) in C57BL/6 J wild-type mice, mice lacking KHK-A alone (KHK-A KO), and mice lacking both KHK-A and KHK-C (KHK-A/C KO). At 35 weeks, renal injury, inflammation, hypoxia, and oxidative stress were examined. Metabolomic analysis including polyol pathway, fructose metabolism, glycolysis, TCA (tricarboxylic acid) cycle, and NAD (nicotinamide adenine dinucleotide) metabolism in kidney and urine was done. Diabetic KHK-A KO mice developed severe renal injury compared to diabetic wild-type mice, and this was associated with further increases of intrarenal fructose, dihydroxyacetone phosphate (DHAP), TCA cycle intermediates levels, and severe inflammation. In contrast, renal injury was prevented in diabetic KHK-A/C KO mice compared to both wild-type and KHK-A KO diabetic mice. Further, diabetic KHK-A KO mice contained decreased renal NAD + level with the increase of renal hypoxia-inducible factor 1-alpha expression despite having increased renal nicotinamide (NAM) level. These results suggest that KHK-C might play a deleterious role in DKD progression through endogenous fructose metabolism, and that KHK-A plays a unique protective role against the development of DKD. Copyright © 2018. Published by Elsevier Inc.

  2. Summary of the mechanism of U-induced renal damage and its biochemical studies

    International Nuclear Information System (INIS)

    Chen Rusong

    1994-05-01

    In China studies on the toxicology of uranium were systematically conducted from the 1960's. Among them the studies of the change of biochemical indicators of U-induced renal damage were involved. On the basis of summarizing the relevant information of our country and the study progress of biochemical methods in recent years, the mechanism of U-induced renal damage and its biochemical basis, the behavior of uranium in kidney and the recent progress to detect renal damage with several biochemical indexes (such as α 1 -or β 2 -microglobulin, N-acetyl-β-D-glucosaminidase and alanine aminopeptidase etc.) are introduced respectively. Finally, the evaluation on the biochemical basis for acquired tolerance to U in kidney is performed. It should be noted that from the clinical viewpoint the tolerance cannot be considered as a practical measure of protection

  3. Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Minglong Shao

    Full Text Available Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR plays a critical role in attenuating insulin resistance, inflammation and oxidative stress.The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms.Mice were fed with a high-fat diet (HFD, 40% of calories from fat for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured.HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2 expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks.These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress.

  4. Basiliximab induced non-cardiogenic pulmonary edema in two pediatric renal transplant recipients.

    LENUS (Irish Health Repository)

    Dolan, Niamh

    2009-11-01

    We report two cases of non-cardiogenic pulmonary edema as a complication of basiliximab induction therapy in young pediatric renal transplant patients identified following a retrospective review of all pediatric renal transplant cases performed in the National Paediatric Transplant Centre, Childrens University Hospital, Temple Street, Dublin, Ireland. Twenty-eight renal transplantations, of which five were living-related (LRD) and 23 were from deceased donors (DD), were performed in 28 children between 2003 and 2006. In six cases, transplantations were pre-emptive. Immunosuppression was induced pre-operatively using a combination of basiliximab, tacrolimus and methylprednisolone in all patients. Basiliximab induction was initiated 2 h prior to surgery in all cases and, in 26 patients, basiliximab was re-administered on post-operative day 4. Two patients, one LRD and one DD, aged 6 and 11 years, respectively, developed acute non-cardiogenic pulmonary edema within 36 h of surgery. Renal dysplasia was identified as the primary etiological factor for renal failure in both cases. Both children required assisted ventilation for between 4 and 6 days. While both grafts had primary function, the DD transplant patient subsequently developed acute tubular necrosis and was eventually lost within 3 weeks due to thrombotic microangiopathy and severe acute antibody-mediated rejection despite adequate immunosuppression. Non-cardiogenic pulmonary edema is a potentially devastating post-operative complication of basiliximab induction therapy in young pediatric patients following renal transplantation. Early recognition and appropriate supportive therapy is vital for patient and, where possible, graft survival.

  5. Tributyltin chloride induces renal dysfunction by inflammation and oxidative stress in female rats.

    Science.gov (United States)

    Coutinho, João V S; Freitas-Lima, Leandro C; Freitas, Frederico F C T; Freitas, Flávia P S; Podratz, Priscila L; Magnago, Rafaella P L; Porto, Marcella L; Meyrelles, Silvana S; Vasquez, Elisardo C; Brandão, Poliane A A; Carneiro, Maria T W D; Paiva-Melo, Francisca D; Miranda-Alves, Leandro; Silva, Ian V; Gava, Agata L; Graceli, Jones B

    2016-10-17

    Tributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rate and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle actin (α-SMA) protein expression were observed in TBT kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and estrogen receptor-α (ERα) protein expression in renal cortex. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications, such as inflammation and fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Everolimus-induced pneumonitis associates with favourable outcome in patients with metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Penttilä, P; Donskov, F; Rautiola, J

    2017-01-01

    BACKGROUND: Mammalian target of rapamycin inhibitors may induce pneumonitis. We analysed the association of pneumonitis with outcomes in everolimus treated metastatic renal cell carcinoma (mRCC) patients. PATIENTS AND METHODS: Eighty-five mRCC patients received everolimus at Helsinki University...

  7. Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

    Directory of Open Access Journals (Sweden)

    Xue-ying Chang

    2017-01-01

    Full Text Available Background. This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d, 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS/p38 mitogen activated protein kinase (p38MAPK pathway was determined to explore the potential mechanism. Results. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA and creatinine levels, malonaldehyde (MDA content, and superoxide dismutase (SOD activity in serum and the increases of calcium and alkaline phosphatase (ALP activity in the aorta (P<0.05 and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. Conclusions. Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

  8. Mitochondria-Targeted Antioxidant Mito-Tempo Protects Against Aldosterone-Induced Renal Injury In Vivo

    Directory of Open Access Journals (Sweden)

    Wei Ding

    2017-11-01

    Full Text Available Background/Aims: Growing evidence suggests mitochondrial dysfunction (MtD and the Nlrp3 inflammasome play critical roles in chronic kidney disease (CKD progression. We previously reported that Aldosterone (Aldo-induced renal injury in vitro is directly caused by mitochondrial reactive oxygen species (mtROS-mediated activation of the Nlrp3 inflammasome. Here we aimed to determine whether a mitochondria-targeted antioxidant (Mito-Tempo could prevent Aldo-induced kidney damage in vivo. Methods: C57BL/6J mice were treated with Aldo and/or Mito-Tempo (or ethanol as a control for 4 weeks. Renal injury was evaluated by Periodic Acid-Schiff reagent or Masson’s trichrome staining and electron microscopy. ROS were measured by DCFDA fluorescence and ELISA. MtD was determined by real-time PCR and electron microscopy. Activation of the Nlrp3 inflammasome and endoplasmic reticulum stress (ERS was detected via western blot. Results: Compared with control mice, Aldo-infused mice showed impaired renal function, increased mtROS production and MtD, Nlrp3 inflammasome activation, and elevated ERS. We showed administration of Mito-Tempo significantly improved renal function and MtD, and reduced Nlrp3 inflammasome activation and ERS in vivo. Conclusion: Mitochondria-targeted antioxidants may attenuate Aldo-infused renal injury by inhibiting MtD, the Nlrp3 inflammasome, and ERS in vivo. Therefore, targeting mtROS might be an effective strategy for preventing CKD.

  9. Prior intake of Brazil nuts attenuates renal injury induced by ischemia and reperfusion

    Directory of Open Access Journals (Sweden)

    Natassia Alberici Anselmo

    2018-04-01

    Full Text Available ABSTRACT Introduction: Ischemia-reperfusion (IR injury results from inflammation and oxidative stress, among other factors. Because of its anti-inflammatory and antioxidant properties, the Brazil nut (BN might attenuate IR renal injury. Objective: The aim of the present study was to investigate whether the intake of BN prevents or reduces IR kidney injury and inflammation, improving renal function and decreasing oxidative stress. Methods: Male Wistar rats were distributed into six groups (N=6/group: SHAM (control, SHAM treated with 75 or 150 mg of BN, IR, and IR treated with 75 or 150 mg of BN. The IR procedure consisted of right nephrectomy and occlusion of the left renal artery with a non-traumatic vascular clamp for 30 min. BN was given daily and individually for 7 days before surgery (SHAM or IR and maintained until animal sacrifice (48h after surgery. We evaluated the following parameters: plasma creatinine, urea, and phosphorus; proteinuria, urinary output, and creatinine clearance; plasmatic TBARS and TEAC; kidney expression of iNOS and nitrotyrosine, and macrophage influx. Results: Pre-treatment with 75 mg of BN attenuated IR-induced renal changes, with elevation of creatinine clearance and urinary output, reducing proteinuria, urea, and plasmatic phosphorus as well as reducing kidney expression of iNOS, nitrotyrosine, and macrophage influx. Conclusion: Low intake of BN prior to IR-induced kidney injury improves renal function by inhibition of macrophage infiltration and oxidative stress.

  10. Tetracycline-induced renal failure after dental treatment.

    Science.gov (United States)

    Miller, Craig S; McGarity, Gary J

    2009-01-01

    Tetracyclines are broad-spectrum antibiotics used by dental practitioners in the treatment of periodontal disease. They generally are safe in adults. However, caution is advised in patients who have pre-existing kidney disease. A 42-year-old woman with polycystic kidney disease received a prescription for tetracycline (250 milligrams, four times daily) after undergoing tooth extractions. She developed nausea, vomiting and diarrhea within days and end-stage renal disease within two weeks of taking the antibiotic. Hemodialysis was required to stabilize the patient's condition. Use of the Naranjo nomogram demonstrated an association between the two events. This case illustrates the importance of obtaining a thorough medical history and understanding potential adverse drug effects before prescribing a common antibiotic.

  11. Impact of Mannose-Binding Lectin Deficiency on Radiocontrast-Induced Renal Dysfunction

    Directory of Open Access Journals (Sweden)

    Michael Osthoff

    2013-01-01

    Full Text Available Contrast-induced nephropathy (CIN is the third leading cause of acute renal failure in hospitalized patients. Endothelial dysfunction, renal medullary ischemia, and tubular toxicity are regarded as the most important factors in the pathogenesis of CIN. Mannose-binding lectin (MBL, a pattern recognition protein of the lectin pathway of complement, has been found to aggravate and mediate tissue damage during experimental renal ischemia/reperfusion (I/R injury which was alleviated by inhibition with C1 inhibitor, a potent MBL, and lectin pathway inhibitor. In this paper, we highlight the potential role of MBL in the pathogenesis of human CIN. In experimental I/R models, MBL was previously found to induce tubular cell death independent of the complement system. In addition, after binding to vascular endothelial cells, MBL and its associated serine proteases were able to trigger a proinflammatory reaction and contribute to endothelial dysfunction. In humans, urinary MBL was increased after administration of contrast media and in individuals with CIN. Moreover, individuals with normal/high MBL levels were at increased risk to develop radiocontrast-induced renal dysfunction. Hence, MBL and the lectin pathway seem to be a promising target given that a licensed, powerful, human recombinant inhibitor exits to be added to the scarce armamentarium currently available for prophylaxis of CIN.

  12. Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats.

    Science.gov (United States)

    El-Kashef, Dalia H; El-Kenawi, Asmaa E; Abdel Rahim, Mona; Suddek, Ghada M; Salem, Hatem A

    2016-03-01

    The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.

  13. Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats.

    Science.gov (United States)

    Chang, Xue-Ying; Cui, Lei; Wang, Xing-Zhi; Zhang, Lei; Zhu, Dan; Zhou, Xiao-Rong; Hao, Li-Rong

    2017-01-01

    This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta ( P chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

  14. Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

    Science.gov (United States)

    Chang, Xue-ying; Cui, Lei; Wang, Xing-zhi; Zhang, Lei; Zhu, Dan

    2017-01-01

    Background This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Results Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta (P chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway. PMID:28691026

  15. Amlodipine-induced gingival hyperplasia in chronic renal failure: a ...

    African Journals Online (AJOL)

    Amlodipine is a dihydropyridine calcium channel blocker that is used in the management of both hypertension and angina. Amlodipine induced side effects are headache, dizziness, edema, flushing, palpitations, and rarely gingival hyperplasia. The exact reason of amlodipine-induced gingival hyperplasia is not known.

  16. Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity

    Directory of Open Access Journals (Sweden)

    Aicha Fassi Fihri

    2016-06-01

    Full Text Available Background/Aims: Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Methods: Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily; group 2: received oral lead acetate (2 g/kg.b.wt/daily; group 3: treated with oral honey (1g /kg.b.wt/daily and oral lead (2 g/kg.b.wt/daily, and group 4: received oral honey (1 g/kg.b.wt/daily. Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Results: Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. Conclusion: It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects.

  17. Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity.

    Science.gov (United States)

    Fihri, Aicha Fassi; Al-Waili, Noori S; El-Haskoury, Redouan; Bakour, Meryem; Amarti, Afaf; Ansari, Mohammad J; Lyoussi, Badiaa

    2016-01-01

    Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily); group 2: received oral lead acetate (2 g/kg.b.wt/daily); group 3: treated with oral honey (1g /kg.b.wt/daily) and oral lead (2 g/kg.b.wt/daily), and group 4: received oral honey (1 g/kg.b.wt/daily). Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects. © 2016 The Author(s) Published by S. Karger AG, Basel.

  18. Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

    International Nuclear Information System (INIS)

    Huang, J.-S.; Chuang, L.-Y.; Guh, J.-Y.; Yang, Y.-L.; Hsu, M.-S.

    2008-01-01

    Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE, or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27 Kip1 , collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells

  19. Immunological tolerance induced by galectin-1 in rat allogeneic renal transplantation.

    Science.gov (United States)

    Xu, Gaosi; Tu, Weiping; Xu, Chengyun

    2010-06-01

    The existed literatures indicated that galectin-1 has anti-inflammatory effects and plays a pivotal role in autoimmune diseases. Present study was to identify the roles of galectin-1 in acute animal renal allograft rejection. Rat acute rejection models were erected by allogeneic renal transplantation. Galectin-1 injection was performed in different concentrations in renal recipients post-transplantation. Recipient survivals, CD8+ T cell proliferation, production of IFN-gamma, levels of serum CD30, enzyme-linked immunoabsorbent spot assay (ELISPOT) and immunohistochemistry were observed or tested 7days after renal transplantation. Galectin-1 injection can prolong the recipient animal survival, reduce the serum levels of IFN-gamma, soluble CD30, percentage of CD8+ T cell subset, CD8+ T cell-mediated cytotoxicity, and IFN-gamma ELISPOT frequency for allograft recipients. The therapeutic effects of galectin-1 injection on recipient rats were dose-dependent. Galectin-1 plays an important role in CD8+ T cell-mediated renal rejection by inducing immunological tolerance. Copyright 2010 Elsevier B.V. All rights reserved.

  20. Curcumin inhibits adenosine deaminase and arginase activities in cadmium-induced renal toxicity in rat kidney

    Directory of Open Access Journals (Sweden)

    Ayodele Jacob Akinyemi

    2017-04-01

    Full Text Available In this study, the effect of enzymes involved in degradation of renal adenosine and l-arginine was investigated in rats exposed to cadmium (Cd and treated with curcumin, the principal active phytochemical in turmeric rhizome. Animals were divided into six groups (n = 6: saline/vehicle, saline/curcumin 12.5 mg/kg, saline/curcumin 25 mg/kg, Cd/vehicle, Cd/curcumin 12.5 mg/kg, and Cd/curcumin 25 mg/kg. The results of this study revealed that the activities of renal adenosine deaminase and arginase were significantly increased in Cd-treated rats when compared with the control (p < 0.05. However, co-treatment with curcumin inhibits the activities of these enzymes compared with Cd-treated rats. Furthermore, Cd intoxication increased the levels of some renal biomarkers (serum urea, creatinine, and electrolytes and malondialdehyde level with a concomitant decrease in functional sulfhydryl group and nitric oxide (NO. However, co-treatment with curcumin at 12.5 mg/kg and 25 mg/kg, respectively, increases the nonenzymatic antioxidant status and NO in the kidney, with a concomitant decrease in the levels of malondialdehyde and renal biomarkers. Therefore, our results reinforce the importance of adenosine deaminase and arginase activities in Cd poisoning conditions and suggest some possible mechanisms of action by which curcumin prevent Cd-induced renal toxicity in rats.

  1. Lin28 sustains early renal progenitors and induces Wilms tumor

    Science.gov (United States)

    Urbach, Achia; Yermalovich, Alena; Zhang, Jin; Spina, Catherine S.; Zhu, Hao; Perez-Atayde, Antonio R.; Shukrun, Rachel; Charlton, Jocelyn; Sebire, Neil; Mifsud, William; Dekel, Benjamin; Pritchard-Jones, Kathy; Daley, George Q.

    2014-01-01

    Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in a pathology highly reminiscent of Wilms tumor. Using lineage-specific promoters to target Lin28 to specific cell types, we observed Wilms tumor only when Lin28 is aberrantly expressed in multiple derivatives of the intermediate mesoderm, implicating the cell of origin as a multipotential renal progenitor. We show that withdrawal of Lin28 expression reverts tumorigenesis and markedly expands the numbers of glomerulus-like structures and that tumor formation is suppressed by enforced expression of Let-7 microRNA. Finally, we demonstrate overexpression of the LIN28B paralog in a significant percentage of human Wilms tumor. Our data thus implicate the Lin28/Let-7 pathway in kidney development and tumorigenesis. PMID:24732380

  2. Vitamin C-induced hyperoxaluria causing reversible tubulointerstitial nephritis and chronic renal failure: a case report

    Directory of Open Access Journals (Sweden)

    Rathi Shradha

    2007-11-01

    Full Text Available Abstract Vitamin C is a precursor of oxalate and promoter of its absorption, potentially causing hyperoxaluria. Malabsorption causes Calcium (Ca chelation with fatty acids, producing enteric hyperoxaluria. Case A 73-year-old man with both risk factors was hospitalized with serum creatinine of 8.4 mg/dL (versus 1.2 mg/dL four months earlier (normal 0.6–1.3 mg/dL. Given his oxalate-rich diet, chronic diarrhea, and daily 680 mg vitamin C and furosemide, we postulated Ca oxalate-induced nephropathy, a diagnosis confirmed by documenting hyperoxaluria, and finding of diffuse intraluminal crystals and extensive interstitial fibrosis on biopsy. He was hemodialysed 6 times to remove excess oxalate. Two weeks off vitamin C, his creatinine spontaneously fell to 3.1 mg/dL. Three months later, on low oxalate diet and 100 mg vitamin B6, urine oxalate to creatinine ratio decreased from 0.084 to 0.02 (normal Conclusion 1 High-dose vitamin C can induce hyperoxaluric nephropathy and progressive renal failure, especially if aggravated by diarrhea, oxalate-rich diet, metabolic acidosis, and dehydration. 2 The diagnosis should be suspected in unexplained renal insufficiency when associated with these risk factors. 3 Since prompt treatment could avert end-stage renal disease, we recommend monitoring urinary oxalate in patients on high-dose vitamin C and renal biopsy if necessary.

  3. Salt-induced changes in cardiac phosphoproteome in a rat model of chronic renal failure.

    Directory of Open Access Journals (Sweden)

    Zhengxiu Su

    Full Text Available Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model or sham operation were treated for 2 weeks with a normal-(0.4% NaCl, or high-salt (4% NaCl diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54% phosphopeptides upregulated and 76 (46% phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49% phosphopeptides and downregulation of 88 (51% phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed.

  4. Role of mitochondrial permeability transition in human renal tubular epithelial cell death induced by aristolochic acid

    International Nuclear Information System (INIS)

    Qi Xinming; Cai Yan; Gong Likun; Liu Linlin; Chen Fangping; Xiao Ying; Wu Xiongfei; Li Yan; Xue Xiang; Ren Jin

    2007-01-01

    Aristolochic acid (AA), a natural nephrotoxin and carcinogen, can induce a progressive tubulointerstitial nephropathy. However, the mechanism by which AA causes renal injury remains largely unknown. Here we reported that the mitochondrial permeability transition (MPT) plays an important role in the renal injury induced by aristolochic acid I (AAI). We found that in the presence of Ca 2+ , AAI caused mitochondrial swelling, leakage of Ca 2+ , membrane depolarization, and release of cytochrome c in isolated kidney mitochondria. These alterations were suppressed by cyclosporin A (CsA), an agent known to inhibit MPT. Culture of HK-2 cell, a human renal tubular epithelial cell line for 24 h with AAI caused a decrease in cellular ATP, mitochondrial membrane depolarization, cytochrome c release, and increase of caspase 3 activity. These toxic effects of AAI were attenuated by CsA and bongkrekic acid (BA), another specific MPT inhibitor. Furthermore, AAI greatly inhibited the activity of mitochondrial adenine nucleotide translocator (ANT) in isolated mitochondria. We suggested that ANT may mediate, at least in part, the AAI-induced MPT. Taken together, these results suggested that MPT plays a critical role in the pathogenesis of HK-2 cell injury induced by AAI and implied that MPT might contribute to human nephrotoxicity of aristolochic acid

  5. Cinnamaldehyde impairs high glucose-induced hypertrophy in renal interstitial fibroblasts

    International Nuclear Information System (INIS)

    Chao, Louis Kuoping; Chang, W.-T.; Shih, Y.-W.; Huang, J.-S.

    2010-01-01

    Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. To explore whether cinnamaldehyde was linked to altered high glucose (HG)-mediated renal tubulointerstitial fibrosis in diabetic nephropathy (DN), the molecular mechanisms of cinnamaldehyde responsible for inhibition of HG-induced hypertrophy in renal interstitial fibroblasts were examined. We found that cinnamaldehyde caused inhibition of HG-induced cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, cleaved poly(ADP-ribose) polymerase (PARP) protein expression, and mitochondrial cytochrome c release in HG or cinnamaldehyde treatments in these cells. HG-induced extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) (but not the Janus kinase 2/signal transducers and activators of transcription) activation was markedly blocked by cinnamaldehyde. The ability of cinnamaldehyde to inhibit HG-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of collagen IV, fibronectin, and α-smooth muscle actin (α-SMA). The results obtained in this study suggest that cinnamaldehyde treatment of renal interstitial fibroblasts that have been stimulated by HG reduces their ability to proliferate and hypertrophy through mechanisms that may be dependent on inactivation of the ERK/JNK/p38 MAPK pathway.

  6. Renal and Myocardial Histopathology and Morphometry in Rats with Adenine - Induced Chronic Renal Failure: Influence of Gum Acacia

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    Badreldin H. Ali

    2014-08-01

    Full Text Available Background/Aim: Chronic kidney disease (CKD is associated with increased occurrence of cardiovascular system dysfunction. Previous studies have revealed a number of alterations in the kidneys and heart during CKD. However, unbiased quantitative studies on these structures in this disease have so far not been addressed. Materials and Methods: We induced CKD in rats by feeding adenine (0.75% w/w, four weeks and using unbiased stereological methods, investigated the effect of the ensuing CKD on the kidneys and left ventricular structure. Since gum acacia (GA has previously been shown to ameliorate the severity of CKD in humans and rodents, we investigated the effect of giving GA (15% w/v in the drinking water concomitantly with adenine on the kidneys and left ventricular structure using the above model. Results: The CKD was confirmed by standard biochemical indices in plasma and urine and by accumulation of the uremic toxin indoxyl sulfate. Additionally, it increased blood pressure. In rats with CKD absolute volume of left ventricle was significantly increased, and the volume density and absolute volume of myocardial capillaries were decreased, whilst the same parameters of myocardium and interstitial tissue were increased. Renal morphometry demonstrated significant increase in kidney volume and interstitial tissue in adenine- treated rats. Similarly, glomerular Bowman's capsule was significantly thickened. The myocardial and renal changes were significantly mitigated by GA treatment. Conclusions: These results add to our existing knowledge of the pathophysiology of adenine - CKD and provides plausible histopathological and morphometric evidence for the usefulness of GA in CKD.

  7. Piroxicam-Induced Hepatic and Renal Histopathological Changes in ...

    African Journals Online (AJOL)

    Piroxicam is a non-steroidal anti-inflammatory drug widely used in rheumatic diseases. The aim of this study was to investigate Piroxicam-induced histopathological changes in livers and kidneys of male albino mice. Methods: Animals were classified into a control group and 4 treated groups. Piroxicam was injected ...

  8. Pre-stimulation of the kallikrein system in cisplatin-induced acute renal injury: An approach to renoprotection

    Energy Technology Data Exchange (ETDEWEB)

    Aburto, Andrés [Program of M.Sc., Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile); Barría, Agustín [School of Biochemistry, Faculty of Sciences, Universidad Austral de Chile, Valdivia (Chile); Cárdenas, Areli [Ph.D. Program, Faculty of Sciences, Universidad Austral de Chile, Valdivia (Chile); Carpio, Daniel; Figueroa, Carlos D. [Department of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia (Chile); Burgos, Maria E. [Department of Nephrology, Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile); Ardiles, Leopoldo, E-mail: leopoldoardiles@gmail.com [Department of Nephrology, Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile)

    2014-10-15

    Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a group of rats was submitted to high potassium diet to stimulate the synthesis and excretion of tissue kallikrein 1 (rKLK1) previous to an intraperitoneal injection of 7 mg/kg cisplatin. A significant reduction in lipoperoxidation, evidenced by urinary excretion of malondialdehyde and renal immunostaining of hidroxy-nonenal, was accompanied by a decline in apoptosis. Coincident with these findings we observed a reduction in the expression of renal KIM-1 suggesting that renoprotection may be occurring. Stimulation or indemnity of the renal kinin system deserves to be evaluated as a complementary pharmacological measure to diminish cisplatin nephrotoxicity. - Highlights: • Mechanisms of cisplatin-induced-renal damage have not been completely clarified. • Cisplatin induces oxidative stress and apoptosis. • The renal kallikrein-kinin system is protective in experimental acute renal damage. • Kallikrein stimulation reduces oxidative stress and apoptosis induced by cisplatin. • Protection of the kallikrein-kinin system may reduce cisplatin toxicity.

  9. Pre-stimulation of the kallikrein system in cisplatin-induced acute renal injury: An approach to renoprotection

    International Nuclear Information System (INIS)

    Aburto, Andrés; Barría, Agustín; Cárdenas, Areli; Carpio, Daniel; Figueroa, Carlos D.; Burgos, Maria E.; Ardiles, Leopoldo

    2014-01-01

    Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a group of rats was submitted to high potassium diet to stimulate the synthesis and excretion of tissue kallikrein 1 (rKLK1) previous to an intraperitoneal injection of 7 mg/kg cisplatin. A significant reduction in lipoperoxidation, evidenced by urinary excretion of malondialdehyde and renal immunostaining of hidroxy-nonenal, was accompanied by a decline in apoptosis. Coincident with these findings we observed a reduction in the expression of renal KIM-1 suggesting that renoprotection may be occurring. Stimulation or indemnity of the renal kinin system deserves to be evaluated as a complementary pharmacological measure to diminish cisplatin nephrotoxicity. - Highlights: • Mechanisms of cisplatin-induced-renal damage have not been completely clarified. • Cisplatin induces oxidative stress and apoptosis. • The renal kallikrein-kinin system is protective in experimental acute renal damage. • Kallikrein stimulation reduces oxidative stress and apoptosis induced by cisplatin. • Protection of the kallikrein-kinin system may reduce cisplatin toxicity

  10. Hordenine protects against hyperglycemia-associated renal complications in streptozotocin-induced diabetic mice.

    Science.gov (United States)

    Su, Shuhao; Cao, Meng; Wu, Guangyuan; Long, Zi; Cheng, Xiaodong; Fan, Junshu; Xu, Zhongrui; Su, Hongfei; Hao, Yiming; Li, Ge; Peng, Jie; Li, Shuang; Wang, Xin

    2018-05-15

    The worldwide prevalence of diabetes and associated metabolic diseases has dramatically increased. Pharmacological treatment of diabetes is still limited. Hordenine (HOR), a phenethylamine alkaloid, is a natural constituent in many plants. The present study was designed to explore the possible anti-diabetic effect of HOR in streptozotocin (STZ)-induced diabetic mice. Combined treatment of HOR and insulin significantly reduced fasting and postprandial blood glucose level in diabetic mice. HOR and insulin did not show evident protective effect against structural and functional injuries of pancreas. Renal histological and functional injuries were significantly improved by HOR or insulin treatment. Moreover, combined treatment of HOR and insulin resulted in a more significant amelioration of renal histological and functional injuries in diabetic mice. HOR induced a decrease of renal IL-1α/β and IL-6 expression, and a reduction of Col1α1 and MMP9 expression and PAS-stained mesangial expansion in glomeruli of diabetic mice. In diabetic mice, HOR significantly decreased Nrf2 expression and increased hnRNPF and hnRNPK expression in kidney. Moreover, HOR showed a synergistic effect with insulin on the expression of these regulators. Renal ROS level and TBARS content in diabetic mice were decreased by HOR. The reduction of renal expression of antioxidant enzymes in diabetic mice was inhibited by HOR and insulin. Furthermore, HOR and insulin function synergistically to play an antioxidant role against oxidative injury in diabetic nephropathy. In conclusion, to the best of our knowledge, we, for the first time, found the anti-diabetic, anti-inflammatory, and anti-fibrotic role of HOR in combination with insulin. HOR functions synergistically with insulin and prevents diabetic nephropathy. However, the molecular mechanism of the synergistic effect of HOR and insulin needs to be elucidated. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. Application of path analysis to urinary findings of cadmium-induced renal dysfunction.

    Science.gov (United States)

    Abe, T; Kobayashi, E; Okubo, Y; Suwazono, Y; Kido, T; Shaikh, Z A; Nogawa, K

    2001-01-01

    In order to identify some causal relations among various urinary indices of cadmium-induced renal dysfunction, such as glucose, total protein, amino nitrogen, beta 2-microglobulin (beta 2-m), metallothionein (MT), and cadmium (Cd), we applied path analysis method to previous epidemiological studies targeting the residents of the Cd-polluted Kakehashi River basin of Ishikawa Prefecture, Japan. We obtained a diagram-termed path model, representing some causal relations among the above urinary indices. It shows that urinary Cd is located at the beginning point in the diagram, and Cd-induced renal dysfunction develops in the following order: Cd exposure-->increase of beta 2-m and/or MT excretion-->increase of amino-N and/or total protein excretion-->increase of glucose excretion. It was proved mathematically, that in the case of both males and females, increased excretions of beta 2-m and/or MT were the most sensitive urinary indices of the early stage of chronic Cd-induced renal dysfunction.

  12. Cinnabar-Induced Subchronic Renal Injury Is Associated with Increased Apoptosis in Rats

    Directory of Open Access Journals (Sweden)

    Ying Wang

    2015-01-01

    Full Text Available The aim of this study was to explore the role of apoptosis in cinnabar-induced renal injury in rats. To test this role, rats were dosed orally with cinnabar (1 g/kg/day for 8 weeks or 12 weeks, and the control rats were treated with 5% carboxymethylcellulose solution. Levels of urinary mercury (UHg, renal mercury (RHg, serum creatinine (SCr, and urine kidney injury molecule 1 (KIM-1 were assessed, and renal pathology was analyzed. Apoptotic cells were identified and the apoptotic index was calculated. A rat antibody array was used to analyze expression of cytokines associated with apoptosis. Results from these analyses showed that UHg, RHg, and urine KIM-1, but not SCr, levels were significantly increased in cinnabar-treated rats. Renal pathological changes in cinnabar-treated rats included vacuolization of tubular cells, formation of protein casts, infiltration of inflammatory cells, and increase in the number of apoptotic tubular cells. In comparison to the control group, expression of FasL, Fas, TNF-α, TRAIL, activin A, and adiponectin was upregulated in the cinnabar-treated group. Collectively, our results suggest that prolonged use of cinnabar results in kidney damage due to accumulation of mercury and that the underlying mechanism involves apoptosis of tubular cells via a death receptor-mediated pathway.

  13. Effect of atracylodes rhizome polysaccharide in rats with adenine-induced chronic renal failure.

    Science.gov (United States)

    Yang, C; Liu, C; Zhou, Q; Xie, Y C; Qiu, X M; Feng, X

    2015-01-01

    The aim of the study was to elucidate the therapeutic effects of Atracylodes rhizome polysaccharide on adenine-induced chronic renal failure in rats. Fifty male Sprague Dawley rats were selected and randomly divided in to 5 groups (n=10 rats per group): The normal control group, the chronic renal failure pathological control group, the dexamethasone treatment group and two Atracylodes rhizome polysaccharide treatment groups, treated with two different concentrations of the polysaccharide, the Atracylodes rhizome polysaccharide high group and the Atracylodes rhizome polysaccharide low group. All the rats, except those in the normal control group were fed adenine-enriched diets, containing 10 g adenine per kg food for 3 weeks. After being fed with adenine, the dexamethasone treatment group, Atracylodes rhizome polysaccharide high group and Atracylodes rhizome polysaccharide low group rats were administered the drug orally for 2 weeks. On day 35, the kidney coefficient of the rats and the serum levels of creatinine, blood urea nitrogen, total protein and hemalbumin were determined. Subsequent to experimentation on a model of chronic renal failure in rats, the preparation was proven to be able to reduce serum levels of creatinine, blood urea nitrogen and hemalbumin levels (Prenal function. Atracylodes rhizome polysaccharide had reversed the majority of the indices of chronic renal failure in rats.

  14. Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

    International Nuclear Information System (INIS)

    Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing; He, Xiaoyun; Huang, Kunlun; Luo, Yunbo; Xu, Wentao

    2014-01-01

    Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation

  15. Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); He, Xiaoyun; Huang, Kunlun; Luo, Yunbo [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Xu, Wentao, E-mail: xuwentao@cau.edu.cn [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China)

    2014-11-01

    Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation.

  16. Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity

    OpenAIRE

    Aicha Fassi Fihri; Noori S. Al-Waili; Redouan El-Haskoury; Meryem Bakour; Afaf Amarti; Mohammad J. Ansari; Badiaa Lyoussi

    2016-01-01

    Background/Aims: Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Methods: Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily); group 2: received oral lead acetate (2 g/kg.b.wt/daily); group 3: tr...

  17. Central Diabetes Insipidus and Cisplatin-Induced Renal Salt Wasting Syndrome: A Challenging Combination.

    Science.gov (United States)

    Cortina, Gerard; Hansford, Jordan R; Duke, Trevor

    2016-05-01

    We describe a 2-year-old female with a suprasellar primitive neuroectodermal tumor and central diabetes insipidus (DI) who developed polyuria with natriuresis and subsequent hyponatremia 36 hr after cisplatin administration. The marked urinary losses of sodium in combination with a negative sodium balance led to the diagnosis of cisplatin-induced renal salt wasting syndrome (RSWS). The subsequent clinical management is very challenging. Four weeks later she was discharged from ICU without neurological sequela. The combination of cisplatin-induced RSWS with DI can be confusing and needs careful clinical assessment as inaccurate diagnosis and management can result in increased neurological injury. © 2016 Wiley Periodicals, Inc.

  18. Colchicine-induced myoneuropathy in a cyclosporine-treated renal transplant recipient

    Directory of Open Access Journals (Sweden)

    Kyungmin Huh

    2013-06-01

    Full Text Available Colchicine is a relatively safe medication that is widely used for both prevention and treatment of gout attack. However, serious adverse events, including myoneuropathy and multiorgan failure, have been reported. We report a case of colchicine-induced myoneuropathy in a female kidney transplant recipient who had been taking cyclosporine. She developed gastrointestinal discomfort and paresthesia 5 days after the initiation of colchicine. She showed signs of myoneuropathy, and hepatic and renal injury. Colchicine toxicity was suspected, and colchicine was discontinued. Her symptoms and laboratory findings improved gradually. Literature was reviewed for previous reports of colchicine-induced myoneuropathy in solid organ transplant recipients.

  19. Renal Alterations in Feline Immunodeficiency Virus (FIV-Infected Cats: A Natural Model of Lentivirus-Induced Renal Disease Changes

    Directory of Open Access Journals (Sweden)

    Mauro Pistello

    2012-08-01

    Full Text Available Human immunodeficiency virus (HIV is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.

  20. Renal alterations in feline immunodeficiency virus (FIV)-infected cats: a natural model of lentivirus-induced renal disease changes.

    Science.gov (United States)

    Poli, Alessandro; Tozon, Natasa; Guidi, Grazia; Pistello, Mauro

    2012-09-01

    Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.

  1. Citrus bergamia Risso & Poiteau juice protects against renal injury of diet-induced hypercholesterolemia in rats.

    Science.gov (United States)

    Trovato, Ada; Taviano, Maria F; Pergolizzi, Simona; Campolo, Loredana; De Pasquale, Rita; Miceli, Natalizia

    2010-04-01

    The present study was designed to evaluate the protective effect of treatment with Citrus bergamia juice (1 mL/day, for 30 days) against hypercholesterolemic diet-induced renal injury in rat.C. bergamia juice provoked a significant reduction in the plasma levels of cholesterol, triglycerides and LDL, and an increase in HDL levels, versus hyperlipidemic controls (p juice administration significantly decreased MDA levels elevations compared with hyperlipidemic controls (4.10 +/- 0.10 nmol/mg protein and 4.78 +/- 0.15 nmol/mg protein, respectively).Histological observations of the kidney supported the biochemical data and indicated a protective effect of C. bergamia juice on the development of renal damage in hypercholesterolemic rats.The antioxidant potential of C. bergamia juice was examined in two in vitro systems: in the DPPH test the juice showed a noticeable effect on scavenging free radicals (IC(50) = 25.01 +/- 0.70 +/-L); in the reducing power assay it showed a strong activity, too (1.44 +/- 0.01 ASE/mL).These findings suggest that C. bergamia juice has a protective role in hypercholesterolemic diet-induced renal damage, which may be attributed to its antioxidant properties. Copyright (c) 2009 John Wiley & Sons, Ltd.

  2. A Rare Case of Acute Renal Failure Secondary to Rhabdomyolysis Probably Induced by Donepezil

    Directory of Open Access Journals (Sweden)

    Osman Zikrullah Sahin

    2014-01-01

    Full Text Available Introduction. Acute renal failure (ARF develops in 33% of the patients with rhabdomyolysis. The main etiologic factors are alcoholism, trauma, exercise overexertion, and drugs. In this report we present a rare case of ARF secondary to probably donepezil-induced rhabdomyolysis. Case Presentation. An 84-year-old male patient was admitted to the emergency department with a complaint of generalized weakness and reduced consciousness for two days. He had a history of Alzheimer’s disease for one year and he had taken donepezil 5 mg daily for two months. The patient’s physical examination revealed apathy, loss of cooperation, and decreased muscle strength. Laboratory studies revealed the following: urea: 128 mg/dL; Creatinine 6.06 mg/dL; creatine kinase: 3613 mg/dL. Donepezil was discontinued and the patient’s renal function tests improved gradually. Conclusion. Rhabdomyolysis-induced acute renal failure may develop secondary to donepezil therapy.

  3. Urinary excretion of furosemide in rats with HgCl sub 2 -induced acute renal damage

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    Fujimura, Akio; Sudoh, Toshiaki; Ohashi, Kyoichi; Ebihara, Akio (Jichi Medical School, Tochigi (Japan))

    1992-01-01

    To examine the influence of mercuric chloride (HgCl{sub 2})-induced acute renal damage on urinary excretion of furosemide, HgCl{sub 2} or its vehicle along was given intraperitoneally to Wistar rats. The following two experiments were done. Study 1: three percent body weight (b.w.) of 1% NaCl solution or furosemide in 3% b.w. of 1% NaCl solution was given orally before and after HgCl{sub 2} treatment, and an 8-hour urine was collected. Study 2: furosemide was given orally, and blood samples were obtained at 1, 2, 3, 4, 6 and 8 hours after administration. Urinary excretion of N-acetyl-{beta}-D-glucosaminidase increased, and urine volume and urinary excretions of furosemide and sodium decreased in the HgCl{sub 2}-treated rats. There were significant correlations between the urinary furosemide and its diuretic effects. Regression lines after HgCl{sub 2} were significantly different from those before treatment. The values of absorption as well as elimination rate constant were smaller, while the time to maximum concentration and the elimination half-life were longer in the HgCl{sub 2}-treated rats compared to vehicle-treated animals. These results suggest that the urinary excretion of furosemide and the responsiveness of renal tubular cells to this agent are impaired in rats with HgCl{sub 2}-induced acute renal damage.

  4. N-acetylcysteine reduces the renal oxidative stress and apoptosis induced by hemorrhagic shock.

    Science.gov (United States)

    Moreira, Miriam Aparecida; Irigoyen, Maria Claudia; Saad, Karen Ruggeri; Saad, Paulo Fernandes; Koike, Marcia Kiyomi; Montero, Edna Frasson de Souza; Martins, José Luiz

    2016-06-01

    Renal ischemia/reperfusion injury induced by hemorrhagic shock (HS) and subsequent fluid resuscitation is a common cause of acute renal failure. The objective of this study was to evaluate the effect of combining N-acetylcysteine (NAC) with fluid resuscitation on renal injury in rats that underwent HS. Two groups of male Wistar rats were induced to controlled HS at 35 mm Hg mean arterial pressure for 60 min. After this period, the HS and fluid resuscitation (HS/R) group was resuscitated with lactate containing 50% of the blood that was withdrawn. The HS/R + NAC group was resuscitated with Ringer's lactate combined with 150 mg/kg of NAC and blood. The sham group animals were catheterized but were not subjected to shock. All animals were kept under anesthesia and euthanized after 120 min of fluid resuscitation or observation. Animals treated with NAC presented attenuation of histologic lesions, reduced oxidative stress, and apoptosis markers when compared with animals from the HS/R group. The serum creatinine was similar in all the groups. NAC is a promising drug for combining with fluid resuscitation to attenuate the kidney injury associated with HS. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. BAG3 regulates ECM accumulation in renal proximal tubular cells induced by TGF-β1.

    Science.gov (United States)

    Du, Feng; Li, Si; Wang, Tian; Zhang, Hai-Yan; Li, De-Tian; Du, Zhen-Xian; Wang, Hua-Qin; Wang, Yan-Qiu

    2015-01-01

    Previously we have demonstrated that Bcl-2-associated athanogene 3 (BAG3) is increased in renal fibrosis using a rat unilateral ureteral obstruction model. The current study investigated the role of BAG3 in renal fibrosis using transforming growth factor (TGF)-β1-treated human proximal tubular epithelial (HK-2) cells. An upregulation of BAG3 in vitro models was observed, which correlated with the increased synthesis of extracellular matrix (ECM) proteins and expression of tissue-type plasminogen activator inhibitor (PAI)-1. Blockade of BAG3 induction by shorting hairpin RNA suppressed the expression of ECM proteins but had no effect on PAI-1 expression induced by TGF-β1. Forced overexpression of BAG3 selectively increased collagens. TGF-β1-induced BAG3 expression in HK-2 cells was attenuated by ERK1/2 and JNK MAPK inhibitors. In addition, forced BAG3 overexpression blocked attenuation of collagens expression by ERK1/2 and JNK inhibitors. These data suggest that ERK1/2 and JNK signaling events are involved in modulating the expression of BAG3, which would ultimately contribute to renal fibrosis by enhancing the synthesis and deposition of ECM proteins.

  6. Nephroprotective Effect of Bauhinia tomentosa Linn against Cisplatin-Induced Renal Damage.

    Science.gov (United States)

    Kannan, Narayanan; Sakthivel, Kunnathur Murugesan; Guruvayoorappan, Chandrasekaran

    2016-01-01

    Cisplatin (CP) is an important chemotherapeutic drug used for the treatment of a wide variety of solid tumors. However, clinical use of CP has been limited due to its adverse effect of nephrotoxicity. In the present study, we evaluate the nephroprotective effect of Bauhinia tomentosa against CP-induced renal damage in rats. Administration of methonolic extract of B. tomentosa (250 mg/kg b.w.) results in a significant increase in antioxidant enzymes including superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). Furthermore, treatment with B. tomentosa increased body weight and relative organ weight when compared with that of the CP-induced control group. Moreover, treatment with B. tomentosa extract significantly decreased lipid peroxidation(LPO), serum urea, and creatinine when compared with the CP-induced control group. Thus, the present study highlights the potential role of B. tomentosa and its use as a new protective strategy against CP-induced nephrotoxicity.

  7. Piroxicam-Induced hepatic and renal Histopathological changes in mice

    Directory of Open Access Journals (Sweden)

    Amany Tohamy

    2007-02-01

    Full Text Available Piroxicam is a non-steroidal anti-inflammatory drug widely used in rheumatic diseases. The aim of this study was to investigate Piroxicam-induced histopathological changes in livers and kidneys of male albino mice. Methods: Animals were classified into a control group and 4 treated groups. Piroxicam was injected intraperitoneally using 0.3 mg/kg every day for four weeks. Each week a group of mice was sacrificed. Liver and kidneys were obtained for histological and histochemical examination.Animals were classified into a control group and 4 treated groups. Piroxicam was injected intraperitoneally using 0.3 mg/kg every day for four weeks. Each week a group of mice was sacrificed. Liver and kidneys were obtained for histological and histochemical examination.Results: Liver sections appeared with inflammatory cellular infiltration, vacuolated hepatocytes, dilated sinusoids, and increased number of Kupffer cells. Kidney sections appeared with some cellular inflammations. The glomeruli were shrunk resulting in widening of the urinary space. Oedema and vacuolations were noticed in the tubular cells. There was a positive correlation between these pathological changes and the increased treatment periods. Histochemical staining revealed that glycogen and protein contents had decreased in the hepatocytes. This depletion worsened gradually in liver cells after two, three, and four weeks. Similar depletion of the glycogen content was observed in kidney tissue. However, protein content appeared to be slightly decreased in the kidney tubules and glomeruli. Incensement of coarse chromatin in the nuclei of hepatocytes, Kupffer cells and most inflammatory cells were detected by Fuelgen method. Kidney tissues appeared with a severe decrease in coarse chromatin in the nuclei.Liver sections appeared with inflammatory cellular infiltration, vacuolated hepatocytes, dilated sinusoids, and increased number of Kupffer cells. Kidney sections appeared with some cellular

  8. Differentiation of murine embryonic stem and induced pluripotent stem cells to renal lineage in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Morizane, Ryuji [Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan); Monkawa, Toshiaki, E-mail: monkawa@sc.itc.keio.ac.jp [Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan); Itoh, Hiroshi [Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan)

    2009-12-25

    Embryonic stem (ES) cells which have the unlimited proliferative capacity and extensive differentiation potency can be an attractive source for kidney regeneration therapies. Recent breakthroughs in the generation of induced pluripotent stem (iPS) cells have provided with another potential source for the artificially-generated kidney. The purpose of this study is to know how to differentiate mouse ES and iPS cells into renal lineage. We used iPS cells from mouse fibroblasts by transfection of four transcription factors, namely Oct4, Sox2, c-Myc and Klf4. Real-time PCR showed that renal lineage markers were expressed in both ES and iPS cells after the induction of differentiation. It also showed that a tubular specific marker, KSP progressively increased to day 18, although the differentiation of iPS cells was slower than ES cells. The results indicated that renal lineage cells can be differentiated from both murine ES and iPS cells. Several inducing factors were tested whether they influenced on cell differentiation. In ES cells, both of GDNF and BMP7 enhanced the differentiation to metanephric mesenchyme, and Activin enhanced the differentiation of ES cells to tubular cells. Activin also enhanced the differentiation of iPS cells to tubular cells, although the enhancement was lower than in ES cells. ES and iPS cells have a potential to differentiate to renal lineage cells, and they will be an attractive resource of kidney regeneration therapy. This differentiation is enhanced by Activin in both ES and iPS cells.

  9. Mineralocorticoid-induced sodium appetite and renal salt retention: Evidence for common signaling and effector mechanisms

    Science.gov (United States)

    Fu, Yiling; Vallon, Volker

    2014-01-01

    An increase in renal sodium chloride (salt) retention and an increase in sodium appetite is the body's response to salt restriction or depletion in order to restore salt balance. Renal salt retention and increased sodium appetite can also be maladaptive and sustain the pathophysiology in conditions like salt-sensitive hypertension and chronic heart failure. Here we review the central role of the mineralocorticoid aldosterone in both the increase in renal salt reabsorption and sodium appetite. We discuss the working hypothesis that aldosterone activates similar signaling and effector mechanisms in the kidney and brain, including the mineralocorticoid receptor, the serum-and-glucocorticoid-induced kinase SGK1, the ubiquitin ligase NEDD4-2, and the epithelial sodium channel ENaC. The latter also mediates the gustatory salt sensing in the tongue, which is required for the manifestation of increased salt intake. Effects of aldosterone on both brain and kidney synergize with the effects of angiotensin II. Thus, mineralocorticoids appear to induce similar molecular pathways in the kidney, brain, and possibly tongue, which could provide opportunities for more effective therapeutic interventions. Inhibition of renal salt reabsorption is compensated by stimulation of salt appetite and vice versa; targeting both mechanisms should be more effective. Inhibiting the arousal to consume salty food may improve a patient's compliance to reducing salt intake. While a better understanding of the molecular mechanisms is needed and will provide new options, current pharmacological interventions that target both salt retention and sodium appetite include mineralocorticoid receptor antagonists and potentially inhibitors of angiotensin II and ENaC. PMID:25376899

  10. Hydrogen sulfide: A novel nephroprotectant against cisplatin-induced renal toxicity.

    Science.gov (United States)

    Dugbartey, George J; Bouma, Hjalmar R; Lobb, Ian; Sener, Alp

    2016-07-01

    Cisplatin is a potent chemotherapeutic agent for the treatment of various solid-organ cancers. However, a plethora of evidence indicates that nephrotoxicity is a major side effect of cisplatin therapy. While the antineoplastic action of cisplatin is due to formation of cisplatin-DNA cross-links, which damage rapidly dividing cancer cells upon binding to DNA, its nephrotoxic effect results from metabolic conversion of cisplatin into a nephrotoxin and production of reactive oxygen species, causing oxidative stress leading to renal tissue injury and potentially, kidney failure. Despite therapeutic targets in several pre-clinical and clinical studies, there is still incomplete protection against cisplatin-induced nephrotoxicity. Hydrogen sulfide (H2S), the third discovered gasotransmitter next to nitric oxide and carbon monoxide, has recently been identified in several in vitro and in vivo studies to possess specific antioxidant, anti-inflammatory and anti-apoptotic properties that modulate several pathogenic pathways involved in cisplatin-induced nephrotoxicity. The current article reviews the molecular mechanisms underlying cisplatin-induced nephrotoxicity and displays recent findings in the H2S field that could disrupt such mechanisms to ameliorate cisplatin-induced renal injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Antihypertensive effect of rhizome part of Acorus calamus on renal artery occlusion induced hypertension in rats

    Directory of Open Access Journals (Sweden)

    Pinal Patel

    2012-05-01

    Full Text Available Objective: The rhizomes part of Acorus calamus (AC having the calcium inhibitory effect and diuretic activity which may potentiate Na+ excretion in hypertension induced by occlusion of renal artery. Therefore this study was aimed to investigate the effect of AC on experimentally induced hypertension. Methods: Hypertension in rats was induced by clamping the left renal artery for 4h by arterial clamp (2K1C. At the end of experiment animal were anesthetized with ketamine (50 mg/kg. Carotid artery was cannulated which was connected to pressure transducer for estimation of blood pressure. Results: Ethyl acetate extract of Acorus calamus rhizomes (EAAC treated rats that underwent hypertension, demonstrated significant (P < 0.01 lower systolic blood pressure and diastolic blood pressure when compared with 2K1C rats indicated blood pressure lowering activity. Plasma renin activity was significantly (P < 0.05 decreased in EAAC treated rats compared to 2K1C rats. EAAC treated rats that underwent hypertension demonstrated significant (P < 0.01 lower mean blood urea nitrogen and creatinine when compared with 2K1C rats. Lipid peroxidation was significantly (P < 0.001 decreased, where as nitric oxide level in tissue was significantly elevated in EAAC treated rats. Antioxidant enzymes like glutathione, superoxide dismutase and catalase were significantly (P < 0.05, P < 0.01, P < 0.001 increased in EAAC treated rats when compared to 2K1C rats. Conclusions: In conclusions, EAAC treatment attenuated renal artery occlusion induced hypertension via nitric oxide generation and decreases the plasma renin activity.

  12. Involvement of caspase-12-dependent apoptotic pathway in ionic radiocontrast urografin-induced renal tubular cell injury

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Cheng Tien [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Weng, Te I. [Department of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Chen, Li Ping [Department of Dentistry, Chang Gang Memorial Hospital, Chang Gang University, Taoyuan, Taiwan (China); Chiang, Chih Kang [Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Liu, Shing Hwa, E-mail: shinghwaliu@ntu.edu.tw [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China)

    2013-01-01

    Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This toxic effect subjects in the disorder of CM-induced nephropathy. Our previous work has demonstrated that CM shows to activate the endoplasmic reticulum (ER)-related adaptive unfolding protein response (UPR) activators. Glucose-regulated protein 78 (GRP78)/eukaryotic initiation factor 2α (eIF2α)-related pathways play a protective role during the urografin (an ionic CM)-induced renal tubular injury. However, the involvement of ER stress-related apoptotic signals in the urografin-induced renal tubular cell injury remains unclear. Here, we examined by the in vivo and in vitro experiments to explore whether ER stress-regulated pro-apoptotic activators participate in urografin-induced renal injury. Urografin induced renal tubular dilation, tubular cells detachment, and necrosis in the kidneys of rats. The tubular apoptosis, ER stress-related pro-apoptotic transcriptional factors, and kidney injury marker-1 (kim-1) were also conspicuously up-regulated in urografin-treated rats. Furthermore, treatment of normal rat kidney (NRK)-52E tubular cells with urografin augmented the expressions of activating transcription factor-6 (ATF-6), C/EBP homologous protein (CHOP), Bax, caspase-12, JNK, and inositol-requiring enzyme (IRE) 1 signals. Urografin-induced renal tubular cell apoptosis was not reversed by the inhibitors of ATF-6, JNK signals or CHOP siRNA transfection, but it could be partially reversed by the inhibitor of caspase-12. Taken together, the present results and our previous findings suggest that exposure of CM/urografin activates the ER stress-regulated survival- and apoptosis-related signaling pathways in renal tubular cells. Caspase-12-dependent apoptotic pathway may be partially involved in the urografin-induced nephropathy. -- Highlights: ► Ionic contrast medium-urografin induces renal tubular cell apoptosis. ► Urografin induces the ER stress-regulated survival and apoptosis

  13. Renal dysfunction induced by long-term exposure to depleted uranium in rats

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Guoying; Xiang, Xiqiao; Chen, Xiao; Wang, Lihua; Hu, Heping; Weng, Shifang [Fudan University, Institute of Radiation Medicine, Shanghai (China)

    2009-01-15

    Depleted uranium (DU) is a kind of radioactive heavy metal which can enter into the body via inhalation (aerosols), ingestion (drinking and eating) and wounds (embedded), and causes chemical and/or radiation-induced toxicities. In this study, male Sprague Dawley rats were surgically implanted in gastrocnemius muscle with DU fragments at three dose levels (low-dose, medium-dose and high-dose), with biologically inert tantalum (Ta) fragments served as controls. At 1 day, 7 days, and 3, 6, and 12 months after implantation, the rats were euthanized and tissue samples were collected, and uranium levels were measured in a variety of tissues by inductively coupled plasma-mass spectrometry (ICP-MS) to analyze the dynamic changes and distribution of uranium in rats. Thereafter, at 3, 6 and 12 months after implantation, the rats were euthanized after the collection of 24 h urine, blood and kidney samples were collected for analysis of DU-induced renal histopathologic changes and renal dysfunction. It was observed that DU concentrations in all the DU implanted groups were higher than that in Ta control group, and DU concentrations in the kidney increased with the implanted times, peaked at the 90 days after implantation, with a high correlation to the implanted DU doses, and then began to decrease gradually and slowly, and the DU concentrations in kidney still maintained at a relatively high level even at the 360 days after implantation. Otherwise, chronic DU contamination could induce the pathological changes of renal glomeruli, tubules and mesenchyme, such as interstitial fibrosis, enlarged interstice of renal tubular epithelial cells, tumefactions and necrosis of epithelial cells, shrinkage and disappearance of cavity of Bowman's capsule. By TEM, it was shown that the basement membrane of glomerulus was incrassated, mitochondrial of kidney proximal tubule had visible tumefaction and became bigger, and the mitochondrial cristae became shorter and disorderly in

  14. Renal dysfunction induced by long-term exposure to depleted uranium in rats

    International Nuclear Information System (INIS)

    Zhu, Guoying; Xiang, Xiqiao; Chen, Xiao; Wang, Lihua; Hu, Heping; Weng, Shifang

    2009-01-01

    Depleted uranium (DU) is a kind of radioactive heavy metal which can enter into the body via inhalation (aerosols), ingestion (drinking and eating) and wounds (embedded), and causes chemical and/or radiation-induced toxicities. In this study, male Sprague Dawley rats were surgically implanted in gastrocnemius muscle with DU fragments at three dose levels (low-dose, medium-dose and high-dose), with biologically inert tantalum (Ta) fragments served as controls. At 1 day, 7 days, and 3, 6, and 12 months after implantation, the rats were euthanized and tissue samples were collected, and uranium levels were measured in a variety of tissues by inductively coupled plasma-mass spectrometry (ICP-MS) to analyze the dynamic changes and distribution of uranium in rats. Thereafter, at 3, 6 and 12 months after implantation, the rats were euthanized after the collection of 24 h urine, blood and kidney samples were collected for analysis of DU-induced renal histopathologic changes and renal dysfunction. It was observed that DU concentrations in all the DU implanted groups were higher than that in Ta control group, and DU concentrations in the kidney increased with the implanted times, peaked at the 90 days after implantation, with a high correlation to the implanted DU doses, and then began to decrease gradually and slowly, and the DU concentrations in kidney still maintained at a relatively high level even at the 360 days after implantation. Otherwise, chronic DU contamination could induce the pathological changes of renal glomeruli, tubules and mesenchyme, such as interstitial fibrosis, enlarged interstice of renal tubular epithelial cells, tumefactions and necrosis of epithelial cells, shrinkage and disappearance of cavity of Bowman's capsule. By TEM, it was shown that the basement membrane of glomerulus was incrassated, mitochondrial of kidney proximal tubule had visible tumefaction and became bigger, and the mitochondrial cristae became shorter and disorderly in alignment

  15. COX2 inhibition during nephrogenic period induces ANG II hypertension and sex-dependent changes in renal function during aging.

    Science.gov (United States)

    Reverte, Virginia; Tapia, Antonio; Loria, Analia; Salazar, Francisco; Llinas, M Teresa; Salazar, F Javier

    2014-03-01

    This study was performed to test the hypothesis that ANG II contributes to the hypertension and renal functional alterations induced by a decrease of COX2 activity during the nephrogenic period. It was also examined whether renal functional reserve and renal response to volume overload and high sodium intake are reduced in 3-4- and 9-11-mo-old male and female rats treated with vehicle or a COX2 inhibitor during nephrogenic period (COX2np). Our data show that this COX2 inhibition induces an ANG II-dependent hypertension that is similar in male and female rats. Renal functional reserve is reduced in COX2np-treated rats since their renal response to an increase in plasma amino acids levels is abolished, and their renal ability to eliminate a sodium load is impaired (P renal excretory ability is similar in both sexes during aging but does not induce the development of a sodium-sensitive hypertension. However, the prolonged high-sodium intake at 9-11 mo of age leads to a greater proteinuria in male than in female (114 ± 12 μg/min vs. 72 ± 8 μg/min; P Renal hemodynamic sensitivity to acute increments in ANG II is unaltered in both sexes and at both ages in COX2np-treated rats. In summary, these results indicate that the reduction of COX2 activity during nephrogenic period programs for the development of an ANG II-dependent hypertension, reduces renal functional reserve to a similar extent in both sexes, and increases proteinuria in males but not in females when there is a prolonged increment in sodium intake.

  16. Combination Anti-Apoptotic Effect of Erythropoietin and Melatonin on Ischemia Reperfusion-Induced Renal Injury in Rats

    Directory of Open Access Journals (Sweden)

    Shokofeh Banaei

    2016-11-01

    Full Text Available Renal ischemia-reperfusion (IR contributes to the development of acute renal failure (ARF. Oxygen free radicals are considered to be principal components involved in the pathophysiological tissue alterations observed during renal IR. The purpose of this study was to investigate the combination effect of melatonin (MEL and erythropoietin (EPO, which are a potent antioxidant and anti-apoptotic agents, in IR-induced renal injury in rats. Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. MEL (10 mg/kg, i.p and EPO (5000 U/kg, i.p were administered prior to ischemia. After 24 h reperfusion, following decapitation, blood samples were collected for the determination of superoxide dismutase (SOD, glutathione peroxidase (GPx, and malondialdehyde (MDA levels. Also, renal samples were taken for histological evaluation and apoptosis assay. Ischemia-reperfusion increased SOD, GPx, MDA levels, and TUNEL positive cells. Histopathological findings of the IR group confirmed that there was renal impairment in the tubular epithelium. Treatment with EPO and MEL decreased SOD, GPx, and MDA levels, histopathological changes, and TUNEL positive cells. These results indicated that the combination of MEL and EPO could not exert more nephroprotective and anti-apoptotic effects than MEL treatment in renal ischemia-reperfusion injury.

  17. Ciglitazone induces caspase-independent apoptosis via p38-dependent AIF nuclear translocation in renal epithelial cells

    International Nuclear Information System (INIS)

    Kwon, Chae Hwa; Yoon, Chang Soo; Kim, Yong Keun

    2008-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) agonists have been reported to induce apoptosis in a variety of cell types including renal proximal epithelial cells. However, the underlying mechanism of cell death induced by PPARγ agonists has not been clearly defined in renal proximal tubular cells. This study was therefore undertaken to determine the mechanism by which ciglitazone, a synthetic PPARγ agonist, induces apoptosis in opossum kidney (OK) cells, an established renal epithelial cell line. Ciglitazone treatment induced apoptotic cell death in a dose- and time-dependent manner. Ciglitazone caused a transient activation of ERK and sustained activation of p38 MAP kinase. Ciglitazone-mediated cell death was attenuated by the p38 inhibitor SB203580 and transfection of dominant-negative form of p38, but not by the MEK inhibitor U0126, indicating that p38 MAP kinase activation is involved in the ciglitazone-induced cell death. Although ciglitazone-induced caspase-3 activation, the ciglitazone-mediated cell death was not affected by the caspase-3 inhibitor DEVD-CHO. Ciglitazone-induced mitochondrial membrane depolarization and apoptosis-inducing factor (AIF) nuclear translocation and these effects were prevented by the p38 inhibitor. These results suggest that ciglitazone induces caspase-independent apoptosis through p38 MAP kinase-dependent AIF nuclear translocation in OK renal epithelial cells

  18. Ceramide-Induced Apoptosis in Renal Tubular Cells: A Role of Mitochondria and Sphingosine-1-Phoshate

    Science.gov (United States)

    Ueda, Norishi

    2015-01-01

    Ceramide is synthesized upon stimuli, and induces apoptosis in renal tubular cells (RTCs). Sphingosine-1 phosphate (S1P) functions as a survival factor. Thus, the balance of ceramide/S1P determines ceramide-induced apoptosis. Mitochondria play a key role for ceramide-induced apoptosis by altered mitochondrial outer membrane permeability (MOMP). Ceramide enhances oligomerization of pro-apoptotic Bcl-2 family proteins, ceramide channel, and reduces anti-apoptotic Bcl-2 proteins in the MOM. This process alters MOMP, resulting in generation of reactive oxygen species (ROS), cytochrome C release into the cytosol, caspase activation, and apoptosis. Ceramide regulates apoptosis through mitogen-activated protein kinases (MAPKs)-dependent and -independent pathways. Conversely, MAPKs alter ceramide generation by regulating the enzymes involving ceramide metabolism, affecting ceramide-induced apoptosis. Crosstalk between Bcl-2 family proteins, ROS, and many signaling pathways regulates ceramide-induced apoptosis. Growth factors rescue ceramide-induced apoptosis by regulating the enzymes involving ceramide metabolism, S1P, and signaling pathways including MAPKs. This article reviews evidence supporting a role of ceramide for apoptosis and discusses a role of mitochondria, including MOMP, Bcl-2 family proteins, ROS, and signaling pathways, and crosstalk between these factors in the regulation of ceramide-induced apoptosis of RTCs. A balancing role between ceramide and S1P and the strategy for preventing ceramide-induced apoptosis by growth factors are also discussed. PMID:25751724

  19. Ameliorating activity of ginger (Zingiber officinale) extract against lead induced renal toxicity in male rats.

    Science.gov (United States)

    Reddy, Y Amarnath; Chalamaiah, M; Ramesh, B; Balaji, G; Indira, P

    2014-05-01

    Lead poisoning has been known to be associated with structural and functional abnormalities of multiple organ systems of human body. The aim of this investigation was to study the renal protective effects of ginger (Zingiber officinale) extract in lead induced toxicity rats. In this study renal glutathione (GSH) level, glutathione peroxidase (GPX), glutathione-s-transferase (GST), and catalase enzymes were measured in lead nitrate (300 mg/kg BW), and lead nitrate plus ginger extract (150 mg/kg BW) treated rat groups for 1 week and 3 weeks respectively. The glutathione level and GSH dependent antioxidant enzymes such as glutathione peroxidase, glutathione-s-transferase, and catalase significantly (P < 0.05) increased in ginger extract treated rat groups. In addition, histological studies showed lesser renal changes in lead plus ginger extract treated rat groups than that of lead alone treated rat groups. These results indicate that ginger extract alleviated lead toxic effects by enhancing the levels of glutathione, glutathione peroxidase, glutathione-s-transferase and catalase.

  20. The feasibility of using microwave-induced thermoacoustic tomography for detection and evaluation of renal calculi

    International Nuclear Information System (INIS)

    Cao Caijun; Nie Liming; Lou Cunguang; Xing Da

    2010-01-01

    Imaging of renal calculi is important for patients who suffered a urinary calculus prior to treatment. The available imaging techniques include plain x-ray, ultrasound scan, intravenous urogram, computed tomography, etc. However, the visualization of a uric acid calculus (radiolucent calculi) is difficult and often impossible by the above imaging methods. In this paper, a new detection method based on microwave-induced thermoacoustic tomography was developed to detect the renal calculi. Thermoacoustic images of calcium oxalate and uric acid calculus were compared with their x-ray images. The microwave absorption differences among the calcium oxalate calculus, uric acid calculus and normal kidney tissue could be evaluated by the amplitude of the thermoacoustic signals. The calculi hidden in the swine kidney were clearly imaged with excellent contrast and resolution in the three orthogonal thermoacoustic images. The results indicate that thermoacoustic imaging may be developed as a complementary method for detecting renal calculi, and its low cost and effective feature shows high potential for clinical applications.

  1. Potential immunotoxic effects of trichloroethylene-induced IV allergic reaction in renal impairment

    Directory of Open Access Journals (Sweden)

    Jun-Feng Yu

    2017-08-01

    Full Text Available Trichloroethylene (TCE is known to induce allergic contact dermatitis and subsequent occupational medicamentosa-like dermatitis (OMLD with multi-system injuries, including liver, kidney, and skin injuries. However, the mechanisms underlying immune system dysfunction that result in organ injury have not yet been clearly elucidated. In the present study, we measured the levels of secreted cytokines by effect or T cells in TCE-treated guinea pigs to better understand the contribution of allergic disorders in renal injuries. We immunized guinea pigs with trichloroethylene using the Guinea Pig Maximization Test (GPMT and scored the inflammation on the guinea pigs’ skin. The kidney function and ultra-structural changes in the kidneys were detected using biochemical methods and electron microscopy. The deposition of cytokines was determined using immunohistochemistry. The sensitization rate was 63.16% in the TCE-sensitized groups. The electron microscopy results showed tubular epithelial cell mitochondrial swelling, vacuolar degeneration, and atrophy of the microvillus in the sensitized groups. A high degree of cytokine deposition was observed in the renal tubular proximal epithelial cells in the TCE-sensitized groups. As observed in this study, the variation in the level of immune system activation not only indicates that TCE can largely magnify the immune reaction but also suggests a potential role of immune dysfunction in renal impairment.

  2. Amla as an antihyperglycemic and hepato-renal protective agent in fluoride induced toxicity

    Directory of Open Access Journals (Sweden)

    Rupal A Vasant

    2012-01-01

    Full Text Available Purpose of the study was to examine the antihyperglycemic and hepato-renal protective effects of Emblica officinalis (Eo fruit as a food supplement in fluoride induced toxicity. Eo fruit powder was incorporated into the diet (2.5, 5 and 10 gm % of fluoride exposed animals for a duration of 30 days. Fluoride exposure caused significant elevation in plasma glucose, serum glutamate oxaloacetate transaminase (SGOT, serum glutamate pyruvate transaminase (SGPT, acid phosphatase (ACP, alkaline phosphatase (ALP activities, hepatic glucose-6-phosphatase (G-6-Pase and decreased hepatic glycogen content, hexokinase activity and antioxidant profiles (hepatic and renal. An inclusion of Eo fruit powder significantly reduced plasma glucose levels, SGOT, SGPT, ACP and ALP activities, hepatic G-6-Pase activity and increased hepatic glycogen content and hexokinase activity. Hepatic and renal antioxidant status of fluoride exposed animals improved upon feeding Eo fruit powder. We, therefore, conclude that E. officinalis fruit could be useful in regulating hyperglycemia and enhances antioxidant status of fluoride exposed animals.

  3. Gum acacia mitigates genetic damage in adenine-induced chronic renal failure in rats.

    Science.gov (United States)

    Ali, B H; Al Balushi, K; Al-Husseini, I; Mandel, P; Nemmar, A; Schupp, N; Ribeiro, D A

    2015-12-01

    Subjects with chronic renal failure (CRF) exhibit oxidative genome damage, which may predispose to carcinogenesis, and Gum acacia (GumA) ameliorates this condition in humans and animals. We evaluated here renal DNA damage and urinary excretion of four nucleic acid oxidation adducts namely 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxoguanosine (8-oxoGuo) and 8-hydroxy-2-deoxyguanisone (8-OHdg) in rats with adenine (ADE)-induced CRF with and without GumA treatment. Twenty-four rats were divided into four equal groups and treated for 4 weeks. The first group was given normal food and water (control). The second group was given normal food and GumA (15% w/v) in drinking water. The third group was fed powder diet containing adenine (ADE) (0·75% w/w in feed). The fourth group was fed like in the third group, plus GumA in drinking water (15%, w/v). ADE feeding induced CRF (as measured by several physiological, biochemical and histological indices) and also caused a significant genetic damage and significant decreases in urinary 8-oxo Gua and 8-oxoGuo, but not in the other nucleic acids. However, concomitant GumA treatment reduced the level of genetic damage in kidney cells as detected by Comet assay and significantly reversed the effect of adenine on urinary 8-oxoGuo. Treatment with GumA is able to mitigate genetic damage in renal tissues of rats with ADE-induced CRF. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

  4. A study on renal damage in rats induced by different concentrations and osmolarities of diatrizoate

    International Nuclear Information System (INIS)

    Park, Ki Soon; Sung, Dong Wook; Yoon, Yup; Lim, Jae Hoon

    1992-01-01

    There has been few papers regarding the pathologic changes of kidney induced by contrast media, especially in terms of iodine concentration or osmolarity. In order to evaluate histopathologic changes, a series of rat kidneys, after injection of iodinated contrast media, were examined. A total of 220 rats were divided into two groups:those given Urografin-60% by 6.3ml/Kg(1840mg/6.3ml):those given Urografin-76% by 5ml/Kg(1850mg/5ml). The kidneys were removed and microscopically examined on 1, 2, 3, 5, 7,10th days, 2nd, 3rd, 4th, 6th and 12th weeks after injection of contrast media, respectively. The results were as follows: Renal pathologic changes induced by contrast media were congestion and ectatic change of the interstitial vessels, epithelial degeneration and necrosis of the collecting ducts. Congestion of interstitial vessels and epithelial degeneration and necrosis of the collecting ducts were serve in the higher iodine concentration Urografin-76% group(2100 Osm/Kg H 2 O) than the Urografin-60% group (1500 Osm/Kg H 2 O). And above pathological changes persisted for 12 weeks without significant interval changes. The authors conclude that the renal damage induced by ionic contrast media becomes more severe in higher concentrations or osmolarities in spite of the same amount of iodine and that the pathologic changes persisted until 12 weeks without improvement

  5. Postural Effect on Renal Function In Cases of Pregnancy-Induced Hypertension

    OpenAIRE

    丸山, 晋司; Maruyama, Shinji

    1989-01-01

    Postual effect on renal function was analysed on the cases of pregnancy-induced hypertension (PIH) (n=11) compared with cases of normotensive pregnancies (n=12) and non-pregnant women (n=9). In non-pregnant women, GFR, RBF and RPF showed no changes in relation to the changing posture (supine and left lateral). In normal pregnant women and cases of PIH, GFR, RBF and RPF significantly increased on changing their posture from supine to left lateral at third trimester. Especially, patients with P...

  6. Hyperglycemia induced damage to mitochondrial respiration in renal mesangial and tubular cells: Implications for diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Anna Czajka

    2016-12-01

    Full Text Available Damage to renal tubular and mesangial cells is central to the development of diabetic nephropathy (DN, a complication of diabetes which can lead to renal failure. Mitochondria are the site of cellular respiration and produce energy in the form of ATP via oxidative phosphorylation, and mitochondrial dysfunction has been implicated in DN. Since the kidney is an organ with high bioenergetic needs, we postulated that hyperglycemia causes damage to renal mitochondria resulting in bioenergetic deficit. The bioenergetic profiles and the effect of hyperglycemia on cellular respiration of human primary mesangial (HMCs and proximal tubular cells (HK-2 were compared in normoglycemic and hyperglycemic conditions using the seahorse bio-analyzer. In normoglycemia, HK-2 had significantly lower basal, ATP-linked and maximal respiration rates, and lower reserve capacity compared to HMCs. Hyperglycemia caused a down-regulation of all respiratory parameters within 4 days in HK-2 but not in HMCs. After 8 days of hyperglycemia, down-regulation of respiratory parameters persisted in tubular cells with compensatory up-regulated glycolysis. HMCs had reduced maximal respiration and reserve capacity at 8 days, and by 12 days had compromised mitochondrial respiration despite which they did not enhance glycolysis. These data suggest that diabetes is likely to lead to a cellular deficit in ATP production in both cell types, although with different sensitivities, and this mechanism could significantly contribute to the cellular damage seen in the diabetic kidney. Prevention of diabetes induced damage to renal mitochondrial respiration may be a novel therapeutic approach for the prevention/treatment of DN.

  7. In vivo and in vitro assessment of pathways involved in contrast media-induced renal cells apoptosis

    Science.gov (United States)

    Quintavalle, C; Brenca, M; De Micco, F; Fiore, D; Romano, S; Romano, M F; Apone, F; Bianco, A; Zabatta, M A; Troncone, G; Briguori, C; Condorelli, G

    2011-01-01

    Contrast-induced nephropathy accounts for >10% of all causes of hospital-acquired renal failure, causes a prolonged in-hospital stay and represents a powerful predictor of poor early and late outcome. Mechanisms of contrast-induced nephropathy are not completely understood. In vitro data suggests that contrast media (CM) induces a direct toxic effect on renal tubular cells through the activation of the intrinsic apoptotic pathway. It is unclear whether this effect has a role in the clinical setting. In this work, we evaluated the effects of CM both in vivo and in vitro. By analyzing urine samples obtained from patients who experienced contrast-induced acute kidney injury (CI-AKI), we verified, by western blot and immunohistochemistry, that CM induces tubular renal cells apoptosis. Furthermore, in cultured cells, CM caused a dose–response increase in reactive oxygen species (ROS) production, which triggered Jun N-terminal kinases (JNK1/2) and p38 stress kinases marked activation and thus apoptosis. Inhibition of JNK1/2 and p38 by different approaches (i.e. pharmacological antagonists and transfection of kinase-death mutants of the upstream p38 and JNK kinases) prevented CM-induced apoptosis. Interestingly, N-acetylcysteine inhibited ROS production, and thus stress kinases and apoptosis activation. Therefore, we conclude that CM-induced tubular renal cells apoptosis represents a key mechanism of CI-AKI. PMID:21562587

  8. Anti-inflammatory effects of royal jelly on ethylene glycol induced renal inflammation in rats

    Directory of Open Access Journals (Sweden)

    Zeyneb Aslan

    2015-10-01

    Full Text Available ABSTRACT Objective: In this study, anti-inflammatory effects of Royal Jelly were investigated by inducing renal inflammation in rats with the use of ethylene glycol. For this purpose, the calcium oxalate urolithiasis model was obtained by feeding rats with ethylene glycol in drinking water. Materials and Methods: The rats were divided in five study groups. The 1st group was determined as the control group. The rats in the 2nd group received ethylene glycol (1% in drinking water. The rats in the 3rd group were daily fed with Royal Jelly by using oral gavage. The 4th group was determined as the preventive group and the rats were fed with ethylene glycol (1% in drinking water while receiving Royal Jelly via oral gavage. The 5th group was determined as the therapeutic group and received ethylene glycol in drinking water during the first 2 weeks of the study and Royal Jelly via oral gavage during the last 2 weeks of the study. Results: At the end of the study, proinflammatory/anti-inflammatory cytokines, TNF-α, IL-1β and IL-18 levels in blood and renal tissue samples from the rats used in the application were measured. Conclusion: The results have shown that ethylene glycol does induce inflammation and renal damage. This can cause the formation of reactive oxygen species. Royal Jelly is also considered to have anti-inflammatory effects due to its possible antiradical and antioxidative effects. It can have positive effects on both the prevention of urolithiasis and possible inflammation during the existing urolithiasis and support the medical treatment.

  9. Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

    Energy Technology Data Exchange (ETDEWEB)

    Taub, Mary, E-mail: biochtau@buffalo.edu

    2016-03-11

    Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10{sup −5} M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

  10. Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

    International Nuclear Information System (INIS)

    Taub, Mary

    2016-01-01

    Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10"−"5 M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

  11. Gold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats.

    Science.gov (United States)

    Reshi, Mohd Salim; Shrivastava, Sadhana; Jaswal, Amita; Sinha, Neelu; Uthra, Chhavi; Shukla, Sangeeta

    2017-04-04

    Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2g/kg p.o. once only. After 24h of APAP intoxication, animals were treated with three different doses of AuNPs (50μg/kg, 100μg/kg, 150μg/kg) orally or silymarin at a dose of 50mg/kg p.o., once only. Animals of all the groups were sacrificed after 24h of last treatment. APAP administered group showed a significant rise in the AST, ALT, SALP, LDH, cholesterol, bilirubin, albumin, urea and creatinine in serum which indicated the hepato-renal damage. A significantly enhanced LPO and a depleted level of GSH were observed in APAP intoxicated rats. Declined activities of SOD and Catalase, after acetaminophen exposure indicated oxidative stress in liver and kidney. The activities of ATPase and glucose-6-Phosphatase were significantly inhibited after APAP administration. AuNPs treatment reversed all variables significantly towards normal level and was found nontoxic. Thus it is concluded that gold nanoparticles played a beneficial role in reducing acetaminophen induced toxicity and can be used in the development of drug against hepatic as well as renal diseases, after further preclinical and clinical studies. Copyright © 2017 Elsevier GmbH. All rights reserved.

  12. An experimental study on renal damage induced by ionic contrast media in relation to iodine concentration

    International Nuclear Information System (INIS)

    Sung, Dong Wook; Yoon, Yup; Lim, Jae Hoon; Yang, Moon Ho

    1990-01-01

    Renal injury caused by iodinated contrast media has been widely known, but there has been few papers regarding the pathological change. A series of kidneys after injection of iodinated contrast media was examined to document pathological change. A total of 80 rats was divided into two groups; those given Urografin-60% by 5ml/kg; those given Urografin-76% by 5ml/kg. The kidneys were removed out 1, 2, 3, 5, 7, 10, 14 and 21 days after injection of contrast media and microscopically examined. The resulted were as follows: 1. Pathological changes induced by ionic contrast media were deposition of proteinaceous materials in the proximal convoluted tubules, congestion of interstitial vessels, and vasa rectae, and epithelial degeneration of collecting ducts. There was no detectable pathological changes in the glomerulus, loop of Henle, and distal convoluted tubules. 2. All pathological changes were severe, as the concentration of contrast media increased. 3. These pathologic changes appeared 1 day after injection of contrast media and persisted at least 3 weeks without improvement. Author concludes that the renal damage induced by ionic contrast media becomes severe with increase in concentration, and pathologic changes are not influence with time interval

  13. Inhibition of Extracellular Signal-Regulated Kinases Ameliorates Hypertension-Induced Renal Vascular Remodeling in Rat Models

    Directory of Open Access Journals (Sweden)

    Li Jing

    2011-11-01

    Full Text Available The aim of this study is to investigate the effect of the extracellular signal-regulated kinases 1/2 (ERK1/2 inhibitor, PD98059, on high blood pressure and related vascular changes. Blood pressure was recorded, thicknesses of renal small artery walls were measured and ERK1/2 immunoreactivity and erk2 mRNA in renal vascular smooth muscle cells (VSMCs and endothelial cells were detected by immunohistochemistry and in situ hybridization in normotensive wistar kyoto (WKY rats, spontaneously hypertensive rats (SHR and PD98059-treated SHR. Compared with normo-tensive WKY rats, SHR developed hypertension at 8 weeks of age, thickened renal small artery wall and asymmetric arrangement of VSMCs at 16 and 24 weeks of age. Phospho-ERK1/2 immunoreactivity and erk2 mRNA expression levels were increased in VSMCs and endothelial cells of the renal small arteries in the SHR. Treating SHR with PD98059 reduced the spontaneous hypertension-induced vascular wall thickening. This effect was associated with suppressions of erk2 mRNA expression and ERK1/2 phosphorylation in VSMCs and endothelial cells of the renal small arteries. It is concluded that inhibition of ERK1/2 ameliorates hypertension induced vascular remodeling in renal small arteries.

  14. The Protective Role of Tempol Against Oxidative Stress-Related Renal Impairment Induced by Gamma Rays in Rats

    International Nuclear Information System (INIS)

    Mekawy, H.M.S.; Elkhouly, W.A.; Tawfik, S.S.

    2015-01-01

    Tempol (4-hydroxy-2,2,6,6-tetramethyl-piperidine-1 oxyl) is a naturally occurring substance that counteracts the harmful and damaging effects of oxidation in animal tissues and has been reported to permeate the biological membranes. In this study, tempol with dose of 18 mg/kg/day for 2 weeks has been shown to be effective in preventing several of the adverse consequences of oxidative stress and inflammation that underlie radiation damage. Adult rats were exposed to a total dose of 6 Gy gamma rays to determine the protective role of tempol on the biochemistry of the injured kidney because gamma rays displayed significant augmentation in renal oxidative modifications markers.The results indicated that plasma renal function tests; urea (Ur), creatinine (Cr), uric acid (UA) and sodium (Na), and plasma renal tubular injury markers; γ -glutamyltransferase ( γ -GT), aspartate aminotransferase (AST), creatine phosphokinase (CPK) and lactate dehydrogenase (LDH), were increased significantly in gamma rays group. In addition, the renal oxidative stress parameters; malondialdehyde (MDA), total cholesterol (TC) and protein carbonyl (PC), were increased significantly, and reduced glutathione (GSH) was decreased significantly in gamma rays group. Moreover, the levels of renal antioxidant enzymes; superoxide dismutase (SOD) and catalase (CAT), were decreased significantly, and myeloperoxidase (MPO) was in creased significantly in gamma rays group.The antioxidant treatment with tempol ameliorates gamma rays-induced biochemical alterations and dysfunction of kidney.Tempol, at levels within tolerable nutritional strategy, reduced the oxidative modification-related renal impairment induced by gamma radiation in rats.

  15. Protective Immunity and Reduced Renal Colonization Induced by Vaccines Containing Recombinant Leptospira interrogans Outer Membrane Proteins and Flagellin Adjuvant

    Science.gov (United States)

    Monaris, D.; Sbrogio-Almeida, M. E.; Dib, C. C.; Canhamero, T. A.; Souza, G. O.; Vasconcellos, S. A.; Ferreira, L. C. S.

    2015-01-01

    Leptospirosis is a global zoonotic disease caused by different Leptospira species, such as Leptospira interrogans, that colonize the renal tubules of wild and domestic animals. Thus far, attempts to develop effective leptospirosis vaccines, both for humans and animals, have failed to induce immune responses capable of conferring protection and simultaneously preventing renal colonization. In this study, we evaluated the protective immunity induced by subunit vaccines containing seven different recombinant Leptospira interrogans outer membrane proteins, including the carboxy-terminal portion of the immunoglobulinlike protein A (LigAC) and six novel antigens, combined with aluminum hydroxide (alum) or Salmonella flagellin (FliC) as adjuvants. Hamsters vaccinated with the different formulations elicited high antigen-specific antibody titers. Immunization with LigAC, either with alum or flagellin, conferred protective immunity but did not prevent renal colonization. Similarly, animals immunized with LigAC or LigAC coadministered with six leptospiral proteins with alum adjuvant conferred protection but did not reduce renal colonization. In contrast, immunizing animals with the pool of seven antigens in combination with flagellin conferred protection and significantly reduced renal colonization by the pathogen. The present study emphasizes the relevance of antigen composition and added adjuvant in the efficacy of antileptospirosis subunit vaccines and shows the complex relationship between immune responses and renal colonization by the pathogen. PMID:26108285

  16. Effects of acetylcysteine and probucol on contrast medium-induced depression of intrinsic renal glutathione peroxidase activity in diabetic rats.

    Science.gov (United States)

    Yen, Hsueh-Wei; Lee, Hsiang-Chun; Lai, Wen-Te; Sheu, Sheng-Hsiung

    2007-04-01

    Antioxidants such as N-acetylcysteine and probucol have been used to protect patients from contrast media-induced nephrotoxicity. The mechanisms underlying these protective effects are not well understood. We hypothesized that acetylcysteine and probucol alter the activity of endogenous antioxidant enzyme activity. Four weeks after induction of diabetes with streptozotocin, diabetic and nondiabetic rats were divided into three groups. Group 1 rats did not receive any antioxidant agents. Group 2 rats were treated with acetylcysteine and group 3 rats with probucol for 1 week before injection of the contrast medium diatrizoate (DTZ). We found that diabetic rats had higher renal glutathione peroxidase (GPx) activity than normal rats. DTZ suppressed renal GPx activity significantly in both group 1 diabetic and normal rats. Interestingly, renal GPx activity in both diabetic and normal rats pretreated with acetylcysteine or probucol was not inhibited by DTZ. Renal superoxide dismutase (SOD) increased significantly in normal rats after DTZ injection, but not in diabetic rats. Finally, acetylcysteine or probucol did not significantly influence renal SOD. These findings suggest that the renal protective effects of acetylcysteine and probucol against contrast-induced oxidative stress and nephrotoxicity may be mediated by altering endogenous GPx activity.

  17. Changes in expression of renal Oat1, Oat3 and Mrp2 in cisplatin-induced acute renal failure after treatment of JBP485 in rats

    International Nuclear Information System (INIS)

    Liu, Tao; Meng, Qiang; Wang, Changyuan; Liu, Qi; Guo, Xinjin; Sun, Huijun; Peng, Jinyong

    2012-01-01

    The purpose of this study is to investigate whether the effect of cyclo-trans-4-L-hydroxyprolyl-L-serine (JBP485) on acute renal failure (ARF) induced by cisplatin is related to change in expression of renal Oat1, Oat3 and Mrp2 in rats. JBP485 reduced creatinine, blood urea nitrogen (BUN) and indoxyl sulfate (IS) in plasma and malondialdehyde (MDA) in kidney, and recovered the glomerular filtration rate (GFR) and the activity of superoxide dismutase (SOD) in cisplatin-treated rats. The plasma concentration of PAH (para-aminohippurate) determined by LC–MS/MS was increased markedly after intravenous administration of cisplatin, whereas cumulative urinary excretion of PAH and the uptake of PAH in kidney slices were significantly decreased. qRT-PCR and Western-blot showed a decrease in mRNA and protein of Oat1 and Oat3, an increase in mRNA and protein of Mrp2 in cisplatin-treated rats, and an increase in IS (a uremic toxin) after co-treatment with JBP485. It indicated that JBP485 promoted urinary excretion of toxins by upregulating renal Mrp2. This therefore gives in part the explanation about the mechanism by which JBP485 improves ARF induced by cisplatin in rats. -- Highlights: ► Cisplatin induces acute renal failure (ARF). ► The expression of Oat1, Oat3 and Mrp2 were changed during ARF. ► The regulated expression of Oat1, Oat3 and Mrp2 is an adaptive protected response. ► JBP485 could facilitate the adaptive protective action.

  18. Changes in expression of renal Oat1, Oat3 and Mrp2 in cisplatin-induced acute renal failure after treatment of JBP485 in rats

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Tao, E-mail: liutaomedical@qq.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Meng, Qiang, E-mail: mengq531@yahoo.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Wang, Changyuan, E-mail: wangcyuan@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Liu, Qi, E-mail: llaqii@yahoo.com.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Guo, Xinjin, E-mail: guo.xinjin@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Sun, Huijun, E-mail: sunhuijun@hotmail.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); Peng, Jinyong, E-mail: jinyongpeng2005@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044 (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University (China); and others

    2012-11-01

    The purpose of this study is to investigate whether the effect of cyclo-trans-4-L-hydroxyprolyl-L-serine (JBP485) on acute renal failure (ARF) induced by cisplatin is related to change in expression of renal Oat1, Oat3 and Mrp2 in rats. JBP485 reduced creatinine, blood urea nitrogen (BUN) and indoxyl sulfate (IS) in plasma and malondialdehyde (MDA) in kidney, and recovered the glomerular filtration rate (GFR) and the activity of superoxide dismutase (SOD) in cisplatin-treated rats. The plasma concentration of PAH (para-aminohippurate) determined by LC–MS/MS was increased markedly after intravenous administration of cisplatin, whereas cumulative urinary excretion of PAH and the uptake of PAH in kidney slices were significantly decreased. qRT-PCR and Western-blot showed a decrease in mRNA and protein of Oat1 and Oat3, an increase in mRNA and protein of Mrp2 in cisplatin-treated rats, and an increase in IS (a uremic toxin) after co-treatment with JBP485. It indicated that JBP485 promoted urinary excretion of toxins by upregulating renal Mrp2. This therefore gives in part the explanation about the mechanism by which JBP485 improves ARF induced by cisplatin in rats. -- Highlights: ► Cisplatin induces acute renal failure (ARF). ► The expression of Oat1, Oat3 and Mrp2 were changed during ARF. ► The regulated expression of Oat1, Oat3 and Mrp2 is an adaptive protected response. ► JBP485 could facilitate the adaptive protective action.

  19. Cell cycle progression, but not genotoxic activity, mainly contributes to citrinin-induced renal carcinogenesis

    International Nuclear Information System (INIS)

    Kuroda, Ken; Ishii, Yuji; Takasu, Shinji; Kijima, Aki; Matsushita, Kohei; Watanabe, Maiko; Takahashi, Haruo; Sugita-Konishi, Yoshiko; Sakai, Hiroki; Yanai, Tokuma; Nohmi, Takehiko; Ogawa, Kumiko; Umemura, Takashi

    2013-01-01

    Citrinin (CTN) is a food-contaminating mycotoxin that efficiently induces renal tumors in rats. However, the modes of carcinogenic action are still unknown, preventing assessment of the risks of CTN in humans. In the present study, the proliferative effects of CTN and its causal factors were investigated in the kidneys of gpt delta rats. In addition, three in vivo genotoxicity assays (reporter gene mutation using gpt delta rats and comet and micronucleus assays using F344 rats) were performed to clarify whether CTN was genotoxic in vivo. CTN was administrated at 20 and 40 mg/kg/day, the higher dose being the maximal tolerated dose and a nearly carcinogenic dose. In the kidney cortex of gpt delta rats, significant increases in the labeling indices of proliferating cell nuclear antigen (PCNA)-positive cells were observed at all doses of CTN. Increases in the mRNA expression levels of Ccna2, Ccnb1, Ccne1, and its transcription factor E2f1 were also detected, suggesting induction of cell cycle progression at all tested doses of CTN. However, histopathological changes were found only in rats treated with the higher dose of CTN, which was consistent with increases in the mRNA expression levels of mitogenic factors associated with tissue damage/regeneration, such as Hgf and Lcn2, at the same dose. Thus, the proliferative effects of CTN may result not only from compensatory reactions, but also from direct mitogenic action. Western blot analysis showed that ERK phosphorylation was increased at all doses, implying that cell cycle progression may be mediated by activation of the ERK pathway. On the other hand, in vivo genotoxicity analyses were negative, implying that CTN did not have the potential for inducing DNA damage, gene mutations, or chromosomal aberrations. The overall data clearly demonstrated the molecular events underlying CTN-induced cell cycle progression, which could be helpful to understand CTN-induced renal carcinogenesis

  20. Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2016-05-01

    Full Text Available Background/Aims: Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Methods: Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks, which is known to involve inflammation and oxidative stress. DEP (0.5m/kg was intratracheally (i.t. instilled every 4th day for 4 weeks (7 i.t. instillation. Four days following the last exposure to either DEP or saline (control, various renal endpoints were measured. Results: While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Conclusion: Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic

  1. Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure.

    Science.gov (United States)

    Nemmar, Abderrahim; Karaca, Turan; Beegam, Sumaya; Yuvaraju, Priya; Yasin, Javed; Hamadi, Naserddine Kamel; Ali, Badreldin H

    2016-01-01

    Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP) on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks), which is known to involve inflammation and oxidative stress. DEP (0.5m/kg) was intratracheally (i.t.) instilled every 4th day for 4 weeks (7 i.t. instillation). Four days following the last exposure to either DEP or saline (control), various renal endpoints were measured. While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic renal failure. Our data provide biological plausibility that air

  2. Effects of Sodium Selenite on Formaldehyde Induced Renal Toxicity in Mice

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    Shabnam Mohammadi 1,2 * , Maryam Moghimian 3, Hanieh Torabzadeh 4, Mahla Langari 4, Roghayeh Nazeri 4, Zahra Karimi 4, Elham Sangari 4, Najmeh Jagarmi 5, Alireza Mohammad Zadeh 3, Mehdi Karimi 7, Kamyar Tavakkoli 8, Ali Delshad 9, Fatemeh Mohammadzadeh 3, Majid Ghayour-Mobarhan 10

    2016-12-01

    Full Text Available Background: Formaldehyde is widely used for industrial applications. Renal injury is an adverse effect associated with formaldehyde. Few studies have explored the potential benefits of protective factors on formaldehyde induced renal toxicity. This study evaluated the dose dependent effects of sodium selenite on the biochemical and histopathological effects of formaldehyde on murine kidney. Methods: Forty eight adult Balb/c male mice were randomized into six groups: a control group, a formaldehyde group and experimental III-VI groups. Formaldehyde group was injected with 10 mg/kg formaldehyde and groups III-VI received intraperitoneally doses of 0.1, 0.2, 0.4, 0.8 mg/kg selenium. After two weeks, a stereological study was done in accordance with the principle of Cavalieri and serum concentrations of urea and creatinine were measured. Data were analyzed using ANOVA and SPSS software. Results: Glomerosclerosis, necrosis and vacuolization were observed in the convoluted tubules of animals treated with formaldehyde. The biochemical markers, volume and count of glomeruli in the group treated with formaldehyde was significantly difference compared to the control group (P<0.05. The volume of the glomeruli in the group treated with 0.2 and 0.4 mg selenium and urea level in the group treated with 0.4 and 0.1 mg/kg selenium was significantly difference compared to the control group (P <0.05. The count of glomeruli and creatinine level in the selenium group was significantly difference compared to the control group (P ≤ 0.0001. Conclusions: A dose of 0.2 mg/kg of sodium selenite caused partial protective effect on the renal tissue and function in exposed to formaldehyde.

  3. Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis.

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    María F Ferrer

    Full Text Available Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.

  4. Calcium, zinc and vitamin E ameliorate cadmium-induced renal oxidative damage in albino Wistar rats

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    Pradeepkiran Jangampalli Adi

    Full Text Available This study was aimed to examine the protective effects of supplementation with calcium + zinc (Ca + Zn or vitamin E (Vit-E on Cd-induced renal oxidative damage. Young albino Wistar rats (180 ± 10 g (n = 6 control rats, Cd, Cd + Ca + Zn, and Cd + Vit-E experimental groups and the experimental period was 30 days. Rats were exposed to Cd (20 mg/kg body weight alone treated as Cd treated group and the absence or presence of Ca + Zn (2 mg/kg each or Vit-E (20 mg/kg body weight supplementation treated as two separate groups. The activities of the stress marker enzymes superoxide dismutase (SOD, catalase (CAT, glutathione reductase (GR, glutathione peroxidase (GPx, glutathione-S-transferase (GST and lipid peroxidase (LPx were determined in renal mitochondrial fractions of experimental rats. We observed quantitative changes in SOD isoenzymatic patterns by non-denaturing PAGE analysis, and quantified band densities. These results showed that Cd exposure leads to decreases in SOD, CAT, GR, and GPx activities and a concomitant increase in LPx and GST activities. Ca + Zn and Vit-E administration with Cd significantly reversed Cd-induced perturbations in oxidative stress marker enzymes. However, Vit-E showed more inhibitory activity against Cd than did Ca + Zn, and it protected against Cd-induced nephrotoxicity. Keywords: Cadmium (Cd, Oxidative stress, Lipid peroxidation, Nephrotoxicity, PAGE analysis

  5. The Protective Effect of Omega-3 Against Thioacetamide Induced Lipid and Renal Dysfunction in Male Rats

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    Davood Moghadamnia

    2016-10-01

    Full Text Available Background Thioacetamide causes lipid and kidney dysfunction.Omega-3 unsaturated fatty acids prevent the progression of renal diseases. Objectives This study aimed to assess the protective effects of omega-3 fish oil supplement on thioacetamide induced lipid and kidney dysfunction in male rats. Methods In this experimental study, 42 male rats were divided into 6 groups of 7: control group sham group which received 0.4 mL olive oil as a solvent, Thioacetamide group receiving thioacetamide at a dose of 150 mg/kg once as intraperitoneal injection, Experimental groups of 1, 2 and 3 which received omega-3 fish oil supplement at the doses of 100, 200, 300 mg/kg orally for 3 months respectively and then they received thioacetamide at the dose of 150 mg/kg intraperitoneally for once. The levels of serum creatinine, BUN, total cholesterol, LDL, HDL, FBS, triglyceride, sodium and potassium were measured. The pathological changes of tissue samples of the kidneys were studied after hematoxylin-eosin staining. The data were analyzed by SPSS-18 software and using one way ANOVA and Tukey as post hoc test. Significant level was considered to be P < 0.05. Results The mean serum levels of potassium in the second experimental group significantly decreased (5.26 ± 0.02 compared to the group receiving thioacetamide (6.50 ± 0. The mean serum sodium in all experimental groups decreased significantly compared to the group receiving thioacetamide. The mean serum levels of total cholesterol in experimental group 3 (66.80 ± 1.46 significantly decreased compared to the group receiving thioacetamide (84 ± 0.57. No significant changes were observed in the mean serum levels of FBS, BUN, HDL, LDL, triglycerides and creatinine in all experimental groups compared to the group receiving thioacetamide. All the experimental groups improved renal histological changes induced by thioacetamide and these protective effects were dose-dependent (P ≤ 0.05. Conclusions The results of

  6. Thiazolidinediones and Edema: Recent Advances in the Pathogenesis of Thiazolidinediones-Induced Renal Sodium Retention

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    Shoko Horita

    2015-01-01

    Full Text Available Thiazolidinediones (TZDs are one of the major classes of antidiabetic drugs that are used widely. TZDs improve insulin resistance by activating peroxisome proliferator-activated receptor gamma (PPARγ and ameliorate diabetic and other nephropathies, at least, in experimental animals. However, TZDs have side effects, such as edema, congestive heart failure, and bone fracture, and may increase bladder cancer risk. Edema and heart failure, which both probably originate from renal sodium retention, are of great importance because these side effects make it difficult to continue the use of TZDs. However, the pathogenesis of edema remains a matter of controversy. Initially, upregulation of the epithelial sodium channel (ENaC in the collecting ducts by TZDs was thought to be the primary cause of edema. However, the results of other studies do not support this view. Recent data suggest the involvement of transporters in the proximal tubule, such as sodium-bicarbonate cotransporter and sodium-proton exchanger. Other studies have suggested that sodium-potassium-chloride cotransporter 2 in the thick ascending limb of Henle and aquaporins are also possible targets for TZDs. This paper will discuss the recent advances in the pathogenesis of TZD-induced sodium reabsorption in the renal tubules and edema.

  7. Thiazolidinediones and Edema: Recent Advances in the Pathogenesis of Thiazolidinediones-Induced Renal Sodium Retention.

    Science.gov (United States)

    Horita, Shoko; Nakamura, Motonobu; Satoh, Nobuhiko; Suzuki, Masashi; Seki, George

    2015-01-01

    Thiazolidinediones (TZDs) are one of the major classes of antidiabetic drugs that are used widely. TZDs improve insulin resistance by activating peroxisome proliferator-activated receptor gamma (PPARγ) and ameliorate diabetic and other nephropathies, at least, in experimental animals. However, TZDs have side effects, such as edema, congestive heart failure, and bone fracture, and may increase bladder cancer risk. Edema and heart failure, which both probably originate from renal sodium retention, are of great importance because these side effects make it difficult to continue the use of TZDs. However, the pathogenesis of edema remains a matter of controversy. Initially, upregulation of the epithelial sodium channel (ENaC) in the collecting ducts by TZDs was thought to be the primary cause of edema. However, the results of other studies do not support this view. Recent data suggest the involvement of transporters in the proximal tubule, such as sodium-bicarbonate cotransporter and sodium-proton exchanger. Other studies have suggested that sodium-potassium-chloride cotransporter 2 in the thick ascending limb of Henle and aquaporins are also possible targets for TZDs. This paper will discuss the recent advances in the pathogenesis of TZD-induced sodium reabsorption in the renal tubules and edema.

  8. Microbubbles induce renal hemorrhage when exposed to diagnostic ultrasound in anesthetized rats.

    Science.gov (United States)

    Wible, James H; Galen, Karen P; Wojdyla, Jolette K; Hughes, Michael S; Klibanov, Alexander L; Brandenburger, Gary H

    2002-01-01

    The generation of ultrasound (US) bioeffects using a clinical imaging system is controversial. We tested the hypothesis that the presence of microbubbles in the US field of a medical imager induces biologic effects. Both kidneys of anesthetized rats were insonified for 5 min using a medical imaging system after the administration of microbubbles. One kidney was insonified using a continuous mode (30 Hz) and the opposite kidney was insonified using an intermittent (1 Hz) technique. The microbubbles were exposed to three different transducer frequencies and four transducer output powers. After insonification, the animals were euthanized, the kidneys were removed and their gross appearance scored under "blinded" conditions using a defined scale. After the administration of microbubbles, US imaging of the kidney caused hemorrhage in the renal tissue. The severity and area of hemorrhage increased with an increase in the transducer power and a decrease in the transducer frequency. Intermittent insonification in the presence of microbubbles produced a greater degree of renal hemorrhage than continuous imaging techniques.

  9. Low sodium intake does not impair renal compensation of hypoxia-induced respiratory alkalosis.

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    Höhne, Claudia; Boemke, Willehad; Schleyer, Nora; Francis, Roland C; Krebs, Martin O; Kaczmarczyk, Gabriele

    2002-05-01

    Acute hypoxia causes hyperventilation and respiratory alkalosis, often combined with increased diuresis and sodium, potassium, and bicarbonate excretion. With a low sodium intake, the excretion of the anion bicarbonate may be limited by the lower excretion rate of the cation sodium through activated sodium-retaining mechanisms. This study investigates whether the short-term renal compensation of hypoxia-induced respiratory alkalosis is impaired by a low sodium intake. Nine conscious, tracheotomized dogs were studied twice either on a low-sodium (LS = 0.5 mmol sodium x kg body wt-1 x day-1) or high-sodium (HS = 7.5 mmol sodium x kg body wt-1 x day-1) diet. The dogs breathed spontaneously via a ventilator circuit during the experiments: first hour, normoxia (inspiratory oxygen fraction = 0.21); second to fourth hour, hypoxia (inspiratory oxygen fraction = 0.1). During hypoxia (arterial PO2 34.4 +/- 2.1 Torr), plasma pH increased from 7.37 +/- 0.01 to 7.48 +/- 0.01 (P respiratory alkalosis was not impaired by a low sodium intake. The increased sodium excretion during hypoxia seems to be combined with a decrease in plasma aldosterone and angiotensin II in LS as well as in HS dogs. Other factors, e.g., increased mean arterial blood pressure, minute ventilation, and renal blood flow, may have contributed.

  10. Involvement of endoplasmic reticulum stress in albuminuria induced inflammasome activation in renal proximal tubular cells.

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    Li Fang

    Full Text Available Albuminuria contributes to the progression of tubulointerstitial fibrosis. Although it has been demonstrated that ongoing albuminuria leads to tubular injury manifested by the overexpression of numerous proinflammatory cytokines, the mechanism remains largely unknown. In this study, we found that the inflammasome activation which has been recognized as one of the cornerstones of intracellular surveillance system was associated with the severity of albuminuria in the renal biopsies specimens. In vitro, bovine serum albumin (BSA could also induce the activation of NLRP3 inflammasome in the cultured kidney epithelial cells (NRK-52E. Since there was a significant overlap of NLRP3 with the ER marker calreticulin, the ER stress provoked by BSA seemed to play a crucial role in the activation of inflammasome. Here, we demonstrated that the chemical chaperone taurine-conjugated ursodeoxycholic acid (TUDCA which was proved to be an enhancer for the adaptive capacity of ER could attenuate the inflammasome activation induced by albuminuria not only in vitro but also in diabetic nephropathy. Taken together, these data suggested that ER stress seemed to play an important role in albuminuria-induced inflammasome activation, elimination of ER stress via TUDCA might hold promise as a novel avenue for preventing inflammasome activation ameliorating kidney epithelial cells injury induced by albuminuria.

  11. Uric Acid Induces Renal Inflammation via Activating Tubular NF-κB Signaling Pathway

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    Zhou, Yang; Fang, Li; Jiang, Lei; Wen, Ping; Cao, Hongdi; He, Weichun; Dai, Chunsun; Yang, Junwei

    2012-01-01

    Inflammation is a pathologic feature of hyperuricemia in clinical settings. However, the underlying mechanism remains unknown. Here, infiltration of T cells and macrophages were significantly increased in hyperuricemia mice kidneys. This infiltration of inflammatory cells was accompanied by an up-regulation of TNF-α, MCP-1 and RANTES expression. Further, infiltration was largely located in tubular interstitial spaces, suggesting a role for tubular cells in hyperuricemia-induced inflammation. In cultured tubular epithelial cells (NRK-52E), uric acid, probably transported via urate transporter, induced TNF-α, MCP-1 and RANTES mRNA as well as RANTES protein expression. Culture media of NRK-52E cells incubated with uric acid showed a chemo-attractive ability to recruit macrophage. Moreover uric acid activated NF-κB signaling. The uric acid-induced up-regulation of RANTES was blocked by SN 50, a specific NF-κB inhibitor. Activation of NF-κB signaling was also observed in tubule of hyperuricemia mice. These results suggest that uric acid induces renal inflammation via activation of NF-κB signaling. PMID:22761883

  12. Clinical Studies Applying Cytokine-Induced Killer Cells for the Treatment of Renal Cell Carcinoma

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    Clara E. Jäkel

    2012-01-01

    Full Text Available Metastatic renal cell carcinoma (RCC seems to be resistant to conventional chemo- and radiotherapy and the general treatment regimen of cytokine therapy produces only modest responses while inducing severe side effects. Nowadays standard of care is the treatment with VEGF-inhibiting agents or mTOR inhibition; nevertheless, immunotherapy can induce complete remissions and long-term survival in selected patients. Among different adoptive lymphocyte therapies, cytokine-induced killer (CIK cells have a particularly advantageous profile as these cells are easily available, have a high proliferative rate, and exhibit a high antitumor activity. Here, we reviewed clinical studies applying CIK cells, either alone or with standard therapies, for the treatment of RCC. The adverse events in all studies were mild, transient, and easily controllable. In vitro studies revealed an increased antitumor activity of peripheral lymphocytes of participants after CIK cell treatment and CIK cell therapy was able to induce complete clinical responses in RCC patients. The combination of CIK cell therapy and standard therapy was superior to standard therapy alone. These studies suggest that CIK cell immunotherapy is a safe and competent treatment strategy for RCC patients and further studies should investigate different treatment combinations and schedules for optimal application of CIK cells.

  13. Adalimumab (TNFα Inhibitor Therapy Exacerbates IgA Glomerulonephritis Acute Renal Injury and Induces Lupus Autoantibodies in a Psoriasis Patient

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    S. S. Wei

    2013-01-01

    Full Text Available Adalimumab (Humira is a tumour necrosis factor α (TNFα inhibitor that is approved for the treatment of rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn's disease, ankylosing spondylitis, and juvenile idiopathic arthritis (Sullivan and Preda (2009, Klinkhoff (2004, and Medicare Australia. Use of TNFα inhibitors is associated with the induction of autoimmunity (systemic lupus erythematosus, vasculitis, and sarcoidosis or sarcoid-like granulomas (Ramos-Casals et al. (2010. We report a patient with extensive psoriasis presenting with renal failure and seropositive lupus markers without classical lupus nephritis after 18 months treatment with adalimumab. He has renal biopsy proven IgA nephritis instead. Renal biopsy is the key diagnostic tool in patients presenting with adalimumab induced nephritis and renal failure. He made a remarkable recovery after adalimumab cessation and steroid treatment. To our knowledge, this is a unique case of a psoriasis patient presenting with seropositive lupus markers without classical lupus nephritis renal failure and had renal biopsy proven IgA glomerulonephritis after receiving adalimumab.

  14. Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

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    Bo Hu

    2018-02-01

    Full Text Available Background/Aims: Renal ischemia/reperfusion (I/R injury (RI/RI is a common complication of diabetes, and it may be involved in altering intracellular calcium concentrations at its onset, which can result in inflammation, abnormal lipid metabolism, the production of reactive oxygen species (ROS, and nitroso-redox imbalance. The calcium-sensing receptor (CaSR is a G-protein coupled receptor, however, the functional involvement of CaSR in diabetic RI/ RI remains unclear. The present study was intended to investigate the role of CaSR on RI/RI in diabetes mellitus (DM. Methods: The bilateral renal arteries and veins of streptozotocin (STZ-induced diabetic rats were subjected to 45-min ischemia followed by 2-h reperfusion with or without R-568 (agonist of CaSR and NPS-2143 (antagonist of CaSR at the beginning of I/R procedure. DM without renal I/R rats served as control group. The expressions of CaSR, calmodulin (CaM, and p47phox in the renal tissue were analyzed by qRT-PCR and Western blot. The renal pathomorphology, renal function, oxidative stress, inflammatory response, and calcium disorder were evaluated by detection of a series of indices by hematoxylin-eosin (HE staining, transmission electron microscope (TEM, commercial kits, enzyme-linked immunosorbent assay (ELISA, and spectrophotofluorometry, respectively. Results: Results showed that the expressions of CaSR, CaM, and p47phox in I/R group were significantly up-regulated as compared with those in DM group, which were accompanied by renal tissue injury, increased calcium, oxidative stress, inflammation, and nitroso-redox imbalance. Conclusion: These results suggest that activation of CaSR is involved in the induction of damage of renal tubular epithelial cell during diabetic RI/RI, resulting in lipid peroxidation, inflammatory response, nitroso-redox imbalance, and apoptosis.

  15. Autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury induced by albumin overload.

    Science.gov (United States)

    Tan, Jin; Wang, Miaohong; Song, Shuling; Miao, Yuyang; Zhang, Qiang

    2018-01-10

    Proteinuria (albuminuria) is an important cause of aggravating tubulointerstitial injury. Previous studies have shown that autophagy activation can alleviate renal tubular epithelial cell injury caused by urinary protein, but the mechanism is not clear. Here, we investigated the role of clearance of damaged mitochondria in this protective effect. We found that albumin overload induces a significant increase in turnover of LC3-II and decrease in p62 protein level in renal proximal tubular (HK-2) cells in vitro. Albumin overload also induces an increase in mitochondrial damage. ALC, a mitochondrial torpent, alleviates mitochondrial damage induced by albumin overload and also decreases autophagy, while mitochondrial damage revulsant CCCP further increases autophagy. Furthermore, pretreatment of HK-2 cells with rapamycin reduced the amount of damaged mitochondria and the level of apoptosis induced by albumin overload. In contrast, blocking autophagy with chloroquine exerted an opposite effect. Taken together, our results indicated autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury caused by albumin overload. This further confirms previous research that autophagy activation is an adaptive response in renal tubular epithelial cells after urinary protein overload.

  16. Coupling-induced complexity in nephron models of renal blood flow regulation

    DEFF Research Database (Denmark)

    Laugesen, Jakob Lund; Sosnovtseva, Olga; Mosekilde, Erik

    2010-01-01

    Marsh DJ. Coupling-induced complexity in nephron models of renal blood flow regulation. Am J Physiol Regul Integr Comp Physiol 298: R997-R1006, 2010. First published February 10, 2010; doi: 10.1152/ajpregu.00714.2009.-Tubular pressure and nephron blood flow time series display two interacting...... oscillations in rats with normal blood pressure. Tubulo-glomerular feedback (TGF) senses NaCl concentration in tubular fluid at the macula densa, adjusts vascular resistance of the nephron's afferent arteriole, and generates the slower, larger-amplitude oscillations (0.02-0.04 Hz). The faster smaller...... of glomerular pressure caused by fluctuations of blood pressure. The oscillations become irregular in animals with chronic high blood pressure. TGF feedback gain is increased in hypertensive rats, leading to a stronger interaction between the two mechanisms. With a mathematical model that simulates tubular...

  17. Rhabdomyolysis-Induced Acute Renal Failure Following Fenofibrate Therapy: A Case Report and Literature Review

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    Ramazan Danis

    2010-01-01

    Full Text Available Fenofibrate, a fibric acid derivative, is used to treat diabetic dyslipidemia, hypertriglyceridemia, and combined hyperlipidemia, administered alone or in combination with statins. Rhabdomyolysis is defined as a pathological condition involving skeletal muscle cell damage leading to the release of toxic intracellular material into circulation. Its major causes include muscle compression or overexertion; trauma; ischemia; toxins; cocaine, alcohol, and drug use; metabolic disorders; infections. However, rhabdomyolysis associated with fenofibrate is extremely rare. Herein we report a 45-year-old female patient who was referred to our department because of generalized muscle pain, fatigue, weakness, and oliguria over the preceding 3 weeks. On the basis of the pathogenesis and clinical and laboratory examinations, a diagnosis of acute renal failure secondary to fenofibrate-induced rhabdomyolysis was made. Weekly followups for patients who are administered fenofibrate are the most important way to prevent possible complications.

  18. Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma

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    Raissouni Soundouss

    2012-08-01

    Full Text Available Abstract Background Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. Case presentation A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. Conclusion We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders.

  19. Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma.

    Science.gov (United States)

    Raissouni, Soundouss; Raissouni, Ferdaous; Rais, Ghizlane; Aitelhaj, Meryem; Lkhoyaali, Siham; Latib, Rachida; Mohtaram, Amina; Rais, Fadoua; Mrabti, Hind; Kabbaj, Nawal; Amrani, Naima; Errihani, Hassan

    2012-08-09

    Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders.

  20. Protective effect of zinc aspartate against acetaminophen induced hepato-renal toxicity in albino rats

    International Nuclear Information System (INIS)

    Mohamed, E.T.; Said, A.I.; El-Sayed, S.A.

    2011-01-01

    Zinc is an essential nutrient that is required in humans and animals for many physiological functions, including antioxidant functions. The evidence to date indicates that zinc is an important element that links antioxidant system and tissue damage. Acetaminophen (AP), a widely used analgesic and antipyretic, produces hepatocyte and renal tubular necrosis in human and animals following overdose. In human, AP is one of the most common causes of acute liver failure as a result of accidental or deliberate overdose. Moreover, the initial event in AP toxicity is a toxic metabolic injury with the release of free radicals and subsequent cellular death by necrosis and apoptosis. This study was designed to evaluate the potential protective role of zinc aspartate in case of acetaminophen induced hepato-renal toxicity in rats. A total number of 32 adult male albino rats were divided into 4 equal groups: group I (control group), group II (zinc aspartate treated group), group III (acetaminophen treated group; by a single oral dose of 750 mg/kg body weight) and group IV acetaminophen plus zinc treated group; (zinc aspartate was intraperitoneally given one hour after acetaminophen administration in a dose of 30 mg/kg body weight). Serum levels of: alanine aminotransferase, aspartate aminotransferase, direct bilirubin, blood urea nitrogen, creatinine, uric acid, xanthine oxidase (XO), glutathione (GSH), malonaldehyde (MDA) and nitric oxide (NO) were assessed in all groups. The results of this study showed that treatment with acetaminophen alone (group III) produced a significant increase in serum levels of the liver enzymes and direct bilirubin. Moreover, in the same group there was a significant increase in the blood urea nitrogen and serum creatinine compared to the control group. In addition, there was a significant increase in XO and MDA and a significant decrease in GSH and NO level. Injection of rats with zinc aspartate after acetaminophen treatment could produce a

  1. A high-fat diet increases oxidative renal injury and protein glycation in D-galactose-induced aging rats and its prevention by Korea red ginseng.

    Science.gov (United States)

    Park, Sok; Kim, Chan-Sik; Min, Jinah; Lee, Soo Hwan; Jung, Yi-Sook

    2014-01-01

    Declining renal function is commonly observed with age. Obesity induced by a high-fat diet (HFD) may reduce renal function. Korean red ginseng (KRG) has been reported to ameliorate oxidative tissue injury and have an anti-aging effect. This study was designed to investigate whether HFD would accelerate the D-galactose-induced aging process in the rat kidney and to examine the preventive effect of KRG on HFD and D-galactose-induced aging-related renal injury. When rats with D-galactose-induced aging were fed an HFD for 9 wk, enhanced oxidative DNA damage, renal cell apoptosis, protein glycation, and extracellular high mobility group box 1 protein (HMGB1), a signal of tissue damage, were observed in renal glomerular cells and tubular epithelial cells. However, treatment of rats with HFD- plus D-galactose-induced aging with KRG restored all of these renal changes. Our data suggested that a long-term HFD may enhance D-galactose-induced oxidative renal injury in rats and that this age-related renal injury could be suppressed by KRG through the repression of oxidative injury.

  2. Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells

    OpenAIRE

    Kyoung-jin Min; Ju-Ock Nam; Taeg Kyu Kwon

    2017-01-01

    Fisetin is a natural compound found in fruits and vegetables such as strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer effects, including anti-proliferation and anti-migration, we investigated whether fisetin induced apoptosis in human renal carcinoma (Caki) cells. Fisetin markedly induced sub-G1 population and cleavage of poly (ADP-ribose) polymerase (PARP), which is a marker of apoptosis, and increased caspase activation. We found that pan-caspase inhibitor (...

  3. Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation

    Directory of Open Access Journals (Sweden)

    Li Gao

    2016-12-01

    Full Text Available Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress and programmed cell death of renal tubular epithelial cells. All of which lead to higher mortality rates in patients. In this study we examined the protective effect of protocatechuic aldehyde (PA in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza. Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA largely blocked cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients with cisplatin treatment.

  4. S3226, a novel NHE3 inhibitor, attenuates ischemia-induced acute renal failure in rats.

    Science.gov (United States)

    Hropot, M; Juretschke, H P; Langer, K H; Schwark, J R

    2001-12-01

    Acute renal failure (ARF) remains a major problem in clinical nephrology characterized by sudden loss of the kidney function due to ischemia, trauma, and/or nephrotoxic drugs. The current therapy of ARF is symptomatic with mortality rates exceeding 50%. The aim of this study was to investigate the effects of an intravenous infusion of S3226 (3-[2-(3-guanidino-2-methyl-3-oxopropenyl)-5-methyl-phenyl]-N-isopropylidene-2-methyl-acrylamide dihydrochloride), a selective Na+/H+ exchange subtype 3 (NHE3) blocker, in ischemia-induced ARF in rats. In a second series of experiments cytosolic pH (pHi) changes in the kidney during ARF were continuously measured by means of nuclear magnetic resonance spectroscopy (MRS). ARF was induced by bilateral occlusion of renal arteries for 40 minutes in three groups of anaesthetized Wistar rats. Control rats (N = 12) were infused with saline (6.25 mL/kg over 30 min) before occlusion and the compound groups (each N = 12) were infused with S3226 at a dose of 20 mg/kg over 30 minutes either before initiation of ischemia or immediately after release of clamps. Plasma creatinine (PCr), creatinine clearance (CCr), urine volume, sodium, and potassium excretion were determined up to seven days after release of clamps. In the second series of experiments in anaesthetized rats the left kidney was exposed by flank incision and fixed in a non-magnetic device. An inflatable cuff was positioned around the pedicle to induce ischemia without removing animals from the magnet. A double-tuned 1H-31P home-built surface coil was placed above the exposed kidney for the detection of pHi. At day 1 after ischemia CCr in the control group was significantly lower as compared to S3226-treated animals (control 0.30 +/- 0.05 vs. before 0.90 +/- 0.26 and reperfusion 0.83 +/- 0.15 mL/min/kg, respectively). PCr increased from 18 +/- 0.1 micromol/L before occlusion to 245 +/- 7 micromol/L in the control. The increase in PCr was significantly lower in the S3226 treated

  5. Antifibrillatory effects of renal denervation on ventricular fibrillation in a canine model of pacing-induced heart failure.

    Science.gov (United States)

    Luo, Qingzhi; Jin, Qi; Zhang, Ning; Huang, Shangwei; Han, Yanxin; Lin, Changjian; Ling, Tianyou; Chen, Kang; Pan, Wenqi; Wu, Liqun

    2018-01-01

    What is the central question of this study? In the present study, we investigated the effects of renal denervation on the vulnerability to ventricular fibrillation and the ventricular electrical properties in a rapid pacing-induced heart failure canine model. What is the main finding and its importance? Renal denervation significantly attenuated the process of heart failure and improved left ventricular systolic dysfunction, stabilized ventricular electrophysiological properties and decreased the vulnerability of the heart to ventricular fibrillation during heart failure. Thus, renal denervation can attenuate ventricular electrical remodelling and exert a potential antifibrillatory action in a pacing-induced heart failure canine model. In this study, we investigated the effects of renal denervation (RDN) on the vulnerability to ventricular fibrillation (VF) and the ventricular electrical properties in a canine model of pacing-induced heart failure (HF). Eighteen beagles were divided into the following three groups: control (n = 6), HF (n = 6) and HF+RDN (n = 6). Heart failure was induced by rapid right ventricular pacing. Renal denervation was performed simultaneously with the pacemaker implantation in the HF+RDN group. A 64-unipolar basket catheter was used to perform global endocardial mapping of the left ventricle. The restitution properties and dispersion of refractoriness were estimated from the activation recovery intervals (ARIs) by a pacing protocol. The VF threshold (VFT) was defined as the maximal pacing cycle length required to induce VF using a specific pacing protocol. The defibrillation threshold (DFT) was measured by an up-down algorithm. Renal denervation partly restored left ventricular systolic function and attenuated the process of HF. Compared with the control group, the VFT in the HF group was decreased by 27% (106 ± 8.0 versus 135 ± 10 ms, P Renal denervation significantly flattened the ventricular ARI restitution curve by 15% (1

  6. Modulatory effect of fenugreek seed mucilage and spent turmeric on intestinal and renal disaccharidases in streptozotocin induced diabetic rats.

    Science.gov (United States)

    Kumar, G Suresh; Shetty, A K; Salimath, P V

    2005-06-01

    To elucidate the effect of feeding fenugreek seed mucilage and spent turmeric (10%) on disaccharidases activities, the specific activities of intestinal and renal disaccharidases viz., sucrase, maltase and lactase were measured in streptozotocin induced diabetic rats. Specific activities of intestinal disaccharidases were increased significantly during diabetes and amelioration of these activities during diabetes was clearly visible by supplementing fenugreek seed mucilage and spent turmeric in the diet. However during diabetes renal disaccharidases activities were significantly lower than those in the control rats. Fenugreek seed mucilage and spent turmeric supplementations were beneficial in alleviating the reduction in maltase activity during diabetes, however not much change in the activities of sucrase and lactase was observed upon feeding. This positive influence of feeding fenugreek seed mucilage and spent turmeric on intestinal and renal disaccharidases clearly indicates their beneficial role in the management of diabetes.

  7. Preclinical evaluation of nephroprotective potential of a probiotic formulation LOBUN on Cyclosporine-A induced renal dysfunction in Wistar rats

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    Kambham Venkateswarlu

    2017-06-01

    Full Text Available ABSTRACT The aim of present study was to evaluate the nephroprotective effect of probiotic formulation LOBUN on Cyclosporine A (CsA induced renal dysfunction in Wistar rats. CsA (20 mg/kg body weight s.c was administered for 15 days to cause renal dysfunction in Wistar rats. The probiotic formulation LOBUN was administered with the dose of 500 mg/kg body weight (p.o for twice (TGI and thrice a day (TGII. The samples were analyzed for the parameters like blood urine nitrogen (BUN, serum creatinine, serum uric acid, total serum protein and urine proteins, urine potassium, urine sodium. The renal functional and histopathological studies revealed that the oral administration of probiotic formulation LOBUN has provided appreciable renoprotection and possibly alleviated the symptoms of Chronic Kidney Disease (CKD at the dose of 500 mg/kg body weight administered thrice a day and also the results were supported by histopathological findings.

  8. Gemfibrozil-induced myositis in a patient with normal renal function.

    Science.gov (United States)

    Hahn, Martin; Sriharan, Kalavally; McFarland, M Shawn

    2010-01-01

    To describe a case of gemfibrozil monotherapy-induced myositis in a patient with normal renal function A 68-year-old white man presented to his primary care clinic complaining of a 6-month history of total body pain. His past medical history was significant for hypertension, diabetes mellitus, hyperlipidemia, gastroesophageal reflux disease, benign prostatic hypertrophy, arthritis, impotence, and pancreatic cancer that required excision of part of his pancreas. His home drug regimen included bupropion 75 mg twice daily, gemfibrozil 600 mg twice daily for the past 8 months, glimiperide 1 mg daily, insulin glargine 5 units at bedtime, insulin aspart 5 units in the evening, lisinopril 10 mg daily, omeprazole 40 mg daily, pregabalin 100 mg daily, and sildenafil 100 mg as needed. Laboratory test results were significant for elevated aspartate aminotransferase (AST) 78 U/L (reference range 15-46 U/L), alanine aminotransferase (ALT) 83 U/L (13-69 U/L), and creatine kinase (CK) 3495 U/L (55-170 U/L). Serum creatinine was normal at 1.19 mg/dL. The physician determined that the elevated CK indicated myositis secondary to gemfibrozil use, and gemfibrozil was subsequently discontinued. The patient returned 1 week later to repeat the laboratory tests. Results were CK 220 U/L, AST 26 U/L, ALT 43 U/L, and serum creatinine 1.28 mg/dL. The patient was asked to return in 3 weeks to repeat the laboratory tests. At that time, CK had continued to decrease to 142 U/L, and the AST and ALT had returned to normal, at 22 and 29 U/L, respectively. The patient reported complete resolution of total body pain 3 weeks after discontinuation of gemfibrozil. Follow-up 5 weeks after discontinuation revealed no change compared to the 3-week follow-up. Myositis most often produces weakness and elevated CK levels more than 10 times the upper limit of normal. The risk of developing myositis, myopathy, or rhabdomyolysis is low (1%) when fibrates such as gemfibrozil are used as monotherapy. Evaluation of

  9. Sorafenib ameliorates renal fibrosis through inhibition of TGF-β-induced epithelial-mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Lining Jia

    sorafenib may useful for the treatment of renal fibrosis through the suppression of TGF-β/Smad3-induced EMT signaling.

  10. Effect of Regular Exercise on the Histochemical Changes of d-Galactose-Induced Oxidative Renal Injury in High-Fat Diet-Fed Rats

    International Nuclear Information System (INIS)

    Park, Sok; Kim, Chan-Sik; Lee, Jin; Suk Kim, Jung; Kim, Junghyun

    2013-01-01

    Renal lipid accumulation exhibits slowly developing chronic kidney disease and is associated with increased oxidative stress. The impact of exercise on the obese- and oxidative stress-related renal disease is not well understood. The purpose of this study was to investigate whether a high-fat diet (HFD) would accelerate d-galactose-induced aging process in rat kidney and to examine the preventive effect of regular exercise on the obese- and oxidative stress-related renal disease. Oxidative stress was induced by an administration of d-galactose (100 mg/kg intraperitoneally injected) for 9 weeks, and d-galactose-treated rats were also fed with a high-fat diet (60% kcal as fat) for 9 weeks to induce obesity. We investigated the efficacy of regular exercise in reducing renal injury by analyzing Nε-carboxymethyllysine (CML), 8-hydroxygluanine (8-OHdG) and apoptosis. When rats were fed with a HFD for 9 weeks in d-galactose-treated rats, an increased CML accumulation, oxidative DNA damage and renal podocyte loss were observed in renal glomerular cells and tubular epithelial cells. However, the regular exercise restored all these renal changes in HFD plus d-galactose-treated rats. Our data suggested that long-term HFD may accelerate the deposition of lipoxidation adducts and oxidative renal injury in d-galactose-treated rats. The regular exercise protects against obese- and oxidative stress-related renal injury by inhibiting this lipoxidation burden

  11. Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and Inflammation in Diet-Induced Obesity.

    Science.gov (United States)

    Huang, Ji; Rajapakse, Angana; Xiong, Yuyan; Montani, Jean-Pierre; Verrey, François; Ming, Xiu-Fen; Yang, Zhihong

    2016-01-01

    Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase-II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT) C57BL/6 mice and mice deficient in Arg-II gene (Arg-II -/- ) were fed with either a normal chow (NC) or a high-fat-diet (HFD) for 14 weeks (starting at the age of 7 weeks) to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal reactive oxygen species (ROS) levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II -/- mice. Moreover, mesangial expansion as analyzed by Periodic Acid Schiff (PAS) staining and renal expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg-II -/- mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II -/- mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development.

  12. Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and Inflammation in Diet-Induced Obesity

    Directory of Open Access Journals (Sweden)

    Ji Huang

    2016-11-01

    Full Text Available Obesity is associated with development and progression of chronic kidney disease (CKD. Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I and arginase-II (Arg-II in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS, leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT C57BL/6 mice and mice deficient in Arg-II gene (Arg-II-/- were fed with either a normal chow (NC or a high-fat-diet (HFD for 14 weeks (starting at the age of 7 weeks to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal ROS levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II-/- mice. Moreover, mesangial expansion as analysed by Periodic Acid Schiff (PAS staining and renal expression of vascular adhesion molecule-1 (VCAM-1 and intercellular adhesion molecule-1 (ICAM-1 in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg-II-/- mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II-/- mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development.

  13. Induced renal artery stenosis in rabbits: magnetic resonance imaging, angiography, and radionuclide determination of blood volume and blood flow

    International Nuclear Information System (INIS)

    Mitchell, D.G.; Tobin, M.; LeVeen, R.; Tomaczewski, J.; Alavi, A.; Staum, M.; Kundel, H.

    1988-01-01

    To investigate the ability of MRI to detect alterations due to renal ischemia, a rabbit renal artery stenosis (RAS) model was developed. Seven rabbits had RAS induced by surgically encircling the artery with a polyethylene band which had a lumen of 1 mm, 1 to 2 weeks prior to imaging. The stenosis was confirmed by angiography, and the rabbits were then imaged in a 1.4 T research MRI unit. T1 was calculated using four inversion recovery sequences with different inversion times. Renal blood flow, using 113 Sn-microspheres, and regional water content by drying were then measured. The average T1 of the inner medulla was shorter for the ischemia (1574 msec) than for the contralateral kidney (1849 msec), while no change ws noted in the cortex. Ischemic kidneys had less distinct outer medullary zones on IR images with TI = 600 msec than did contralateral or control kidneys. Blood flow to both the cortex and medulla were markedly reduced in ischemic kidneys compared with contralateral kidneys (119.5 vs. 391 ml/min/100 gm for cortex and 19.8 vs. 50.8 ml/min/100 gm for medulla). Renal water and blood content were less affected. Our rabbit model of renal artery stenosis with MRI, radionuclide, and angiographic correlation has the potential to increase our understanding of MR imaging of the rabbit kidney

  14. Anemia and the risk of contrast-induced nephropathy in patients with renal insufficiency undergoing contrast-enhanced MDCT

    International Nuclear Information System (INIS)

    Murakami, Ryusuke; Kumita, Shin-ichiro; Hayashi, Hiromitsu; Sugizaki, Ken-ichi; Okazaki, Emi; Kiriyama, Tomonari; Hakozaki, Kenta; Tani, Hitomi; Miki, Izumi; Takeda, Minako

    2013-01-01

    Purpose: The purpose of this study was to assess the effect of anemia on the incidence of contrast-induced nephropathy (CIN) in patients with renal impairment undergoing MDCT. Materials and methods: Institutional review board approval was waived for this retrospective review of 843 patients with stable renal insufficiency (eGFR between 15 and 60 mL/min) who had undergone contrast-enhanced MDCT. Baseline hematocrit and hemoglobin values were measured. Serum creatinine (SCr) was assessed at the baseline and at 48–72 h after contrast administration. Results: The overall incidence of CIN in the patient population with renal insufficiency was 6.9%. CIN developed in 7.8% (54 of 695) of anemic patients, and in 2.8% (4 of 148) of non-anemic patients (P = .027). After adjustment for confounders, low hemoglobin and low hematocrit values remained independent predictors of CIN (odds ratio 4.6, 95% CI 1.0–20.5, P = .046). Conclusions: Anemia is associated with a higher incidence of CIN in patients with renal insufficiency. Anemia is a potentially modifiable risk factor for CIN, and has an unfavorable impact on prognosis in patients with renal insufficiency undergoing contrast-enhanced MDCT

  15. Anemia and the risk of contrast-induced nephropathy in patients with renal insufficiency undergoing contrast-enhanced MDCT

    Energy Technology Data Exchange (ETDEWEB)

    Murakami, Ryusuke, E-mail: rywakana@nms.ac.jp; Kumita, Shin-ichiro; Hayashi, Hiromitsu; Sugizaki, Ken-ichi; Okazaki, Emi; Kiriyama, Tomonari; Hakozaki, Kenta; Tani, Hitomi; Miki, Izumi; Takeda, Minako

    2013-10-01

    Purpose: The purpose of this study was to assess the effect of anemia on the incidence of contrast-induced nephropathy (CIN) in patients with renal impairment undergoing MDCT. Materials and methods: Institutional review board approval was waived for this retrospective review of 843 patients with stable renal insufficiency (eGFR between 15 and 60 mL/min) who had undergone contrast-enhanced MDCT. Baseline hematocrit and hemoglobin values were measured. Serum creatinine (SCr) was assessed at the baseline and at 48–72 h after contrast administration. Results: The overall incidence of CIN in the patient population with renal insufficiency was 6.9%. CIN developed in 7.8% (54 of 695) of anemic patients, and in 2.8% (4 of 148) of non-anemic patients (P = .027). After adjustment for confounders, low hemoglobin and low hematocrit values remained independent predictors of CIN (odds ratio 4.6, 95% CI 1.0–20.5, P = .046). Conclusions: Anemia is associated with a higher incidence of CIN in patients with renal insufficiency. Anemia is a potentially modifiable risk factor for CIN, and has an unfavorable impact on prognosis in patients with renal insufficiency undergoing contrast-enhanced MDCT.

  16. MANAGEMENT OF ACUTE RENAL FAILURE WITH DELAYED HYPERCALCEMIA SECONDARY TO SARCOCYSTIS NEURONA-INDUCED MYOSITIS AND RHABDOMYOLYSIS IN A CALIFORNIA SEA LION (ZALOPHUS CALIFORNIANUS).

    Science.gov (United States)

    Alexander, Amy B; Hanley, Christopher S; Duncan, Mary C; Ulmer, Kyle; Padilla, Luis R

    2015-09-01

    A 3-yr-old captive-born California sea lion (Zalophus californianus) developed Sarcocystis neurona-induced myositis and rhabdomyolysis that led to acute renal failure. The sea lion was successfully managed with fluid therapy, antiprotozoals, antibiotics, anti-inflammatories, antiemetics, gastroprotectants, and diuretics, but developed severe delayed hypercalcemia, a syndrome identified in humans after traumatic or exertion-induced rhabdomyolysis. Treatment with calcitonin was added to the management, and the individual recovered fully. The case emphasizes that animals with rhabdomyolysis-induced renal failure risk developing delayed hypercalcemia, which may be life threatening, and calcium levels should be closely monitored past the resolution of renal failure.

  17. Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (Kim-1) over time

    NARCIS (Netherlands)

    Kramer, Andrea B.; van Timmeren, Mirjan M.; Schuurs, Theo A.; Vaidya, Vishal S.; Bonventre, Joseph V.; van Goor, Harry; Navis, Gerjan

    Kramer AB, van Timmeren MM, Schuurs TA, Vaidya VS, Bonventre JV, van Goor H, Navis G. Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (Kim-1) over time. Am J Physiol Renal Physiol 296: F1136-F1145, 2009. First published February

  18. THE FAILURE OF CHLOROFORM ADMINISTERED IN THE DRINKING WATER TO INDUCE RENAL TUBULAR CELL NEOPLASIA IN MALE F344/N RATS

    Science.gov (United States)

    The failure of chloroform administered in drinking water to induce renal tubular cell neoplasia in male F344/N rats Chloroform (TCM) has been demonstrated to be a renal carcinogen in the male Osborne-Mendel rat when administered either by corn oil gavage or in drin...

  19. Glucose supplementation does not interfere with fasting-induced protection against renal ischemia/reperfusion injury in mice.

    Science.gov (United States)

    Verweij, Mariëlle; van de Ven, Marieke; Mitchell, James R; van den Engel, Sandra; Hoeijmakers, Jan H J; Ijzermans, Jan N M; de Bruin, Ron W F

    2011-10-15

    Preoperative fasting induces robust protection against renal ischemia/reperfusion (I/R) injury in mice but is considered overcautious and possibly detrimental for postoperative recovery in humans. Furthermore, fasting seems to conflict with reported benefits of preoperative nutritional enhancement with carbohydrate-rich drinks. Here, we investigated whether preoperative ingestion of a glucose solution interferes with fasting-induced protection against renal I/R injury. Mice were randomized into the following groups: fasted for 3 days with access to water (fasted) or a glucose solution (fasted+glc) and fed ad libitum with water (fed) or a glucose solution (fed+glc). After induction of bilateral renal I/R injury, all animals had free access to food and water. Calorie intake, body weight, insulin sensitivity, kidney function, and animal survival were determined. Fed+glc mice had a comparable daily calorie intake as fed mice, but 50% of those calories were obtained from the glucose solution. Fasted+glc mice had a daily calorie intake of approximately 75% of the intake of both fed groups. This largely prevented the substantial body weight loss seen in fasted animals. Preoperative insulin sensitivity was significantly improved in fasted+glc mice versus fed mice. After I/R injury, kidney function and animal survival were superior in both fasted groups. The benefits of fasting and preoperative nutritional enhancement with carbohydrates are not mutually exclusive and may be a clinically feasible regimen to protect against renal I/R injury.

  20. Attenuation of hyperlipidemia- and diabetes-induced early-stage apoptosis and late-stage renal dysfunction via administration of fibroblast growth factor-21 is associated with suppression of renal inflammation.

    Directory of Open Access Journals (Sweden)

    Chi Zhang

    Full Text Available BACKGROUND: Lipotoxicity is a key feature of the pathogenesis of diabetic kidney disease, and is attributed to excessive lipid accumulation (hyperlipidemia. Increasing evidence suggests that fibroblast growth factor (FGF21 has a crucial role in lipid metabolism under diabetic conditions. OBJECTIVE: The present study investigated whether FGF21 can prevent hyperlipidemia- or diabetes-induced renal damage, and if so, the possible mechanism. METHODS: Mice were injected with free fatty acids (FFAs, 10 mg/10 g body weight or streptozotocin (150 mg/kg to establish a lipotoxic model or type 1 diabetic model, respectively. Simultaneously the mice were treated with FGF21 (100 µg/kg for 10 or 80 days. The kidney weight-to-tibia length ratio and renal function were assessed. Systematic and renal lipid levels were detected by ELISA and Oil Red O staining. Renal apoptosis was examined by TUNEL assay. Inflammation, oxidative stress, and fibrosis were assessed by Western blot. RESULTS: Acute FFA administration and chronic diabetes were associated with lower kidney-to-tibia length ratio, higher lipid levels, severe renal apoptosis and renal dysfunction. Obvious inflammation, oxidative stress and fibrosis also observed in the kidney of both mice models. Deletion of the fgf21 gene further enhanced the above pathological changes, which were significantly prevented by administration of exogenous FGF21. CONCLUSION: These results suggest that FFA administration and diabetes induced renal damage, which was further enhanced in FGF21 knock-out mice. Administration of FGF21 significantly prevented both FFA- and diabetes-induced renal damage partially by decreasing renal lipid accumulation and suppressing inflammation, oxidative stress, and fibrosis.

  1. Nephron segment specific microRNA biomarkers of pre-clinical drug-induced renal toxicity: Opportunities and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Nassirpour, Rounak, E-mail: Rounak.nassirpour@pfizer.com [Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810 (United States); Ramaiah, Shashi K. [Drug Safety, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139 (United States); Whiteley, Laurence O. [Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810 (United States)

    2016-12-01

    Drug-induced nephrotoxicity is a common drug development complication for pharmaceutical companies. Sensitive, specific, translatable and non-invasive biomarkers of renal toxicity are urgently needed to diagnose nephron segment specific injury. The currently available gold standard biomarkers for nephrotoxicity are not kidney-specific, lack sensitivity for early detection, and are not suitable for renal damage localization (glomerular vs tubulointerstitial injury). MicroRNAs (miRNAs) are increasingly gaining momentum as promising biomarkers of various organ toxicities, including drug induced renal injury. This is mostly due to their stability in easily accessible biofluids, ease of developing nucleic acids detection compared to protein detection assays, as well as their interspecies translatability. Increasing concordance of miRNA findings by standardizing methodology most suitable for their detection and quantitation, as well as characterization of their expression pattern in a cell type specific manner, will accelerate progress toward validation of these miRNAs as biomarkers in pre-clinical, and clinical settings. This review aims to highlight the current pre-clinical findings surrounding miRNAs as biomarkers in two important segments of the nephron, the glomerulus and tubules. - Highlights: • miRNAs are promising biomarkers of drug-induced kidney injury. • Summarized pre-clinical miRNA biomarkers of drug-induced nephrotoxicity. • Described the strengths and challenges associated with miRNAs as biomarkers.

  2. Diosmin Attenuates Methotrexate-Induced Hepatic, Renal, and Cardiac Injury: A Biochemical and Histopathological Study in Mice

    Science.gov (United States)

    Khalifa, Hesham A.; Al-Quraishy, Saleh A.

    2017-01-01

    The current study was designed to investigate the beneficial role of diosmin, a biologically active flavonoid, against methotrexate- (MTX-) induced hepatic, renal, and cardiac injuries in mice. Male Swiss albino mice received a single intraperitoneal injection of MTX (at 20 mg/kg, body weight) either alone or in combination with oral diosmin (at 50 or 100 mg/kg body weight, for 10 days). Serum was used to evaluate tissue injury markers, while hepatic, renal, and cardiac tissue samples were obtained for determination of antioxidant activity as well as histopathological examination. Diosmin treatment ameliorated the MTX-induced elevation of serum alkaline phosphatase, aminotransferases, urea, creatinine, lactate dehydrogenase, and creatine kinases as well as plasma proinflammatory cytokines (interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha). Additionally, both diosmin doses significantly reduced tissue levels of malondialdehyde and nitric oxide and increased those of glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase, and catalase, compared to the MTX-intoxicated group. Histopathological examination showed that diosmin significantly minimized the MTX-induced histological alterations and nearly restored the normal architecture of hepatic, renal, and cardiac tissues. Based on these findings, diosmin may be a promising agent for protection against MTX-induced cytotoxicity in patients with cancer and autoimmune diseases. PMID:28819543

  3. Suprarenal fixation barbs can induce renal artery occlusion in endovascular aortic aneurysm repair.

    Science.gov (United States)

    Subedi, Shree K; Lee, Andy M; Landis, Gregg S

    2010-01-01

    Renal artery occlusion following endovascular abdominal aortic aneurysm repair with suprarenal fixation is uncommon. We report one patient who was found to develop renal artery occlusion and parenchymal infarction 6 months after repair using an endovascular graft with suprarenal fixation. Our patient underwent emergent endovascular repair of a symptomatic 6 cm abdominal aortic aneurysm. The covered portion of the endograft was inadvertently deployed well below the renal artery orifices. At the completion of the procedure both renal arteries were confirmed to be patent. One month postoperatively, a computed tomographic (CT) scan showed exclusion of the aortic sac and normal enhancement of both kidneys. At 6 months, the patient was found to have elevated serum creatinine levels despite having no clinical symptoms. CT scanning revealed a nonenhancing left kidney, and angiography demonstrated an occlusion of the left renal artery. A barb welded to the bare metal stent appeared to be impinging on the renal artery. We believe that renal artery occlusion after endovascular repair can occur due to repetitive injury to the renal artery orifice from barbs welded to the bare metal stent. To our knowledge, this is the first reported case of renal artery occlusion caused by repetitive injury from transrenal fixation systems. Copyright 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

  4. Silymarin and Nigella sativa extract ameliorate paracetamol induced oxidative stress and renal dysfunction in male mice

    Directory of Open Access Journals (Sweden)

    Reham Zakaria Hamza

    2015-06-01

    Full Text Available Objective: To evaluate the ameliorative role of silymarin or/and Nigella sativa (N. sativa water extract against N-acetyl-p-aminophenol (APAP-induced renal function deterioration in male mice at the biochemical levels. Methods: The mice were divided into seven groups (10/group. The first group was served as control. The second group was treated with dose of APAP. The third and fourth groups were treated with silymarin alone and N. sativa water extract alone, respectively. The fifth and sixth groups were treated with combination of APAP with silymarin and APAP with N. sativa water extract, respectively. The seventh group was treated with a combination of both ameliorative compounds (silymarin and N. sativa water extract with APAP and all animals were treated for a period of 30 days. Results: Exposure to APAP at the treated dose for mice led to an alteration of kidney function parameters, increase in the level of serum urea and creatinine. Also, paracetamol administration induced oxidative stress in kidney homogenates by increasing malondialdhyde level and decreasing superoxide dismutase and catalase activities and this stress was ameliorated by administration of either silymarin or N. sativa water extract. Conclusions: Administration of silymarin or/and N. sativa water extract to APAP-treated mice alleviate the toxicity of APAP, and this appeared clearly by biochemical improvement of kidney function parameters and antioxidant parameters. But, the alleviation is more pronounced with the both antioxidants. Thus, the pronounce effect of silymarin and N. sativa water extract is most effective in reducing the toxicity induced by APAP and improving the kidney function parameters and antioxidant status of kidney of male mice.

  5. Respiration-induced movement correlation for synchronous noninvasive renal cancer surgery.

    Science.gov (United States)

    Abhilash, Rakkunedeth H; Chauhan, Sunita

    2012-07-01

    Noninvasive surgery (NIS), such as high-intensity focused ultrasound (HIFU)-based ablation or radiosurgery, is used for treating tumors and cancers in various parts of the body. The soft tissue targets (usually organs) deform and move as a result of physiological processes such as respiration. Moreover, other deformations induced during surgery by changes in patient position, changes in physical properties caused by repeated exposures and uncertainties resulting from cavitation also occur. In this paper, we present a correlation-based movement prediction technique to address respiration-induced movement of the urological organs while targeting through extracorporeal trans-abdominal route access. Among other organs, kidneys are worst affected during respiratory cycles, with significant three-dimensional displacements observed on the order of 20 mm. Remote access to renal targets such as renal carcinomas and cysts during noninvasive surgery, therefore, requires a tightly controlled real-time motion tracking and quantitative estimate for compensation routine to synchronize the energy source(s) for precise energy delivery to the intended regions. The correlation model finds a mapping between the movement patterns of external skin markers placed on the abdominal access window and the internal movement of the targeted kidney. The coarse estimate of position is then fine-tuned using the Adaptive Neuro-Fuzzy Inference System (ANFIS), thereby achieving a nonlinear mapping. The technical issues involved in this tracking scheme are threefold: the model must have sufficient accuracy in mapping the movement pattern; there must be an image-based tracking scheme to provide the organ position within allowable system latency; and the processing delay resulting from modeling and tracking must be within the achievable prediction horizon to accommodate the latency in the therapeutic delivery system. The concept was tested on ultrasound image sequences collected from 20 healthy

  6. Slit2 ameliorates renal inflammation and fibrosis after hypoxia-and lipopolysaccharide-induced epithelial cells injury in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xiangjun [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Yao, Qisheng, E-mail: yymcyqs@126.com [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Sun, Xinbo; Gong, Xiaoxin; Yang, Yong; Chen, Congbo [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Shan, Guang [Department of Urology, Renmin Hospital of Wuhan University, Hubei (China)

    2017-03-01

    Hypoxic acute kidney injury (AKI) is often incompletely repaired and leads to chronic kidney disease (CKD), which is characterized by tubulointerstitial inflammation and fibrosis. The Slit2 family of secreted glycoproteins is expressed in the kidney, it has been shown to exert an anti-inflammatory activity and prevent ischemic renal injury in vivo. However, whether Slit2 reduces renal fibrosis and inflammation after hypoxic and inflammatory epithelial cells injury in vitro remains unknown. In this study, we aimed to evaluate whether Slit2 ameliorated fibrosis and inflammation in two renal epithelial cells line challenged with hypoxia and lipopolysaccharide (LPS). Renal epithelial cells were treated with hypoxia and LPS to induce cell injury. Hoechst staining and Western blot analysis was conducted to examine epithelial cells injury. Immunofluorescence staining and Western blot analysis was performed to evaluate tubulointerstitial fibrosis. Real-time polymerase chain reaction (PCR) tested the inflammatory factor interleukin (IL)−1β and tumor necrosis factor (TNF)-α, and Western blot analysis determined the hypoxia-inducible factor (HIF)−1α, Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB. Results revealed that hypoxia induced epithelial cells apoptosis, inflammatory factor IL-1β and TNF-α release and tubulointerstitial fibrosis. LPS could exacerbate hypoxia -induced epithelial cells apoptosis, IL-1β and TNF-α release and fibrosis. Slit2 reduced the expression of fibronectin, the rate of epithelial cell apoptosis, and the expression of inflammatory factor. Slit2 could also inhibit the expression of TLR4 and NF-κB, but not the expression of HIF-1α. Therefore, Slit2 attenuated inflammation and fibrosis after LPS- and hypoxia-induced epithelial cells injury via the TLR4/NF-κB signaling pathway, but not depending on the HIF-1α signaling pathway. - Highlights: • Slit2 ameliorates inflammation after hypoxia-and LPS-induced epithelial cells injury

  7. The role of renal proximal tubule P450 enzymes in chloroform-induced nephrotoxicity: Utility of renal specific P450 reductase knockout mouse models

    International Nuclear Information System (INIS)

    Liu, Senyan; Yao, Yunyi; Lu, Shijun; Aldous, Kenneth; Ding, Xinxin; Mei, Changlin; Gu, Jun

    2013-01-01

    The kidney is a primary target for numerous toxic compounds. Cytochrome P450 enzymes (P450) are responsible for the metabolic activation of various chemical compounds, and in the kidney are predominantly expressed in proximal tubules. The aim of this study was to test the hypothesis that renal proximal tubular P450s are critical for nephrotoxicity caused by chemicals such as chloroform. We developed two new mouse models, one having proximal tubule-specific deletion of the cytochrome P450 reductase (Cpr) gene (the enzyme required for all microsomal P450 activities), designated proximal tubule-Cpr-null (PTCN), and the other having proximal tubule-specific rescue of CPR activity with the global suppression of CPR activity in all extra-proximal tubular tissues, designated extra-proximal tubule-Cpr-low (XPT-CL). The PTCN, XPT-CL, Cpr-low (CL), and wild-type (WT) mice were treated with a single oral dose of chloroform at 200 mg/kg. Blood, liver and kidney samples were obtained at 24 h after the treatment. Renal toxicity was assessed by measuring BUN and creatinine levels, and by pathological examination. The blood and tissue levels of chloroform were determined. The severity of toxicity was less in PTCN and CL mice, compared with that of WT and XPT-CL mice. There were no significant differences in chloroform levels in the blood, liver, or kidney, between PTCN and WT mice, or between XPT-CL and CL mice. These findings indicate that local P450-dependent activities play an important role in the nephrotoxicity induced by chloroform. Our results also demonstrate the usefulness of these novel mouse models for studies of chemical-induced kidney toxicity. - Highlights: • New mouse models were developed with varying P450 activities in the proximal tubule. • These mouse models were treated with chloroform, a nephrotoxicant. • Studies showed the importance of local P450s in chloroform-induced nephrotoxicity

  8. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) enhances vascular and renal damage induced by hyperlipidemic diet in ApoE-knockout mice.

    Science.gov (United States)

    Muñoz-García, Begoña; Moreno, Juan Antonio; López-Franco, Oscar; Sanz, Ana Belén; Martín-Ventura, José Luis; Blanco, Julia; Jakubowski, Aniela; Burkly, Linda C; Ortiz, Alberto; Egido, Jesús; Blanco-Colio, Luis Miguel

    2009-12-01

    Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily of cytokines. TWEAK binds and activates the Fn14 receptor, and may regulate apoptosis, inflammation, and angiogenesis, in different pathological conditions. We have evaluated the effect of exogenous TWEAK administration as well as the role of endogenous TWEAK on proinflammatory cytokine expression and vascular and renal injury severity in hyperlipidemic ApoE-knockout mice. ApoE(-/-) mice were fed with hyperlipidemic diet for 4 to 10 weeks, then randomized and treated with saline (controls), TWEAK (10 microg/kg/d), anti-TWEAK neutralizing mAb (1000 microg/kg/d), TWEAK plus anti-TWEAK antibody (10 microg TWEAK +1000 microg anti-TWEAK/kg/d), or nonspecific IgG (1000 microg/kg/d) daily for 9 days. In ApoE(-/-) mice, exogenous TWEAK administration in ApoE(-/-) mice induced activation of NF-kappaB, a key transcription factor implicated in the regulation of the inflammatory response, in vascular and renal lesions. Furthermore, TWEAK treatment increased chemokine expression (RANTES and MCP-1), as well as macrophage infiltration in atherosclerotic plaques and renal lesions. These effects were associated with exacerbation of vascular and renal damage. Conversely, treatment of ApoE(-/-) mice with an anti-TWEAK blocking mAb decreased NF-kappaB activation, proinflammatory cytokine expression, macrophage infiltration, and vascular and renal injury severity, indicating a pathological role for endogenous TWEAK. Finally, in murine vascular smooth muscle cells or tubular cells, either ox-LDL or TWEAK treatment increased expression and secretion of both RANTES and MCP-1. Furthermore, ox-LDL and TWEAK synergized for induction of MCP-1 and RANTES expression and secretion. Our results suggest that TWEAK exacerbates the inflammatory response associated with a high lipid-rich diet. TWEAK may be a novel therapeutic target to prevent vascular and renal damage associated with

  9. Far infrared radiation promotes rabbit renal proximal tubule cell proliferation and functional characteristics, and protects against cisplatin-induced nephrotoxicity.

    Science.gov (United States)

    Chiang, I-Ni; Pu, Yeong-Shiau; Huang, Chao-Yuan; Young, Tai-Horng

    2017-01-01

    Far infrared radiation, a subdivision of the electromagnetic spectrum, is beneficial for long-term tissue healing, anti-inflammatory effects, growth promotion, sleep modulation, acceleration of microcirculation, and pain relief. We investigated if far infrared radiation is beneficial for renal proximal tubule cell cultivation and renal tissue engineering. We observed the effects of far infrared radiation on renal proximal tubules cells, including its effects on cell proliferation, gene and protein expression, and viability. We also examined the protective effects of far infrared radiation against cisplatin, a nephrotoxic agent, using the human proximal tubule cell line HK-2. We found that daily exposure to far infrared radiation for 30 min significantly increased rabbit renal proximal tubule cell proliferation in vitro, as assessed by MTT assay. Far infrared radiation was not only beneficial to renal proximal tubule cell proliferation, it also increased the expression of ATPase Na+/K+ subunit alpha 1 and glucose transporter 1, as determined by western blotting. Using quantitative polymerase chain reaction, we found that far infrared radiation enhanced CDK5R1, GNAS, NPPB, and TEK expression. In the proximal tubule cell line HK-2, far infrared radiation protected against cisplatin-mediated nephrotoxicity by reducing apoptosis. Renal proximal tubule cell cultivation with far infrared radiation exposure resulted in better cell proliferation, significantly higher ATPase Na+/K+ subunit alpha 1 and glucose transporter 1 expression, and significantly enhanced expression of CDK5R1, GNAS, NPPB, and TEK. These results suggest that far infrared radiation improves cell proliferation and differentiation. In HK-2 cells, far infrared radiation mediated protective effects against cisplatin-induced nephrotoxicity by reducing apoptosis, as indicated by flow cytometry and caspase-3 assay.

  10. Hypoxia inducible factor 1-alpha (HIF-1 alpha is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival.

    Directory of Open Access Journals (Sweden)

    Elisa Conde

    Full Text Available Acute tubular necrosis (ATN caused by ischemia/reperfusion (I/R during renal transplantation delays allograft function. Identification of factors that mediate protection and/or epithelium recovery could help to improve graft outcome. We studied the expression, regulation and role of hypoxia inducible factor 1-alpha (HIF-1 α, using in vitro and in vivo experimental models of I/R as well as human post-transplant renal biopsies. We found that HIF-1 α is stabilized in proximal tubule cells during ischemia and unexpectedly in late reperfusion, when oxygen tension is normal. Both inductions lead to gene expression in vitro and in vivo. In vitro interference of HIF-1 α promoted cell death and in vivo interference exacerbated tissue damage and renal dysfunction. In pos-transplant human biopsies, HIF-1 α was expressed only in proximal tubules which exhibited normal renal structure with a significant negative correlation with ATN grade. In summary, using experimental models and human biopsies, we identified a novel HIF-1 α induction during reperfusion with a potential critical role in renal transplant.

  11. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine

    DEFF Research Database (Denmark)

    Tepel, Martin; van der Giet, M; Schwarzfeld, C

    2000-01-01

    Radiographic contrast agents can cause a reduction in renal function that may be due to reactive oxygen species. Whether the reduction can be prevented by the administration of antioxidants is unknown.......Radiographic contrast agents can cause a reduction in renal function that may be due to reactive oxygen species. Whether the reduction can be prevented by the administration of antioxidants is unknown....

  12. Ischemia-induced glomerular parietal epithelial cells hyperplasia: Commonly misdiagnosed cellular crescent in renal biopsy.

    Science.gov (United States)

    Zeng, Yeting; Wang, Xinrui; Xie, Feilai; Zheng, Zhiyong

    2017-08-01

    Ischemic pseudo-cellular crescent (IPCC) that is induced by ischemia and composed of hyperplastic glomerular parietal epithelial cells resembles cellular crescent. In this study, we aimed to assess the clinical and pathological features of IPCC in renal biopsy to avoid over-diagnosis and to determine the diagnostic basis. 4 IPCC cases diagnosed over a 4-year period (2012-2015) were evaluated for the study. Meanwhile, 5 cases of ANCA-associated glomerulonephritis and 5 cases of lupus nephritis (LN) were selected as control. Appropriate clinical data, morphology, and immunohistochemical features of all cases were retrieved. Results showed that the basement membrane of glomerulus with IPCC appeared as a concentric twisted ball, and glomerular cells of the lesion were reduced even entirely absent, and the adjacent afferent arterioles showed sclerosis or luminal stenosis. Furthermore, immune globulin deposition, vasculitis, and fibrinous exudate have not been observed in IPCC. While the cellular crescents showed diverse characteristics in both morphology and immunostaining in the control group. Therefore, these results indicated that IPCC is a sort of ischemic reactive hyperplasia and associated with sclerosis, stenosis, or obstruction of adjacent afferent arterioles, which is clearly different from cellular crescents result from glomerulonephritis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  13. Cisplatin-Induced Renal Salt Wasting Requiring over 12 Liters of 3% Saline Replacement

    Directory of Open Access Journals (Sweden)

    Phuong-Chi Pham

    2017-01-01

    Full Text Available Cisplatin is known to induce Fanconi syndrome and renal salt wasting (RSW. RSW typically only requires transient normal saline (NS support. We report a severe RSW case that required 12 liters of 3% saline. A 57-year-old woman with limited stage small cell cancer was admitted for cisplatin (80 mg/m2 and etoposide (100 mg/m2 therapy. Patient’s serum sodium (SNa decreased from 138 to 133 and 125 mEq/L within 24 and 48 hours of cisplatin therapy, respectively. A diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH was initially made. Despite free water restriction, patient’s SNa continued to decrease in association with acute onset of headaches, nausea, and dizziness. Three percent saline (3%S infusion with rates up to 1400 mL/day was required to correct and maintain SNa at 135 mEq/L. Studies to evaluate Fanconi syndrome revealed hypophosphatemia and glucosuria in the absence of serum hyperglycemia. The natriuresis slowed down by 2.5 weeks, but 3%S support was continued for a total volume of 12 liters over 3.5 weeks. Attempts of questionable benefits to slow down glomerular filtration included the administration of ibuprofen and benazepril. To our knowledge, this is the most severe case of RSW ever reported with cisplatin.

  14. Generation of induced pluripotent stem cells with high efficiency from human embryonic renal cortical cells.

    Science.gov (United States)

    Yao, Ling; Chen, Ruifang; Wang, Pu; Zhang, Qi; Tang, Hailiang; Sun, Huaping

    2016-01-01

    Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) emerges as a prospective therapeutic angle in regenerative medicine and a tool for drug screening. Although increasing numbers of iPSCs from different sources have been generated, there has been limited progress in yield of iPSC. Here, we show that four Yamanaka factors Oct4, Sox2, Klf4 and c-Myc can convert human embryonic renal cortical cells (hERCCs) to pluripotent stem cells with a roughly 40-fold higher reprogramming efficiency compared with that of adult human dermal fibroblasts. These iPSCs show pluripotency in vitro and in vivo, as evidenced by expression of pluripotency associated genes, differentiation into three embryonic germ layers by teratoma tests, as well as neuronal fate specification by embryoid body formation. Moreover, the four exogenous genes are effectively silenced in these iPSCs. This study highlights the use of hERCCs to generate highly functional human iPSCs which may aid the study of genetic kidney diseases and accelerate the development of cell-based regenerative therapy.

  15. Melatonin protects against lead-induced hepatic and renal toxicity in male rats

    International Nuclear Information System (INIS)

    El-Sokkary, Gamal H.; Abdel-Rahman, Gamal H.; Kamel, Esam S.

    2005-01-01

    The present study was designed to investigate the potential protective effect of melatonin against the hepatic and renal toxicity of lead in male rats. Three groups of animals were used in this study (control, lead acetate-treated (100 mg/kg), and lead acetate plus melatonin (10 mg/kg) for 30 days. Levels of lipid peroxidation (LPO) products, superoxide dismutase (SOD) activity, total glutathione (GSH), histopathological changes in the liver and kidneys were investigated. In addition, nuclear area (NA), nuclear volume (NV) and the ratio of nuclear volume/cellular volume (N/C) were measured in the liver. The results revealed increased LPO and decreased SOD, GSH, NA, NV and N/C in the studied organs of lead-treated rats. Histopathological observations showed severe damage in the liver and kidneys. Melatonin co-treatment to the lead-administered rats attenuated the increase of LPO and restored the activity of SOD and levels of GSH as well as the mean values of NA, NV and N/C. Also, the morphological damage in the liver and kidneys was reduced and the tissues appeared like those of controls. The present study suggests that melatonin may be useful in combating free radical-induced damage due to lead toxicity

  16. NO-independent mechanism mediates tempol-induced renal vasodilation in SHR

    DEFF Research Database (Denmark)

    de Richelieu, Louise Tilma; Sørensen, Charlotte Mehlin; Salomonsson, Max

    2005-01-01

    whether the effects of tempol were due to a restored NO system, we used the NOS inhibitor N(w)-nitro-L-arginine methyl ester (L-NAME). Renal blood flow (RBF) and mean arterial pressure (MAP) were measured in vivo by electromagnetic flowmetry and arterial catheterization in 10- to 12-wk-old anesthetized......We investigated whether tempol, a superoxide dismutase mimetic, affected renal hemodynamics and arterial pressure in spontaneously hypertensive rats (SHR) and Sprague-Dawley (SD) rats. We also examined whether tempol affected exaggerated renal vasoconstrictor responses to ANG II in SHR. To test...... used as controls. ANG II (1-4 ng) was administered as a bolus via a renal artery catheter. L-NAME was administered intravenously for 15-20 min. Renal vascular resistance (RVR) was elevated in SHR-C compared with SD-C. In SHR-T, baseline RVR was not different from SD-C and SD-T rats. Tempol had...

  17. An integrative view of cisplatin-induced renal and cardiac toxicities: molecular mechanisms, current treatment challenges and potential protective measures

    Science.gov (United States)

    Dugbartey, George J.; Peppone, Luke J.; de Graaf, Inge A.M.

    2017-01-01

    Cisplatin is currently one of the most widely-used chemotherapeutic agents against various malignancies. Its clinical application is limited, however, by inherent renal and cardiac toxicities and other side effects, of which the underlying mechanisms are only partly understood. Experimental studies show cisplatin generates reactive oxygen species, which impair the cell’s antioxidant defense system, causing oxidative stress and potentiating injury, thereby culminating in kidney and heart failure. Understanding the molecular mechanisms of cisplatin-induced renal and cardiac toxicities may allow clinicians to prevent or treat this problem better and may also provide a model for investigating drug-induced organ toxicity in general. This review discusses some of the major molecular mechanisms of cisplatin-induced renal and cardiac toxicities including disruption of ionic homeostasis and energy status of the cell leading to cell injury and cell death. We highlight clinical manifestations of both toxicities as well as (novel)biomarkers such as kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also present some current treatment challenges and propose potential protective strategies with novel pharmacological compounds that might mitigate or prevent these toxicities, which include the use of hydrogen sulfide. PMID:27717837

  18. Kidney stone matrix proteins ameliorate calcium oxalate monohydrate induced apoptotic injury to renal epithelial cells.

    Science.gov (United States)

    Narula, Shifa; Tandon, Simran; Singh, Shrawan Kumar; Tandon, Chanderdeep

    2016-11-01

    Kidney stone formation is a highly prevalent disease, affecting 8-10% of the human population worldwide. Proteins are the major constituents of human kidney stone's organic matrix and considered to play critical role in the pathogenesis of disease but their mechanism of modulation still needs to be explicated. Therefore, in this study we investigated the effect of human kidney stone matrix proteins on the calcium oxalate monohydrate (COM) mediated cellular injury. The renal epithelial cells (MDCK) were exposed to 200μg/ml COM crystals to induce injury. The effect of proteins isolated from human kidney stone was studied on COM injured cells. The alterations in cell-crystal interactions were examined by phase contrast, polarizing, fluorescence and scanning electron microscopy. Moreover, its effect on the extent of COM induced cell injury, was quantified by flow cytometric analysis. Our study indicated the antilithiatic potential of human kidney stone proteins on COM injured MDCK cells. Flow cytometric analysis and fluorescence imaging ascertained that matrix proteins decreased the extent of apoptotic injury caused by COM crystals on MDCK cells. Moreover, the electron microscopic studies of MDCK cells revealed that matrix proteins caused significant dissolution of COM crystals, indicating cytoprotection against the impact of calcium oxalate injury. The present study gives insights into the mechanism implied by urinary proteins to restrain the pathogenesis of kidney stone disease. This will provide a better understanding of the formation of kidney stones which can be useful for the proper management of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Cellular Changes during Renal Failure-Induced Inflammatory Aortic Valve Disease.

    Directory of Open Access Journals (Sweden)

    Mony Shuvy

    Full Text Available Aortic valve calcification (AVC secondary to renal failure (RF is an inflammation-regulated process, but its pathogenesis remains unknown. We sought to assess the cellular processes that are involved in the early phases of aortic valve disease using a unique animal model of RF-associated AVC.Aortic valves were obtained from rats that were fed a uremia-inducing diet exclusively for 2, 3, 4, 5, and 6 weeks as well as from controls. Pathological examination of the valves included histological characterization, von Kossa staining, and antigen expression analyses.After 2 weeks, we noted a significant increase in urea and creatinine levels, reflecting RF. RF parameters exacerbated until the Week 5 and plateaued. Whereas no histological changes or calcification was observed in the valves of any study group, macrophage accumulation became apparent as early as 2 weeks after the diet was started and rose after 3 weeks. By western blot, osteoblast markers were expressed after 2 weeks on the diet and decreased after 6 weeks. Collagen 3 was up-regulated after 3 weeks, plateauing at 4 weeks, whereas collagen 1 levels peaked at 2 and 4 weeks. Fibronectin levels increased gradually until Week 5 and decreased at 6 weeks. We observed early activation of the ERK pathway, whereas other pathways remained unchanged.We concluded that RF induces dramatic changes at the cellular level, including macrophage accumulation, activation of cell signaling pathway and extracellular matrix modification. These changes precede valve calcification and may increase propensity for calcification, and have to be investigated further.

  20. Angiotensin-(1-7 relieved renal injury induced by chronic intermittent hypoxia in rats by reducing inflammation, oxidative stress and fibrosis

    Directory of Open Access Journals (Sweden)

    W. Lu

    Full Text Available We aimed to study the renal injury and hypertension induced by chronic intermittent hypoxia (CIH and the protective effects mediated by angiotensin 1-7 [Ang(1-7]. We randomly assigned 32 male Sprague-Dawley rats (body weight 180-200 g to normoxia control, CIH, Ang(1-7-treated normoxia, and Ang(1-7-treated CIH groups. Systolic blood pressure (SBP was monitored at the start and end of each week. Renal sympathetic nerve activity (RSNA was recorded. CTGF and TGF-β were detected by immunohistochemistry and western blotting. Tissue parameters of oxidative stress were also determined. In addition, renal levels of interleukin-6, tumor necrosis factor-α, nitrotyrosine, and hypoxia-inducible factor-1α were determined by immunohistochemistry, immunoblotting, and ELISA. TUNEL assay results and cleaved caspase 3 and 12 were also determined. Ang(1-7 induced a reduction in SBP together with a restoration of RSNA in the rat model of CIH. Ang(1-7 treatment also suppressed the production of reactive oxygen species, reduced renal tissue inflammation, ameliorated mesangial expansion, and decreased renal fibrosis. Thus, Ang(1-7 treatment exerted renoprotective effects on CIH-induced renal injury and was associated with a reduction of oxidative stress, inflammation and fibrosis. Ang(1-7 might therefore represent a promising therapy for obstructive sleep apnea-related hypertension and renal injury.

  1. Pretreatment of Sialic Acid Efficiently Prevents Lipopolysaccharide-Induced Acute Renal Failure and Suppresses TLR4/gp91-Mediated Apoptotic Signaling

    Directory of Open Access Journals (Sweden)

    Shih-Ping Hsu

    2016-05-01

    Full Text Available Background/Aims: Lipopolysaccharides (LPS binding to Toll-like receptor 4 (TLR4 activate NADPH oxidase gp91 subunit-mediated inflammation and oxidative damage. Recognizing the high binding affinity of sialic acid (SA with LPS, we further explored the preventive potential of SA pretreatment on LPS-evoked acute renal failure (ARF. Methods: We determined the effect of intravenous SA 30 min before LPS-induced injury in urethane-anesthetized female Wistar rats by evaluating kidney reactive oxygen species (ROS responses, renal and systemic hemodynamics, renal function, histopathology, and molecular mechanisms. Results: LPS time-dependently reduced arterial blood pressure, renal microcirculation, and increased blood urea nitrogen and creatinine in the rats. LPS enhanced monocyte/macrophage infiltration and ROS production, and subsequently impaired kidneys with the enhancement of TLR4/NADPH oxidase gp91/Caspase 3/poly-(ADP-ribose-polymerase (PARP-mediated apoptosis in the kidneys. SA pretreatment effectively alleviated LPS-induced ARF. The levels of LPS-increased ED-1 infiltration and ROS production in the kidney were significantly depressed by SA pretreatment. Furthermore, SA pretreatment significantly depressed TLR4 activation, gp91 expression, and Caspase 3/PARP induced apoptosis in the kidneys. Conclusion: We suggest that pretreatment of SA significantly and preventively attenuated LPS-induced detrimental effects on systemic and renal hemodynamics, renal ROS production and renal function, as well as, LPS-activated TLR4/gp91/Caspase3 mediated apoptosis signaling.

  2. Cell-type-specific activation of mitogen-activated protein kinases in PAN-induced progressive renal disease in rats

    International Nuclear Information System (INIS)

    Park, Sang-Joon; Jeong, Kyu-Shik

    2004-01-01

    We examined the time-course activation and the cell-type specific role of MAP kinases in puromycin aminonucleoside (PAN)-induced renal disease. The maximal activation of c-Jun-NH 2 -terminal kinase (JNK), extracellular signal regulated kinase (ERK), and p38 MAP kinase was detected on Days 52, 38, and 38 after PAN-treatment, respectively. p-JNK was localized in mesangial and proximal tubular cells at the early renal injury. It was expressed, therefore, in the inflammatory cells of tubulointerstitial lesions. While, p-ERK was markedly increased in the glomerular regions and macrophages p-p38 was observed in glomerular endothelial cells, tubular cells, and some inflammatory cells. The results show that the activation of MAP kinases in the early renal injury by PAN-treatment involves cellular changes such as cell proliferation or apoptosis in renal native cells. The activation of MAP kinases in infiltrated inflammatory cells and fibrotic cells plays an important role in destructive events such as glomerulosclerosis and tubulointerstitial fibrosis

  3. Mitochondrial bioenergetics during the initiation of mercuric chloride-induced renal injury. I. Direct effects of in vitro mercuric chloride on renal cortical mitochondrial function

    Energy Technology Data Exchange (ETDEWEB)

    Weinberg, J.M. (Veterans Administration Medical Center, Ann Arbor, MI); Harding, P.G.; Humes, H.D.

    1982-01-01

    Increasing data suggest that mitochondrial dysfunction may be an important early component of nephrotoxin-induced changes in renal cell function and viability. This study was designed to obtain more detailed information about the effects on several basic bioenergetic parameters of the direct interaction of Hg/sup 2 +/ with renal cortical mitochondria in vitro as a necessary prelude to studies of mitochondrial functional changes after treatment with mercuric chloride in vivo. Beginning at a threshhold level of 2 nmol of Hg/sup 2 +//mg of mitochondrial protein Hg/sup 2 +/ induced marked stimulation of State 4 respiration, mild inhibition of State 3 respiration, and 2,4-dinitrophenol uncoupled respiration, a striking increase in atractyloside-insensitive ADP uptake and stimulation of both basal- and Mg/sup 2 +/-activated oligomycin-sensitive mitochondrial ATPase activity. These effects of Hg/sup 2 +/ could be prevented and reversed by the sulfhydryl reagent dithioerythritol and by albumin but were not affected by Mg/sup 2 +/. Detailed studies on the addition of HgCl/sub 2/ to the preparation at different stages of the mitochondrial isolation procedure demonstrated that the presence of other proteins decreased mitochondrial Hg/sup 2 +/ binding, that the Hg/sup 2 +/ was not readily washed off the mitochondria by nonprotein-containing solutions, and that prolonged exposure of mitochondria to Hg/sup 2 +/ during the isolation procedure did not markedly alter its functional effects on their reversibility as assessed on the final mitochondrial preparation. These data provide an important basis for critically assessing the changes in function of mitochondria isolated after in vivo treatment with mercuric chloride.

  4. Renal Protective Effects of Low Molecular Weight of Inonotus obliquus Polysaccharide (LIOP on HFD/STZ-Induced Nephropathy in Mice

    Directory of Open Access Journals (Sweden)

    Yen-Jung Chou

    2016-09-01

    Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage renal disease in diabetes mellitus. Oxidative stress, insulin resistance and pro-inflammatory cytokines have been shown to play an important role in pathogeneses of renal damage on type 2 diabetes mellitus (DM. Inonotus obliquus (IO is a white rot fungus that belongs to the family Hymenochaetaceae; it has been used as an edible mushroom and exhibits many biological activities including anti-tumor, anti-oxidant, anti-inflammatory and anti-hyperglycemic properties. Especially the water-soluble Inonotus obliquus polysaccharides (IOPs have been previously reported to significantly inhibit LPS-induced inflammatory cytokines in mice and protect from streptozotocin (STZ-induced diabetic rats. In order to identify the nephroprotective effects of low molecular weight of IOP fraction (LIOP, from the fruiting bodies of Inonotus obliquus, high-fat diet (HFD plus STZ-induced type 2-like diabetic nephropathy C57BL/6 mice were investigated in this study. Our data showed that eight weeks of administration of 10–100 kDa, LIOP (300 mg/kg had progressively increased their sensitivity to glucose (less insulin tolerance, reduced triglyceride levels, elevated the HDL/LDL ratio and decreased urinary albumin/creatinine ratio(ACR compared to the control group. By pathological and immunohistochemical examinations, it was indicated that LIOP can restore the integrity of the glomerular capsules and increase the numbers of glomerular mesangial cells, associated with decreased expression of TGF-β on renal cortex in mice. Consistently, three days of LIOP (100 μg/mL incubation also provided protection against STZ + AGEs-induced glucotoxicity in renal tubular cells (LLC-PK1, while the levels of NF-κB and TGF-β expression significantly decreased in a dose-dependent manner. Our findings demonstrate that LIOP treatment could ameliorate glucolipotoxicity-induced renal fibrosis, possibly partly via the inhibition of NF

  5. Trimethoprim-sulfamethoxazole induced acute interstitial nephritis in renal allografts; clinical course and outcome.

    LENUS (Irish Health Repository)

    Garvey, J P

    2009-11-01

    Acute interstitial nephritis (AIN) secondary to trimethoprim-sulfamethoxazole (TMP-SMX) is well documented as a cause of acute renal failure in native kidneys. TMP-SMX is the standard prophylactic agent against pneumocystis carinii (PCP) used in the early post-transplant period, however, it has to date only been indirectly associated with AIN in renal allografts. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: We describe eleven renal transplant patients with acute allograft dysfunction in whom a transplant biopsy demonstrated primary histopathologic features of allergic AIN, all of whom were receiving TMP-SMX in addition to other medications known to cause AIN.

  6. Role of annexin A5 in cisplatin-induced toxicity in renal cells: molecular mechanism of apoptosis.

    Science.gov (United States)

    Jeong, Jin-Joo; Park, Nahee; Kwon, Yeo-Jung; Ye, Dong-Jin; Moon, Aree; Chun, Young-Jin

    2014-01-24

    Annexin A5 belongs to a large family of calcium-binding and phospholipid-binding proteins and may act as an endogenous regulator of various pathophysiological processes. There is increasing evidence that annexin A5 is related to cytotoxicity, but the precise function of this protein has yet to be elucidated. In this study, we aimed to verify the function of annexin A5 in the apoptosis of renal epithelial cells. Real-time PCR and Western blot analysis, together with immunofluorescence analysis, showed that the expression of annexin A5 significantly increased in the presence of cisplatin in both human and rat renal epithelial cells. With regard to the mechanism of cisplatin-induced apoptosis, apoptosis-inducing factor (AIF) release into the cytosol was observed, and the underlying mechanism was identified as voltage-dependent anion channel (VDAC) oligomerization. Mitochondrial membrane potential (Δψm) was found to be greatly disrupted in cisplatin-treated cells. Moreover, cisplatin strongly induced translocation of annexin A5 into mitochondria. To understand the functional significance of annexin A5 in renal cell death, we used a siRNA-mediated approach to knock down annexin A5. Annexin A5 depletion by siRNA led to decreased annexin A5 translocation into mitochondria and significantly reduced VDAC oligomerization and AIF release. Annexin A5 siRNA also increased cell viability compared with the control. Moreover, expression of annexin A5 was induced by other nephrotoxicants such as CdCl2 and bacitracin. Taken together, our data suggest that annexin A5 may play a crucial role in cisplatin-induced toxicity by mediating the mitochondrial apoptotic pathway via the induction and oligomerization of VDAC.

  7. Multiple carcinomas in the hemodialysis access induced ischemic hand of a renal transplant patient.

    NARCIS (Netherlands)

    Hoek, F. van; Tits, H.W.H.J.; Lijnschoten, I. Van; Haas, B.D. De; Scheltinga, M.R.M.

    2010-01-01

    Long term immunosuppression following organ transplantation promotes the onset of skin cancers. A renal transplant patient developed multiple hyperkeratotic nodi in the left hand and digital pain following prolonged immunosuppression. Several skin abnormalities were observed in an ischemic and

  8. Hypokalemic Rhabdomyolysis Induced Acute Renal Failure As a Presentation of Coeliac Disease

    Directory of Open Access Journals (Sweden)

    Funda Sarı

    2012-03-01

    Full Text Available Adult coeliac disease commonly presents without classical symptoms as chronic diarrhea and weight loss. We describe the case of a 31-year-old woman with persistent life-threatening hypokalemia, acute renal failure, and acute quadriplegia due to diarrhea that had continued for one month. Although there are cases of coeliac disease diagnosed with hypokalemic rhabdomyolysis in the literature, none of the cases developed acute renal failure. This is the first case in the literature diagnosed with acute renal failure due to hypokalemic rhabdomyolysis as a presentation of coeliac disease. In acute renal failure cases that present with hypokalemic rhabdomyolysis due to severe diarrhea, coeliac disease should be considered as a differential diagnosis despite the negative antigliadin IgA antibody.

  9. Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells

    Directory of Open Access Journals (Sweden)

    Kyoung-jin Min

    2017-08-01

    Full Text Available Fisetin is a natural compound found in fruits and vegetables such as strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer effects, including anti-proliferation and anti-migration, we investigated whether fisetin induced apoptosis in human renal carcinoma (Caki cells. Fisetin markedly induced sub-G1 population and cleavage of poly (ADP-ribose polymerase (PARP, which is a marker of apoptosis, and increased caspase activation. We found that pan-caspase inhibitor (z-VAD-fmk inhibited fisetin-induced apoptosis. In addition, fisetin induced death receptor 5 (DR5 expression at the transcriptional level, and down-regulation of DR5 by siRNA blocked fisetin-induced apoptosis. Furthermore, fisetin induced p53 protein expression through up-regulation of protein stability, whereas down-regulation of p53 by siRNA markedly inhibited fisetin-induced DR5 expression. In contrast, fisetin induced up-regulation of CHOP expression and reactive oxygen species production, which had no effect on fisetin-induced apoptosis. Taken together, our study demonstrates that fisetin induced apoptosis through p53 mediated up-regulation of DR5 expression at the transcriptional level.

  10. Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells.

    Science.gov (United States)

    Min, Kyoung-Jin; Nam, Ju-Ock; Kwon, Taeg Kyu

    2017-08-02

    Fisetin is a natural compound found in fruits and vegetables such as strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer effects, including anti-proliferation and anti-migration, we investigated whether fisetin induced apoptosis in human renal carcinoma (Caki) cells. Fisetin markedly induced sub-G1 population and cleavage of poly (ADP-ribose) polymerase (PARP), which is a marker of apoptosis, and increased caspase activation. We found that pan-caspase inhibitor (z-VAD-fmk) inhibited fisetin-induced apoptosis. In addition, fisetin induced death receptor 5 (DR5) expression at the transcriptional level, and down-regulation of DR5 by siRNA blocked fisetin-induced apoptosis. Furthermore, fisetin induced p53 protein expression through up-regulation of protein stability, whereas down-regulation of p53 by siRNA markedly inhibited fisetin-induced DR5 expression. In contrast, fisetin induced up-regulation of CHOP expression and reactive oxygen species production, which had no effect on fisetin-induced apoptosis. Taken together, our study demonstrates that fisetin induced apoptosis through p53 mediated up-regulation of DR5 expression at the transcriptional level.

  11. Effect of Hydroalcholic Extract of Curcuma longa on Adriamycin-Induced Renal Damage in Rats

    OpenAIRE

    R. Mohebbati; A.A. Abbasnezhad; A. Khajavi Rad; M. Haghshenas; M.R. Khazdeir

    2016-01-01

    Aims: Adriamycin is one of the anti-cancer medications. Nevertheless, the medication causes renal damage. Curcuma longa has anti-inflammatory and anti-oxidant effects. The aim of this study was to determine the effects of hydroalcoholic extract of Curcuma longa on renal damage due to Adriamycin in the rat. Materials & Methods: In the experimental study, 32 male Wistar rats were studied. Via simple random method, the rats were divided into four groups including control, Adriamycin (5mg/Kg)...

  12. Effect of saline loading on uranium-induced acute renal failure in rats

    International Nuclear Information System (INIS)

    Hishida, A.; Yonemura, K.; Ohishi, K.; Yamada, M.; Honda, N.

    1988-01-01

    Studies were performed to examine the effect of saline loading on uranium-induced acute renal failure (ARF) in rats. Forty-eight hours after the i.v. injection of uranyl acetate (UA, 5 mg/kg), inulin clearance rate (Cin) decreased to approximately 43% of the control value in water drinking rats (P less than 0.005). Animals receiving continuous isotonic saline infusion following UA showed higher urine flow and Cin (60% of control, P less than 0.01), and lessened intratubular cast formation when compared with water-drinking ARF rats. A short-term saline infusion following UA did not attenuate the decline in Cin (43% of control). An inverse relationship was found between Cin and the number of casts (r = -0.75, P less than 0.01). Multiple regression analysis showed that standardized partial regression coefficient is statistically significant between Cin and cast formation (-0.69, P less than 0.05), but not between Cin and tubular necrosis (-0.07, P greater than 0.05). Renin depletion caused by DOCA plus saline drinking did not attenuate the decline in Cin in ARF (47% of control). No significant difference was found in urinary uranium excretion between water-drinking and saline-infused ARF rats. The findings suggest that continuous saline infusion following UA attenuates the decline in Cin in ARF rats; and that this beneficial effect of saline loading is associated with lessened cast formation rather than with suppressed renin-angiotensin activity or enhanced urinary-uranium excretion

  13. β-Catenin promotes cell proliferation, migration, and invasion but induces apoptosis in renal cell carcinoma

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    Yang CM

    2017-02-01

    Full Text Available Chun-ming Yang,1 Shan Ji,2 Yan Li,3 Li-ye Fu,3 Tao Jiang,3 Fan-dong Meng31Department of Urology, The First Affiliated Hospital, China Medical University, 2Department of Endocrinology, The Fifth People’s Hospital of Shenyang, 3Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital, China Medical University, Shenyang, ChinaAbstract: β-Catenin (CTNNB1 gene coding protein is a component of the Wnt signaling pathway that has been shown to play an important role in the formation of certain cancers. Abnormal accumulation of CTNNB1 contributes to most cancers. This research studied the involvement of β-catenin in renal cell carcinoma (RCC cell proliferation, apoptosis, migration, and invasion. Proliferation, cell cycle, and apoptosis were analyzed by using Cell Counting Kit-8 and by flow cytometry. Migration and invasion assays were measured by transwell analysis. Real-time polymerase chain reaction and Western blot analysis were used to detect the expression of CTNNB1, ICAM-1, VCAM-1, CXCR4, and CCL18 in RCC cell lines. It was found that CTNNB1 knockdown inhibited cell proliferation, migration, and invasion and induced apoptosis of A-498 cells. CTNNB1 overexpression promoted cell proliferation, migration, and invasion and inhibited apoptosis of 786-O cells. Moreover, knockdown of CTNNB1 decreased the levels of ICAM-1, VCAM-1, CXCR4, and CCL18 expression, but CTNNB1 overexpression increased the expression of ICAM-1, VCAM-1, CXCR4, and CCL18. Further in vivo tumor formation study in nude mice indicated that inhibition of CTNNB1 delayed the progress of tumor formation through inhibiting PCNA and Ki67 expression. These results indicate that CTNNB1 could act as an oncogene and may serve as a promising therapeutic strategy for RCC.Keywords: kidney cancer, oncogene, β-catenin, survival time, tumor migration-related protein

  14. TEM and SEM observation of uranium induced renal necrosis and the result of chelates treatment on rats

    International Nuclear Information System (INIS)

    Sun Shiquan; Li Baoxing; Lai Chixiang; You Zhanyun

    1987-01-01

    The TEM (transmission electron microscope) and SEM (scanning electron microscope) observation of uranium induced renal necrosis and the result of chelates treatment on rats are reported. Ultrastructural changes in kidney related with the impairment of intracellular fluid transportation can be found after acute uranium intoxication in rats, such as: condensation and swelling of mitochondria, matrix edema, dilatation of intercellular space, disappearance of basal folds, thickening of basal web, intensification of basal lamina of the proximal convoluted tubule epithelium cells, and foot processes swelling, diminishing of endothelium fenestrae of the renal glomerulus. Heavy metal chelates DTPA and H-73-10 treatment may result in intracellular fluid accumulation and condensed grannule formation in lysosome. Treatment with these chelates in the critical stage of uranium intoxication may accelerate the necrosis instead of diminishing. This may be related to the augment of the load of lysosome and intracellular system of fluid transportation

  15. Gluteal Black Market Silicone-induced Renal Failure: A Case Report and Literature Review.

    Science.gov (United States)

    Matson, Andrea; Faibisoff, Burt

    2017-11-01

    Very few cases of successful surgical treatment for renal failure due to gluteal silicone injections have been reported in the literature. The silicone toxicity and subsequent renal failure seem to follow repetitive silicone injections and silicone injections in large quantities. This is a case of a 31-year-old woman who developed renal failure after 6 years of gluteal silicone injections who underwent radical resection of bilateral gluteal regions in an attempt to mitigate her impending complete renal failure. A systematic review of the literature was conducted using PubMed database and with assistance from medical library staff to conduct keyword searches for "Silicone," "Renal failure," "Silicone emboli syndrome," "Silicone granuloma," and "Silicone end organ toxicity." The search results were reviewed by the authors and selected based on the relevance to the case report presented. Extensive literature relating to silicone granulomas and their systemic effects supports the use of steroids for immediate treatment and eventual surgical resection for cure of the various silicone-related end-organ toxicities including renal failure.

  16. Gluteal Black Market Silicone–induced Renal Failure: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Andrea Matson, DO, PGY-2

    2017-11-01

    Full Text Available Summary:. Very few cases of successful surgical treatment for renal failure due to gluteal silicone injections have been reported in the literature. The silicone toxicity and subsequent renal failure seem to follow repetitive silicone injections and silicone injections in large quantities. This is a case of a 31-year-old woman who developed renal failure after 6 years of gluteal silicone injections who underwent radical resection of bilateral gluteal regions in an attempt to mitigate her impending complete renal failure. A systematic review of the literature was conducted using PubMed database and with assistance from medical library staff to conduct keyword searches for “Silicone,” “Renal failure,” “Silicone emboli syndrome,” “Silicone granuloma,” and “Silicone end organ toxicity.” The search results were reviewed by the authors and selected based on the relevance to the case report presented. Extensive literature relating to silicone granulomas and their systemic effects supports the use of steroids for immediate treatment and eventual surgical resection for cure of the various silicone-related end-organ toxicities including renal failure.

  17. Sirt1 protects against oxidative stress-induced renal tubular cell apoptosis by the bidirectional regulation of catalase expression

    International Nuclear Information System (INIS)

    Hasegawa, Kazuhiro; Wakino, Shu; Yoshioka, Kyoko; Tatematsu, Satoru; Hara, Yoshikazu; Minakuchi, Hitoshi; Washida, Naoki; Tokuyama, Hirobumi; Hayashi, Koichi; Itoh, Hiroshi

    2008-01-01

    NAD + -dependent protein deacetylase Sirt1 regulates cellular apoptosis. We examined the role of Sirt1 in renal tubular cell apoptosis by using HK-2 cells, proximal tubular cell lines with or without reactive oxygen species (ROS), H 2 O 2 . Without any ROS, Sirt1 inhibitors enhanced apoptosis and the expression of ROS scavenger, catalase, and Sirt1 overexpression downregulated catalase. When apoptosis was induced with H 2 O 2 , Sirt1 was upregulated with the concomitant increase in catalase expression. Sirt1 overexpression rescued H 2 O 2 -induced apoptosis through the upregulation of catalase. H 2 O 2 induced the nuclear accumulation of forkhead transcription factor, FoxO3a and the gene silencing of FoxO3a enhanced H 2 O 2 -induced apoptosis. In conclusion, endogenous Sirt1 maintains cell survival by regulating catalase expression and by preventing the depletion of ROS required for cell survival. In contrast, excess ROS upregulates Sirt1, which activates FoxO3a and catalase leading to rescuing apoptosis. Thus, Sirt1 constitutes a determinant of renal tubular cell apoptosis by regulating cellular ROS levels

  18. Leptin Induces Oxidative Stress Through Activation of NADPH Oxidase in Renal Tubular Cells: Antioxidant Effect of L-Carnitine.

    Science.gov (United States)

    Blanca, Antonio J; Ruiz-Armenta, María V; Zambrano, Sonia; Salsoso, Rocío; Miguel-Carrasco, José L; Fortuño, Ana; Revilla, Elisa; Mate, Alfonso; Vázquez, Carmen M

    2016-10-01

    Leptin is a protein involved in the regulation of food intake and in the immune and inflammatory responses, among other functions. Evidences demonstrate that obesity is directly associated with high levels of leptin, suggesting that leptin may directly link obesity with the elevated cardiovascular and renal risk associated with increased body weight. Adverse effects of leptin include oxidative stress mediated by activation of NADPH oxidase. The aim of this study was to evaluate the effect of L-carnitine (LC) in rat renal epithelial cells (NRK-52E) exposed to leptin in order to generate a state of oxidative stress characteristic of obesity. Leptin increased superoxide anion (O2 (•) -) generation from NADPH oxidase (via PI3 K/Akt pathway), NOX2 expression and nitrotyrosine levels. On the other hand, NOX4 expression and hydrogen peroxide (H2 O2 ) levels diminished after leptin treatment. Furthermore, the expression of antioxidant enzymes, catalase, and superoxide dismutase, was altered by leptin, and an increase in the mRNA expression of pro-inflammatory factors was also found in leptin-treated cells. LC restored all changes induced by leptin to those levels found in untreated cells. In conclusion, stimulation of NRK-52E cells with leptin induced a state of oxidative stress and inflammation that could be reversed by preincubation with LC. Interestingly, LC induced an upregulation of NOX4 and restored the release of its product, hydrogen peroxide, which suggests a protective role of NOX4 against leptin-induced renal damage. J. Cell. Biochem. 117: 2281-2288, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Effects of low-molecular-weight-chitosan on the adenine-induced chronic renal failure rats in vitro and in vivo

    Science.gov (United States)

    Zhi, Xuan; Han, Baoqin; Sui, Xianxian; Hu, Rui; Liu, Wanshun

    2015-02-01

    The effects of low-molecular-weight-chitosan (LMWC) on chronic renal failure (CRF) rats induced by adenine were investigated in vivo and in vitro. Chitosan were hydrolyzed using chitosanase at pH 6-7 and 37° for 24 h to obtain LMWC. In vitro, the effect of LMWC on the proliferation of renal tubular epithelial cells (RTEC) showed that it had no cytotoxic effect and could promote cell growth. For the in vivo experiment, chronic renal failure rats induced by adenine were randomly divided into control group, Niaoduqing group, and high-, medium- and low-dose LMWC groups. For each group, we detected serum creatinine (SCR), blood urea nitrogen (BUN), and total superoxide dismutase (T-SOD), glutathione oxidase (GSH-Px) activities of renal tissue, and obtained the ratio of kidney weight/body weight, pathological changes of kidney. The levels of serum SCR, BUN were higher in the adenine-induced rats than those in the control group, indicating that the rat chronic renal failure model worked successfully. The results after treatment showed that LMWC could reduce the SCR and BUN levels and enhance the activities/levels of T-SOD and GSH-PX in kidney compared to control group. Histopathological examination revealed that adenine-induced renal alterations were restored by LMWC at three tested dosages, especially at the low dosage of 100 mg kg-1 d-1.

  20. Effect of bariatric surgery-induced weight loss on renal and systemic inflammation and blood pressure: a 12-month prospective study.

    Science.gov (United States)

    Fenske, Wiebke K; Dubb, Sukhpreet; Bueter, Marco; Seyfried, Florian; Patel, Karishma; Tam, Frederick W K; Frankel, Andrew H; le Roux, Carel W

    2013-01-01

    Bariatric surgery improves arterial hypertension and renal function; however, the underlying mechanisms and effect of different surgical procedures are unknown. In the present prospective study, we compared the 12-month follow-up results after Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, and laparoscopic sleeve gastrectomy on weight loss, hypertension, renal function, and inflammatory status. A total of 34 morbidly obese patients were investigated before, one and 12 months after Roux-en-Y gastric bypass (n = 10), laparoscopic adjustable gastric banding (n = 13), and laparoscopic sleeve gastrectomy (n = 11) for hypertension, kidney function, urinary and serum cytokine levels of macrophage migration inhibitory factor, monocyte chemotactic protein-1, and chemokine ligand-18. At 12 months after surgery, the patients in all 3 treatment arms showed a significant decrease in the mean body mass index, mean arterial pressure, and urinary and serum inflammatory markers (all P .8 mg/L) had a marked improvement in renal function 12 months after surgery (P < .05). Surgically induced weight loss is associated with a marked decrease in renal and systemic inflammation and arterial hypertension and improvement in renal function in patients with pre-existing renal impairment. These effects appear to be independent of surgical procedure. The improvement in renal inflammation could be 1 of the mechanisms contributing to the beneficial effects of bariatric surgery on arterial blood pressure, proteinuria, and renal function. Copyright © 2013 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  1. High anion gap metabolic acidosis induced by cumulation of ketones, L- and D-lactate, 5-oxoproline and acute renal failure.

    Science.gov (United States)

    Heireman, Laura; Mahieu, Boris; Helbert, Mark; Uyttenbroeck, Wim; Stroobants, Jan; Piqueur, Marian

    2017-07-27

    Frequent causes of high anion gap metabolic acidosis (HAGMA) are lactic acidosis, ketoacidosis and impaired renal function. In this case report, a HAGMA caused by ketones, L- and D-lactate, acute renal failure as well as 5-oxoproline is discussed. A 69-year-old woman was admitted to the emergency department with lowered consciousness, hyperventilation, diarrhoea and vomiting. The patient had suffered uncontrolled type 2 diabetes mellitus, underwent gastric bypass surgery in the past and was chronically treated with high doses of paracetamol and fosfomycin. Urosepsis was diagnosed, whilst laboratory analysis of serum bicarbonate concentration and calculation of the anion gap indicated a  HAGMA. L-lactate, D-lactate, β-hydroxybutyric acid, acetone and 5-oxoproline serum levels were markedly elevated and renal function was impaired. We concluded that this case of HAGMA was induced by a variety of underlying conditions: sepsis, hyperglycaemia, prior gastric bypass surgery, decreased renal perfusion and paracetamol intake. Risk factors for 5-oxoproline intoxication present in this case are female gender, sepsis, impaired renal function and uncontrolled type 2 diabetes mellitus. Furthermore, chronic antibiotic treatment with fosfomycin might have played a role in the increased production of 5-oxoproline. Paracetamol-induced 5-oxoproline intoxication should be considered as a cause of HAGMA in patients with female gender, sepsis, impaired renal function or uncontrolled type 2 diabetes mellitus, even when other more obvious causes of HAGMA such as lactate, ketones or renal failure can be identified.

  2. Icariin protects rats against 5/6 nephrectomy-induced chronic kidney failure by increasing the number of renal stem cells.

    Science.gov (United States)

    Huang, Zhongdi; He, Liqun; Huang, Di; Lei, Shi; Gao, Jiandong

    2015-10-21

    Chronic kidney disease poses a serious health problem worldwide with increasing prevalence and lack of effective treatment. This study aimed to investigate the mechanism of icariin in alleviating chronic renal failure induced by 5/6 nephrectomy in rats. The chronic renal failure model was established by a two-phased 5/6 nephrectomy procedure. The model rats were given daily doses of water or icariin for 8 weeks. The kidney morphology was checked by HE staining. The levels of blood urea nitrogen, serum creatinine, and serum uric acid were measured by colometric methods. The expression of specified genes was analyzed by quantitative real-time PCR and immunohistochemical staining. The number of renal stem/progenitor cells was analyzed by CD133 and CD24 immunohistochemical staining. Icariin protected against CDK-caused damages to kidney histology and improved renal function, significantly reduced levels of BUN, creatinine, and uric acid. Icariin inhibited the expression level of TGF-β1 whereas upregulated HGF, BMP-7, WT-1, and Pax2 expression. Moreover, ccariin significantly increased the expression of CD24, CD133, Osr1, and Nanog in remnant kidney and the numbers of CD133(+)/CD24(+) renal stem/progenitor cells. These data demonstrated that icariin effectively alleviated 5/6 nephrectomy induced chronic renal failure through increasing renal stem/progenitor cells.

  3. The optimal timing of continuous renal replacement therapy for patients with sepsis-induced acute kidney injury.

    Science.gov (United States)

    Tian, Huanhuan; Sun, Ting; Hao, Dong; Wang, Tao; Li, Zhi; Han, Shasha; Qi, Zhijiang; Dong, Zhaoju; Lv, Changjun; Wang, Xiaozhi

    2014-10-01

    High mortality in the intensive care unit (ICU) is probably associated with sepsis-induced acute kidney injury (AKI). The aim of this study is to explore which stage of AKI may be the optimal timing for continuous renal replacement therapy (CRRT). A retrospective analysis of 160 critically ill patients with septic AKI, treated with or without CRRT was performed in Binzhou medical college affiliated hospital ICU. The parameters including 28-days mortality rate, renal recovery, ventilation time and ICU stay between CRRT group and control group were assessed. Renal recovery, defined as independence from dialysis at discharge, was documented for 64/76 (84.2 %) of the surviving patients (48.1 % of total subjects included in the study). The mortality rate increased proportionally with acute kidney injury Network stages in CRRT subgroups (P = 0.001) and control groups (P = 0.029). CRRT initiation at stage 2 of AKI significantly reduced the 28-day mortality (P = 0.048) and increased the 28-day survival rate (P = 0.036) compared with those in control group. In addition, the ICU stay and ventilation time were shorter in CRRT group than that of control group in stage 2 of AKI. The stage 2 AKI might be the optimal timing for performing CRRT.

  4. JS-K, a GST-activated nitric oxide donor prodrug, enhances chemo-sensitivity in renal carcinoma cells and prevents cardiac myocytes toxicity induced by Doxorubicin.

    Science.gov (United States)

    Qiu, Mingning; Ke, Longzhi; Zhang, Sai; Zeng, Xin; Fang, Zesong; Liu, Jianjun

    2017-08-01

    Doxorubicin, a highly effective and widely used anthracycline antibiotic in multiple chemotherapy regimens, has been limited by its cardiotoxicity. The aim of this study is to investigate the effect of nitric oxide donor prodrug JS-K on proliferation and apoptosis in renal carcinoma cells and cardiac myocytes toxicity induced by Doxorubicin and to explore possible p53-related mechanism in renal carcinoma cells. The effect of JS-K on anti-cancer activity of Doxorubicin was investigated in renal carcinoma cells via detecting cell proliferation, cytotoxicity, cell death and apoptosis and expressions of apoptotic-related proteins. Effect of p53 on the combination of JS-K and Doxorubicin was determined using p53 inhibitor Pifithrin-α and p53 activator III. Furthermore, the effect of JS-K on cardiac myocytes toxicity of Doxorubicin was investigated in H9c2 (2-1) cardiac myocytes via measuring cell growth, cell death and apoptosis, expressions of proteins involved in apoptosis and intracellular reactive oxygen species. We demonstrated that JS-K could increase Doxorubicin-induced renal carcinoma cell growth suppression and apoptosis and could increase expressions of proteins that are involved in apoptosis. Additionally, Pifithrin-α reversed the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis; conversely, the p53 activator III exacerbated the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis. Furthermore, JS-K protected H9c2 (2-1) cardiac myocytes against Doxorubicin-induced toxicity and decreased Doxorubicin-induced reactive oxygen species production. JS-K enhances the anti-cancer activity of Doxorubicin in renal carcinoma cells by upregulating p53 expression and prevents cardiac myocytes toxicity of Doxorubicin by decreasing oxidative stress.

  5. Astragaloside IV suppresses transforming growth factor-β1 induced fibrosis of cultured mouse renal fibroblasts via inhibition of the MAPK and NF-κB signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Che, Xiajing; Wang, Qin; Xie, Yuanyuan; Xu, Weijia; Shao, Xinghua; Mou, Shan, E-mail: shan_mou@126.com; Ni, Zhaohui, E-mail: doctor_nzh@126.com

    2015-09-04

    Renal fibrosis, a progressive process characterized by the accumulation of extracellular matrix (ECM) leading to organ dysfunction, is a characteristic of chronic kidney diseases. Among fibrogenic factors known to regulate the renal fibrotic process, transforming growth factor-β (TGF-β) plays a central role. In the present study, we examined the effect of Astragaloside IV (AS-IV), a component of the traditional Chinese medicinal plant Astragalus membranaceus, on the processes associated with renal fibrosis in cultured mouse renal fibroblasts treated with TGF-β1. RT-PCR, western blotting, immunofluorescence staining and collagen assays showed that AS-IV suppressed TGF-β1 induced fibroblast proliferation, transdifferentiation, and ECM production in a dose-dependent manner. Examination of the underlying mechanisms showed that the effect of AS-IV on the inhibition of fibroblast differentiation and ECM formation were mediated by its modulation of the activity of the MAPK and NF-κB signaling pathways. Taken together, our results indicate that AS-IV alleviates renal interstitial fibrosis via a mechanism involving the MAPK and NF-κB signaling pathways and demonstrate the therapeutic potential of AS-IV for the treatment of chronic kidney diseases. - Highlights: • AS-IV suppressed TGF-β1 induced renal fibroblast proliferation. • AS-IV suppressed TGF-β1 induced renal fibroblast transdifferentiation. • AS-IV suppressed TGF-β1 induced ECM production. • AS-IV alleviates renal fibrosis via the MAPK and NF-κB signaling pathways.

  6. Resveratrol induces acute endothelium-dependent renal vasodilation mediated through nitric oxide and reactive oxygen species scavenging

    Science.gov (United States)

    Gordish, Kevin L.

    2014-01-01

    Resveratrol is suggested to have beneficial cardiovascular and renoprotective effects. Resveratrol increases endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. We hypothesized resveratrol acts as an acute renal vasodilator, mediated through increased NO production and scavenging of reactive oxygen species (ROS). In anesthetized rats, we found 5.0 mg/kg body weight (bw) of resveratrol increased renal blood flow (RBF) by 8% [from 6.98 ± 0.42 to 7.54 ± 0.17 ml·min−1·gram of kidney weight−1 (gkw); n = 8; P resveratrol before and after 10 mg/kg bw of the NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME). l-NAME reduced the increase in RBF to resveratrol by 54% (from 0.59 ± 0.05 to 0.27 ± 0.06 ml·min−1·gkw−1; n = 10; P resveratrol before and after 1 mg/kg bw tempol, a superoxide dismutase mimetic. Resveratrol increased RBF 7.6% (from 5.91 ± 0.32 to 6.36 ± 0.12 ml·min−1·gkw−1; n = 7; P resveratrol-induced increase in RBF (from 0.45 ± 0.12 to 0.10 ± 0.05 ml·min−1·gkw−1; n = 7; P Resveratrol-induced vasodilation remained unaffected. We conclude intravenous resveratrol acts as an acute renal vasodilator, partially mediated by increased NO production/NO bioavailability and superoxide scavenging but not by inducing vasodilatory cyclooxygenase products. PMID:24431202

  7. Low Protein Diet Inhibits Uric Acid Synthesis and Attenuates Renal Damage in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Jianmin Ran

    2014-01-01

    Full Text Available Aim. Several studies indicated that hyperuricemia may link to the worsening of diabetic nephropathy (DN. Meanwhile, low protein diet (LPD retards exacerbation of renal damage in chronic kidney disease. We then assessed whether LPD influences uric acid metabolism and benefits the progression of DN in streptozotocin- (STZ- induced diabetic rats. Methods. STZ-induced and control rats were both fed with LPD (5% and normal protein diet (18%, respectively, for 12 weeks. Vital signs, blood and urinary samples for UA metabolism were taken and analyzed every 3 weeks. Kidneys were removed at the end of the experiment. Results. Diabetic rats developed into constantly high levels of serum UA (SUA, creatinine (SCr and 24 h amounts of urinary albumin excretion (UAE, creatintine (UCr, urea nitrogen (UUN, and uric acid (UUA. LPD significantly decreased SUA, UAE, and blood glucose, yet left SCr, UCr, and UUN unchanged. A stepwise regression showed that high UUA is an independent risk factor for DN. LPD remarkably ameliorated degrees of enlarged glomeruli, proliferated mesangial cells, and hyaline-degenerated tubular epithelial cells in diabetic rats. Expression of TNF-α in tubulointerstitium significantly decreased in LPD-fed diabetic rats. Conclusion. LPD inhibits endogenous uric acid synthesis and might accordingly attenuate renal damage in STZ-induced diabetic rats.

  8. Polymorphisms in CTLA4 influence incidence of drug-induced liver injury after renal transplantation in Chinese recipients.

    Directory of Open Access Journals (Sweden)

    Yifeng Guo

    Full Text Available Genetic polymorphisms in cytotoxic T lymphocyte-associated antigen 4 (CTLA4 play an influential role in graft rejection and the long-term clinical outcome of organ transplantation. We investigated the association of 5 CTLA4 single-nucleotide polymorphisms (SNPs (rs733618 C/T, rs4553808 A/G, rs5742909 C/T, rs231775 A/G, and rs3087243 G/A with drug-induced liver injury (DILI in Chinese renal transplantation (RT recipients. Each recipient underwent a 24-month follow-up observation for drug-induced liver damage. The CTLA4 SNPs were genotyped in 864 renal transplantation recipients. A significant association was found between the rs231775 genotype and an early onset of DILI in the recipients. Multivariate analyses revealed that a risk factor, recipient rs231775 genotype (p = 0.040, was associated with DILI. Five haplotypes were estimated for 4 SNPs (excluding rs733618; the frequency of haplotype ACGG was significantly higher in the DILI group (68.9% than in the non-DILI group (61.1% (p = 0.041. In conclusion, CTLA4 haplotype ACGG was partially associated with the development of DILI in Chinese kidney transplant recipients. The rs231775 GG genotype may be a risk factor for immunosuppressive drug-induced liver damage.

  9. Role of the adrenal medulla in control of blood pressure and renal function during furosemide-induced volume depletion

    DEFF Research Database (Denmark)

    Hasbak, Philip; Petersen, Jørgen Søberg; Shalmi, Michael

    1995-01-01

    Farmakologi, furosemide, adrenaline, renal function, adrenal medullectomy, arterial blood pressure......Farmakologi, furosemide, adrenaline, renal function, adrenal medullectomy, arterial blood pressure...

  10. Antioxidant effect of vitamin E treatment on some heavy metals-induced renal and testicular injuries in male mice

    OpenAIRE

    Al-Attar, Atef M.

    2010-01-01

    Toxic heavy metals in water, air and soil are global problems that are a growing threat to humanity. Heavy metals are widely distributed in the environment and some of them occur in food, water, air and tissues even in the absence of occupational exposure. The antioxidant and protective influences of vitamin E on a mixture of some heavy metals (Pb, Hg, Cd and Cu)-induced oxidative stress and renal and testicular injuries were evaluated in male mice. Exposure of mice to these heavy metals in d...

  11. Ginger extract diminishes chronic fructose consumption-induced kidney injury through suppression of renal overexpression of proinflammatory cytokines in rats.

    Science.gov (United States)

    Yang, Ming; Liu, Changjin; Jiang, Jian; Zuo, Guowei; Lin, Xuemei; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

    2014-05-27

    The metabolic syndrome is associated with an increased risk of development and progression of chronic kidney disease. Renal inflammation is well known to play an important role in the initiation and progression of tubulointerstitial injury of the kidneys. Ginger, one of the most commonly used spices and medicinal plants, has been demonstrated to improve diet-induced metabolic abnormalities. However, the efficacy of ginger on the metabolic syndrome-associated kidney injury remains unknown. This study aimed to investigate the impact of ginger on fructose consumption-induced adverse effects in the kidneys. The fructose control rats were treated with 10% fructose in drinking water over 5 weeks. The fructose consumption in ginger-treated rats was adjusted to match that of fructose control group. The ethanolic extract of ginger was co-administered (once daily by oral gavage). The indexes of lipid and glucose homeostasis were determined enzymatically, by ELISA and/or histologically. Gene expression was analyzed by Real-Time PCR. In addition to improve hyperinsulinemia and hypertriglyceridemia, supplement with ginger extract (50 mg/kg) attenuated liquid fructose-induced kidney injury as characterized by focal cast formation, slough and dilation of tubular epithelial cells in the cortex of the kidneys in rats. Furthermore, ginger also diminished excessive renal interstitial collagen deposit. By Real-Time PCR, renal gene expression profiles revealed that ginger suppressed fructose-stimulated monocyte chemoattractant protein-1 and its receptor chemokine (C-C motif) receptor-2. In accord, overexpression of two important macrophage accumulation markers CD68 and F4/80 was downregulated. Moreover, overexpressed tumor necrosis factor-alpha, interleukin-6, transforming growth factor-beta1 and plasminogen activator inhibitor (PAI)-1 were downregulated. Ginger treatment also restored the downregulated ratio of urokinase-type plasminogen activator to PAI-1. The present results

  12. ADAMTS-7 Expression Increases in the Early Stage of Angiotensin II-Induced Renal Injury in Elderly Mice

    Directory of Open Access Journals (Sweden)

    Yan-Xiang Gao

    2014-03-01

    Full Text Available Background/Aims: We investigated the recently described family of proteinases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTs, and matrix metalloproteinases (MMPs as inflammatory mediators in inflammatory kidney damage by studying ADAMTS-1, -4, and -7 and MMP-9 expression in elderly mouse kidneys after angiotensin II (Ang II administration. Methods: Ang II (2.5 µg/kg/min or norepinephrine (8.3 µg/kg/min was subcutaneously infused in old mice. Renal injury was assessed by hematoxylin-eosin staining, 24-h albuminuria, and immunohistochemistry to evaluate inflammatory cell markers. The mRNA and protein expression of ADAMTS-1, -4, and -7 and MMP-9 were determined using real-time PCR, Western blot, and immunohistochemistry 3 days after Ang II or norepinephrine administration. Results: Elderly mice in the Ang II group developed hypertension and pathological kidney damage. The mRNA and protein levels of ADAMTS-7 in the Ang II group were 3.3 ± 1.1 (P = 0.019 and 1.6 ± 0.1 (P = 0.047 vs. 1.0 ± 0.1 and 1.0 ± 0.1 in the control group on day 3. In contrast, treatment with the hypertensive agent norepinephrine did not lead to obvious renal damage or an increase in renal ADAMTS-7 expression. Conclusions: Renal ADAMTS-7 expression was induced by Ang II in elderly mice. The overexpression of ADATMTS-7 might contribute to early inflammatory kidney damage associated with aging.

  13. Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic Intermittent Hypoxia Induced Renal Injury, Inflammation, and Apoptosis via P38/JNK Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Xu Wu

    2016-01-01

    Full Text Available Obstructive sleep apnea (OSA associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH triggered tissue damage. Receptor for advanced glycation end product (RAGE and its ligand high mobility group box 1 (HMGB1 are expressed on renal cells and mediate inflammatory responses in OSA-related diseases. To determine their roles in CIH-induced renal injury, soluble RAGE (sRAGE, the RAGE neutralizing antibody, was intravenously administered in a CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis. Rats were divided into four groups: (1 normal air (NA, (2 CIH, (3 CIH+sRAGE, and (4 NA+sRAGE. Our results showed that CIH accelerated renal histological injury and upregulated RAGE-HMGB1 levels involving inflammatory (NF-κB, TNF-α, and IL-6, apoptotic (Bcl-2/Bax, and mitogen-activated protein kinases (phosphorylation of P38, ERK, and JNK signal transduction pathways, which were abolished by sRAGE but p-ERK. Furthermore, sRAGE ameliorated renal dysfunction by attenuating tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL. These findings suggested that RAGE-HMGB1 activated chronic inflammatory transduction cascades that contributed to the pathogenesis of the CIH-induced renal injury. Inhibition of RAGE ligand interaction by sRAGE provided a therapeutic potential for CIH-induced renal injury, inflammation, and apoptosis through P38 and JNK pathways.

  14. Exploring glycosuria as a mechanism for weight and fat mass reduction. A pilot study with remogliflozin etabonate and sergliflozin etabonate in healthy obese subjects

    Directory of Open Access Journals (Sweden)

    Antonella Napolitano

    2014-03-01

    Full Text Available Inhibitors of sodium-dependent glucose co-transporter 2 (SGLT2 increase glucose excretion in the urine and improve blood glucose in Type 2 diabetes mellitus. Glycosuria provides an energy and osmotic drain that could alter body composition. We therefore conducted a pilot study comparing the effects on body composition of two SGLT2 inhibitors, remogliflozin etabonate (RE 250 mg TID (n = 9 and sergliflozin etabonate (SE (1000 mg TID (n = 9, with placebo (n = 12 in obese non-diabetic subjects. Both drugs were well tolerated during 8 weeks of dosing, and the most common adverse event was headache. No urinary tract infections were observed, but there was one case of vaginal candidiasis in the RE group. As expected, RE and SE increased urine glucose excretion, with no change in the placebo group. All the subjects lost weight over 8 weeks, irrespective of treatment assignment. There was a reduction in TBW measured by D2O dilution in the RE group that was significantly greater than placebo (1.4 kg, p = 0.029. This was corroborated by calculation of fat-free mass using a quantitative magnetic resonance technique. All but one subject had a measurable decrease in fat mass. There was significant between-subject variability of weight and fat loss, and no statistically significant differences were observed between groups. Despite a lack of a difference in weight and fat mass loss, the leptin/adiponectin ratio, a measure of insulin resistance, was significantly decreased in the RE group when compared to placebo and SE, suggesting that this SGTL-2 inhibitor may improve metabolic health independent of a change in fat mass.

  15. Abatacept Treatment Does Not Preserve Renal Function in the Streptozocin-Induced Model of Diabetic Nephropathy.

    Directory of Open Access Journals (Sweden)

    Jenny Norlin

    Full Text Available Diabetic nephropathy (DN is one of the most severe complications of diabetes and remains the largest cause of end-stage renal disease in the Western world. Treatment options are limited and novel therapies that effectively slow disease progression are warranted. Previous work suggested that treatment with CTLA4-Ig (abatacept, a molecule that binds and blocks B7-1 and is licensed for the treatment of rheumatoid arthritis, could ameliorate DN. This study was designed to assess whether B7-1 signalling constitutes a promising therapeutic pathway for DN. Mice injected with streptozotocin (STZ were treated with abatacept and glycemia and renal function were assessed. No differences were found in diabetes progression, albumin excretion rates or albumin/creatine ratios, while mesangial expansion was unaltered at endpoint. Except for increased renal CCL5, treatment did not affect a panel of gene expression endpoints reflecting early fibrotic changes, inflammation and kidney injury. Finally, abatacept treatment effectively reduced the accumulation of activated CD4+ T cells in the kidney, suggesting that renal T cell inflammation is not a driving factor in the pathology of the STZ model. In conjunction with the recent data discounting the expression of B7-1 on podocytes, our present data do not support a role for abatacept in DN treatment.

  16. Lithium-induced Nephrotoxicity: A Case Report of Renal Cystic Disease Presenting as a Mass Lesion

    Directory of Open Access Journals (Sweden)

    Yvonne McCartney

    2014-11-01

    Full Text Available Lithium is an effective therapeutic agent used in the management of bipolar disorder. However, lithium is also associated with several side effects, including renal toxicity. We present a case of a symptomatic cystic mass lesion in the kidney of a patient who had a history of lithium therapy for the management of bipolar disorder.

  17. Macrophage-stimulating protein attenuates gentamicin-induced inflammation and apoptosis in human renal proximal tubular epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ko Eun [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Eun Young [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Chang Seong; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Kyung Keun [Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Lee, Jong Un [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Soo Wan, E-mail: skimw@chonnam.ac.kr [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)

    2013-05-10

    Highlights: •MSP/RON system is activated in rat kidney damaged by gentamicin. •MSP inhibits GM-induced cellular apoptosis and inflammation in HK-2 cells. •MSP attenuates GM-induced activation of MAPKs and NF-κB pathways in HK-2 cells. -- Abstract: The present study aimed to investigate whether macrophage-stimulating protein (MSP) treatment attenuates renal apoptosis and inflammation in gentamicin (GM)-induced tubule injury and its underlying molecular mechanisms. To examine changes in MSP and its receptor, recepteur d’origine nantais (RON) in GM-induced nephropathy, rats were injected with GM for 7 days. Human renal proximal tubular epithelial (HK-2) cells were incubated with GM for 24 h in the presence of different concentrations of MSP and cell viability was measured by MTT assay. Apoptosis was determined by flow cytometry of cells stained with fluorescein isothiocyanate-conjugated annexin V protein and propidium iodide. Expression of Bcl-2, Bax, caspase-3, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), IκB-α, and mitogen-activated protein kinases (MAPKs) was analyzed by semiquantitative immunoblotting. MSP and RON expression was significantly greater in GM-treated rats, than in untreated controls. GM-treatment reduced HK-2 cell viability, an effect that was counteracted by MSP. Flow cytometry and DAPI staining revealed GM-induced apoptosis was prevented by MSP. GM reduced expression of anti-apoptotic protein Bcl-2 and induced expression of Bax and cleaved caspase 3; these effects and GM-induced expression of COX-2 and iNOS were also attenuated by MSP. GM caused MSP-reversible induction of phospho-ERK, phospho-JNK, and phospho-p38. GM induced NF-κB activation and degradation of IκB-α; the increase in nuclear NF-κB was blocked by inhibitors of ERK, JNK, p-38, or MSP pretreatment. These findings suggest that MSP attenuates GM-induced inflammation and apoptosis by inhibition of the MAPKs

  18. Functional magnetic resonance imaging for evaluation of radiation-induced renal damage; Funktionelle MRT der Niere zur Erfassung strahleninduzierter Nierenschaedigungen

    Energy Technology Data Exchange (ETDEWEB)

    Haneder, S.; Schoenberg, S.O.; Michaely, H.J. [Universitaetsmedizin Mannheim, Medizinische Fakultaet Mannheim der Universitaet Heidelberg, Institut fuer Klinische Radiologie und Nuklearmedizin, Mannheim (Germany); Boda-Heggemann, J. [Universitaetsmedizin Mannheim, Medizinische Fakultaet Mannheim der Universitaet Heidelberg, Klinik fuer Strahlentherapie und Radioonkologie, Mannheim (Germany)

    2012-03-15

    The diagnosis of radiation-induced (especially chronic) renal alterations/damage is difficult and currently relies primarily on clinical evaluation. The importance of renal diagnostic evaluation will increase continuously due to the increasing number of long-term survivors after radiotherapy. This article evaluates the potentia diagnostic contribution of magnetic resonance (MR) imaging with a focus on functional MRI. The following functional MRI approaches are briefly presented and evaluated: blood oxygenation level-dependent imaging (BOLD), diffusion-weighted imaging (DWI) or diffusion tensor imaging (DTI), MR perfusion measurements and {sup 23}Na imaging. In summary, only DWI and contrast-enhanced MR perfusion currently seem to be suitable approaches for a broader, clinical implementation. However, up to now valid data from larger patient studies are lacking for both techniques in regard to radiation-induced renal alterations. The BOLD and {sup 23}Na imaging procedures have a huge potential but are currently neither sufficiently evaluated with regard to radiation-induced renal alterations nor technically simple and reliable for implementation into the clinical routine. (orig.) [German] Die Diagnostik strahleninduzierter, insbesondere chronischer Schaedigungen der Niere ist nach wie vor schwierig und beruht primaer auf der klinischen Beurteilung. Durch die zunehmende Anzahl von Langzeitueberlebenden nach einer Strahlentherapie wird die Bedeutung dieser Diagnostik jedoch weiter zunehmen. In diesem Beitrag wird der Frage nachgegangen, in wieweit hierzu die MRT-Bildgebung und hier besonders die funktionellen Bildgebungsmodalitaeten ihren Beitrag leisten koennen. Die folgenden Verfahren werden kurz vorgestellt und bewertet: die Blood-oxygenation-level-dependent-Bildgebung (BOLD), die diffusionsgewichtete Bildgebung (''diffusion-weighted imaging'', DWI) bzw. das ''diffusion tensor imaging'' (DTI), die MR-Perfusionsmessungen, und

  19. [The effect of portal blood stasis on lung and renal injury induced by hepatic ischemia reperfusion in a rabbit model].

    Science.gov (United States)

    Wang, Ye; Yang, Jia-mei; Hou, Yuan-kai; Li, Dian-qi; Hu, Ming-hua; Liu, Peng

    2008-04-15

    To investigate the effect and mechanism of portal blood stasis on lung and renal injury induced by hepatic ischemia reperfusion. A rabbit hepatic ischemia reperfusion injury model was established by hepatic portal occlusion and in situ hypothermic irrigation for 30 min. Twenty-four New Zealand white rabbits were employed and randomly divided into 3 groups equally by different dosage of portal blood stasis removal: group A5 (5 ml blood removal), group A10 (10 ml blood removal),and group B (no blood removal). Eight rabbits were served as controls with no hepatic portal occlusion and hypothermic irrigation. After reperfusion 4 h serum endotoxin content, tumor necrosis factor-alpha (TNF-alpha), urea nitrogen (BUN), and creatinine (Cr) were examined respectively, meantime lung and kidney tissues were sampled to determine the content of malondialdehyde (MDA), superoxide dismutase (SOD), the pathology, and wet to dry weight ratio, broncho-alveolar lavage fluid protein content in lung tissues. Removing portal blood stasis ameliorated lung and renal injury as shown by decreasing the level of serum endotoxin, TNF-alpha, BUN, Cr, wet to dry weight ratio, broncho-alveolar lavage fluid protein content, MDA, SOD. TNF-alpha, Cr, broncho-alveolar lavage fluid protein content in lung tissues and MDA in kidney tissue in group A5 were significantly reduced compared with those in group B (P portal blood stasis before the resume of splanchnic circulation may ameliorate the lung and renal injury induced by hepatic ischemia reperfusion. The possible mechanism may be that portal blood stasis removal reduces endotoxin absorption, and further decreases production of serum TNF-alpha.

  20. Prospects of N-Acetylcysteine and Melatonin as Treatments for Tramadol-Induced Renal Toxicity in Albino Rats

    Directory of Open Access Journals (Sweden)

    Elias Adikwu, Bonsome Bokolo

    2017-09-01

    Full Text Available Background: Tramadol (TD has played an important role in the treatment of pain. However, renal toxicity due to TD abuse is a serious clinical challenge. This study assessed the effects of n-acetylcysteine (NAC and melatonin (MT on TD-induced renal toxicity in albino rats. Methods: Rats were randomized into groups and treated with MT (10mg/kg/day, NAC (10mg/kg/day and TD (15, 30, and 45mg/kg/day respectively. Rats were pretreated with MT (10mg/kg/day and NAC (10mg/kg/day prior to treatment with TD (15, 30, and 45mg/kg/day intraperitonialy for 7days respectively. Rats were sacrificed, serum extracted and evaluated for creatinine, urea and uric acid. The kidneys were evaluated for malondialdehyde (MDA, superoxide dismutase (SOD, catalase, (CAT, and glutathione (GSH levels. Results: Treatment with MT and NAC did not produce significant (P>0.05 effects on serum creatinine, urea, uric acid and kidney MDA, SOD, CAT, and GSH levels when compare to saline control. In contrast, serum creatinine, urea, uric acid and kidney MDA levels were increased while kidney SOD, CAT, and GSH levels were decreased significantly (P<0.05 and in a dose-dependent manner in TD-treated rats. Kidneys of TD-treated rats showed varying degrees of damage which were dose-dependent. However, in all evaluated parameters, TD-induced alterations were abrogated in NAC and MT pretreated rats. Abrogations were most evident in rats pretreated with combined doses of NAC and MT. Conclusion: The present study showed prospects of n-acetylcysteine and melatonin as remedies for tramadol associated renal toxicity.

  1. Exercise induced renal dysfunction demonstrated both in hypertensives and normotensive controls studies by Tc-99m-DTPA

    International Nuclear Information System (INIS)

    Mizuiri, S.; Hayashi, I.; Ohara, T.; Hirata, K.; Sasaki, Y.

    1985-01-01

    It was previously reported that the hippurate transport disturbance after exercise is a specific phenomenon to patients with hypertension. The authors' study with Tc-99m-DTPA revealed exercise induced renal dysfunction not only in hypertensives (H) but also in normotensive controls (N). The details of the investigation is presented. Tc-99m-DTPA was intravenously injected at rest and during bicycle ergometric stress to 14 H and 14 N in sitting position. Serial dynamic renal images were taken, of which data were simultaneously stored in a data processor for later analysis. The renogram was drawn setting ROI on each kidney. Peak counts (PC) of vascular phase, peak time (PT) of secretory phase and radioisotope retention rate (RR) at 10 minutes were the parameters being compared between at rest and at exercise. GFR of each kidney was determined. Blood samples were obtained at rest and at the end of exercise for the measurement of aldosterone (ALD), plasma renin activity (PRA) and catecholamines (A, NA). Exercise caused significant lowering of PC, prolongation of PT and increase in RR (10 min. counts/peak counts) both in H and N. GFR (miota/min.) during exercise was significantly lower than at rest in both H (80 +- 22 vs 93.8 +- 16.9, p<0.02) and N (84 +- 17 vs 102 +- 15, p<0.01). ALD, PRA, A and NA are all elevated during exercise both in H and N. None of the rest-exercise differences significantly differed between H and N. The data indicate the exercise induced renal dysfunction demonstrated by Tc-99m-DTPA renograms is not specified to H but can also be observed in N, which may be resulted from the common changes in H and N of GFR and humoral factors

  2. Augmenter of liver regeneration inhibits TGF-β1-induced renal tubular epithelial-to-mesenchymal transition via suppressing TβR II expression in vitro

    International Nuclear Information System (INIS)

    Liao, Xiao-hui; Zhang, Ling; Chen, Guo-tao; Yan, Ru-yu; Sun, Hang; Guo, Hui; Liu, Qi

    2014-01-01

    Tubular epithelial-to-mesenchymal transition (EMT) plays a crucial role in the progression of renal tubular interstitial fibrosis (TIF), which subsequently leads to chronic kidney disease (CKD) and eventually, end-stage renal disease (ESRD). We propose that augmenter of liver regeneration (ALR), a member of the newly discovered ALR/Erv1 protein family shown to ameliorate hepatic fibrosis, plays a similar protective role in renal tubular cells and has potential as a new treatment option for CKD. Here, we showed that recombinant human ALR (rhALR) inhibits EMT in renal tubular cells by antagonizing activation of the transforming growth factor-β1 (TGF-β1) signaling pathway. Further investigation revealed that rhALR suppresses the expression of TGF-β receptor type II (TβR II) and significantly alleviates TGF-β1-induced phosphorylation of Smad2 and nuclear factor-κB (NF-κB). No apparent adverse effects were observed upon the addition of rhALR alone to cells. These findings collectively suggest that ALR plays a role in inhibiting progression of renal tubular EMT, supporting its potential utility as an effective antifibrotic strategy to reverse TIF in CKD. - Highlights: • ALR is involved in the pathological progression of renal EMT in NRK-52E cells. • ALR suppresses the expression of TβRII and the phosphorylation of Smad2 and NF-κB. • ALR plays a role in inhibiting progression of renal tubular EMT

  3. Augmenter of liver regeneration inhibits TGF-β1-induced renal tubular epithelial-to-mesenchymal transition via suppressing TβR II expression in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Xiao-hui [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Zhang, Ling, E-mail: lindazhang8508@hotmail.com [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Chen, Guo-tao; Yan, Ru-yu [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Sun, Hang; Guo, Hui [Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Liu, Qi, E-mail: txzzliuqi@163.com [Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China)

    2014-10-01

    Tubular epithelial-to-mesenchymal transition (EMT) plays a crucial role in the progression of renal tubular interstitial fibrosis (TIF), which subsequently leads to chronic kidney disease (CKD) and eventually, end-stage renal disease (ESRD). We propose that augmenter of liver regeneration (ALR), a member of the newly discovered ALR/Erv1 protein family shown to ameliorate hepatic fibrosis, plays a similar protective role in renal tubular cells and has potential as a new treatment option for CKD. Here, we showed that recombinant human ALR (rhALR) inhibits EMT in renal tubular cells by antagonizing activation of the transforming growth factor-β1 (TGF-β1) signaling pathway. Further investigation revealed that rhALR suppresses the expression of TGF-β receptor type II (TβR II) and significantly alleviates TGF-β1-induced phosphorylation of Smad2 and nuclear factor-κB (NF-κB). No apparent adverse effects were observed upon the addition of rhALR alone to cells. These findings collectively suggest that ALR plays a role in inhibiting progression of renal tubular EMT, supporting its potential utility as an effective antifibrotic strategy to reverse TIF in CKD. - Highlights: • ALR is involved in the pathological progression of renal EMT in NRK-52E cells. • ALR suppresses the expression of TβRII and the phosphorylation of Smad2 and NF-κB. • ALR plays a role in inhibiting progression of renal tubular EMT.

  4. Closure of multiple types of K+ channels is necessar to induce changes in renal vascular resistance in vivo in rats

    DEFF Research Database (Denmark)

    Sørensen, Charlotte Mehlin; Giese, Isaiah; Braunstein, Thomas Hartig

    2011-01-01

    Inhibition of K(+) channels might mediate renal vasoconstriction. As inhibition of a single type of K(+) channel caused minor or no renal vasoconstriction in vivo in rats, we hypothesized that several classes of K(+) channels must be blocked to elicit renal vasoconstriction. We measured renal blo...

  5. Amelioration of pancreatic and renal derangements in streptozotocin-induced diabetic rats by polyphenol extracts of Ginger (Zingiber officinale) rhizome.

    Science.gov (United States)

    Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin

    2015-12-01

    Free and bound polyphenol extracts of Zingiber officinale rhizome were investigated for their antidiabetic potential in the pancreatic and renal tissues of diabetic rats at a dose of 500mg/kg body weight. Forty Wistar rats were completely randomized into five groups: A-E consisting of eight animals each. Group A (control) comprises normal healthy animals and were orally administered 1.0mL distilled water on a daily basis for 42 days while group B-E were made up of 50mg/kg streptozotocin (STZ)-induced diabetic rats. Group C and D received 1.0mL 500mg/kg body weight free and bound polyphenol extracts respectively while group E received 1.0mL 0.6mg/kg of glibenclamide. Administration of the extracts to the diabetic rats significantly reduced (pZingiber officinale could ameliorate diabetes-induced pancreatic and renal derangements in rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

    Energy Technology Data Exchange (ETDEWEB)

    Quoilin, C., E-mail: cquoilin@ulg.ac.be [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium); Mouithys-Mickalad, A. [Center of Oxygen Research and Development, Department of Chemistry, University of Liege, 4000 Liege (Belgium); Duranteau, J. [Department of Anaesthesia and Surgical ICU, CHU Bicetre, University Paris XI Sud, 94275 Le Kremlin Bicetre (France); Gallez, B. [Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Universite catholique de Louvain, 1200 Brussels (Belgium); Hoebeke, M. [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer A HK-2 cells model of inflammation-induced acute kidney injury. Black-Right-Pointing-Pointer Two oximetry methods: high resolution respirometry and ESR spectroscopy. Black-Right-Pointing-Pointer Oxygen consumption rates of renal cells decrease when treated with LPS. Black-Right-Pointing-Pointer Cells do not recover normal respiration when the LPS treatment is removed. Black-Right-Pointing-Pointer This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonance spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.

  7. Contrast Media-Induced Renal Inflammation Is Mediated Through HMGB1 and Its Receptors in Human Tubular Cells.

    Science.gov (United States)

    Guan, Xiao-Feng; Chen, Qing-Jie; Zuo, Xiao-Cong; Guo, Ren; Peng, Xiang-Dong; Wang, Jiang-Lin; Yin, Wen-Jun; Li, Dai-Yang

    2017-01-01

    With the rapid development of imaging diagnosis and interventional therapy, contrast media (CM) are widely used in clinics. However, contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure accounting for 10-12% of all causes of hospital-acquired renal failure. Recent study found that inflammation may participate in the pathogenesis of CIN, but the role of it remains unclear. HK-2 cells were treated with Iohexol, Urografin, and mannitol. Two types of CM increased the release of HMGB1 in cell supernatant accompanied by increased expression of TLR2 and CXCR4. Iohexol and Urografin also caused a significant increase in NF-κB followed by the release of IL-6 and MCP-1. To clarify the role of HMGB1, TLR2, and CXCR4, glycyrrhizin, anti-TLR2-IgG, and AMD3100 were used to inhibit HMGB1, TLR2, and CXCR4, respectively. Significant decrease in the expression of TLR2, CXCR4, nuclear NF-κB, and the release of IL-6 and MCP-1 were observed. These results indicate that TLR2 and CXCR4 signaling are involved in CM-induced HK-2 cell injury model in an HMGB1-dependent pathway, which may provide a new target for the prevention and the treatment of CIN.

  8. Green Tea Polyphenols Ameliorate the Early Renal Damage Induced by a High-Fat Diet via Ketogenesis/SIRT3 Pathway

    Directory of Open Access Journals (Sweden)

    Weijie Yi

    2017-01-01

    Full Text Available Scope. Several reports in the literature have suggested the renoprotective effects of ketone bodies and green tea polyphenols (GTPs. Our previous study found that GTP consumption could elevate the renal expression of the ketogenic rate-limiting enzyme, which was decreased by a high-fat diet (HFD in rats. Here, we investigated whether ketogenesis can mediate renoprotection by GTPs against an HFD. Methods and Results. Wistar rats were fed a standard or HFD with or without GTPs for 18 weeks. The renal oxidative stress level, kidney function, renal expression, and activity levels of mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA synthase 2 (HMGCS2 and sirtuin 3(SIRT3 were detected. The increased renal oxidative stress and the loss of renal function induced by the HFD were ameliorated by GTPs. Renal ketogenesis and SIRT3 expression and activity levels, which were reduced by the HFD, were restored by GTPs. In vitro, HEK293 cells were transfected with the eukaryotic expression plasmid pcDNA HMGCS2. GTP treatment could upregulate HMGCS2 and SIRT3 expression. Although SIRT3 expression was not affected by HMGCS2 transfection, the 4-hydroxy-2-nonenal (4-HNE level and the acetyl-MnSOD (K122/MnSOD ratio were reduced in HMGCS2-transfected cells in the context of H2O2. Conclusion. The ketogenesis/SIRT3 pathway mediates the renoprotection of GTPs against the oxidative stress induced by an HFD.

  9. A survey on the effects of Azithromycin in the treatment of gingival overgrowth induced by Cyclosporin in renal transplant patients

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    Kadkhoda Z.

    2004-07-01

    Full Text Available Statement of Problem: Gingival overgrowth is a side effect commonly induced by Cyclosporin treatment. The effects of Azithromycin, a macrolidic antibiotic, has been focused on gingival enlargement treatment induced by cyclosporine in numerous articles. Purpose: The goal of the present study was to survey the effects of systemic Azithromycin in the treatment of gingival overgrowth induced by cyclosporine among renal transplant patients. Materials and Methods: In this clinical trial study, 18 renal transplant patients (6 females and 12 males with gingival overgrowth were studied. Samples were randomly divided into two groups: case group were treated by systemic Azithromycin and controls were treated by systemic placebo. Periodontal parameters including bleeding on probing (BOP, clinical crown length (CL, periodontal pocket depth (PPD, gingival overgrowth (GOI and stent-IDP (vertical distant between a stent or plate with teeth occlusal planes at least from three of the most anterior contact points to mesial papillae before treatment, two and six weeks after treatment were measured. To analyze the data, Wilcoxon and Mann-Whitney tests were used. Results: Most of the measured indices, among case and control groups, were significantly improved, after two weeks (P<0.05. No statistically significant differences were found between two groups except for BOP index (P<0.05. In other words, more BOP improvement was observed in the case group after six weeks comparing to the control group. Conclusion: Considering the findings of this study, one can assume that the reported effects of Azithromycine on gingival overgrowth, induced by cyclosporine is somehow exaggerated and the effects attributed this medicine is probably inflammation reduction.

  10. Attenuation of everolimus-induced cytotoxicity by a protective autophagic pathway involving ERK activation in renal cell carcinoma cells

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    Zeng, Yizhou; Tian, Xiaofang; Wang, Quan; He, Weiyang; Fan, Jing; Gou, Xin

    2018-01-01

    Aim The mammalian target of rapamycin (mTOR) pathway is a critical target for cancer treatment and the mTOR inhibitor everolimus (RAD001) has been approved for treatment of renal cell carcinoma (RCC). However, the limited efficacy of RAD001 has led to the development of drug resistance. Autophagy is closely related to cell survival and death, which may be activated under RAD001 stimulation. The aim of the present study was to identify the underlying mechanisms of RAD001 resistance in RCC cells through cytoprotective autophagy involving activation of the extracellular signal-regulated kinase (ERK) pathway. Methods and results: RAD001 strongly induced autophagy of RCC cells in a dose- and time-dependent manner, as confirmed by Western blot analysis. Importantly, suppression of autophagy by the pharmacological inhibitor chloroquine effectively enhanced RAD001-induced apoptotic cytotoxicity, as demonstrated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Western blot analysis, indicating a cytoprotective role for RAD001-induced autophagy. In addition, as was shown by the MTT assay, flow cytometry, and Western blot analysis, RAD001 robustly activated ERK, but not c-Jun N-terminal kinase and p38. Activation of ERK was inhibited by the pharmacological inhibitor selumetinib (AZD6244), which effectively promoted RAD001-induced cell death. Moreover, employing AZD6244 markedly attenuated RAD001-induced autophagy and enhanced RAD001-induced apoptosis, which play a central role in RAD001-induced cell death. Furthermore, RAD001-induced autophagy is regulated by ERK-mediated phosphorylation of Beclin-1 and B-cell lymphoma 2, as confirmed by Western blot analysis. Conclusion These results suggest that RAD001-induced autophagy involves activation of the ERK, which may impair cytotoxicity of RAD001 in RCC cells. Thus, inhibition of the activation of ERK pathway-mediated autophagy may be useful to overcome chemoresistance to RAD001. PMID:29719377

  11. 2-Methoxyestradiol Reduces Angiotensin II-Induced Hypertension and Renal Dysfunction in Ovariectomized Female and Intact Male Mice.

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    Pingili, Ajeeth K; Davidge, Karen N; Thirunavukkarasu, Shyamala; Khan, Nayaab S; Katsurada, Akemi; Majid, Dewan S A; Gonzalez, Frank J; Navar, L Gabriel; Malik, Kafait U

    2017-06-01

    Cytochrome P450 1B1 protects against angiotensin II (Ang II)-induced hypertension and associated cardiovascular changes in female mice, most likely via production of 2-methoxyestradiol. This study was conducted to determine whether 2-methoxyestradiol ameliorates Ang II-induced hypertension, renal dysfunction, and end-organ damage in intact Cyp1b1 -/- , ovariectomized female, and Cyp1b1 +/+ male mice. Ang II or vehicle was infused for 2 weeks and administered concurrently with 2-methoxyestradiol. Mice were placed in metabolic cages on day 12 of Ang II infusion for urine collection for 24 hours. 2-Methoxyestradiol reduced Ang II-induced increases in systolic blood pressure, water consumption, urine output, and proteinuria in intact female Cyp1b1 -/- and ovariectomized mice. 2-Methoxyestradiol also reduced Ang II-induced increase in blood pressure, water intake, urine output, and proteinuria in Cyp1b1 +/+ male mice. Treatment with 2-methoxyestradiol attenuated Ang II-induced end-organ damage in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice and Cyp1b1 +/+ male mice. 2-Methoxyestradiol mitigated Ang II-induced increase in urinary excretion of angiotensinogen in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice but not in Cyp1b1 +/+ male mice. The G protein-coupled estrogen receptor 1 antagonist G-15 failed to alter Ang II-induced increases in blood pressure and renal function in Cyp1b1 +/+ female mice. These data suggest that 2-methoxyestradiol reduces Ang II-induced hypertension and associated end-organ damage in intact Cyp1b1 -/- , ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice, and Cyp1b1 +/+ male mice independent of G protein-coupled estrogen receptor 1. Therefore, 2-methoxyestradiol could serve as a therapeutic agent for treating hypertension and associated pathogenesis in postmenopausal females, and in males. © 2017 American Heart Association, Inc.

  12. The anti-inflammatory and antifibrotic effects of Coreopsis tinctoria Nutt on high-glucose-fat diet and streptozotocin-induced diabetic renal damage in rats.

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    Yao, Lan; Li, Linlin; Li, Xinxia; Li, Hui; Zhang, Yujie; Zhang, Rui; Wang, Jian; Mao, Xinmin

    2015-09-07

    Diabetic nephropathy is a serious complication of diabetes whose development process is associated with inflammation, renal hypertrophy, and fibrosis. Coreopsis tinctoria Nutt, traditionally used as a healthcare tea, has anti-inflammatory, anti-hyperlipidemia, and glycemic regulation activities. The aim of our study was to investigate the renal protective effect of ethyl acetate extract of C. tinctoria Nutt (AC) on high-glucose-fat diet and streptozotocin (STZ)-induced diabetic rats. A diabetic rat model was induced by high-glucose-fat diet and intraperitoneal injection of 35 mg/kg STZ. After treatment with AC at a daily dose of 150, 300 or, 600 mg/kg for 4 weeks, metabolic and renal function parameters of serum and urine were examined. Degree of renal damage, renal proinflammatory cytokines, and fibrotic protein expression were analyzed by histopathology and immunohistochemistry. Renal AMP-activated protein kinase (AMPK) and transforming growth factor (TGF)-β1/Smad signaling pathway were determined by western blotting. Diabetic rats showed obvious renal dysfunction, inflammation and fibrosis. However, AC significantly reduced levels of blood glucose, total cholesterol, triglyceride, blood urea nitrogen, serum creatinine and urinary albumin, as well as expression of kidney proinflammatory cytokines of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1. AC also ameliorated renal hypertrophy and fibrosis by reducing fibronectin and collagen IV and suppressing the TGF-β1/Smad signaling pathway. Meanwhile, AMPKα as a protective cytokine was markedly stimulated by AC. In summary, AC controls blood glucose, inhibits inflammatory and fibrotic processes, suppresses the TGF-β1/Smad signaling pathway, and activates phosphorylation of AMPKα in the kidneys, which confirms the protective effects of AC in the early stage of diabetic kidney disease.

  13. Yohimbine-induced cutaneous drug eruption, progressive renal failure, and lupus-like syndrome.

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    Sandler, B; Aronson, P

    1993-04-01

    Yohimbine is an indole alkaloid obtained from the yohimbe tree, a common tree in West Africa. We describe a forty-two-year black man in whom a generalized erythrodermic skin eruption, progressive renal failure, and lupus-like syndrome developed following treatment with the drug, yohimbine. A literature review failed to reveal any reported association of these side effects. We review current information on yohimbine's use in male impotence, reported side effects, and its role as a drug allergen.

  14. Pathological research on acute hepatic and renal tissue damage in Wistar rats induced by cocoa

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    Chiedozie Onyejiaka Ibegbulem

    2016-01-01

    Conclusions: The pattern of alanine aminotransferase activity being more active than aspartate aminotransferase one in serum appeared to correlate with the extent of disarrangement of hepatic tissue architecture. The experimental rat groups exhibited no hyperbilirubinemia. Also, diets containing processed cocoa bean and raw cocoa bean products did not substantially interfere with the capacity of the hepatocytes to biosynthesize plasma proteins and the functionality of renal tissues.

  15. Amelioration of Gamma-hexachlorocyclohexane (Lindane induced renal toxicity by Camellia sinensis in Wistar rats

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    W. L. N. V. Vara Prasad

    2016-11-01

    Full Text Available Aim: A study to assess the toxic effects of gamma-hexachlorocyclohexane (γ-HCH (lindane and ameliorative effects of Camellia sinensis on renal system has been carried out in male Wistar rats. Materials and Methods: Four groups of rats with 18 each were maintained under standard laboratory hygienic conditions and provided feed and water ad libitum. γ-HCH was gavaged at 20 mg/kg b.wt. using olive oil as vehicle to Groups II. C. sinensis at 100 mg/kg b.wt. was administered orally in distilled water to Group IV in addition to γ-HCH 20 mg/kg b.wt. up to 45 days to study ameliorative effects. Groups I and III were treated with distilled water and C. sinensis (100 mg/kg b.wt., respectively. Six rats from each group were sacrificed at fortnight intervals. Serum was collected for creatinine estimation. The kidney tissues were collected in chilled phosphate buffer saline for antioxidant profile and in also 10% buffered formalin for histopathological studies. Results: γ-HCH treatment significantly increased serum creatinine and significantly reduced the renal antioxidative enzymes catalase, superoxide dismutase, and glutathione peroxidase. Grossly, severe congestion was noticed in the kidneys. Microscopically, kidney revealed glomerular congestion, atrophy, intertubular hemorrhages, degenerative changes in tubular epithelium with vacuolated cytoplasm, desquamation of epithelium and urinary cast formation. A significant reduction in serum creatinine levels, significant improvement in renal antioxidant enzyme activities and near to normal histological appearance of kidneys in Group IV indicated that the green tea ameliorated the effects of γ-HCH, on renal toxicity. Conclusion: This study suggested that C. sinensis extract combined with γ-HCH could enhance antioxidant/detoxification system which consequently reduced the oxidative stress thus potentially reducing γ-HCH toxicity and tissue damage.

  16. Urinary neutrophil gelatinase associated lipocalin as a biomarker in ifosfamide induced chronic renal failure.

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    Kesik, V; Demirkaya, E; Buyukpamukçu, M

    2015-12-01

    Neutrophil gelatinase associated lipocalin (NGAL) have been used with great success in acute renal failure and in some cases in chronic nephrotoxicity. In this work, we aimed to investigate urinary NGAL as an early marker of chronic renal failure (CRF). We investigated urinary NGAL of 29 children treated with ifosfamide chemotherapy and compared them with those of 12 healthy children. Urinary β2 microglobulin, serum cystatin C, and creatinine clearance analyses were also studied. The median age was 11 years (4-21) and median remission time was 4.3 years (1.8-14.4). The cumulative dose of ifosfamide was 36 g. Glomerular filtration rate was decreased in 41.4% and urine β2 microglobulin levels and serum cystatin C levels were elevated in 31% of the patients. As the remission time increased, serum creatinine and cystatin C levels were also increased. The sensitivity for β2 microglobulin and cystatin C in demonstrating CRF was 35.2% and 23% and specificity was 33.2% and 50% respectively. The 24-hour urine NGAL cut-off level for demonstrating CRF was found to be 1.065 ng/mL/24 hours. The sensitivity and specificity for this cut-off value were 83% and 77%, respectively. NGAL levels were significantly higher in the study group as compared with the control group. Although ifosfamide treatment was suggested to be safe with no complication of renal failure under a dose of 80 g/m2, chronic renal failure and deficits in glomerular and tubular function could be seen when the remission time increased. Elevated NGAL levels may be a good option in determining CRF.

  17. Pregnancy induced changes in Cox-1, Cox-2 and NOSIII vascular and renal expression.

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    Bobadilla, Rosa A; Bracho, Ismael; Alvarez, Victor M Pérez; Anguiano, Liliana; López, Pedro

    2004-01-01

    In order to establish if there is a mutual regulation between COX and NOS in vascular and renal tissue during pregnancy, we measured the protein expression of COX-1, COX-2 and NOSIII by Western blot comparing the thoracic and abdominal aorta and the renal cortex and medulla of non pregnant and pregnant (21st day) Wistar rats. We found there was no difference in the quantity of protein of any of the two isoforms of COX between the two segments of the aorta of non pregnant animals while an increased expression of both COX-1 And COX-2 was found in the abdominal compared to the thoracic segment of the pregnant rats. An increased expression of NOS III was found in the abdominal segment of the aorta form pregnant rats. No changes were found between pregnant and no pregnant animals in the expression of COX-1 and COX-2 in the renal cortex or medulla while an increased expression of NOS III was found in the cortex from pregnant compared to non pregnant animals. These results suggest the influence of pregnancy is not homogeneous along the aorta and also that a balance between prostaglandins and nitric oxide is responsible of the blunted vascular reactivity during pregnancy in the rat.

  18. Hyperglycemia-induced Renal P2X7 Receptor Activation Enhances Diabetes-related Injury

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    Robert I. Menzies

    2017-05-01

    Full Text Available Diabetes is a leading cause of renal disease. Glomerular mesangial expansion and fibrosis are hallmarks of diabetic nephropathy and this is thought to be promoted by infiltration of circulating macrophages. Monocyte chemoattractant protein-1 (MCP-1 has been shown to attract macrophages in kidney diseases. P2X7 receptors (P2X7R are highly expressed on macrophages and are essential components of pro-inflammatory signaling in multiple tissues. Here we show that in diabetic patients, renal P2X7R expression is associated with severe mesangial expansion, impaired glomerular filtration (≤40 ml/min/1.73 sq. m., and increased interstitial fibrosis. P2X7R activation enhanced the release of MCP-1 in human mesangial cells cultured under high glucose conditions. In mice, P2X7R-deficiency prevented glomerular macrophage attraction and collagen IV deposition; however, the more severe interstitial inflammation and fibrosis often seen in human diabetic kidney diseases was not modelled. Finally, we demonstrate that a P2X7R inhibitor (AZ11657312 can reduce renal macrophage accrual following the establishment of hyperglycemia in a model of diabetic nephropathy. Collectively these data suggest that P2X7R activation may contribute to the high prevalence of kidney disease found in diabetics.

  19. Endogenous EGF as a potential renotrophic factor in ischemia-induced acute renal failure.

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    Schaudies, R P; Nonclercq, D; Nelson, L; Toubeau, G; Zanen, J; Heuson-Stiennon, J A; Laurent, G

    1993-09-01

    The time course for the increases in soluble renal epidermal growth factor (EGF) after ischemia has been established. These elevated levels of EGF have been compared with the degree of tissue injury as well as the extent of cell proliferation in the recovering tissue. Levels of soluble immunoreactive EGF (irEGF) in control animals were 9.74 +/- 1.1 ng/g wet wt (n = 4-8 for all values) and rose to 83.9 +/- 30 ng/g within 12 h after injury. Soluble irEGF content peaked at 88.8 +/- 15 ng/g at 24 h postinjury and returned to control values by 72 h. We previously reported that trypsin digestion of crude renal membranes (CRM) generates rat EGF that is indistinguishable from that isolated from the submandibular gland. Initial levels of trypsin-releasable membrane-associated irEGF were 439 +/- 26 ng/g. These levels fell to 46.6 +/- 9.6 ng/g at 48 h after injury. The total renal EGF demonstrated an 80% decline 48 h after injury but returned to 50% of the initial values after 72 h representing significant new synthesis of EGF-containing proteins between 48 and 72 h postinjury. Immunohistochemical staining of kidney paraffin sections for EGF immunoreactivity demonstrated staining intensities that paralleled the amount of irEGF in the trypsin-digested CRM fraction, suggesting that the membrane-associated irEGF is the predominant form detected by this technique. Regenerative hyperplasia subsequent to tubular insult was monitored by immunostaining nuclei of S phase cells after pulse labeling with the thymidine analogue 5-bromo-2'-deoxyuridine. Cell proliferation was particularly prominent in the outer stripe of outer medulla of kidneys exposed to ischemia and reached a maximum (19-fold higher than the baseline value) 48 h after reperfusion. Renal cell turnover returned to control values by day 7. The observation that the peak in soluble EGF levels (24 h) precedes the peak in tubular regeneration (48 h) by 24 h is consistent with the hypothesis that EGF is one of the mitogenic

  20. GSTA3 Attenuates Renal Interstitial Fibrosis by Inhibiting TGF-Beta-Induced Tubular Epithelial-Mesenchymal Transition and Fibronectin Expression.

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    Yun Xiao

    Full Text Available Tubular epithelial-mesenchymal transition (EMT has been widely accepted as the underlying mechanisms of renal interstitial fibrosis (RIF. The production of reactive oxygen species (ROS plays a vital role in tubular EMT process. The purpose of this study was to investigate the involved molecular mechanisms in TGF-beta-induced EMT and identify the potential role of glutathione S-transferase alpha 3 (GSTA3 in this process. The iTRAQ screening was performed to identify protein alterations of the rats underwent unilateral-ureteral obstruction (UUO. Protein expression of GSTA3 in patients with obstructive nephropathy and UUO rats was detected by immunohistochemistry. Protein and mRNA expression of GSTA3 in UUO rats and NRK-52E cells were determined by Western blot and RT-PCR. siRNA and overexpression plasmid were transfected specifically to assess the role of GSTA3 in RIF. The generation of ROS was measured by dichlorofluorescein fluorescence analysis. GSTA3 protein and mRNA expression was significantly reduced in UUO rats. Immunohistochemical analysis revealed that GSTA3 expression was reduced in renal cortex in UUO rats and patients with obstructive nephropathy. Treating with TGF-β1 down-regulated GSTA3 expression in NRK-52E cells, which have been found to be correlated with the decreased expression in E-cadherin and megalin and increased expression in α-smooth muscle actin. Furthermore, knocking down GSTA3 in NRK-52 cells led to increased production of ROS and tubular EMT, whereas overexpressing GSTA3 ameliorated ROS production and prevented the occurrence of tubular EMT. GSTA3 plays a protective role against tubular EMT in renal fibrosis, suggesting GSTA3 is a potential therapeutic target for RIF.

  1. Potential Cardiovascular and Renal Protective Effects of Vitamin D and Coenzyme Q10 in l-NAME-Induced Hypertensive Rats.

    Science.gov (United States)

    Shamardl, Hanan A; El-Ashmony, Sahar M; Kamel, Hala F; Fatani, Sameer H

    2017-08-01

    Hypertension is one of the primary modifiable risk factors for cardiovascular disease. Adequate vitamin D (vit D) levels have been shown to reduce vascular smooth muscle contraction and to increase arterial compliance, which may be beneficial in hypertension. Further, coenzyme Q10 (COQ10) through its action to lower oxidative stress has been reported to have beneficial effects on hypertension and heart failure. This study examined the possible cardiac and renal protective effects of vit D and COQ10 both separately and in combination with an angiotensin II receptor blocker, valsartan (vals) in l-NAME hypertensive rats. Hypertension was induced in rats by l-NAME administration. Following induction of hypertension, the rats were assigned into the following 6 subgroups: an l-NAME alone group and treated groups receiving the following drugs intraperitoneally for 6 weeks; vals, vit D, COQ10 and combination of vals with either vit D or COQ10. A group of normotensive rats were used as negative controls. At the end of the treatment period, blood pressure, serum creatinine, blood urea nitrogen, lipids and serum, cardiac and renal parameters of oxidative stress were measured. Compared to the l-NAME only group, all treatments lowered systolic, diastolic, mean arterial pressure, total cholesterol, low-density lipoprotein cholesterol, and creatinine levels as well as TNF-α and malondialdehyde. Further, the agents increased serum, cardiac and renal total antioxidant capacity. Interestingly, the combination of agents had further effects on all the parameters compared to treatment with each single agent. The study suggests that the additive protective effects of vit D and COQ10 when used alone or concurrent with vals treatment in hypertensive rats may be due to their effects as antioxidants, anticytokines and blood pressure conservers. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  2. Hibiscus sabdariffa polyphenols prevent palmitate-induced renal epithelial mesenchymal transition by alleviating dipeptidyl peptidase-4-mediated insulin resistance.

    Science.gov (United States)

    Huang, Chien-Ning; Wang, Chau-Jong; Yang, Yi-Sun; Lin, Chih-Li; Peng, Chiung-Huei

    2016-01-01

    Diabetic nephropathy has a significant socioeconomic impact, but its mechanism is unclear and needs to be examined. Hibiscus sabdariffa polyphenols (HPE) inhibited high glucose-induced angiotensin II receptor-1 (AT-1), thus attenuating renal epithelial mesenchymal transition (EMT). Recently, we reported HPE inhibited dipeptidyl-peptidase-4 (DPP-4, the enzyme degrades type 1 glucagon-like peptide (GLP-1)), which mediated insulin resistance signals leading to EMT. Since free fatty acids can realistically bring about insulin resistance, using the palmitate-stimulated cell model in contrast with type 2 diabetic rats, in this study we examined if insulin resistance causes renal EMT, and the preventive effect of HPE. Our findings reveal that palmitate hindered 30% of glucose uptake. Treatment with 1 mg mL(-1) of HPE and the DPP-4 inhibitor linagliptin completely recovered insulin sensitivity and palmitate-induced signal cascades. HPE inhibited DPP-4 activity without altering the levels of DPP-4 and the GLP-1 receptor (GLP-1R). HPE decreased palmitate-induced phosphorylation of Ser307 of insulin receptor substrate-1 (pIRS-1 (S307)), AT-1 and vimentin, while increasing phosphorylation of phosphatidylinositol 3-kinase (pPI3K). IRS-1 knockdown revealed its essential role in mediating downstream AT-1 and EMT. In type 2 diabetic rats, it suggests that HPE concomitantly decreased the protein levels of DPP-4, AT-1, vimentin, and fibronectin, but reversed the in vivo compensation of GLP-1R. In conclusion, HPE improves insulin sensitivity by attenuating DPP-4 and the downstream signals, thus decreasing AT-1-mediated tubular-interstitial EMT. HPE could be an adjuvant to prevent diabetic nephropathy.

  3. Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells

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    Krüger, Katharina; Ziegler, Verena; Hartmann, Christina; Henninger, Christian [Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf (Germany); Thomale, Jürgen [Institute of Cell Biology, University Duisburg-Essen, 45122 Essen (Germany); Schupp, Nicole [Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf (Germany); Fritz, Gerhard, E-mail: fritz@uni-duesseldorf.de [Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf (Germany)

    2016-02-01

    The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model. The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury. - Highlights: • Lovastatin blocks ATM/ATR-regulated DDR of tubular cells following CisPt treatment. • Lovastatin attenuates CisPt-induced activation of protein kinase ATM in vitro. • Statin-mediated DDR inhibition is independent of initial DNA damage formation. • Statin-mediated blockage of Cis

  4. Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells

    International Nuclear Information System (INIS)

    Krüger, Katharina; Ziegler, Verena; Hartmann, Christina; Henninger, Christian; Thomale, Jürgen; Schupp, Nicole; Fritz, Gerhard

    2016-01-01

    The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model. The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury. - Highlights: • Lovastatin blocks ATM/ATR-regulated DDR of tubular cells following CisPt treatment. • Lovastatin attenuates CisPt-induced activation of protein kinase ATM in vitro. • Statin-mediated DDR inhibition is independent of initial DNA damage formation. • Statin-mediated blockage of Cis

  5. Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats.

    Science.gov (United States)

    Geurts, Aron M; Mattson, David L; Liu, Pengyuan; Cabacungan, Erwin; Skelton, Meredith M; Kurth, Theresa M; Yang, Chun; Endres, Bradley T; Klotz, Jason; Liang, Mingyu; Cowley, Allen W

    2015-02-01

    Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats. © 2014 American Heart Association, Inc.

  6. Role of Bone Marrow Derived Mesenchymal Stem Cells and the Protective Effect of Silymarin in Cisplatin-Induced Acute Renal Failure in Rats.

    Science.gov (United States)

    Ibrahim, Mohamed El-Tantawy; Bana, Eman El; El-Kerdasy, Hanan I

    2018-01-01

    Cisplatin is a highly effective antitumor agent whose clinical application is limited by its nephrotoxicity, which is associated with high mortality and morbidity rates. We aimed to study the protective role of silymarin and mesenchymal stem cells as a therapeutic tool of cisplatin nephrotoxicity. We injected rats with cisplatin in a dose of 5mg/kg body weight for 5 days to induce acute renal failure (ARF). Silymarin was administrated 6 hours before cisplatin injection and mesenchymal stem cells were injected 24 hours after cisplatin-induced ARF. We assessed the ARF biochemically by elevation of kidney function tests and histopathologically by an alteration of the histological architecture of the renal cortex in the form of shrinkage of glomeruli, lobulated tufts and glomerular hypertrophy with narrowing capsular space. The tubules showed extensive tubular degeneration with cellular hyaline materials and debris in the lumen of the renal tubules. The renal blood vessels appeared sclerotic with marked thickened walls. When silymarin was given in different doses before cisplatin, it decreased the toxic effect of cisplatin in the kidney but sclerotic blood vessels remained. Injection of mesenchymal stem cells in rats with cisplatin-induced ARF improved the histopathological effects of cisplatin in renal tissues and kidney function tests were significantly improved. There was a significant improvement in kidney function tests and renal histopathology by using silymarin as protective mechanism in cisplatin-induced ARF. Administration of mesenchymal stem cells denoted a more remarkable therapeutic effect in ARF. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  7. Nivolumab-Induced Encephalitis in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome

    Directory of Open Access Journals (Sweden)

    Benjamin Chaucer

    2018-01-01

    Full Text Available The treatment of cancer is a rapidly evolving field. As more chemotherapeutic agents become available, reporting the side effects of these agents in clinical practice becomes increasingly important. Nivolumab is one of the chemotherapeutic agents commonly used for treatment of renal cell carcinoma, metastatic melanoma, and metastatic non-small cell lung cancer. While common side effects are known and well documented, encephalitis is documented as an extremely rare side effect. We present the case of an extremely rare side effect to a common chemotherapeutic agent.

  8. Hemodynamic and renal implications of sodium-glucose cotransporter- 2 inhibitors in type 2 diabetes mellitus.

    Science.gov (United States)

    Tejedor Jorge, Alberto

    2016-11-01

    In DM2, there is increased expression of the proximal glucose transporter SGLT2. The increased glucose reabsorption from the urine to the proximal tubule and subsequently to the bloodstream, has three direct effects on the prognosis of patients with DM2: a) it increases the daily glucose load by raising the renal threshold for glucose, thus augmenting requirements for oral antidiabetics and insulin. This progressive increase occurs throughout the course of the disease and in parallel with the increase in renal mass (renal hypertrophy); b) because of the greater glucose reabsorption, glycosuria is lower than the level corresponding to glycaemia, decreasing the stimulus on the tubuloglomerular feedback system of the distal nephron. As a result, the glomerular vasodilation caused by hyperglycaemia is not arrested, maintaining glomerular hyperfiltration, and c) the excess glucose transported to the proximal tubular cells modifies their redox status, increasing local production of glycosylating products and activating local production of proinflammatory and profibrotic proliferative mediators. These mediators are responsible for the direct free radical damage to proximal tubular cells, for increased SGLT2 expression, increased production of collagen IV and extracellular matrix, and activation of monocyte/macrophages able to cause endothelial injury. The use of SGLT2 inhibitors not only reduces the reabsorption of glucose from the glomerular filtrate back into the circulationthus improving metabolic control in diabetesbut also restores tubuloglomerular feedback by increasing glycosuria and distal urinary flow. However, the most notable effect is due to inhibition of glucose entry to the proximal tubular cells. Glycosuria is toxic to the kidney: it harms glucosetransporting cells, that is, the proximal cells, which contain SGLT2. In animal models, SGLT2 inhibition reduces local production of oxygen-free radicals, the formation of mesangial matrix and collagen IV

  9. High cut-off haemodialysis induces remission of recurrent idiopathic focal segmental glomerulosclerosis after renal transplantation but is no alternative to plasmapheresis

    NARCIS (Netherlands)

    I. Noorlander (Iris); D.A. Hesselink (Dennis); M. Wabbijn (Marike); M.G.H. Betjes (Michiel)

    2011-01-01

    textabstractA 26-year-old male experienced a recurrence of idiopathic focal segmental glomerulosclerosis (iFSGS) after his second renal transplant. Reduction of proteinuria was rapidly induced by plasmapheresis (PP) and the patient has remained in remission with a once-weekly PP regimen, which has

  10. Saline-induced natriuresis and renal blood flow in conscious dogs: effects of sodium infusion rate and concentration

    DEFF Research Database (Denmark)

    Sandgaard, N C F; Andersen, J L; Holstein-Rathlou, N-H

    2005-01-01

    AIM: This study focused on static and dynamic changes in total renal blood flow (RBF) during volume expansion and tested whether a change in RBF characteristics is a necessary effector mechanism in saline-induced natriuresis. METHODS: The aortic flow subtraction technique was used to measure RBF...... continuously. Identical amounts of NaCl (2.4 mmol kg(-1)) were given as slow isotonic (Iso, 120 min), slow hypertonic (Hyper, 120 min), and rapid isotonic loads (IsoRapid, 30 min). RESULTS: During Iso and IsoRapid, arterial blood pressure increased slightly (6-7 mmHg), and during Hyper it remained unchanged...... saline loading simulating daily sodium intake, the rate of sodium excretion may increase 10-20-fold without any change in mean arterial blood pressure or in RBF. Regulatory responses to changes in total body NaCl levels appears, therefore, to be mediated primarily by neurohumoral mechanisms and may occur...

  11. Oxidative stress, mitochondrial perturbations and fetal programming of renal disease induced by maternal smoking.

    Science.gov (United States)

    Stangenberg, Stefanie; Nguyen, Long T; Chen, Hui; Al-Odat, Ibrahim; Killingsworth, Murray C; Gosnell, Martin E; Anwer, Ayad G; Goldys, Ewa M; Pollock, Carol A; Saad, Sonia

    2015-07-01

    An adverse in-utero environment is increasingly recognized to predispose to chronic disease in adulthood. Maternal smoking remains the most common modifiable adverse in-utero exposure leading to low birth weight, which is strongly associated with chronic kidney disease (CKD) in later life. In order to investigate underlying mechanisms for such susceptibility, female Balb/c mice were sham or cigarette smoke-exposed (SE) for 6 weeks before mating, throughout gestation and lactation. Offspring kidneys were examined for oxidative stress, expression of mitochondrial proteins, mitochondrial structure as well as renal functional parameters on postnatal day 1, day 20 (weaning) and week 13 (adult age). From birth throughout adulthood, SE offspring had increased renal levels of mitochondrial-derived reactive oxygen species (ROS), which left a footprint on DNA with increased 8-hydroxydeoxyguanosin (8-OHdG) in kidney tubular cells. Mitochondrial structural abnormalities were seen in SE kidneys at day 1 and week 13 along with a reduction in oxidative phosphorylation (OXPHOS) proteins and activity of mitochondrial antioxidant Manganese superoxide dismutase (MnSOD). Smoke exposure also resulted in increased mitochondrial DNA copy number (day 1-week 13) and lysosome density (day 1 and week 13). The appearance of mitochondrial defects preceded the onset of albuminuria at week 13. Thus, mitochondrial damage caused by maternal smoking may play an important role in development of CKD at adult life. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Glomerular filtration rate measured by {sup 51}Cr-EDTA clearance: evaluation of captopril-induced changes in hypertensive patients with and without renal artery stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Chaves, Anna Alice Rolim; Buchpiguel, Carlos Alberto; Praxedes, Jose Nery; Bortolotto, Luiz Aparecido; Sapienza, Marcelo Tatit, E-mail: annaalice100@yahoo.com.b [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina. Dept. de Neurologia

    2010-07-01

    Introduction: renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid ({sup 51}Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using {sup 51}Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. Methods: this prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis ({sup 51}Cr-EDTA) and {sup 99m}Tc-DMSA scintigraphy were performed before and after captopril administration in all patients. Results: the mean baseline glomerular filtration rate was 48.6+-21.8 ml/kg/1.73 m{sup 2} in the group with renal artery stenosis, which was significantly lower than the GFR of 65.1+-28.7 ml/kg/1.73m{sup 2} in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6+-14.8 ml/kg/1.73m{sup 2}, p=0.001) and an insignificant change in the group without RAS (to 62.2+-23.6 ml/kg/1.73m{sup 2}, p=0.68). Scintigraphy with technetium-99m dimercapto

  13. Glomerular filtration rate measured by 51Cr-EDTA clearance: evaluation of captopril-induced changes in hypertensive patients with and without renal artery stenosis

    International Nuclear Information System (INIS)

    Chaves, Anna Alice Rolim; Buchpiguel, Carlos Alberto; Praxedes, Jose Nery; Bortolotto, Luiz Aparecido; Sapienza, Marcelo Tatit

    2010-01-01

    Introduction: renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid ( 51 Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using 51 Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. Methods: this prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis ( 51 Cr-EDTA) and 99m Tc-DMSA scintigraphy were performed before and after captopril administration in all patients. Results: the mean baseline glomerular filtration rate was 48.6±21.8 ml/kg/1.73 m 2 in the group with renal artery stenosis, which was significantly lower than the GFR of 65.1±28.7 ml/kg/1.73m 2 in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6±14.8 ml/kg/1.73m 2 , p=0.001) and an insignificant change in the group without RAS (to 62.2±23.6 ml/kg/1.73m 2 , p=0.68). Scintigraphy with technetium-99m dimercapto-succinic acid (DMSA) did not show

  14. Punica granatum improves renal function in gentamicin-induced nephropathy in rats via attenuation of oxidative stress.

    Science.gov (United States)

    Mestry, Snehal N; Gawali, Nitin B; Pai, Sarayu A; Gursahani, Malvika S; Dhodi, Jayesh B; Munshi, Renuka; Juvekar, Archana R

    2018-03-16

    Gentamicin is widely used as an antibiotic for the treatment of gram negative infections. Evidences indicates that oxidative stress is involved in gentamicin-induced nephrotoxicity. In Ayurvedic medicine, Punica granatum Linn. is considered as 'a pharmacy unto itself". It has been claimed in traditional literature, to treat various kidney ailments due to its antioxidant potential. To explore the possible mechanism of action of methanolic extract of P.granatum leaves (MPGL) in exerting a protective effect on gentamicin-induced nephropathy. Animals were administered with gentamicin (80 mg/kg/day i.m.) and simultaneously with MPGL (100, 200 and 400 mg/kg p.o.) or metformin (100 mg/kg p.o.) for 8 days. A satellite group was employed in order to check for reversibility of nephrotoxic effects post discontinuation of gentamicin administration. At the end of the study, all the rats were sacrificed and serum-urine parameters were investigated. Antioxidant enzymes and tumor necrosis factor alpha (TNF-α) levels were determined in the kidney tissues along with histopathological examination of kidneys. Increase in serum creatinine, urea, TNF-α, lipid peroxidation along with fall in the antioxidant enzymes activity and degeneration of tubules, arterioles as revealed by histopathological examination confirmed the manifestation of nephrotoxicity caused due to gentamicin. Simultaneous administration of MPGL and gentamicin protected kidneys against nephrotoxic effects of gentamicin as evidenced from normalization of renal function parameters and amelioration of histopathological changes. Data suggests that MPGL attenuated oxidative stress associated renal injury by preserving antioxidant enzymes, reducing lipid peroxidation and inhibiting inflammatory mediators such as TNF-α. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

  15. Withanolide E sensitizes renal carcinoma cells to TRAIL-induced apoptosis by increasing cFLIP degradation.

    Science.gov (United States)

    Henrich, C J; Brooks, A D; Erickson, K L; Thomas, C L; Bokesch, H R; Tewary, P; Thompson, C R; Pompei, R J; Gustafson, K R; McMahon, J B; Sayers, T J

    2015-02-26

    Withanolide E, a steroidal lactone from Physalis peruviana, was found to be highly active for sensitizing renal carcinoma cells and a number of other human cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Withanolide E, the most potent and least toxic of five TRAIL-sensitizing withanolides identified, enhanced death receptor-mediated apoptotic signaling by a rapid decline in the levels of cFLIP proteins. Other mechanisms by which TRAIL sensitizers have been reported to work: generation of reactive oxygen species (ROS), changes in pro-and antiapoptotic protein expression, death receptor upregulation, activation of intrinsic (mitochondrial) apoptotic pathways, ER stress, and proteasomal inhibition proved to be irrelevant to withanolide E activity. Loss of cFLIP proteins was not due to changes in expression, but rather destabilization and/or aggregation, suggesting impairment of chaperone proteins leading to degradation. Indeed, withanolide E treatment altered the stability of a number of HSP90 client proteins, but with greater apparent specificity than the well-known HSP90 inhibitor geldanamycin. As cFLIP has been reported to be an HSP90 client, this provides a potentially novel mechanism for sensitizing cells to TRAIL. Sensitization of human renal carcinoma cells to TRAIL-induced apoptosis by withanolide E and its lack of toxicity were confirmed in animal studies. Owing to its novel activity, withanolide E is a promising reagent for the analysis of mechanisms of TRAIL resistance, for understanding HSP90 function, and for further therapeutic development. In marked contrast to bortezomib, among the best currently available TRAIL sensitizers, withanolide E's more specific mechanism of action suggests minimal toxic side effects.

  16. Renal tissue alterations were size-dependent with smaller ones induced more effects and related with time exposure of gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Jarrar Bashir M

    2011-09-01

    Full Text Available Abstract Background Gold nanoparticles (GNPs have important application for cell labeling and imaging, drug delivery, diagnostic and therapeutic purposes mainly in cancer. Nanoparticles (NPs are being increasingly exploited for medical applications. The aim of the present study was to investigate the particle-size and period effects of administration of GNPs on the renal tissue in an attempt to address their potential toxicity. Methods A total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 μl of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days to investigate particle-size effect of GNPs on the renal tissue. Animals were randomly divided into groups, 6 GNPs-treated rats groups and one control group. Groups 1, 2 and 3 received infusion of 50 μl GNPs of size 10 nm (3 or 7 days, size 20 nm (3 or 7 days and 50 nm (3 or 7 days, respectively; while groups 4, 5 and 6 received infusion of 100 μl GNPs of size 10 nm, size 20 nm and 50 nm, respectively. Stained sections of control and treated rats kidneys were examined for renal tissue alterations induced by GNPs. Results In comparison with respective control rats, exposure to GNPs doses has produced the following renal tubular alterations: cloudy swelling, vacuolar degeneration, hyaline droplets and casts, anisokaryosis, karopyknosis, karyorrhexis and karyolysis. The glomeruli showed moderate congestion with no hypercelluraity, mesangial proliferation or basement membrane thickening. The histological alterations were mainly seen in the cortex and the proximal renal convoluted tubules were more affected than the distal ones. Conclusions The induced histological alterations might be an indication of injured renal tubules due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. The findings may suggest that GNPs interact with proteins and enzymes of the renal tissue

  17. A Rare Cause of Acute Renal Failure: Fenofibrate-Induced Rhabdomyolysis

    Directory of Open Access Journals (Sweden)

    Ferhat Icme

    2013-08-01

    Full Text Available Fibrates are derivative of fibric acid and broad spectrum drugs which are commonly used in the treatment of dyslipidemia and hypertriglyceridemia. Side effects are often related with striated muscles, kidney and liver. Rhabdomyolysis developing with striated muscle destruction is potentially the most lethal of these side effects. Although several case reports of rhabdomyolysis have been reported due to the combination of statin and fenofibrate, fenofibrate alone rarely causes rhabdomyolysis. The purposes of this paper are to present a patient whom we diagnosed with acute renal injury due to use of fenofibrate in order to emphasize the importance of questioning drugs which have been used, and to review management of rhabdomyolysis due to fenofibrate use. [Cukurova Med J 2013; 38(4.000: 800-804

  18. Bee envenomation induced acute renal failure in an 8 year old child

    Directory of Open Access Journals (Sweden)

    Farzana Islam

    2011-01-01

    Full Text Available Massive envenomations by bees are capable of causing multiorgandysfunction as a result of direct toxic effects of the largevenom load received. Although all varieties of honey bee havethe potential for these attacks, the Africanized honey bee (Apismellifera scutellata is the most commonly implicated subspecies.In the United States, the Africanized strain is found primarilyin the southwestern states and is known for its highly defensivebehavior if disturbed. Mechanisms behind the multiorgan dysfunctionproduced by these mass envenomations are not clearly understood.We present a case of an 8-year-old boy who was stung by multiple bees and developed progressive upper-body swelling andsystemic manifestations of mass envenomation including rhabdomyolysis,renal insufficiency, and a transient transaminase elevation. Ibrahim Med. Coll. J. 2011; 5(1: 34-36

  19. Endogenous versus exogenous lithium clearance for evaluation of dopamine-induced changes in renal tubular function

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Fogh-Andersen, N; Strandgaard, S

    1996-01-01

    1. The present randomized, double-blind cross-over study compared endogenous and exogenous lithium clearance (CLi) for estimation of the effect of dopamine on tubular sodium reabsorption. Twelve normal, salt-repleted male subjects were investigated on three different occasions with either placebo...... or 450 mg or 600 mg of lithium given in random order at 22.00 hours. After an overnight fast, renal clearance studies were performed during a 1 h baseline period and subsequently during the second hour of an infusion of 3 micrograms min-1 kg-1 of dopamine. 2. Baseline values of endogenous CLi.......3-31.0)% (P lithium increased the baseline sodium clearance (CNa), but glomerular filtration rate and urine flow rate remained unchanged. 3. Dopamine increased CNa to similar values on the three study days. CLi increased to 40.9 (35.5-46.5) ml/min (endogenous lithium, P

  20. Cleistanthus collinus induces type I distal renal tubular acidosis and type II respiratory failure in rats.

    Science.gov (United States)

    Maneksh, Delinda; Sidharthan, Anita; Kettimuthu, Kavithapriya; Kanthakumar, Praghalathan; Lourthuraj, Amala A; Ramachandran, Anup; Subramani, Sathya

    2010-06-01

    A water decoction of the poisonous shrub Cleistanthus collinus is used for suicidal purposes. The mortality rate is 28%. The clinical profile includes distal renal tubular acidosis (DRTA) and respiratory failure. The mechanism of toxicity is unclear. To demonstrate features of C. collinus toxicity in a rat model and to identify its mechanism(s) of action. Rats were anesthetized and the carotid artery was cannulated. Electrocardiogram and respiratory movements were recorded. Either aqueous extract of C. collinus or control solution was administered intraperitoneally. Serial measurements of blood gases, electrolytes and urinary pH were made. Isolated brush border and basolateral membranes from rat kidney were incubated with C. collinus extract and reduction in ATPase activity was assessed. Venous blood samples from human volunteers and rats were incubated with an acetone extract of C. collinus and plasma potassium was estimated as an assay for sodium-potassium pump activity. The mortality was 100% in tests and 17% in controls. Terminal event in test animals was respiratory arrest. Controls had metabolic acidosis, respiratory compensation acidic urine and hyperkalemia. Test animals showed respiratory acidosis, alkaline urine and low blood potassium as compared to controls. C. collinus extract inhibited ATPase activity in rat kidney. Plasma K(+) did not increase in human blood incubated with C. collinus extract. Active principles of C. collinus inhibit proton pumps in the renal brush border, resulting in type I DRTA in rats. There is no inhibition of sodium-potassium pump activity. Test animals develop respiratory acidosis, and the immediate cause of death is respiratory arrest.

  1. Altered regulation of renal sodium transporters in salt-sensitive hypertensive rats induced by uninephrectomy.

    Science.gov (United States)

    Jung, Ji Yong; Lee, Jay Wook; Kim, Sejoong; Jung, Eun Sook; Jang, Hye Ryoun; Han, Jin Suk; Joo, Kwon Wook

    2009-12-01

    Uninephrectomy (uNx) in young rats causes salt-sensitive hypertension (SSH). Alterations of sodium handling in residual nephrons may play a role in the pathogenesis. Therefore, we evaluated the adaptive alterations of renal sodium transporters according to salt intake in uNx-SSH rats. uNx or sham operations were performed in male Sprague-Dawley rats, and normal-salt diet was fed for 4 weeks. Four experimental groups were used: sham-operated rats raised on a high-salt diet for 2 weeks (CHH) or on a low-salt diet for 1 week after 1 week's high-salt diet (CHL) and uNx rats fed on the same diet (NHH, NHL) as the sham-operated rats were fed. Expression of major renal sodium transporters were determined by semiquantitative immunoblotting. Systolic blood pressure was increased in NHH and NHL groups, compared with CHH and CHL, respectively. Protein abundances of Na(+)/K(+)/2Cl(-) cotransporter (NKCC2) and Na(+)/Cl(-) cotransporter (NCC) in the CHH group were lower than the CHL group. Expression of epithelial sodium channel (ENaC)-γ increased in the CHH group. In contrast, expressions of NKCC2 and NCC in the NHH group didn't show any significant alterations, compared to the NHL group. Expressions of ENaC-α and ENaC-β in the NHH group were higher than the CHH group. Adaptive alterations of NKCC2 and NCC to changes of salt intake were different in the uNx group, and changes in ENaC-α and ENaC-β were also different. These altered regulations of sodium transporters may be involved in the pathogenesis of SSH in the uNx rat model.

  2. Microvesicles derived from human Wharton's Jelly mesenchymal stem cells ameliorate ischemia-reperfusion-induced renal fibrosis by releasing from G2/M cell cycle arrest.

    Science.gov (United States)

    Chen, Wenxia; Yan, Yongbin; Song, Chundong; Ding, Ying; Du, Tao

    2017-12-14

    Studies have demonstrated that microvesicles (MVs) derived from human Wharton's Jelly mesenchymal stromal cells (hWJMSCs) could ameliorate renal ischemia/reperfusion injury (IRI); however, the underlying mechanisms were not clear yet. Here, MVs were isolated and injected intravenously into rats immediately after ischemia of the left kidney, and Erk1/2 activator hepatocyte growth factor (HGF) or inhibitor U0126 was administrated. Tubular cell proliferation and apoptosis were identified by Ki67 or terminal-deoxynucleotidyl transferase-mediated nick end labeling immunostaining. Masson's tri-chrome straining and alpha-smooth muscle actin staining were used for assessing renal fibrosis. The mRNA or protein expression in the kidney was measured by quantitative reverse transcription-PCR or Western blot, respectively. The total collagen concentration was also determined. In vitro , NRK-52E cells that treated with MVs under hypoxia injury and with HGF or U0126 administration were used, and cell cycle analysis was performed. The effects of hWJMSC-MVs on enhancing the proliferation and mitigating the apoptosis of renal cells, abrogating IRI-induced fibrosis, improving renal function, decreasing collagen deposition, and altering the expression levels of epithelial-mesenchymal transition and cell cycle-related proteins in IRI rats were found. In vitro experiment showed that hWJMSC-MVs could induce G2/M cell cycle arrest and decrease the expression of collagen deposition-related proteins in NRK-52E cells after 24 or 48 h. However, U0126 treatment reversed these effects. In conclusion, MVs derived from hWJMSCs ameliorate IR-induced renal fibrosis by inducing G2/M cell cycle arrest via Erk1/2 signaling. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  3. Efficacy and safety of sugammadex in the reversal of deep neuromuscular blockade induced by rocuronium in patients with end-stage renal disease: A comparative prospective clinical trial.

    Science.gov (United States)

    de Souza, Camila M; Tardelli, Maria A; Tedesco, Helio; Garcia, Natalia N; Caparros, Mario P; Alvarez-Gomez, Jose A; de Oliveira Junior, Itamar S

    2015-10-01

    Renal failure affects the pharmacology of nondepolarizing neuromuscular blockers making recovery of neuromuscular function unpredictable. Sugammadex antagonises rocuronium-induced neuromuscular blockade by encapsulating rocuronium, creating a stable complex molecule that is mainly excreted by the kidneys. Previous studies suggest that sugammadex is effective in reversing moderate neuromuscular block in the presence of renal failure, but no data are available regarding reversal of profound neuromuscular block in patients with renal failure. The objective of this study is to compare the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in patients with end-stage renal disease and those with normal renal function. A prospective clinical trial. Two university hospitals, from 1 October 2011 to 31 January 2012. Forty patients undergoing kidney transplant: 20 with renal failure [creatinine clearance (ClCr) 90 ml min). Neuromuscular monitoring was performed by acceleromyography and train-of-four (TOF) stimulation. Profound neuromuscular block (posttetanic count, one to three responses) was maintained during surgery. Sugammadex 4 mg kg was administered on completion of skin closure. Recovery of the TOF ratio to 0.9 was recorded. Monitoring of neuromuscular function continued in the postanesthesia care unit for a further 2 h. The efficacy of sugammadex was evaluated by the time taken for the TOF ratio to recover to 0.9. The safety of sugammadex was assessed by monitoring for recurrence of neuromuscular block every 15 min for 2 h. Secondary variables were time to recovery of TOF ratio to 0.7 and 0.8. After sugammadex administration, the mean time for recovery of the TOF ratio to 0.9 was prolonged in the renal failure group (5.6 ± 3.6 min) compared with the control group (2.7 ± 1.3 min, P = 0.003). No adverse events or evidence of recurrence of neuromuscular block were observed. In patients with

  4. Renal tubular dysfunction nephrocalcinosis in a patient with BetaThalassemia Minor

    International Nuclear Information System (INIS)

    Prabahar, M.R.; Jain, M.; Chandrasekaran, V.; Indumathi, E.; Soundrarajan, P.

    2008-01-01

    Thalassemia is a hereditary anemia resulting from defect in hemoglobinproduction. Beta thalassemia is due to impaired production. Beta thalassemiais due to impaired production of beta globin chains, leading to a relativeexcess of alpha globin chains. The term beta thalassemia minor is used todescribe heterozygotes, who carry one normal beta globin and one betathalassemic allele. The vast majority of these patients are asymptomatic.However, a variety of renal tubular abnormalities including hypercaliuria,hypomagnesemia with renal magnesium wasting, decreased tubular absorption ofphosphorous, hypouricemia with renal uric acid wasting, renal glycosuria andtubular proteinuria have been described even in patients with betathalassemia minor. We here in report a 24-year old patient who was found tohave thalassemia minor and nephrocalcinosis with evidence of renal tubulardysfunction. Investigations revealed normal renal function, hypercalciuria,reduced tubular reabsorption of phosphorous, hypomagnesemia and renalmagnesium wasting. Screening for aminoaciduria was found to be negative. Anacid loading test revealed normal urinary acidification. Ultrasonogram of theabdomen revealed nephrocalcinosis and splenomegaly. Detailed work up foranemia showed normal white cell and platelet count while peripheral smearshowed microcytic hypochromic anemia with few target cells. Hemoglobinelectrophoresis revealed hemoglobin A of 92%, hemoglobin A2 of 6.2% andhemoglobin F of 1.8% consistent with beta thalassemia minor. Her parentalscreening was normal. A diagnosis of beta thalassemia minor with renaltubular dysfunction was made and the patient was started on thiazidediuretics to reduce hypercalciuria and advised regular follow-up. (author)

  5. Renal Epithelial Cell Injury Induced by Calcium Oxalate Monohydrate Depends on their Structural Features: Size, Surface, and Crystalline Structure.

    Science.gov (United States)

    Sun, Xin-Yuan; Ouyang, Jian-Ming; Gan, Qiong-Zhi; Liu, Ai-Jie

    2016-11-01

    Urinary crystals in normal and kidney stone patients often differ in crystal sizes and surface structures, but the effects of different crystal properties on renal tubular epithelial cells remain unclear. This study aimed to compare the cytotoxicity of micron/nano-calcium oxalate monohydrate (COM) crystals with sizes of 50 nm, 200 nm, 1 μm, 3 μm, and 10 μm to African green monkey renal epithelial (Vero) cells, to reveal the effect of crystal size and surface structure on cell injury, and to investigate the pathological mechanism of calcium oxalate kidney stones. Cell viability, cellular biochemical parameters, and internalized crystal amount in Vero cells were closely associated with the size of COM crystals. At the same concentration (200 μg/mL), COM-1 μm induced the most serious injury to Vero cells and caused the most significant change to cellular biochemical parameters, which were related to the specific porous structure and highest internalized amount in Vero cells. By contrast, COM-50 nm and COM-200 nm crystals lost their small size effect because of serious aggregation and weakened their toxicity to cells. COM-3 μm and COM-10 μm crystals were too large for cells to completely internalize; these crystals also exhibited a low specific surface area and thus weakened their toxicity. The excessive expression of intracellular ROS and reduction of the free-radical scavenger SOD were the main reasons for cell injury and eventually caused necrotic cell death. Crystal size, surface structure, aggregation, and internalization amount were closely related to the cytotoxicity of COM crystals.

  6. Protective effect of magnesium lactate gluconate and Garcinia cambogia fruit extract in experimentally induced renal calculi in rats

    Directory of Open Access Journals (Sweden)

    Ashishkumar Kyada

    2017-12-01

    Full Text Available Antiurolithiatic acitivity of magnesium lactate gluconate (MLG and aqueous extract of Garcinia cambogia (GC fruit was studied. Methods: Study was performed during December 2016 to April 2017. Urolithiasis was induced in male Wistar rats by administration of 0.75 % v/v ethylene glycol for 21 days. From 8th day onwards, intervention with MLG (200 and 400 mg/kg b.w. and GC (100 and 200 mg/kg b.w. was started. At the end of treatment period, biochemical parameters affecting renal stone formation were estimated in serum, urine, kidney homogenate and histopathology of harvested kidneys was performed. Results: From in vivo evaluation, it was observed that MLG 400 mg/kg b.w., GC 100 mg/kg b.w. and GC 200 mg/kg b.w. significantly reduced nitrogenous waste products in serum (blood urea nitrogen, creatinine, uric acid as well as calculogenic promoters in urine (phosphate, oxalate and kidney homogenate (calcium, phosphate, oxalate when compared to disease control animals. The MLG 200 and MLG 400 were ineffective in restoring superoxide dismutase (SOD and catalase (CAT enzyme activity whereas GC 100, GC 200 and Cystone® 400 mg/kg b.w. significantly elevated SOD and CAT enzymes in urolithiatic rat kidney. Conclusions: MLG and GC extract are capable of preventing calcium oxalate (CaOx crystal formation and subsequent deposition in renal tubules. The principle mechanism underlying nephroprotective effect of test drugs might be attributed to their calcium ion cheating ability and CaOx crystallization inhibitory activity. It is further asserted that GC was more potent than MLG in overall kidney protection by virtue of its antioxidant potential. [J Complement Med Res 2017; 6(4.000: 378-384

  7. Effect of mitochondrial potassium channel on the renal protection mediated by sodium thiosulfate against ethylene glycol induced nephrolithiasis in rat model

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    N. Baldev

    2015-12-01

    Full Text Available Purpose: Sodium thiosulfate (STS is clinically reported to be a promising drug in preventing nephrolithiasis. However, its mechanism of action remains unclear. In the present study, we investigated the role of mitochondrial KATP channel in the renal protection mediated by STS. Materials and Methods: Nephrolithiasis was induced in Wistar rats by administrating 0.4% ethylene glycol (EG along with 1% ammonium chloride for one week in drinking water followed by only 0.75% EG for two weeks. Treatment groups received STS, mitochondrial KATP channel opener and closer exclusively or in combination with STS for two weeks. Results: Animals treated with STS showed normal renal tissue architecture, supported by near normal serum creatinine, urea and ALP activity. Diazoxide (mitochondria KATP channel opening treatment to the animal also showed normal renal tissue histology and improved serum chemistry. However, an opposite result was shown by glibenclamide (mitochondria KATP channel closer treated rats. STS administered along with diazoxide negated the renal protection rendered by diazoxide alone, while it imparted protection to the glibenclamide treated rats, formulating a mitochondria modulated STS action. Conclusion: The present study confirmed that STS render renal protection not only through chelation and antioxidant effect but also by modulating the mitochondrial KATP channel for preventing urolithiasis.

  8. Protective role of cabbage extract versus cadmium-induced oxidative renal and thyroid hormones dysfunctions in rats

    International Nuclear Information System (INIS)

    FARAG, M. F. S.; OSMAN, N. N.; DARWISH, M.M.

    2011-01-01

    Cadmium (Cd) is an environmental and industrial pollutant that affects various organs in human and experimental animals. A body of evidence has accumulated implicating the free radical generation with subsequent oxidative stress in the biochemical and molecular mechanisms of Cd damage. Cabbage is economically an important cole crop grown and consumed worldwide. It belongs the Cruciferous vegetables (Brassica), which have been reported to have a wide range of pharmacological properties. Since kidney is the critical target organ of chronic Cd damage, we carried out this study to investigate the effects of cabbage extract (C.E.) on Cd-induced dysfunction in the kidney of rats. The thyroid hormones values were also determined. Male Wistar rats were provided with cadmium chloride (100 mg/ L water) as the only drinking fluid and/or cabbage extract (C.E.) (5 ml/ kg body weight /day) for 4 weeks. Oral administration of Cd significantly induced the renal damage which was evident from the significantly (p < 0.05) increased levels of serum urea, uric acid and creatinine with a significant (p < 0.05) decrease in creatinine clearance. It also significantly declined the levels of urea, uric acid and creatinine in urine. Intoxication of Cd to rats reduced serum triiodothyronine (T3) and thyroxine (T4) concentrations. Reduced glutathione (GSH), and enzymatic antioxidants (superoxide dismutase (SOD) and catalase (CAT) were also significantly (p < 0.05) depressed with a concomitant marked enhancement in lipid peroxidation marker (thiobarbituric acid reactive substances, TBARS). Co-administration of C.E. along with Cd resulted in a reversal of the Cd-induced biochemical variables in kidney accompanied by a significant reduction in lipid peroxidation and a higher levels of renal antioxidant defense system. However, incorporation of C.E. to rats whether applied alone or in combination with Cd did not reveal any change in the thyroid hormones levels, which reflect significant drop in

  9. Corosolic Acid Induces Non-Apoptotic Cell Death through Generation of Lipid Reactive Oxygen Species Production in Human Renal Carcinoma Caki Cells

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    Seon Min Woo

    2018-04-01

    Full Text Available Corosolic acid is one of the pentacyclic triterpenoids isolated from Lagerstroemia speciose and has been reported to exhibit anti-cancer and anti-proliferative activities in various cancer cells. In the present study, we investigated the molecular mechanisms of corosolic acid in cancer cell death. Corosolic acid induces a decrease of cell viability and an increase of cell cytotoxicity in human renal carcinoma Caki cells. Corosolic acid-induced cell death is not inhibited by apoptosis inhibitor (z-VAD-fmk, a pan-caspase inhibitor, necroptosis inhibitor (necrostatin-1, or ferroptosis inhibitors (ferrostatin-1 and deferoxamine (DFO. Furthermore, corosolic acid significantly induces reactive oxygen species (ROS levels, but antioxidants (N-acetyl-l-cysteine (NAC and trolox do not inhibit corosolic acid-induced cell death. Interestingly, corosolic acid induces lipid oxidation, and α-tocopherol markedly prevents corosolic acid-induced lipid peroxidation and cell death. Anti-chemotherapeutic effects of α-tocopherol are dependent on inhibition of lipid oxidation rather than inhibition of ROS production. In addition, corosolic acid induces non-apoptotic cell death in other renal cancer (ACHN and A498, breast cancer (MDA-MB231, and hepatocellular carcinoma (SK-Hep1 and Huh7 cells, and α-tocopherol markedly inhibits corosolic acid-induced cell death. Therefore, our results suggest that corosolic acid induces non-apoptotic cell death in cancer cells through the increase of lipid peroxidation.

  10. Antacid-induced hypermagnesemia in a patient with normal renal function and bowel obstruction.

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    McLaughlin, S A; McKinney, P E

    1998-03-01

    To report a case of severe hypermagnesemia caused by magnesium hydroxide in a woman with normal renal function. A 42-year-old Hispanic woman with schizophrenia and bipolar affective disorder was transported from jail to the emergency department with confusion, abdominal pain, vomiting, and constipation. She had been treated in jail with magnesium hydroxide, ordered as milk of magnesia 30 mL po each night and Maalox 30 mL po three times daily. Additional medications included lithium carbonate 300 mg po three times daily, chlorpromazine 150 mg po three times daily, benztropine mesylate 1 mg po twice daily, and docusate sodium 100 mg po each morning. Her temperature was 35.1 degrees C, blood pressure 108/58 mm Hg, heart rate 112 beats/min, and respiratory rate 24 breaths/min. She would respond only briefly to voice or painful stimuli. Her abdomen was distended and diffusely tender. Laboratory tests included serum magnesium concentration 9.1 mEq/L (normal 1.3-2), blood urea nitrogen 16 mg/dL (8-22), creatinine 0.9 mg/dL (0.5-1.1), calcium 3.9 mEq/L (4.2-5.2), and lithium 1.0 mEq/L. A laparotomy was performed, and an adhesive band from a previous oophorectomy was found to be compressing the sigmoid colon. Hypermagnesemia, hypothermia, and hypotension continued in the intensive care unit. Despite successful treatment of the hypermagnesemia with calcium, intravenous fluids, and furosemide, the patient's cardiac rhythm degenerated into fatal, pulseless electrical activity on postoperative day 2. This case of severe hypermagnesemia from magnesium hydroxide ingestion illustrates many of the risk factors for hypermagnesemia in patients with normal renal function. People using magnesium-containing medications for relief of gastrointestinal distress may be at increased risk for hypermagnesemia. A brief review of magnesium physiology, clinical effects, and treatment is provided. Frequent use of the laboratory to identify hypermagnesemia is encouraged because it is often a

  11. Protective effect of Petroselinum crispum extract in abortion using prostadin-induced renal dysfunction in female rats

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    Maryam Rezazad

    2014-09-01

    Full Text Available Objective: Present study investigated the effects of parsley extract on pregnant rat kidneys which have undergone clinical abortion using prostaglandins. The renal protective effect of parsley extract was evaluated in pregnant rats which had an abortion. Parsley was used due to its antioxidant properties. Materials and Methods:  Fifty-four female rats were divided in 9 groups of 6: control pregnant, two pregnant groups which received parsley extract and prostadin, two non-pregnant groups treated with parsley extract and prostadin, a group administered with both treatments, and three groups which received parsley extract in pre-implantation, implantation, and post-implantation periods of embryos. Ethanolic extract (5 mg/kg was given daily to animals for 18 days of pregnancy period. Parameters such as malondialdehyde (MDA, total antioxidant statues (TAS, creatinine, and urea were measured using biochemical assays. Histopathologic studies were also done with Hematoxylin-Eosin staining method. Results: After 18 days of treatment, significant differences were observed in serum creatinine, urea, and MDA and TAS levels. Kidney cross-sections showed edema in prostadin-treated rats while improvements in parsley + prostadin -treated rats were observed. Conclusion: These results suggested that ethanolic extract of Petroselinum crispum reduced the dysfunction in rats kidney caused by prostadin-induced abortion and could have beneficial effect in reducing the progression of prostaglandin-induced edema.

  12. Protective effect of hydroalcoholic extract of tribulus terrestris on cisplatin induced renal tissue damage in male mice

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    Amir Raoofi

    2015-01-01

    Full Text Available Background: According beneficial effects of Tribulus terrestris (TT extract on tissue damage, the present study investigated the influence of hydroalcoholic extract of TT plant on cisplatin (CIS (EBEWE Pharma, Unterach, Austria induced renal tissue damage in male mice. Methods: Thirty mice were divided into five groups (n = 6. The first group (control was treated with normal saline (0.9% NaCl and experimental groups with CIS (E1, CIS + 100 mg/kg extract of TT (E2, CIS + 300 mg/kg extract of TT (E3, CIS + 500 mg/kg extract of TT (E4 intraperitoneally. The kidneys were removed after 4 days of injections, and histological evaluations were performed. Results: The data were analyzed using one-way analysis of variance followed by Tukey′s post-hoc test, paired-sample t-test, Kruskal-Wallis and Mann-Whitney tests. In the CIS treated group, the whole kidney tissue showed an increased dilatation of Bowman′s capsule, medullar congestion, and dilatation of collecting tubules and a decreased in the body weight and kidney weight. These parameters reached to the normal range after administration of fruit extracts of TT for 4 days. Conclusions: The results suggested that the oral administration of TT fruit extract at dose 100, 300 and 500 mg/kg body weight provided protection against the CIS induced toxicity in the mice.

  13. Protective Effect of Hydroalcoholic Extract of Tribulus Terrestris on Cisplatin Induced Renal Tissue Damage in Male Mice

    Science.gov (United States)

    Raoofi, Amir; Khazaei, Mozafar; Ghanbari, Ali

    2015-01-01

    Background: According beneficial effects of Tribulus terrestris (TT) extract on tissue damage, the present study investigated the influence of hydroalcoholic extract of TT plant on cisplatin (CIS) (EBEWE Pharma, Unterach, Austria) induced renal tissue damage in male mice. Methods: Thirty mice were divided into five groups (n = 6). The first group (control) was treated with normal saline (0.9% NaCl) and experimental groups with CIS (E1), CIS + 100 mg/kg extract of TT (E2), CIS + 300 mg/kg extract of TT (E3), CIS + 500 mg/kg extract of TT (E4) intraperitoneally. The kidneys were removed after 4 days of injections, and histological evaluations were performed. Results: The data were analyzed using one-way analysis of variance followed by Tukey's post-hoc test, paired-sample t-test, Kruskal–Wallis and Mann–Whitney tests. In the CIS treated group, the whole kidney tissue showed an increased dilatation of Bowman's capsule, medullar congestion, and dilatation of collecting tubules and a decreased in the body weight and kidney weight. These parameters reached to the normal range after administration of fruit extracts of TT for 4 days. Conclusions: The results suggested that the oral administration of TT fruit extract at dose 100, 300 and 500 mg/kg body weight provided protection against the CIS induced toxicity in the mice. PMID:25789143

  14. Effect of methanolic fraction of Kalanchoe crenata on metabolic parameters in adriamycin-induced renal impairment in rats.

    Science.gov (United States)

    Kamgang, René; Foyet, Angèle F; Essame, Jean-Louis O; Ngogang, Jeanne Y

    2012-01-01

    To investigate the effect of Kalanchoe crenata methanolic fraction (MEKC) on proteinuria, glucosuria, and some other biochemical parameters in adriamycin-induced renal impairment in rats. Ether anesthetized rats received three intravenous injections (days 0, 14, and 28) of 2 mg/kg body weight of adriamycin. Repeated doses of the extract (0, 50, and 68 mg/kg b.w.) and losartan (10 mg/kg b.w.) were administered orally once daily, for 6 weeks, to these rats. Kidney functions were assessed through biochemical parameters. MEKC decreased proteinuria and also the urinary excretion of creatinine, glucose, and urea significantly in diseased rats. A decrease in serum levels of creatinine, urea, potassium, alkaline phosphatase, conjugate bilirubin, and alanine transaminase level was also recorded in nephropathic rats, but plasma levels of uric acid and glucose remained unchanged. Moreover, the plant extract markedly (P < 0.05) increased plasma sodium and decreased (P < 0.01) the urinary sodium and potassium levels. The results indicated that the treatment with the methanolic fraction of K. crenata may improve proteinuria and all other symptoms due to adriamycin-induced nephropathy and, more than losartan, could ameliorate kidney and liver functions. K. crenata could be a potential source of new oral antinephropathic drug.

  15. Protective effect of hydroalcoholic extract of tribulus terrestris on Cisplatin induced renal tissue damage in male mice.

    Science.gov (United States)

    Raoofi, Amir; Khazaei, Mozafar; Ghanbari, Ali

    2015-01-01

    According beneficial effects of Tribulus terrestris (TT) extract on tissue damage, the present study investigated the influence of hydroalcoholic extract of TT plant on cisplatin (CIS) (EBEWE Pharma, Unterach, Austria) induced renal tissue damage in male mice. Thirty mice were divided into five groups (n = 6). The first group (control) was treated with normal saline (0.9% NaCl) and experimental groups with CIS (E1), CIS + 100 mg/kg extract of TT (E2), CIS + 300 mg/kg extract of TT (E3), CIS + 500 mg/kg extract of TT (E4) intraperitoneally. The kidneys were removed after 4 days of injections, and histological evaluations were performed. The data were analyzed using one-way analysis of variance followed by Tukey's post-hoc test, paired-sample t-test, Kruskal-Wallis and Mann-Whitney tests. In the CIS treated group, the whole kidney tissue showed an increased dilatation of Bowman's capsule, medullar congestion, and dilatation of collecting tubules and a decreased in the body weight and kidney weight. These parameters reached to the normal range after administration of fruit extracts of TT for 4 days. The results suggested that the oral administration of TT fruit extract at dose 100, 300 and 500 mg/kg body weight provided protection against the CIS induced toxicity in the mice.

  16. A case of gabapentin-induced rhabdomyolysis requiring renal replacement therapy.

    Science.gov (United States)

    Choi, Min Seok; Jeon, Howook; Kim, Hyo Suk; Jang, Bo Hyun; Lee, Yoon Hee; Park, Hoon Suk; Kim, HyungWook; Jin, Dong Chan

    2017-01-01

    Gabapentin is commonly used for controlling convulsions, restless pain syndrome, and pain in diabetic neuropathy. Common side effects include dizziness, somnolence, ataxia, peripheral edema, and confusion; gabapentin-induced rhabdomyolysis is rarely reported. To date, the reported cases of gabapentin-induced rhabdomyolysis have been associated with patients with multiple underlying diseases and assuming multiple medicines for various reasons. In this report, we describe a case of gabapentin-induced rhabdomyolysis in a 32-year-old woman with no medical history. We also review related literature and discuss the possible mechanism and the association with other factors. This case shows that gabapentin can induce rhabdomyolysis in healthy patients and that clinicians must consider the possible association between gabapentin and rhabdomyolysis. © 2016 International Society for Hemodialysis.

  17. Nephroprotective effects of b-carotene on ACE gene expression, oxidative stress and antioxidant status in thioacetamide induced renal toxicity in rats.

    Science.gov (United States)

    Fazal, Yumna; Fatima, Syeda Nuzhat; Shahid, Syed Muhammad; Mahboob, Tabassum

    2016-07-01

    β -carotene is one of carotenoid natural pigments, which are produced by plants and are accountable for the bright colors of various fruits and vegetables. These pigments have been widely studied for their ability to prevent chronic diseases and toxicities. This study was designed to evaluate the effects of β-carotene on angiotensin converting enzyme (ACE) gene expression, oxidative stress and antioxidant status in thioacetamide induced renal toxicity. Total 24 albino wistar rats of male sex (200-250gm) were divided into 6 groups as Group-1: The control remained untreated; Group-2: Received thioacetamide (200mg/kg b.w; i.p) for 12 weeks; Group-3: Received β-carotene orally (200mg/kg b.w), for 24 weeks; and Group-4: Received thioacetamide (200mg/kg b.w; i.p) for 12 weeks + received β-carotene orally (200mg/kg b.w), for further 12 weeks. The expression of ACE gene in thioacetamide induced renal toxicity in rats as well as supplemented with β-carotene was investigated and compared their level with control groups by using the quantitative RT-PCR method. The ACE gene expression was significantly increase in TAA rats as compare to control rats specifies that TAA induced changes in ACE gene of kidney, elevated renal ACE has been correlated with increase hypertensive end organ renal damage. The quantity of ACE gene were diminish in our rats who received β-Carotene after TAA is administered, for this reason they seemed to be defended against increased ACE levels in kidney bought by TAA. In pre- and post-treatment groups, we studied the role of β-Carotene against thioacetamide in the kidney of Wistar rats. Experimental confirmation from our study illustrates that β-Carotene can certainly work as a successful radical-trapping antioxidant our results proved that TAA injury increased lipid peroxidation and diminish antioxidant GSH, SOD and CAT in renal tissue. Since β-Carotene administration recover renal lipid peroxidation and antioxidants, it give the impression that

  18. Calcineurin inhibitor-induced complement system activation via ERK1/2 signalling is inhibited by SOCS-3 in human renal tubule cells.

    Science.gov (United States)

    Loeschenberger, Beatrix; Niess, Lea; Würzner, Reinhard; Schwelberger, Hubert; Eder, Iris E; Puhr, Martin; Guenther, Julia; Troppmair, Jakob; Rudnicki, Michael; Neuwirt, Hannes

    2018-02-01

    One factor that significantly contributes to renal allograft loss is chronic calcineurin inhibitor (CNI) nephrotoxicity (CIN). Among other factors, the complement (C-) system has been proposed to be involved CIN development. Hence, we investigated the impact of CNIs on intracellular signalling and the effects on the C-system in human renal tubule cells. In a qPCR array, CNI treatment upregulated C-factors and downregulated SOCS-3 and the complement inhibitors CD46 and CD55. Additionally, ERK1/-2 was required for these regulations. Following knock-down and overexpression of SOCS-3, we found that SOCS-3 inhibits ERK1/-2 signalling. Finally, we assessed terminal complement complex formation, cell viability and apoptosis. Terminal complement complex formation was induced by CNIs. Cell viability was significantly decreased, whereas apoptosis was increased. Both effects were reversed under complement component-depleted conditions. In vivo, increased ERK1/-2 phosphorylation and SOCS-3 downregulation were observed at the time of transplantation in renal allograft patients who developed a progressive decline of renal function in the follow-up compared to stable patients. The progressive cohort also had lower total C3 levels, suggesting higher complement activity at baseline. In conclusion, our data suggest that SOCS-3 inhibits CNI-induced ERK1/-2 signalling, thereby blunting the negative control of C-system activation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. MicroRNA-200a-3p suppresses tumor proliferation and induces apoptosis by targeting SPAG9 in renal cell carcinoma

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    Wang, Xinsheng; Jiang, Fuquan; Song, Haitao; Li, Xu; Xian, Jiantao; Gu, Xinquan, E-mail: guxqprofessor@163.com

    2016-02-12

    Sperm-associated antigen 9(SPAG9), as a well-recognized oncogene protein, has a critical effect on renal cell carcinoma (RCC) progression. Our study tried to explore the mediator of miR-200a-3p, a tumor suppressing miRNA on SPAG9 expression and renal cell proliferation and apoptosis. We found the expression of miR-200a-3p was significantly lower in RCC specimens. Based on in vitro assays, we found miR-200a-3p significantly inhibit cancer cell proliferation by inducing apoptosis. In addition, our study uncovered that miR-200a-3p directly regulates oncogenic SPAG9 in 786-O and ACHN cells. Silencing of SPAG9 resulted in significantly decreased in the growth and the cell cycle of the renal cancer cell lines. Understanding of oncogenic SPAG9 regulated by miR-200a-3p might be beneficial to reveal new therapeutic targets for RCC. - Highlights: • MiR-200a-3p is downregulated in renal cell carcinoma. • MiR-200a-3p regulates cell proliferation through inducing apoptosis. • MiR-200a-3p is involved in cell cycle regulation. • SPAG9 is a potential target of miR-200a-3p.

  20. Conversion to Sirolimus Ameliorates Cyclosporine-Induced Nephropathy in the Rat: Focus on Serum, Urine, Gene, and Protein Renal Expression Biomarkers

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    José Sereno

    2014-01-01

    Full Text Available Protocols of conversion from cyclosporin A (CsA to sirolimus (SRL have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear. This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model. Four animal groups (n=6 were tested during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks. Classical and emergent serum, urinary, and kidney tissue (gene and protein expression markers were assessed. Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF-β, NF-κβ, mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF-β and IL-7, TBARs clearance, and kidney TGF-β and mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent/mild grade lesions, while NGAL (serum versus urine seems to be a feasible biomarker of CsA replacement to SRL.

  1. Duration of streptozotocin-induced diabetes differentially affects p38-mitogen-activated protein kinase (MAPK phosphorylation in renal and vascular dysfunction

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    Gupta Akanksha

    2005-03-01

    Full Text Available Abstract Background In the present study we tested the hypothesis that progression of streptozotocin (STZ-induced diabetes (14-days to 28-days would produce renal and vascular dysfunction that correlate with altered p38- mitogen-activated protein kinase (p38-MAPK phosphorylation in kidneys and thoracic aorta. Methods Male Sprague Dawley rats (350–400 g were randomized into three groups: sham (N = 6, 14-days diabetic (N = 6 and 28-days diabetic rats (N = 6. Diabetes was induced using a single tail vein injection of STZ (60 mg/kg, I.V. on the first day. Rats were monitored for 28 days and food, water intake and plasma glucose levels were noted. At both 14-days and 28-days post diabetes blood samples were collected and kidney cortex, medulla and aorta were harvested from each rat. Results The diabetic rats lost body weight at both 14-days (-10% and 28-days (-13% more significantly as compared to sham (+10% group. Glucose levels were significantly elevated in the diabetic rats at both 14-days and 28-days post-STZ administration. Renal dysfunction as evidenced by renal hypertrophy, increased plasma creatinine concentration and reduced renal blood flow was observed in 14-days and 28-days diabetes. Vascular dysfunction as evidenced by decreased carotid blood flow was observed in 14-days and 28-days diabetes. We observed an up-regulation of inducible nitric oxide synthase (iNOS, prepro endothelin-1 (preproET-1 and phosphorylated p38-MAPK in thoracic aorta and kidney cortex but not in kidney medulla in 28-days diabetes group. Conclusion The study provides evidence that diabetes produces vascular and renal dysfunction with a profound effect on signaling mechanisms at later stage of diabetes.

  2. Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of renal (pro)renin receptor and intrarenal renin-angiotensin system.

    Science.gov (United States)

    Wang, Lei; Zhu, Qing; Lu, Aihua; Liu, Xiaofen; Zhang, Linlin; Xu, Chuanming; Liu, Xiyang; Li, Haobo; Yang, Tianxin

    2017-09-01

    Butyrate, a short-chain fatty acid, is the end product of the fermentation of complex carbohydrates by the gut microbiota. Recently, sodium butyrate (NaBu) has been found to play a protective role in a number of chronic diseases. However, it is still unclear whether NaBu has a therapeutic potential in hypertension. The present study was aimed to investigate the role of NaBu in angiotensin II (Ang II)-induced hypertension and to further explore the underlying mechanism. Ang II was infused into uninephrectomized Sprague-Dawley rats with or without intramedullary infusion of NaBu for 14 days. Mean arterial blood pressure was recorded by the telemetry system. Renal tissues, serum samples, and 24-h urine samples were collected to examine renal injury and the regulation of the (pro)renin receptor (PRR) and renin. Intramedullary infusion of NaBu in Sprague-Dawley rats lowered the Ang II-induced mean arterial pressure from 129 ± 6 mmHg to 108 ± 4 mmHg (P renal injury, including urinary albumin, glomerulosclerosis, and renal fibrosis, as well as the expression of inflammatory mediators tumor necrosis factor α, interleukin 6. The renal expression of PRR, angiotensinogen, angiotensin I-converting enzyme and the urinary excretion of soluble PRR, renin, and angiotensinogen were all increased by Ang II infusion but decreased by NaBu treatment. In cultured innermedullary collecting duct cells, NaBu treatment attenuated Ang II-induced expression of PRR and renin. These results demonstrate that NaBu exerts an antihypertensive action, likely by suppressing the PRR-mediated intrarenal renin-angiotensin system.

  3. Curcumin prevents cisplatin-induced renal alterations in mitochondrial bioenergetics and dynamic.

    Science.gov (United States)

    Ortega-Domínguez, Bibiana; Aparicio-Trejo, Omar Emiliano; García-Arroyo, Fernando E; León-Contreras, Juan Carlos; Tapia, Edilia; Molina-Jijón, Eduardo; Hernández-Pando, Rogelio; Sánchez-Lozada, Laura Gabriela; Barrera-Oviedo, Diana; Pedraza-Chaverri, José

    2017-09-01

    Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types of cancer, however, acute kidney injury (AKI) is an important side effect of this treatment. Diverse mechanisms have been involved in cisplatin-induced AKI, such as oxidative stress, apoptosis and mitochondrial damage. On the other hand, curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous studies have shown that curcumin protects against the cisplatin-induced AKI; however, it is unknown whether curcumin can reduce alterations in mitochondrial bioenergetics and dynamic in this model. It was found that curcumin prevents cisplatin-induced: (a) AKI and (b) alterations in the following mitochondrial parameters: bioenergetics, ultrastructure, hydrogen peroxide production and dynamic. In fact, curcumin prevented the increase of mitochondrial fission 1 protein (FIS1), the decrease of optic atrophy 1 protein (OPA1) and the decrease of NAD + -dependent deacetylase sirtuin-3 (SIRT3), a mitochondrial dynamic regulator as well as the increase in the mitophagy associated proteins parkin and phosphatase and tensin homologue (PTEN)-induced putative kinase protein 1 (PINK1). In conclusion, the protective effect of curcumin in cisplatin-induced AKI was associated with the prevention of the alterations in mitochondrial bioenergetics, ultrastructure, redox balance, dynamic, and SIRT3 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Sinomenine alleviates high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the activation of RhoA/ROCK signaling pathway

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    Yin, Qingqiao [Renal Department of Internal Medicine, The Third Hospital of Wuhan (China); Xia, Yuanyu, E-mail: xiayuanyu.wh@gmail.com [Renal Department of Internal Medicine, The Third Hospital of Wuhan (China); Wang, Guan [Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University (China)

    2016-09-02

    As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression in HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders.

  5. Sinomenine alleviates high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the activation of RhoA/ROCK signaling pathway.

    Science.gov (United States)

    Yin, Qingqiao; Xia, Yuanyu; Wang, Guan

    2016-09-02

    As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression in HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Dragon (Repulsive Guidance Molecule RGMb) Inhibits E-cadherin Expression and Induces Apoptosis in Renal Tubular Epithelial Cells*

    Science.gov (United States)

    Liu, Wenjing; Li, Xiaoling; Zhao, Yueshui; Meng, Xiao-Ming; Wan, Chao; Yang, Baoxue; Lan, Hui-Yao; Lin, Herbert Y.; Xia, Yin

    2013-01-01

    Dragon is one of the three members of the repulsive guidance molecule (RGM) family, i.e. RGMa, RGMb (Dragon), and RGMc (hemojuvelin). We previously identified the RGM members as bone morphogenetic protein (BMP) co-receptors that enhance BMP signaling. Our previous studies found that Dragon is highly expressed in the tubular epithelial cells of mouse kidneys. However, the roles of Dragon in renal epithelial cells are yet to be defined. We now show that overexpression of Dragon increased cell death induced by hypoxia in association with increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 levels in mouse inner medullary collecting duct (IMCD3) cells. Dragon also inhibited E-cadherin expression but did not affect epithelial-to-mesenchymal transition induced by TGF-β in IMCD3 cells. Previous studies suggest that the three RGM members can function as ligands for the receptor neogenin. Interestingly, our present study demonstrates that the Dragon actions on apoptosis and E-cadherin expression in IMCD3 cells were mediated by the neogenin receptor but not through the BMP pathway. Dragon expression in the kidney was up-regulated by unilateral ureteral obstruction in mice. Compared with wild-type mice, heterozygous Dragon knock-out mice exhibited 45–66% reduction in Dragon mRNA expression, decreased epithelial apoptosis, and increased tubular E-cadherin expression and had attenuated tubular injury after unilateral ureteral obstruction. Our results suggest that Dragon may impair tubular epithelial integrity and induce epithelial apoptosis both in vitro and in vivo. PMID:24052264

  7. Dragon (repulsive guidance molecule RGMb) inhibits E-cadherin expression and induces apoptosis in renal tubular epithelial cells.

    Science.gov (United States)

    Liu, Wenjing; Li, Xiaoling; Zhao, Yueshui; Meng, Xiao-Ming; Wan, Chao; Yang, Baoxue; Lan, Hui-Yao; Lin, Herbert Y; Xia, Yin

    2013-11-01

    Dragon is one of the three members of the repulsive guidance molecule (RGM) family, i.e. RGMa, RGMb (Dragon), and RGMc (hemojuvelin). We previously identified the RGM members as bone morphogenetic protein (BMP) co-receptors that enhance BMP signaling. Our previous studies found that Dragon is highly expressed in the tubular epithelial cells of mouse kidneys. However, the roles of Dragon in renal epithelial cells are yet to be defined. We now show that overexpression of Dragon increased cell death induced by hypoxia in association with increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 levels in mouse inner medullary collecting duct (IMCD3) cells. Dragon also inhibited E-cadherin expression but did not affect epithelial-to-mesenchymal transition induced by TGF-β in IMCD3 cells. Previous studies suggest that the three RGM members can function as ligands for the receptor neogenin. Interestingly, our present study demonstrates that the Dragon actions on apoptosis and E-cadherin expression in IMCD3 cells were mediated by the neogenin receptor but not through the BMP pathway. Dragon expression in the kidney was up-regulated by unilateral ureteral obstruction in mice. Compared with wild-type mice, heterozygous Dragon knock-out mice exhibited 45-66% reduction in Dragon mRNA expression, decreased epithelial apoptosis, and increased tubular E-cadherin expression and had attenuated tubular injury after unilateral ureteral obstruction. Our results suggest that Dragon may impair tubular epithelial integrity and induce epithelial apoptosis both in vitro and in vivo.

  8. Signal Transduction Pathways Involved in Brain Death-Induced Renal Injury

    NARCIS (Netherlands)

    Bouma, H. R.; Ploeg, R. J.; Schuurs, T. A.

    Kidneys derived from brain death organ donors show an inferior survival when compared to kidneys derived from living donors. Brain death is known to induce organ injury by evoking an inflammatory response in the donor. Neuronal injury triggers an inflammatory response in the brain, leading to

  9. Renal and endocrine changes in rats with inherited stress-induced arterial hypertension (ISIAH)

    DEFF Research Database (Denmark)

    Amstislavsky, Sergej; Welker, Pia; Frühauf, Jan-Henning

    2006-01-01

    Hypertensive inbred rats (ISIAH; inherited stress-induced arterial hypertension) present with baseline hypertension (>170 mmHg in adult rats), but attain substantially higher values upon mild emotional stress. We aimed to characterize key parameters related to hypertension in ISIAH. Kidneys, adre...

  10. Fungal secondary metabolites rasfonin induces autophagy, apoptosis and necroptosis in renal cancer cell line

    Directory of Open Access Journals (Sweden)

    Hui Sun

    2016-04-01

    Full Text Available Rasfonin (A304 is a fungal natural product isolated from the fermentation substrate of Talaromyces sp. 3656-A1, which was named according to its activity against the small G-protein Ras. In a former study, we demonstrated that it induced autophagy and apoptosis; however, whether rasfonin activated necroptosis remained unknown. Moreover, the interplay among different cell death processes induced by rasfonin was unexplored. In the present study, we revealed that, in addition of promoting autophagy and caspase-dependent apoptosis, rasfonin also activated necroptosis. Nectrostatin-1 (Nec-1, an inhibitor of necroptosis, affected rasfonin-induced autophagy in a time-dependent manner concurring with an increased caspase-dependent apoptosis. The aforementioned results were confirmed by knockdown of receptor-interacting protein 1 (RIP1, a crucial necrostatin-1-targeted adaptor kinase mediating cell death and survival. Taken together, the data presented indicate that rasfonin activates various cell death pathways, and RIP1 plays a critical role in rasfonin-induced autophagy and apoptosis.

  11. [Executive summary of the recommendations on the evaluation and management of renal disease in human immunodeficiency virus-infected patients].

    Science.gov (United States)

    Gorriz, José L; Gutiérrez, Félix; Trullàs, Joan C; Arazo, Piedad; Arribas, Jose R; Barril, Guillermina; Cervero, Miguel; Cofán, Frederic; Domingo, Pere; Estrada, Vicente; Fulladosa, Xavier; Galindo, María J; Gràcia, Sílvia; Iribarren, José A; Knobel, Hernando; López-Aldeguer, José; Lozano, Fernando; Martínez-Castelao, Alberto; Martínez, Esteban; Mazuecos, Maria A; Miralles, Celia; Montañés, Rosario; Negredo, Eugenia; Palacios, Rosario; Pérez-Elías, María J; Portilla, Joaquín; Praga, Manuel; Quereda, Carlos; Rivero, Antonio; Santamaría, Juan M; Sanz, José; Sanz, Jesús; Miró, José M

    2014-11-01

    The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in human immunodeficiency virus (HIV)-infected patients. Renal function should be monitored in all HIV-infected patients. The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glycosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir, or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indications for and evaluation and management of dialysis and renal transplantation are also addressed. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  12. Beneficial Effect of Paljeong-san Pharmacopuncture Treatment Combined with Peritoneal Injection on Glycerol-Induced Acute Renal Failure in Rabbits

    Directory of Open Access Journals (Sweden)

    Chi-Yeon Lim

    2010-09-01

    Full Text Available Purpose: The present study was carried out to determine if Paljeong-san extract (PJS treatment exerts beneficial effect against the glycerol-induced acute renal failure in rabbits. Material and Method: PJS was selected in the basis of invigorating kidney which can eliminate pathogens. Rabbits were treated with PJS pharmacopuncture on Shin-shu (BL23 point for 5 days right after the injection of 50% concentration of glycerol (5㎖/㎏ body weight. Results and Conclusions: Glycerol injection caused an increase in serum creatinine and BUN level and urine glucose secretion, which were accompanied by a reduction in GFR. PJS Pharmacopuncture treatment combined with peritoneal injection showed beneficial effect on glycerol-induced acute renal failure by inhibition of serum creatinine increase and GFR decrease.

  13. Low functional programming of renal AT{sub 2}R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

    Energy Technology Data Exchange (ETDEWEB)

    Ao, Ying [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071 (China); Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Li, Bin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Yang, Shuailong; Xia, Liping; Wu, Yong [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Wang, Linlong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); He, Zheng [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071 (China)

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT{sub 2}R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT{sub 1a}R)/AT{sub 2}R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT{sub 2}R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT{sub 2}R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine

  14. Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

    International Nuclear Information System (INIS)

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-01-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT 2 R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT 1a R)/AT 2 R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT 2 R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT 2 R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine exposure inhibits

  15. Gender difference following high cholesterol diet induced renal injury and the protective role of rutin and ascorbic acid combination in Wistar albino rats

    OpenAIRE

    Al-Rejaie, Salim Salih; Abuohashish, Hatem Mustafa; Alkhamees, Osama Abdelrahman; Aleisa, Abdulaziz Mohammed; Alroujayee, Abdulaziz S

    2012-01-01

    Abstract Background An increased interest is given to the impact of high fat diet on health worldwide. Abnormalities in lipid metabolism induced by high cholesterol diet (HCD) were reported to exacerbate renal diseases via oxidative stress pathways. Rutin and ascorbic acid showed a protective role against oxidative stress-mediated diseases. Furthermore, both lipid metabolism and tissue response to oxidative stress damage was found to vary according to animal gender. Thus, the objective of thi...

  16. Low-dose dexamethasone-supplemented fluid resuscitation reverses endotoxin-induced acute renal failure and prevents cortical microvascular hypoxia

    NARCIS (Netherlands)

    Johannes, Tanja; Mik, Egbert G.; Klingel, Karin; Dieterich, Hans-Jürgen; Unertl, Klaus E.; Ince, Can

    2009-01-01

    There is growing evidence that impairment in intrarenal oxygenation and hypoxic injury might contribute to the pathogenesis of septic renal failure. An important molecule known to act on the renal microvascular tone and therefore consequently being involved in the regulation of intrarenal oxygen

  17. Mitochondrial bioenergetics during the initiation of mercuric chloride-induced renal activity. II. Functional alterations of renal cortical mitochondria isolated after mercuric chloride treatment

    Energy Technology Data Exchange (ETDEWEB)

    Weinberg, J.M. (Veterans Administration Medical Center, Ann Arbor, MI); Harding, P.G.; Humes, H.D.

    1982-01-01

    The mitochondrial functional defects occurring in the early stages of nephrotoxic renal injury secondary to mercuric chloride have been characterized. No loss of cellular integrity or major mitochondrial structural alterations occurred within the first 3 hr after a subcutaneous injection of 5 mg/kg of HgCl/sub 2/. At 3 h, levels of Hg/sup 2 +/ in renal cortex and isolated renal cortical mitochondria were 1.87 and 0.72 nmol/mg of protein, respectively. Much evidence suggested that this Hg/sup 2 +/ had reached the mitochondria in situ and not during the isolation process. Mitochondria isolated beginning 1 h after treatment with HgCl/sub 2/ showed depressed ADP uptake. At 2 h, inhibitions of State 3 and 2,4-dinitrophenol uncoupled respiration were detected. Inhibition of 2,4-dinitrophenol-activated mitochondrial ATPase activity was present when measured on mitochondria isolated at 3 h. These effects were not reversed by 2 mM dithioerythritol, 50 mg/ml of albumin or 5 mM MgCl/sub 2/. Analysis of the data in the context of information available on the in vitro effects of HgCl/sub 2/ (Weinberg, J.M., Harding, P.G., and Humes, H.D. (1982) J. Biol. Chem. 257, 60-67) indicated that the mitochondrial functional effects could not be attributed to interaction of the mitochondria with Hg/sup 2 +/ during their isolation. These studies implicate compromised mitochondrial bioenergetic function as one of the earliest intracellular effects of Hg/sup 2 +/ in the production of nephrotoxicity but suggest that the intracellular process involves events in addition to those seen with direct exposure of mitochondria to Hg/sup 2 +/ in vitro.

  18. MiR-30c regulates cisplatin-induced apoptosis of renal tubular epithelial cells by targeting Bnip3L and Hspa5.

    Science.gov (United States)

    Du, Bin; Dai, Xiao-Meng; Li, Shuang; Qi, Guo-Long; Cao, Guang-Xu; Zhong, Ying; Yin, Pei-di; Yang, Xue-Song

    2017-08-10

    As a common anticancer drug, cisplatin has been widely used for treating tumors in the clinic. However, its side effects, especially its nephrotoxicity, noticeably restrict the application of cisplatin. Therefore, it is imperative to investigate the mechanism of renal injury and explore the corresponding remedies. In this study, we showed the phenotypes of the renal tubules and epithelial cell death as well as elevated cleaved-caspase3- and TUNEL-positive cells in rats intraperitoneally injected with cisplatin. Similar cisplatin-induced cell apoptosis was found in HK-2 and NRK-52E cells exposed to cisplatin as well. In both models of cisplatin-induced apoptosis in vivo and in vitro, quantitative PCR data displayed reductions in miR-30a-e expression levels, indicating that miR-30 might be involved in regulating cisplatin-induced cell apoptosis. This was further confirmed when the effects of cisplatin-induced cell apoptosis were found to be closely correlated with alterations in miR-30c expression, which were manipulated by transfection of either the miR-30c mimic or miR-30c inhibitor in HK-2 and NRK-52E cells. Using bioinformatics tools, including TargetScan and a gene expression database (Gene Expression Omnibus), Adrb1, Bnip3L, Hspa5 and MAP3K12 were predicted to be putative target genes of miR-30c in cisplatin-induced apoptosis. Subsequently, Bnip3L and Hspa5 were confirmed to be the target genes after determining the expression of these putative genes following manipulation of miR-30c expression levels in HK-2 cells. Taken together, our current experiments reveal that miR-30c is certainly involved in regulating the renal tubular cell apoptosis induced by cisplatin, which might supply a new strategy to minimize cisplatin-induced nephrotoxicity.

  19. Total glucosides of paeony attenuate renal tubulointerstitial injury in STZ-induced diabetic rats: role of Toll-like receptor 2.

    Science.gov (United States)

    Zhang, Wei; Zhao, Li; Su, Shuang-Quan; Xu, Xing-Xin; Wu, Yong-Gui

    2014-01-01

    Accumulating evidence suggested that macrophages induce tubulointerstitial injury. Total glucosides of paeony (TGP), extracted from Paeonia lactiflora, has presented anti-inflammatory activities in diabetic kidney disease. This research will investigate the protective effect of TGP on renal tubulointerstitium and its mechanism in streptozotocin-induced diabetic rats. TGP was administered orally at a dose of 50, 100, and 200 mg·kg(-1)·d(-1) for 8 weeks. Tubulointerstitial injury was quantified, followed by immunohistochemistry analysis of renal α-smooth muscle actin (α-SMA), E-cadherin (E-cad) expression, nuclear factor kappa B (NF-κB)-p-p-65(+), Toll-like receptor (TLR)2(+), and ED-1(+) cell infiltration in renal tubulointerstitium. Renal TLR2(+) macrophages were detected by double immunohistochemical staining. Western blotting was used to detect the TLR2 expression. Histologically, there was marked accumulation of TLR2(+), NF-κB-p-p-65(+), ED-1(+) cells, and ED-1(+)TLR2(+) cells (macrophages) in the diabetic kidney and TGP treatment could alleviate it. Accompanying with that, the tubulointerstitial injury was ameliorated, α-SMA expression was lower, and E-cad expression was higher compared with the diabetic rats. Western blot analysis showed that the expression of TLR2 protein was significantly increased in the kidney of the diabetic rats, whereas TGP treatment reduced it. Our study showed that TGP could prevent renal tubulointerstitium injury in diabetic rats through a mechanism that may be at least partly correlated with suppression of increased macrophage infiltration and the expression of TLR2.

  20. Protective Effect of Carvacrol on Renal Functional and Histopathological Changes in Gentamicin-Induced-Nephrotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Hassan Ahmadvand

    2016-04-01

    Full Text Available Background Nephrotoxicity is one of the most important side effects of the use of gentamicin sulphate (GS resulted in reactive oxygen species generation. Antioxidant compounds played effective roles in reduction of renal injuries caused by using of gentamicin. Carvacrol is a strong antioxidant compound. Objectives The aim of this study is to explore the effect of carvacrol inhibition in lesions of gentamicin-induced nephrotoxicity. Materials and Methods In this experimental study, 32 male mature Sprague-Dawley rats were divided into 4 groups of 8; group1: control, group 2 sham received daily carvacrol injection (74 mg/kg for 12 days, group 3 received daily GS injection (100 mg/kg for 12 days, group 4 received daily GS (100 mg/kg and carvacrol (74 mg/kg for 12 days. After 12 days, rats were anaesthetized, blood sample were obtained and kidneys were removed then stained with hematoxylin and eosin method and then were studied histophatologically. Serum creatinine and urea were measured. Results Flow treatment of nephrotoxic animals with carvacrol could significantly inhibit leukocyte infiltration (9.42% and tubular necrosis (38.18% in comparison with the nephrotoxic untreated group. Carvacrol significantly decreased the levels of urea and creatinine in treated group compared with the nephrotoxic untreated group. Conclusions The findings showed that carvacrol alleviates loss of leukocyte infiltration (9.42% and tubular necrosis and exerts beneficial effects on kidney function test in nephrotoxic group.

  1. Letrozole induced low estrogen levels affected the expressions of duodenal and renal calcium-processing gene in laying hens.

    Science.gov (United States)

    Li, Qiao; Zhao, Xingkai; Wang, Shujie; Zhou, Zhenlei

    2018-01-01

    Estrogen regulates the calcium homeostasis in hens, but the mechanisms involved are still unclear fully. In this study, we investigated whether letrozole (LZ) induced low estrogen levels affected the calcium absorption and transport in layers. In the duodenum, we observed a significant decrease of mRNA expressions of Calbindin-28k (CaBP-28k) and plasma membrane Ca 2+ -ATPase (PMCA 1b) while CaBP-28k protein expression was declined in birds with LZ treatment, and the mRNA levels of duodenal transient receptor potential vanilloid 6 (TRPV6) and Na + /Ca 2+ exchanger 1 (NCX1) were not affected. Interestingly, we observed the different changes in the kidney. The renal mRNA expressions of TRPV6 and NCX1 were unregulated while the PMCA1b was down-regulated in low estrogen layers, however, the CaBP-28k gene and protein expressions were no changed in the kidney. Furthermore, it showed that the duodenal estradiol receptor 2 (ESR2) transcripts rather than parathyroid hormone 1 receptor (PTH1R) and calcitonin receptor (CALCR) played key roles to down-regulate calcium transport in LZ-treated birds. In conclusion, CaBP-28k, PMCA 1b and ESR2 genes in the duodenum may be primary targets for estrogen regulation in order to control calcium homeostasis in hens. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Differential changes in functional activity of organic cation transporters in rats with uranyl nitrate-induced acute renal failure.

    Science.gov (United States)

    Maeng, Han-Joo; Shim, Won-Sik; Ahn, Sun-Joo; Yu, Sang-Soo; Kim, Dae-Duk; Shim, Chang-Koo; Chung, Suk-Jae

    2012-08-01

    We studied the impact of experimental kidney failure on the pharmacokinetics of a model organic cation and investigated the underlying mechanism(s) of the organic cation transporters. The systemic pharmacokinetics and tissue distribution of triethylmethylammonium (TEMA), a model organic cation, were characterized after intravenous doses of 0.3-30 μmol/kg in rats with or without uranyl nitrate-induced acute renal failure (UN-ARF). To study the effect of endogenous substrates in plasma from UN-ARF rats on organic cation transport, rOCT- or rOCT2-dependent uptake of tetraethylammonium (TEA) was studied in rOCT1-transfected or rOCT2-transfected LLC-PK1 cells, respectively. As a result, the AUC for TEMA was increased, probably because of decreased total clearance, and the tissue-to-plasma concentration ratio (T/P ratio) of TEMA was unchanged in the liver but decreased significantly in the kidneys of UN-ARF rats. In vitro, the uptake of TEA was decreased significantly by adding UN-ARF plasma, compared with control plasma, in rOCT2-overexpressing LLC-PK1 cells, but not in rOCT1-overexpressing LLC-PK1 cells. These observations suggest that the induction of UN-ARF leads to an accumulation of endogenous organic cation(s), probably rOCT2 substrate(s), in the plasma, thereby affecting the TEMA pharmacokinetics and distribution to the kidneys in rats.

  3. Limited Link between Oxidative Stress and Ochratoxin A—Induced Renal Injury in an Acute Toxicity Rat Model

    Directory of Open Access Journals (Sweden)

    Liye Zhu

    2016-12-01

    Full Text Available Ochratoxin A (OTA displays nephrotoxicity and hepatotoxicity. However, in the acute toxicity rat model, there is no evidence on the relationship between OTA and nephrotoxicity and hepatotoxicity. Based on this, the integrated analysis of physiological status, damage biomarkers, oxidative stress, and DNA damage were performed. After OTA treatment, the body weight decreased and AST, ALP, TP, and BUN levels in serum increased. Hydropic degeneration, swelling, vacuolization, and partial drop occurred in proximal tubule epithelial cells. PCNA and Kim-1 were dose-dependently increased in the kidney, but Cox-2 expression and proliferation were not found in the liver. In OTA-treated kidneys, the mRNA expressions of Kim-1, Cox-2, Lcn2, and Clu were dose-dependently increased. The mRNA expressions of Vim and Cox-2 were decreased in OTA-treated livers. Some oxidative stress indicators were altered in the kidneys (ROS and SOD and livers (SOD and GSH. DNA damage and oxidative DNA damage were not found. In conclusion, there is a limited link between oxidative stress and OTA-induced renal injury in an acute toxicity rat model.

  4. Renal Kallikrein Activation and Renoprotection after Dual Blockade of Renin-Angiotensin System in Diet-Induced Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Xia Zou

    2015-01-01

    Full Text Available Purpose. The objective of this study is to investigate the effect of dual blockage of renin-angiotensin system (RAS on renal kallikrein expression and inflammatory response in diabetic nephropathy (DN. Methods. Rats were randomly divided into 5 groups with 10 rats in each group: normal control; DN model induced by high fat and high sucrose diets; and DN treated with either benazepril 10 mg/kg/d, irbesartan 30 mg/kg/d, or both. After 8-week treatment, we examined changes in the kidney histopathology, function and immunohistochemical stain of kallikrein, macrophage marker CD68, and profibrotic markers transforming growth factor- (TGF- β and α-smooth muscle action (SMA. Results. DN rats showed enlarged kidneys with glomerulosclerosis, interstitial chronic inflammation and fibrosis, and proteinuria. All the pathological damage and functional impairments were improved after the RAS blockades (all P<0.05. Compared with monotherapy, combined treatment further alleviated the kidney impairments in parallel to increased tubular immunoreactivity for kallikrein and decreased immunopositive cells for CD68, TGF-β, and α-SMA. Conclusion. The renoprotective effects of the dual RAS blockade in diabetic nephropathy may be attributed to improved tubular kallikrein expression and interstitial inflammatory response.

  5. Imoxin attenuates high fructose-induced oxidative stress and apoptosis in renal epithelial cells via downregulation of protein kinase R pathway.

    Science.gov (United States)

    Kalra, Jaspreet; Mangali, Suresh Babu; Bhat, Audesh; Dhar, Indu; Udumula, Mary Priyanka; Dhar, Arti

    2018-02-11

    Double-stranded RNA (dsRNA)-activated protein kinase R (PKR), a ubiquitously expressed serine/threonine kinase, is a key inducer of inflammation, insulin resistance, and glucose homeostasis in obesity. Recent studies have demonstrated that PKR can respond to metabolic stress in mice as well as in humans. However, the underlying molecular mechanism is not fully understood. The aim of this study was to examine the effect of high fructose (HF) in cultured renal tubular epithelial cells (NRK-52E) derived from rat kidney and to investigate whether inhibition of PKR could prevent any deleterious effects of HF in these cells. PKR expression was determined by immunofluorescence staining and Western blotting. Oxidative damage and apoptosis were measured by flow cytometry. HF-treated renal cells developed a significant increase in PKR expression. A significant increase in reactive oxygen species generation and apoptosis was also observed in HF-treated cultured renal epithelial cells. All these effects of HF were attenuated by a selective PKR inhibitor, imoxin (C16). In conclusion, our study demonstrates PKR induces oxidative stress and apoptosis, is a significant contributor involved in vascular complications and is a possible mediator of HF-induced hypertension. Inhibition of PKR pathway can be used as a therapeutic strategy for the treatment of cardiovascular and metabolic disorders. © 2018 Société Française de Pharmacologie et de Thérapeutique.

  6. [Decursin reduces reactive oxygen species and inhibits cisplatin-induced apoptosis in rat renal tubular epithelial cells].

    Science.gov (United States)

    Li, Cuiqiong; Li, Jianchun; Fan, Junming; Meng, Lifeng; Cao, Ling

    2017-10-01

    Objective To study the mechanism underlying the inhibitory effect of decursin on the apoptosis of rat renal tubular epithelial cells NRK-52E induced by cisplatin. Methods First, CCK-8 assay was used to detect the effects of 0, 10, 20, 40, 80, 100, 150, 200 μmol/L decursin and 0, 5, 10, 20, 30, 40, 50 μg/mL cispatin treatment for 24 hours on cell proliferation in NRK-52E cells via determining the half inhibitory concentration (IC 50 ). Then, NRK-52E cells were stimulated with 20 μg/mL cisplatin combined with 10, 50, 100 μmol/L decursin, and cell activity was detected by CCK-8 assay. The cells were divided into normal control group, 20 μg/mL cisplatin stimulation group, and 10, 50, 100 μmol/L decursin treated groups. Cell morphological changes was observed under inverted microscope, morphological changes of nucleus was detected by DAPI staining, cell apoptosis was detected by flow cytometry, the level of intracellular ROS was detected by DCFH-DA staining, and the apoptosis marker proteins cleaved-caspase-3 and cleaved-PARP were examined by Western blot analysis. Results Compared with the normal control group, cisplatin significantly inhibited the activity of the cells, and IC 50 was about 20 μg/mL; compared with the model group, in the decursin pretreatment groups, the level of intracellular ROS decreased remarkably, the expressions of cleaved-casspase-3 and cleaved-PARP proteins were reduced, and cell apoptosis was depressed. Conclusion Decursin can decrease the intracellular ROS level and inhibit the apoptosis of NRK-52E cells induced by cisplatin.

  7. Renal Function in Hypothyroidism

    International Nuclear Information System (INIS)

    Khalid, S.; Khalid, M; Elfaki, M.; Hassan, N.; Suliman, S.M.

    2007-01-01

    Background Hypothyroidism induces significant changes in the function of organ systems such as the heart, muscles and brain. Renal function is also influenced by thyroid status. Physiological effects include changes in water and electrolyte metabolism, notably hyponatremia, and reliable alterations of renal hemodynamics, including decrements in renal blood flow, renal plasma flow, glomerular filtration rate (GFR). Objective Renal function is profoundly influenced by thyroid status; the purpose of the present study was to determine the relationship between renal function and thyroid status of patients with hypothyroidism. Design and Patients In 5 patients with primary hypothyroidism and control group renal functions are measured by serum creatinine and glomerular filtration rate (GFR) using modified in diet renal disease (MDRD) formula. Result In hypothyroidism, mean serum creatinine increased and mean estimated GFR decreased, compared to the control group mean serum creatinine decreased and mean estimated GFR Increased. The hypothyroid patients showed elevated serum creatinine levels (> 1.1mg/dl) compared to control group (p value .000). In patients mean estimated GFR decreased, compared to mean estimated GFR increased in the control group (p value= .002).

  8. Renal Function in Hypothyroidism

    International Nuclear Information System (INIS)

    Khalid, A. S; Ahmed, M.I; Elfaki, H.M; Hassan, N.; Suliman, S. M.

    2006-12-01

    Background hypothyroidism induces significant changes in the function of organ systems such as the heart, muscles and brain. Renal function is also influenced by thyroid status. Physiological effects include changes in water and electrolyte metabolism, notably hyponatraemia, and reliable alterations of renal hemodynamics, including decrements in renal blood flow, renal plasma flow, glomerular filtration rate (GFR). Objective renal function is profoundly influenced by thyroid status, the purpose of the present study was to determine the relationship between renal function and thyroid status of patients with hypothyroidism. Design and patients in 5 patients with primary hypothyroidism and control group renal functions are measured by serum creatinine and glomerular filtration rate(GFR) using modified in diet renal disease (MDRD) formula. Result in hypothyroidism, mean serum creatinine increased and mean estimated GFR decreased, compared to the control group mean serum creatinine decreased and mean estimated GFR increased. The hypothyroid patients showed elevated serum creatinine levels(>1.1 mg/d1) compared to control group (p value= 000). In patients mean estimated GFR increased in the control group (p value=.002).Conclusion thus the kidney, in addition to the brain, heart and muscle, is an important target of the action of thyroid hormones.(Author)

  9. Urinary proteomic profiling reveals diclofenac-induced renal injury and hepatic regeneration in mice

    Energy Technology Data Exchange (ETDEWEB)

    Swelm, Rachel P.L. van [Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Laarakkers, Coby M.M. [Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Pertijs, Jeanne C.L.M.; Verweij, Vivienne; Masereeuw, Rosalinde [Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Russel, Frans G.M., E-mail: F.Russel@pharmtox.umcn.nl [Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands)

    2013-06-01

    Diclofenac (DF) is a widely used non-steroidal anti-inflammatory drug for the treatment of rheumatic disorders, but is often associated with liver injury. We applied urinary proteomic profiling using MALDI-TOF MS to identify biomarkers for DF-induced hepatotoxicity in mice. Female CH3/HeOUJIco mice were treated with 75 mg/kg bw DF by oral gavage and 24 h urine was collected. Proteins identified in urine of DF-treated mice included epidermal growth factor, transthyretin, kallikrein, clusterin, fatty acid binding protein 1 and urokinase, which are related to liver regeneration but also to kidney injury. Both organs showed enhanced levels of oxidative stress (TBARS, p < 0.01). Kidney injury was confirmed by histology and increased Kim1 and Il-6 mRNA expression levels (p < 0.001 and p < 0.01). Liver histology and plasma ALT levels in DF-treated mice were not different from control, but mRNA expression of Stat3 (p < 0.001) and protein expression of PCNA (p < 0.05) were increased, indicating liver regeneration. In conclusion, urinary proteome analysis revealed that DF treatment in mice induced kidney and liver injury. Within 24 h, however, the liver was able to recover by activating tissue regeneration processes. Hence, the proteins found in urine of DF-treated mice represent kidney damage rather than hepatic injury. - Highlights: • The urinary proteome shows biological processes involved in adverse drug reactions. • Urine proteins of DF-treated mice relate to kidney injury rather than liver injury. • Liver regeneration, not liver injury, is apparent 24h after oral DF administration. • Pretreatment with LPS does not enhance DF-induced liver injury in mice.

  10. Structural transition of kidney cystatin in dimethylnitrosamine-induced renal cancer in rats: identification as a novel biomarker for kidney cancer and prognosis.

    Science.gov (United States)

    Shamsi, Anas; Ahmed, Azaj; Bano, Bilqees

    2017-04-01

    In our study, renal cancer is induced in rats making use of dimethylnitrosamine (DMN). G1 - Group 1 were control rats and G2 - Group 2 rats were given a single intra-peritoneal injection of DMN of 50 mg/kg body weight resulting in 100% incidences of renal tumors after 12 months. SEM and histopathology confirmed the presence of renal cancer in the DMN-treated rats. Making use of ammonium sulfate precipitation and gel filtration chromatography on Sephacryl S-100HR column, a thiol protease inhibitor was isolated from kidney of control rats known as Rat kidney Cystatin (RKC) as well as from kidney of cancerous rat called as Cancerous Rat Kidney Cystatin (CRKC). Both these inhibitors were characterized, and interestingly, it was found that CRKC showed greater anti-papain activity and also it was stable in a broad pH and temperature range thus implying that CRKC is more stable as compared to RKC. UV and fluorescence spectroscopy point out in structural difference between RKC and CRKC which was further confirmed by Circular dichroism (CD) and FTIR spectroscopy. Our study clearly showed that kidney cystatin is structurally modified in the case of renal cancer and performs its role in a more efficacious manner.

  11. Magnesium Lithospermate B from Salvia miltiorrhiza Bunge Ameliorates Aging-Induced Renal Inflammation and Senescence via NADPH Oxidase-Mediated Reactive Oxygen Generation.

    Science.gov (United States)

    Park, Chan Hum; Shin, Sung Ho; Lee, Eun Kyeong; Kim, Dae Hyun; Kim, Min-Jo; Roh, Seong-Soo; Yokozawa, Takako; Chung, Hae Young

    2017-05-01

    The present study was conducted to examine whether magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix was renoprotective in pathways related to age-related oxidative stress in aged rats. Magnesium lithospermate B was orally administered at a dose of 2- or 8-mg/kg body weight for 16 consecutive days, and the effects were compared with those of vehicle in old and young rats. Magnesium lithospermate B administration to old rats ameliorated renal oxidative stress through reduction of reactive oxygen species. The old rats exhibited a dysregulation of the expression of proteins related to oxidative stress and inflammation in the kidneys, and MLB administration significantly reduced the protein expression of major subunits of nicotinamide adenine dinucleotide phosphate oxidase (Nox4 and p22 phox ), phospho-p38, nuclear factor-kappa B p65, cyclooxygenase-2, and inducible nitric oxide synthase. In addition, MLB-treated old rats showed lower levels of senescence-related proteins such as p16, ADP-ribosylation factor 6, p53, and p21 through effects on the mitogen-activated protein kinase pathway. Magnesium lithospermate B administration also significantly attenuated the age-related increase in serum urea nitrogen, reflecting renal dysfunction, up-regulated podocyte structural proteins, and reduced renal structural injury. Our results provide important evidence that MLB reduces the renal damage of oxidative stress in old rats. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Effect of ipsilateral ureteric obstruction on contralateral kidney and role of renin angiotensin system blockade on renal recovery in experimentally induced unilateral ureteric obstruction

    Directory of Open Access Journals (Sweden)

    Shasanka S Panda

    2013-01-01

    Full Text Available Aims: To study, the effects of ipsilateral ureteric obstruction on contralateral kidney and the role of renin angiotensin system (RAS blockade on renal recovery in experimentally induced unilateral ureteric obstruction. Materials and Methods: Unilateral upper ureteric obstruction was created in 96 adult Wistar rats that were reversed after pre-determined intervals. Losartan and Enalapril were given to different subgroups of rats following relief of obstruction. Results: The severity of dilatation on the contralateral kidney varied with duration of ipsilateral obstruction longer the duration more severe the dilatation. There is direct correlation between renal parenchymal damage, pelvi-ureteric junction (PUJ fibrosis, inflammation and severity of pelvi-calyceal system dilatation of contralateral kidney with duration of ipsilateral PUJ obstruction. Conclusions: Considerable injury is also inflicted to the contralateral normal kidney while ipsilateral kidney remains obstructed. Use of RAS blocking drugs has been found to significantly improve renal recovery on the contralateral kidney. It can, thus, be postulated that contralateral renal parenchymal injury was mediated through activation of RAS.

  13. Renal Osteodystrophy

    Directory of Open Access Journals (Sweden)

    Aynur Metin Terzibaşoğlu

    2004-12-01

    Full Text Available Chronic renal insufficiency is a functional definition which is characterized by irreversible and progressive decreasing in renal functions. This impairment is in collaboration with glomeruler filtration rate and serum creatinine levels. Besides this, different grades of bone metabolism disorders develop in chronic renal insufficiency. Pathologic changes in bone tissue due to loss of renal paranchyme is interrelated with calcium, phosphorus vitamine-D and parathyroid hormone. Clinically we can see high turnover bone disease, low turnover bone disease, osteomalacia, osteosclerosis and osteoporosis in renal osteodystropy. In this article we aimed to review pathology of bone metabolism disorders due to chronic renal insufficiency, clinic aspects and treatment approaches briefly.

  14. RF Ablation of Giant Hemangiomas Inducing Acute Renal Failure: A Report of Two Cases

    Energy Technology Data Exchange (ETDEWEB)

    Tilborg, Aukje A. J. M. van, E-mail: a.vantilborg@vumc.nl [VU University Medical Center, Departments of Radiology and Nuclear Medicine (Netherlands); Dresselaars, Helena F. [VU University Medical Center, Department of Nefrology (Netherlands); Scheffer, Hester J. [VU University Medical Center, Departments of Radiology and Nuclear Medicine (Netherlands); Nielsen, Karin [VU University Medical Center (Netherlands); Sietses, Colin [Gelderse Vallei Hospital, Department of Surgical Oncology (Netherlands); Tol, Petrousjka M. van den [VU University Medical Center (Netherlands); Meijerink, Martijn R. [VU University Medical Center, Departments of Radiology and Nuclear Medicine (Netherlands)

    2016-11-15

    ObjectiveIn patients that require treatment for hepatic giant cavernous hemangiomas (GCH), radiofrequency ablation (RFA) has been suggested to represent a safe and effective alternative to invasive surgery. In a recent report of bipolar RFA, using two expandable needle electrodes, was uneventfully performed in patients with large GCH (>10 cm). The objective of this report is to present two cases in which bipolar RFA of symptomatic GCH was complicated by acute kidney injury.Materials and methodsIn 2015 we treated two patients for very large symptomatic GCH (15.7 and 25.0 cm) with bipolar RFA during open laparotomy.ResultsIn both patients the urine showed a red–brown discoloration directly after the ablation. They became anuric and presented with progressive dyspnea, tachypnea, and tachycardia, requiring hemodialysis for a period of 1 month in one case. Lab results revealed hemepigment-induced acute kidney. Both patients fully recovered and both showed a complete relief of symptoms at 3 months following the procedure.ConclusionRFA for large GCHs can cause hemepigment-induced acute kidney injury due to massive intravascular hemolysis. The presented cases suggest that caution is warranted and advocate an upper limit regarding the volume of GCHs that can be safely ablated.

  15. Protective Effect of Royal Jelly against Renal Damage in Streptozotocin Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Elham Ghanbari

    2015-03-01

    Full Text Available Background: Royal jelly has been shown to have antioxidant and antidiabetic effects. The objective of this study was to evaluate the protective effect of RJ against kidney damage in streptozotocin induced diabetic rats. Methods: Thirty two male Wistar rats were divided randomly into four groups (n=8 per group. Normal control and diabetic control groups received 1cc/day distilled water, normal RJ-treated and diabetic RJ-treated groups received 100mg RJ/kg body weight daily. Diabetes was induced by intraperitoneal injection of streptozotocin. At the end of the experiment, urine and kidney samples were collected for biochemical and histopathological analysis. Results: The results showed that diabetes could increase levels of urine urea, total protein and albumin significantly, and could decrease the levels of creatinine and uric acid in urine. In the kidney tissue homogenates, catalase activity and antioxidant power were significantly lower, whereas malondialdehyde levels were significantly higher in diabetic group when compared with control group. Diabetic rats showed severe histological changes in kidney tissues. Treatment of diabetic rats with RJ improved significantly all of these parameters. Conclusion: The present study revealed that treatment with RJ resulted in significant improvement in histopathological alterations in kidney tissue and urine parameters of diabetic rats. This could be due to its antioxidant activity and the ability of RJ for scavenging the free radicals released in diabetes. These findings suggest that RJ has protective effects on kidneys affected by diabetes mellitus.

  16. Renal excretion of prostaglandin metabolites, arginine vasopressin, and sodium during endotoxin and endogenous pyrogen induced fever in the goat.

    Science.gov (United States)

    Jónasson, H; Basu, S; Andersson, B; Kindahl, H

    1984-04-01

    Responses to intravenous injections of an endotoxin (E. coli-lipopolysaccharide, 1 microgram/kg b.wt.) and endogenous pyrogen were studied in euhydrated and hyperhydrated goats. The biphasic febrile response to the endotoxin was associated with a pronounced increase in the renal excretion of measured prostaglandin (PG) metabolites (11-ketotetranor PGF metabolites). This increase was time-correlated with the elevation of the rectal temperature, and (in hyperhydrated animals) with an inhibition of the water diuresis and an increase in renal excretion of arginine vasopressin (AVP). Other effects of the endotoxin were an immediate depression of renal Na and K excretion followed by the development of pronounced natriuresis, and a reduction of plasma Fe and Zn concentrations. The appearance of the febrile reactions (peripheral vasoconstriction and shivering) was accompanied by miosis. The maximum elevation of the rectal temperature was significantly greater during euhydration than during hyperhydration. Also endogenous pyrogen elicited miosis concomitant with febrile reactions, and an elevation of the renal excretion of PG metabolites which was closely correlated in time with the monophasic febrile response, and (during hyperhydration) with temporary inhibition of the water diuresis and an increase in the renal AVP excretion. However, the responses were much weaker than the corresponding endotoxin effects. No appreciable changes in renal excretion of Na and K were observed in response to the endogenous pyrogen. It is concluded that the observed effects on renal cation excretion were manifestations of direct endotoxin influences on kidney function.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. The Role of Biotransformation and Oxidative Stress in 3,5-Dichloroaniline (3,5-DCA) Induced Nephrotoxicity in Isolated Renal Cortical Cells from Male Fischer 344 Rats

    Science.gov (United States)

    Racine, Christopher R.; Ferguson, Travis; Preston, Debbie; Ward, Dakota; Ball, John; Anestis, Dianne; Valentovic, Monica; Rankin, Gary O.

    2016-01-01

    Among the mono- and dichloroanilines, 3,5-Dichloroaniline (3,5-DCA) is the most potent nephrotoxicant in vivo and in vitro. However, the role of renal biotransformation in 3,5-DCA induced nephrotoxicity is unknown. The current study was designed to determine the in vitro nephrotoxic potential of 3,5-DCA in isolated renal cortical cells (IRCC) obtained from male Fischer 344 rats, and the role of renal bioactivation and oxidative stress in 3,5-DCA nephrotoxicity. IRCC (~4 million cells/ml) from male rats were exposed to 3,5-DCA (0-1.0 mM) for up to 120 min. In IRCC, 3,5-DCA was cytotoxic at 1.0 mM by 60 min as evidenced by the increased release of lactate dehydrogenase (LDH), but 120 min was required for 3,5-DCA 0.5 mM to increase LDH release. In subsequent studies, IRCC were exposed to a pretreatment (antioxidant or enzyme inhibitor) prior to exposure to 3,5-DCA (1.0 mM) for 90 min. Cytotoxicity induced by 3,5-DCA was attenuated by pretreatment with inhibitors of flavin-containing monooxygenase (FMO; methimazole, N-octylamine), cytochrome P450 (CYP; piperonyl butoxide, metyrapone), or peroxidase (indomethacin, mercaptosuccinate) enzymes. Use of more selective CYP inhibitors suggested that the CYP 2C family contributed to 3,5-DCA bioactivation. Antioxidants (glutathione, N-acetyl-L-cysteine, α-tocopherol, ascorbate, pyruvate) also attenuated 3,5-DCA nephrotoxicity, but oxidized glutathione levels and the oxidized/reduced glutathione ratios were not increased. These results indicate that 3,5-DCA may be activated via several renal enzyme systems to toxic metabolites, and that free radicals, but not oxidative stress, contribute to 3,5-DCA induced nephrotoxicity in vitro. PMID:26808022

  18. JBP485 improves gentamicin-induced acute renal failure by regulating the expression and function of Oat1 and Oat3 in rats

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Xinjin [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Meng, Qiang; Liu, Qi; Wang, Changyuan; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian Medical University, Liaoning (China); Kaku, Taiichi [Japan Bioproducts Industry Co. Ltd., Tomigaya, Shibuya-ku, Tokyo (Japan); Liu, Kexin, E-mail: kexinliu@dlmedu.edu.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian Medical University, Liaoning (China)

    2013-09-01

    We investigated the effects of JBP485 (an anti-inflammatory dipeptide and a substrate of OAT) on regulation of the expression and function of renal Oat1 and Oat3, which can accelerate the excretion of accumulated uremic toxins (e.g. indoxyl sulfate) in the kidney to improve gentamicin-induced ARF in rats. JBP485 caused a significant decrease in the accumulation of endogenous substances (creatinine, blood urea nitrogen and indoxyl sulfate) in vivo, an increase in the excretion of exogenous compounds (lisinopril and inulin) into urine, and up-regulation of the expressions of renal Oat1 and Oat3 in the kidney tissues and slices via substrate induction. To determine the effect of JBP485 on the accelerated excretion of uremic toxins mediated by Oat1 and Oat3, the mRNA and protein expression levels of renal basolateral Oats were assessed by quantitative real-time PCR, western blot, immunohistochemical analysis and an immunofluorescence method. Gentamicin down-regulated the expression of Oats mRNA and protein in rat kidney, and these effects were reversed after administration of JBP485. In addition, JBP485 caused a significant decrease in MPO and MDA levels in the kidney, and improved the pathological condition of rat kidney. These results indicated that JBP485 improved acute renal failure by increasing the expression and function of Oat1 and Oat3, and by decreasing overoxidation of the kidney in gentamicin-induced ARF rats. - Highlights: • JBP485 could up-regulate function and expression of Oat1 and Oat3 in kidney. • Effects of JBP485 on ARF are mediated by stimulating excretion of uremic toxins. • JBP485 protected against gentamicin-induced ARF by decreasing MPO and MDA.

  19. DHEA-induced modulation of renal gluconeogenesis, insulin sensitivity and plasma lipid profile in the control- and dexamethasone-treated rabbits. Metabolic studies.

    Science.gov (United States)

    Kiersztan, Anna; Nagalski, Andrzej; Nalepa, Paweł; Tempes, Aleksandra; Trojan, Nina; Usarek, Michał; Jagielski, Adam K

    2016-02-01

    In view of antidiabetic and antiglucocorticoid effects of dehydroepiandrosterone (DHEA) both in vitro and in vivo studies were undertaken: (i) to elucidate the mechanism of action of both dexamethasone phosphate (dexP) and DHEA on glucose synthesis in primary cultured rabbit kidney-cortex tubules and (ii) to investigate the influence of DHEA on glucose synthesis, insulin sensitivity and plasma lipid profile in the control- and dexP-treated rabbits. Data show, that in cultured kidney-cortex tubules dexP significantly stimulated gluconeogenesis by increasing flux through fructose-1,6-bisphosphatase (FBPase). DexP-induced effects were dependent only upon glucocorticoid receptor. DHEA decreased glucose synthesis via inhibition of glucose-6-phosphatase (G6Pase) and suppressed the dexP-induced stimulation of renal gluconeogenesis. Studies with the use of inhibitors of DHEA metabolism in cultured renal tubules showed for the first time that DHEA directly affects renal gluconeogenesis. However, in view of analysis of glucocorticoids and DHEA metabolites levels in urine, it seems likely, that testosterone may also contribute to DHEA-evoked effects. In dexP-treated rabbits, plasma glucose level was not altered despite increased renal and hepatic FBPase and G6Pase activities, while a significant elevation of both plasma insulin and HOMA-IR was accompanied by a decline of ISI index. It thus appears that increased insulin levels were required to maintain normoglycaemia and to compensate the insulin resistance. DHEA alone affected neither plasma glucose nor lipid levels, while it increased insulin sensitivity and diminished both renal and hepatic G6Pase activities. Surprisingly, DHEA co-administrated with dexP did not alter insulin sensitivity, while it partially suppressed the dexP-induced elevation of renal G6Pase activity and plasma cholesterol and triglyceride contents. As (i) gluconeogenic pathway in rabbit is similar to that in human, and (ii) DHEA counteracts several

  20. Effect of corn silk extract on acetaminophen induced renal damage in mice

    International Nuclear Information System (INIS)

    Mehboob, F.; Tahir, M.

    2015-01-01

    To evaluate the protective role of Corn Silk extract on Acetaminophen induced nephrotoxicity in albino mice. Study Design: Laboratory based randomized controlled trials. Place and Duration of Study: The study was carried out in experimental research laboratory University of Health Sciences and Anatomy department, Lahore. The study duration was one year from February 2012 to February 2013. Material and Methods: Twenty seven male albino mice, 6-8 weeks old weighing 30 + 5 gm, were used; these animals were randomly divided into three groups having nine mice in each group. Group A served as control and was given 16.6ml/kg normal saline intraperitoneally on first day of experiment and was sacrificed on 10th day of the experiment. Group B was treated with acetaminophen 600 mg/kg dissolved in 16.6 ml of normal saline intraperitoneally on 1st day of experiment and was sacrificed after 48 hours. Group C was given acetaminophen at a dose of 600 mg/kg intraperitoneally on first day of experiment and then corn silk extract was given by oral route at a dose of 400 mg/kg for next 8 days. The animals were sacrificed on 10th day of the experiment, the kidneys were removed; 3mm three tissue pieces were fixed in 10% formaline; processed and stained with H and E for histological study. Results: It was observed on microscopic examination that Corn silk extract reduced deleterious effects of acetaminophen on tubules of kidney as evidenced by reduction of tubular vacuolation and necrosis, absence of protein casts, vascular congestion and inflammation. Conclusion: It is concluded from current results that corn silk extract protects acetaminophen induced nephrotoxicity. (author)

  1. Renal venogram

    Science.gov (United States)

    ... be black. Other structures will be shades of gray. Veins are not normally seen in an x- ... Venogram - kidney; Renal vein thrombosis - venogram Images Kidney anatomy Kidney - blood and urine flow Renal veins References ...

  2. A novel chalcone derivative attenuates the diabetes-induced renal injury via inhibition of high glucose-mediated inflammatory response and macrophage infiltration

    International Nuclear Information System (INIS)

    Fang, Qilu; Zhao, Leping; Wang, Yi; Zhang, Yali; Li, Zhaoyu; Pan, Yong; Kanchana, Karvannan; Wang, Jingying; Tong, Chao; Li, Dan; Liang, Guang

    2015-01-01

    Inflammation plays a central role in the development and progression of diabetic nephropathy (DN). Researches on novel anti-inflammatory agents may offer new opportunities for the treatment of DN. We previously found a chalcone derivative L6H21 could inhibit LPS-induced cytokine release from macrophages. The aim of this study was to investigate whether L6H21 could ameliorate the high glucose-mediated inflammation in NRK-52E cells and attenuate the inflammation-mediated renal injury. According to the results, L6H21 showed a great inhibitory effect on the expression of pro-inflammatory cytokines, cell adhesion molecules, chemokines, and macrophage adhesion via down-regulation of NF-κB/MAPKs activity in high glucose-stimulated renal NRK-52E cells. Further, in vivo oral administration with L6H21 at a dosage of 20 mg/kg/2 days showed a decreased expression of pro-inflammatory cytokines, cell adhesion molecules, which subsequently contributed to the inhibition on renal macrophage infiltration, the reduction of serum creatinine and BUN levels, and the improvement on the fibrosis and pathological changes in the renal tissues of diabetic mice. These findings provided that chalcone derived L6H21 may be a promising anti-inflammatory agent and have the potential in the therapy of diabetic nephropathy, and importantly, MAPK/NF-κB signaling system may be a novel therapeutic target for human DN in the future. - Highlights: • Inflammation plays a central role in the development of diabetic nephropathy. • Compound L6H21 reduced the high glucose-mediated inflammation in NRK-52E cells. • Compound L6H21 attenuated the inflammation-mediated renal injury. • L6H21 exhibited anti-inflammatory effects via inactivation of NF-κB/MAPKs. • MAPKs/NF-κB may be a novel therapeutic target in diabetic nephropathy treatment

  3. A novel chalcone derivative attenuates the diabetes-induced renal injury via inhibition of high glucose-mediated inflammatory response and macrophage infiltration

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Qilu [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zhao, Leping [Department of Pharmacy, the Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wang, Yi; Zhang, Yali [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Zhaoyu [Department of International High School, Shanghai Jiaotong University Nanyang Affiliated (Kunshan) School, Minhang District, Shanghai (China); Pan, Yong; Kanchana, Karvannan; Wang, Jingying; Tong, Chao [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Dan, E-mail: yqyyld@163.com [Department of Nephrology, the Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang (China); Liang, Guang, E-mail: wzmcliangguang@163.com [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)

    2015-01-15

    Inflammation plays a central role in the development and progression of diabetic nephropathy (DN). Researches on novel anti-inflammatory agents may offer new opportunities for the treatment of DN. We previously found a chalcone derivative L6H21 could inhibit LPS-induced cytokine release from macrophages. The aim of this study was to investigate whether L6H21 could ameliorate the high glucose-mediated inflammation in NRK-52E cells and attenuate the inflammation-mediated renal injury. According to the results, L6H21 showed a great inhibitory effect on the expression of pro-inflammatory cytokines, cell adhesion molecules, chemokines, and macrophage adhesion via down-regulation of NF-κB/MAPKs activity in high glucose-stimulated renal NRK-52E cells. Further, in vivo oral administration with L6H21 at a dosage of 20 mg/kg/2 days showed a decreased expression of pro-inflammatory cytokines, cell adhesion molecules, which subsequently contributed to the inhibition on renal macrophage infiltration, the reduction of serum creatinine and BUN levels, and the improvement on the fibrosis and pathological changes in the renal tissues of diabetic mice. These findings provided that chalcone derived L6H21 may be a promising anti-inflammatory agent and have the potential in the therapy of diabetic nephropathy, and importantly, MAPK/NF-κB signaling system may be a novel therapeutic target for human DN in the future. - Highlights: • Inflammation plays a central role in the development of diabetic nephropathy. • Compound L6H21 reduced the high glucose-mediated inflammation in NRK-52E cells. • Compound L6H21 attenuated the inflammation-mediated renal injury. • L6H21 exhibited anti-inflammatory effects via inactivation of NF-κB/MAPKs. • MAPKs/NF-κB may be a novel therapeutic target in diabetic nephropathy treatment.

  4. Effect of Γ-aminobutyric acid on kidney injury induced by renal ischemia-reperfusion in male and female rats: Gender-related difference.

    Science.gov (United States)

    Vafapour, Marzieh; Nematbakhsh, Mehdi; Monajemi, Ramesh; Mazaheri, Safoora; Talebi, Ardeshir; Talebi, Nahid; Shirdavani, Soheyla

    2015-01-01

    The most important cause of kidney injury is renal ischemia/reperfusion injury (IRI), which is gender-related. This study was designed to investigate the protective role of Γ-aminobutyric acid (GABA (against IRI in male and female rats. Thirty-six female and male wistar rats were assigned to six experimental groups. The IRI was induced by clamping renal vessels for 45 min then was performed reperfusion for 24 h. The group sex posed to IRI were pretreated with GABA and were compared with the control groups. Serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score increased in the IRI alone groups, (P GABA decreased these parameters in female significantly (P GABA. Testis weight did not alter in male rats. Serum level of nitrite and kidney level of malondialdehyde (MDA) had no significant change in both female and male rats. Kidney level of nitrite increased significantly in female rats experienced IRI and serum level of MDA increased significantly in males that were exposed to IRI (P GABA could ameliorate kidney injury induced by renal IRI in a gender dependent manner.

  5. CD44-deficiency attenuates the immunologic responses to LPS and delays the onset of endotoxic shock-induced renal inflammation and dysfunction.

    Directory of Open Access Journals (Sweden)

    Elena Rampanelli

    Full Text Available Acute kidney injury (AKI is a common complication during systemic inflammatory response syndrome (SIRS, a potentially deadly clinical condition characterized by whole-body inflammatory state and organ dysfunction. CD44 is a ubiquitously expressed cell-surface transmembrane receptor with multiple functions in inflammatory processes, including sterile renal inflammation. The present study aimed to assess the role of CD44 in endotoxic shock-induced kidney inflammation and dysfunction by using CD44 KO and WT mice exposed intraperitoneally to LPS for 2, 4, and 24 hours . Upon LPS administration, CD44 expression in WT kidneys was augmented at all time-points. At 2 and 4 hours, CD44 KO animals showed a preserved renal function in comparison to WT mice. In absence of CD44, the pro-inflammatory cytokine levels in plasma and kidneys were lower, while renal expression of the anti-inflammatory cytokine IL-10 was higher. The cytokine levels were associated with decreased leukocyte influx and endothelial activation in CD44 KO kidneys. Furthermore, in vitro assays demonstrated a role of CD44 in enhancing macrophage cytokine responses to LPS and leukocyte migration. In conclusion, our study demonstrates that lack of CD44 impairs the early pro-inflammatory cytokine response to LPS, diminishes leukocyte migration/chemotaxis and endothelial activation, hence, delays endotoxic shock-induced AKI.

  6. Hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose adefovir dipivoxil: a case report and literature review suggesting ethnic predisposition.

    Science.gov (United States)

    Wu, C; Zhang, H; Qian, Y; Wang, L; Gu, X; Dai, Z

    2013-08-01

    Adefovir dipivoxil (ADV) is one of the commonly used antiviral agents in the treatment of chronic hepatitis B (CHB) infection. Safety of a daily dose of 10 mg ADV is advocated by the registration trials. We report a case of severe hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose ADV in a CHB-related cirrhosis patient, and discuss the case through a thorough review of other cases reported in the literature. A 48-yr-old Chinese man with CHB-related cirrhosis developed severe progressive generalized bone pain and muscle weakness after receiving ADV 10 mg daily for 54 months. The laboratory results showed severe hypophosphatemia and features of proximal renal tubule dysfunction. Imaging studies were consistent with osteomalacia. After discontinuation of ADV, his symptoms resolved, laboratory abnormalities normalized and imaging studies showed improvement. In addition to our case, 12 other patients have been reported to have developed hypophosphatemic osteomalacia induced by low-dose ADV. Most of the reported cases were of subjects of East-Asian ethnicity. After discontinuation or reduction of ADV, serum phosphate level increased and clinical symptoms significantly improved in all cases. Hypophosphatemic osteomalacia and renal Fanconi syndrome can be associated with low-dose ADV. Clinicians treating CHB patients with ADV 10 mg daily over long periods of time should be aware of this infrequent but serious complication. © 2013 John Wiley & Sons Ltd.

  7. Mitigation of diazinon-induced cardiovascular and renal dysfunction by gallic acid

    Science.gov (United States)

    Ajibade, Temitayo Olabisi; Omobowale, Temidayo Olutayo; Asenuga, Ebunoluwa Racheal; Afolabi, Jeremiah Moyinoluwa; Adedapo, Adeolu Alex

    2016-01-01

    Studies of the link between environmental pollutants and cardiovascular dysfunction, neglected for decades, have recently provided new insights into the pathology and consequences of these killers. In this study, rats were divided into four groups, each containing 10 rats. The rats in group one served as controls and were administered normal saline, whereas the rats in group two were orally gavaged with 3 mg/kg of diazinon (DZN) alone for twenty one consecutive days. The rats in groups 3 and 4 were administered respective 60 mg/kg and 120 mg/kg gallic acid (GA) in addition to DZN for twenty one consecutive days. Exposure of rats to diazinon significantly (pgallic acid in diazinon-induced anemia and associated cardiovascular dysfunction in rats. Treatment with gallic acid reversed the oxidative stress markers studied, increased the antioxidant defence system and reduced deleterious effects on hematological parameters in rats. Pathologic findings of the heart and kidney were also found to be lessened. PMID:28652848

  8. Risperidone-Induced Renal Damage and Metabolic Side Effects: The Protective Effect of Resveratrol

    Directory of Open Access Journals (Sweden)

    Sedat Bilgiç

    2017-01-01

    Full Text Available Objective. The aim of the study was to investigate the possible protective qualities of resveratrol (RSV against the side effects of risperidone (RIS in an experimental model in rat kidneys with histologic and biochemical assessments. Materials and Methods. Experimental procedures were performed on 35 female Sprague Dawley rats. Rats were randomly divided into five groups: control, untreated rats (n=7 were in group 1; group 2 was given 2 mg/kg/day RIS (n=7; group 3 was treated with 2 mg/kg/day RIS and 20 mg/kg/day RSV (n=7; group 4 was treated with 2 mg/kg/day RIS and 40 mg/kg/day RSV (n=7; and group 5 was treated with 2 mg/kg/day RIS and 80 mg/kg/day RSV (n=7. All treatments were administered for two weeks by gavage. On treatment day 15, kidney tissues were removed for analysis. Results. The results showed that RSV treatment reduced weight gain induced by RIS. In addition, RSV increased the total antioxidant status (TAS and decreased serum creatinine (Cr, blood urea nitrogen (BUN, oxidative stress index (OSI, and total oxidant status (TOS levels significantly (p<0.05. Conclusion. This study revealed that treatment with RSV might protect kidney tissues against the side effects of RIS. RSV could be an effective course of therapy to enhance therapeutic efficacy.

  9. Trichloroethylene and trichloroethanol-induced formic aciduria and renal injury in male F-344 rats following 12 weeks exposure

    International Nuclear Information System (INIS)

    Yaqoob, Noreen; Evans, Andrew; Foster, John R.; Lock, Edward A.

    2014-01-01

    Trichloroethylene (TCE) is widely used as a cleaning and decreasing agent and has been shown to cause liver tumours in rodents and a small incidence of renal tubule tumours in male rats. The basis for the renal tubule injury is believed to be related to metabolism of TCE via glutathione conjugation to yield the cysteine conjugate that can be activated by the enzyme cysteine conjugate β-lyase in the kidney. More recently TCE and its major metabolite trichloroethanol (TCE-OH) have been shown to cause formic aciduria which can cause renal injury after chronic exposure in rats. In this study we have compared the renal toxicity of TCE and TCE-OH in rats to try and ascertain whether the glutathione pathway or formic aciduria can account for the toxicity. Male rats were given TCE (500 mg/kg/day) or TCE-OH at (100 mg/kg/day) for 12 weeks and the extent of renal injury measured at several time points using biomarkers of nephrotoxicity and prior to termination assessing renal tubule cell proliferation. The extent of formic aciduria was also determined at several time points, while renal pathology and plasma urea and creatinine were determined at the end of the study. TCE produced a very mild increase in biomarkers of renal injury, total protein, and glucose over the first two weeks of exposure and increased Kim-1 and NAG in urine after 1 and 5 weeks exposure, while TCE-OH did not produce a consistent increase in these biomarkers in urine. However, both chemicals produced a marked and sustained increase in the excretion of formic acid in urine to a very similar extent. The activity of methionine synthase in the liver of TCE and TCE-OH treated rats was inhibited by about 50% indicative of a block in folate synthesis. Both renal pathology and renal tubule cell proliferation were reduced after TCE and TCE-OH treatment compared to controls. Our findings do not clearly identify the pathway which is responsible for the renal toxicity of TCE but do provide some support for

  10. Trichloroethylene and trichloroethanol-induced formic aciduria and renal injury in male F-344 rats following 12 weeks exposure.

    Science.gov (United States)

    Yaqoob, Noreen; Evans, Andrew; Foster, John R; Lock, Edward A

    2014-09-02

    Trichloroethylene (TCE) is widely used as a cleaning and decreasing agent and has been shown to cause liver tumours in rodents and a small incidence of renal tubule tumours in male rats. The basis for the renal tubule injury is believed to be related to metabolism of TCE via glutathione conjugation to yield the cysteine conjugate that can be activated by the enzyme cysteine conjugate β-lyase in the kidney. More recently TCE and its major metabolite trichloroethanol (TCE-OH) have been shown to cause formic aciduria which can cause renal injury after chronic exposure in rats. In this study we have compared the renal toxicity of TCE and TCE-OH in rats to try and ascertain whether the glutathione pathway or formic aciduria can account for the toxicity. Male rats were given TCE (500mg/kg/day) or TCE-OH at (100mg/kg/day) for 12 weeks and the extent of renal injury measured at several time points using biomarkers of nephrotoxicity and prior to termination assessing renal tubule cell proliferation. The extent of formic aciduria was also determined at several time points, while renal pathology and plasma urea and creatinine were determined at the end of the study. TCE produced a very mild increase in biomarkers of renal injury, total protein, and glucose over the first two weeks of exposure and increased Kim-1 and NAG in urine after 1 and 5 weeks exposure, while TCE-OH did not produce a consistent increase in these biomarkers in urine. However, both chemicals produced a marked and sustained increase in the excretion of formic acid in urine to a very similar extent. The activity of methionine synthase in the liver of TCE and TCE-OH treated rats was inhibited by about 50% indicative of a block in folate synthesis. Both renal pathology and renal tubule cell proliferation were reduced after TCE and TCE-OH treatment compared to controls. Our findings do not clearly identify the pathway which is responsible for the renal toxicity of TCE but do provide some support for metabolism

  11. Effect of Unripe Plantain (Musa paradisiaca) and Ginger (Zingiber officinale) on Renal Dysfunction in Streptozotocin-Induced Diabetic Rats.

    Science.gov (United States)

    Iroaganachi, Mercy; Eleazu, Chinedum; Okafor, Polycarp

    2015-03-20

    Although unripe plantain (Musa paradisiaca) and ginger (Zingiber officinale) are used as single plants to manage diabetes mellitus in Nigeria, the possibility of combining them in a typical diabetic diet and the glycemic response elicited as a result of such combination has not been investigated. To determine the effect of unripe plantain and ginger on serum total proteins, albumin, creatinine and urea levels of streptozotocin induced diabetic rats. Twenty four male albino rats were used and were divided into 4 groups of 6 rats each. Group 1 (non-diabetic) received standard rat feeds; Group 2 (diabetic) received standard rat feeds; Group 3 received unripe plantain pellets and Group 4 received unripe plantain+ginger pellets. There were significant increases (P=0.045) of both serum urea and creatinine, but significant decreases (P=0.045) of both serum total protein and albumin levels, in Group 2 rats compared with Group 1. There were significant decreases (P=0.033) of both serum urea and creatinine levels of Group 3 and 4 rats compared with Group 2. In addition, there were significant increases of both serum total protein and albumin levels (P=0.033) in Group 3 rats compared with Group 2, but the comparison of serum total protein and albumin levels between Group 4 and Group 2 did not reach the significant level (P=0.056 and P=0.065 for serum total protein and albumin levels, respectively. Combination of unripe plantain and ginger at the ratio used in the management of renal dysfunction in diabetics was not very effective compared with unripe plantain alone.

  12. Evaluating ESWL-induced renal injury based on urinary TNF-α, IL-1α, and IL-6 levels.

    Science.gov (United States)

    Goktas, Cemal; Coskun, Abdurrahman; Bicik, Zerrin; Horuz, Rahim; Unsal, Ibrahim; Serteser, Mustafa; Albayrak, Selami; Sarıca, Kemal

    2012-10-01

    Extracorporeal shockwave lithotripsy (ESWL) has dramatically changed the treatment of urinary lithiasis and has been the first treatment option for the majority of patients for more than two decades. Despite its significant benefits, it induces acute renal injury that extends from the papilla to the outer cortex. We evaluated the severity of the inflammatory response to ESWL by measuring the urinary excretion of the cytokines TNF-α, IL-1α, and IL-6. The study included 21 selected patients and 14 control subjects. All patients underwent the same ESWL procedure (2,500 shockwaves at 100 shockwaves/min and 0.039 J from the lithotripter). Urine TNF-α, IL-1α, and IL-6 levels were measured using standard ELISA kits. In the study population (patients and controls), we did not detect TNF-α in the urine samples. The levels of both IL-1α (2.5 pg/ml) and IL-6 (3.8 pg/ml) measured before ESWL were not significantly different from the control group (2.5 and 5.2 pg/ml, respectively; p > 0.05). Twenty-four hours after ESWL, in contrast to IL-1α (4 pg/ml), urine IL-6 (19.7 pg/ml) increased significantly (p ESWL, IL-1α increased to 5 pg/ml, while IL-6 (7 pg/ml) decreased to the control level. Urine cytokine levels may be used to evaluate the inflammatory response to ESWL. After ESWL, IL-6 levels increased in the early phase, while IL-1α levels increased later. These two markers may be used to measure the severity of inflammation. In contrast to IL-1α and IL-6, urine TNF-α excretion was not increased by ESWL. We believe that the inflammatory response to ESWL can be detected by the urinary excretion of IL-1α for up to 14 days.

  13. Original article. Mitigation of diazinon-induced cardiovascular and renal dysfunction by gallic acid

    Directory of Open Access Journals (Sweden)

    Ajibade Temitayo Olabisi

    2016-06-01

    Full Text Available Studies of the link between environmental pollutants and cardiovascular dysfunction, neglected for decades, have recently provided new insights into the pathology and consequences of these killers. In this study, rats were divided into four groups, each containing 10 rats. The rats in group one served as controls and were administered normal saline, whereas the rats in group two were orally gavaged with 3 mg/kg of diazinon (DZN alone for twenty one consecutive days. The rats in groups 3 and 4 were administered respective 60 mg/kg and 120 mg/kg gallic acid (GA in addition to DZN for twenty one consecutive days. Exposure of rats to diazinon significantly (p<0.05 reduced the activities of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx, glutathione-S-transferase (GST and reduced glutathione (GSH content. Malondialdehyde, hydrogen peroxide (H2O2 and nitric oxide (NO contents were also significantly (p<0.05 elevated following DZN exposure. DZN further caused a significant (p<0.05 decrease of heart rate and QT interval prolongation. Hematologic analysis revealed significant reduction (p<0.05 in packed cell volume (PCV, hemoglobin concentration (Hb, red blood cell (RBC count, and total white blood cell count of rats administered only DZN. Observations in this study suggest a modulatory role of gallic acid in diazinon-induced anemia and associated cardiovascular dysfunction in rats. Treatment with gallic acid reversed the oxidative stress markers studied, increased the antioxidant defence system and reduced deleterious effects on hematological parameters in rats. Pathologic findings of the heart and kidney were also found to be lessened.

  14. Camel Milk Ameliorates 5-Fluorouracil-Induced Renal Injury in Rats: Targeting MAPKs, NF-κB and PI3K/Akt/eNOS Pathways

    Directory of Open Access Journals (Sweden)

    Hany H. Arab

    2018-04-01

    Full Text Available Background/Aims: The clinical utility of 5-fluorouracil (5-FU is limited by its nephrotoxicity. Camel milk (CM has previously displayed beneficial effects in toxicant-induced nephropathies. The current study aimed to investigate the potential of CM to attenuate 5-FU-induced nephrotoxicity in rats. Methods: Renal tissues were studied in terms of oxidative stress, inflammation and apoptosis. The levels of renal injury markers, inflammatory cytokines along with NOX-1, Nrf-2 and HO-1 were assessed by ELISA. The expression of MMP-2, MMP-9, NF-κBp65, p53, Bax and PCNA were detected by Immunohistochemistry. To gain an insight into the molecular signaling mechanisms, we determined the effect of CM on MAPKs, NF-κB and PI3K/Akt/eNOS pathways by Western blotting. Results: CM lowered 5-FU-triggered increase of creatinine, BUN, Kim-1 and NGAL renal injury biomarkers and attenuated the histopathological aberrations. It suppressed oxidative stress and augmented renal antioxidant armory (GSH, SOD, GPx, TAC with restoration of NOX-1, Nrf-2 and HO-1 levels. CM also suppressed renal inflammation as indicated by inhibition of MPO, TNF-α, IL-1β, IL-18 and MCP-1 proinflammatory mediators and downregulation of MMP-2 and MMP-9 expression with boosting of IL-10. Regarding MAPKs signaling, CM suppressed the phosphorylation of p38 MAPK, JNK1/2 and ERK1/2 and inhibited NF-κB activation. For apoptosis, CM downregulated p53, Bax, CytC and caspase-3 proapoptotic signals with enhancement of Bcl-2 and PCNA. It also enhanced PI3K p110α, phospho-Akt and phospho-eNOS levels with augmentation of renal NO, favoring cell survival. Equally important, CM preconditioning enhanced 5-FU cytotoxicity in MCF-7, HepG-2, HCT-116 and PC-3 cells, thus, justifying their concomitant use. Conclusion: The current findings pinpoint, for the first time, the marked renoprotective effects of CM that were mediated via ROS scavenging, suppression of MAPKs and NF-κB along with activation of PI3K

  15. Antigen-specific immature dendritic cell vaccine ameliorates anti-dsDNA antibody-induced renal damage in a mouse model.

    Science.gov (United States)

    Xia, Yumin; Jiang, Shan; Weng, Shenhong; Lv, Xiaochun; Cheng, Hong; Fang, Chunhong

    2011-12-01

    Dendritic cells (DCs) can inhibit immune response by clonal anergy when immature. Recent studies have shown that immature DCs (iDCs) may serve as a live cell vaccine after specific antigen pulse based on its potential of blocking antibody production. In this study, we aimed to investigate the effects of nuclear antigen-pulsed iDCs in the treatment of lupus-like renal damages induced by anti-dsDNA antibodies. iDCs were generated from haemopoietic stem cells in bone marrow and then pulsed in vitro with nuclear antigen. The iDC vaccine and corresponding controls were injected into mice with lupus-like renal damages. The evaluation of disease was monitored by biochemical parameters and histological scores. Anti-dsDNA antibody isotypes and T-lymphocyte-produced cytokines were analysed for elucidating therapeutic mechanisms. RESULTS; The mice treated with antigen-pulsed iDCs had a sustained remission of renal damage compared with those injected with non-pulsed iDCs or other controls, including decreased anti-dsDNA antibody level, less proteinuria, lower blood urea nitrogen and serum creatinine values, and improved histological evaluation. Analysis on isotypes of anti-dsDNA antibody showed that iDC vaccine preferentially inhibited the production of IgG3, IgG2b and IgG2a. Furthermore, administration of antigen-treated iDCs to mice resulted in significantly reduced IL-2, IL-4 and IL-12 and IFN-γ produced by T-memory cells. Conversely, the vaccination of antigen-pulsed mature DCs led to increased anti-dsDNA antibody production and an aggravation of lupus-like disease in the model. CONCLUSIONS; These results suggested the high potency of iDC vaccine in preventing lupus-like renal injuries induced by pathogenic autoantibodies.

  16. Environmental exposure to cadmium at a level insufficient to induce renal tubular dysfunction does not affect bone density among female Japanese farmers

    International Nuclear Information System (INIS)

    Horiguchi, Hyogo; Oguma, Etsuko; Sasaki, Satoshi; Miyamoto, Kayoko; Ikeda, Yoko; Machida, Munehito; Kayama, Fujio

    2005-01-01

    Some recent research suggests that environmental exposure to cadmium, even at low levels, may increase the risk of osteoporosis, and that the bone demineralization is not just a secondary effect of renal dysfunction induced by high doses of cadmium as previously reported. To investigate the effect of exposure to cadmium at a level insufficient to induce kidney damage on bone mineral density (BMD) and bone metabolism, we conducted health examinations on 1380 female farmers from five districts in Japan who consumed rice contaminated by low-to-moderate levels of cadmium. We collected peripheral blood and urine samples and medical and nutritional information, and measured forearm BMD. Analysis of the data for subjects grouped by urinary cadmium level and age-related menstrual status suggested that cadmium accelerates both the increase of urinary calcium excretion around the time of menopause and the subsequent decrease in bone density after menopause. However, multivariate analyses showed no significant contribution of cadmium to bone density or urinary calcium excretion, indicating that the results mentioned above were confounded by other factors. These results indicate that environmental exposure to cadmium at levels insufficient to induce renal dysfunction does not increase the risk of osteoporosis, strongly supporting the established explanation for bone injury induced by cadmium as a secondary effect

  17. NPRL-Z-1, as a new topoisomerase II poison, induces cell apoptosis and ROS generation in human renal carcinoma cells.

    Science.gov (United States)

    Wu, Szu-Ying; Pan, Shiow-Lin; Xiao, Zhi-Yan; Hsu, Jui-Ling; Chen, Mei-Chuan; Lee, Kuo-Hsiung; Teng, Che-Ming

    2014-01-01

    NPRL-Z-1 is a 4β-[(4"-benzamido)-amino]-4'-O-demethyl-epipodophyllotoxin derivative. Previous reports have shown that NPRL-Z-1 possesses anticancer activity. Here NPRL-Z-1 displayed cytotoxic effects against four human cancer cell lines (HCT 116, A549, ACHN, and A498) and exhibited potent activity in A498 human renal carcinoma cells, with an IC50 value of 2.38 µM via the MTT assay. We also found that NPRL-Z-1 induced cell cycle arrest in G1-phase and detected DNA double-strand breaks in A498 cells. NPRL-Z-1 induced ataxia telangiectasia-mutated (ATM) protein kinase phosphorylation at serine 1981, leading to the activation of DNA damage signaling pathways, including Chk2, histone H2AX, and p53/p21. By ICE assay, the data suggested that NPRL-Z-1 acted on and stabilized the topoisomerase II (TOP2)-DNA complex, leading to TOP2cc formation. NPRL-Z-1-induced DNA damage signaling and apoptotic death was also reversed by TOP2α or TOP2β knockdown. In addition, NPRL-Z-1 inhibited the Akt signaling pathway and induced reactive oxygen species (ROS) generation. These results demonstrated that NPRL-Z-1 appeared to be a novel TOP2 poison and ROS generator. Thus, NPRL-Z-1 may present a significant potential anticancer candidate against renal carcinoma.

  18. Vascular toxicity of urea, a new "old player" in the pathogenesis of chronic renal failure induced cardiovascular diseases.

    Science.gov (United States)

    Giardino, Ida; D'Apolito, Maria; Brownlee, Michael; Maffione, Angela Bruna; Colia, Anna Laura; Sacco, Michele; Ferrara, Pietro; Pettoello-Mantovani, Massimo

    2017-12-01

    Chronic kidney disease in children is an irreversible process that may lead to end-stage renal disease. The mortality rate in children with end-stage renal disease who receive dialysis increased dramatically in the last decade, and it is significantly higher compared with the general pediatric population. Furthermore, dialysis and transplant patients, who have developed end-stage renal disease during childhood, live respectively far less as compared with age/race-matched populations. Different reports show that cardiovascular disease is the leading cause of death in children with end-stage renal disease and in adults with childhood-onset chronic kidney disease, and that children with chronic kidney disease are in the highest risk group for the development of cardiovascular disease. Urea, which is generated in the liver during catabolism of amino acids and other nitrogenous metabolites, is normally excreted into the urine by the kidneys as rapidly as it is produced. When renal function is impaired, increasing concentrations of blood urea will steadily accumulate. For a long time, urea has been considered to have negligible toxicity. However, the finding that plasma urea is the only significant predictor of aortic plaque area fraction in an animal model of chronic renal failure -accelerated atherosclerosis, suggests that the high levels of urea found in chronic dialysis patients might play an important role in accelerated atherosclerosis in this group of patients. The aim of this review was to provide novel insights into the role played by urea in the pathogenesis of accelerated cardiovascular disease in renal failure.

  19. Vascular toxicity of urea, a new “old player” in the pathogenesis of chronic renal failure induced cardiovascular diseases

    Science.gov (United States)

    D’Apolito, Maria; Brownlee, Michael; Maffione, Angela Bruna; Colia, Anna Laura; Sacco, Michele; Ferrara, Pietro; Pettoello-Mantovani, Massimo

    2017-01-01

    Chronic kidney disease in children is an irreversible process that may lead to end-stage renal disease. The mortality rate in children with end-stage renal disease who receive dialysis increased dramatically in the last decade, and it is significantly higher compared with the general pediatric population. Furthermore, dialysis and transplant patients, who have developed end-stage renal disease during childhood, live respectively far less as compared with age/race-matched populations. Different reports show that cardiovascular disease is the leading cause of death in children with end-stage renal disease and in adults with childhood-onset chronic kidney disease, and that children with chronic kidney disease are in the highest risk group for the development of cardiovascular disease. Urea, which is generated in the liver during catabolism of amino acids and other nitrogenous metabolites, is normally excreted into the urine by the kidneys as rapidly as it is produced. When renal function is impaired, increasing concentrations of blood urea will steadily accumulate. For a long time, urea has been considered to have negligible toxicity. However, the finding that plasma urea is the only significant predictor of aortic plaque area fraction in an animal model of chronic renal failure -accelerated atherosclerosis, suggests that the high levels of urea found in chronic dialysis patients might play an important role in accelerated atherosclerosis in this group of patients. The aim of this review was to provide novel insights into the role played by urea in the pathogenesis of accelerated cardiovascular disease in renal failure. PMID:29483797

  20. Mitochondrial Modulation by Epigallocatechin 3-Gallate Ameliorates Cisplatin Induced Renal Injury through Decreasing Oxidative/Nitrative Stress, Inflammation and NF-kB in Mice

    Science.gov (United States)

    Wang, Xueping; Wang, Ping; Fu, Guanghou; Meng, Hongzhou; Wang, Yimin; Jin, Baiye

    2015-01-01

    Cancer chemotherapy drug cisplatin is known for its nephrotoxicity. The aim of this study is to investigate whether Epigallocatechin 3-Gallate (EGCG) can reduce cisplatin mediated side effect in kidney and to understand its mechanism of protection against tissue injury. We used a well-established 3-day cisplatin induced nephrotoxicity mice model where EGCG were administered. EGCG is a major active compound in Green Tea and have strong anti-oxidant and anti-inflammatory properties. EGCG protected against cisplatin induced renal dysfunction as measured by serum creatinine and blood urea nitrogen (BUN). EGCG improved cisplatin induced kidney structural damages such as tubular dilatation, cast formation, granulovaculoar degeneration and tubular cell necrosis as evident by PAS staining. Cisplatin induced kidney specific mitochondrial oxidative stress, impaired activities of mitochondrial electron transport chain enzyme complexes, impaired anti-oxidant defense enzyme activities such as glutathione peroxidase (GPX) and manganese superoxide dismutase (MnSOD) in mitochondria, inflammation (tumor necrosis factor α and interleukin 1β), increased accumulation of NF-κB in nuclear fraction, p53 induction, and apoptotic cell death (caspase 3 activity and DNA fragmentation). Treatment of mice with EGCG markedly attenuated cisplatin induced mitochondrial oxidative/nitrative stress, mitochondrial damages to electron transport chain activities and antioxidant defense enzyme activities in mitochondria. These mitochondrial modulations by EGCG led to protection mechanism against cisplatin induced inflammation and apoptotic cell death in mice kidney. As a result, EGCG improved renal function in cisplatin mediated kidney damage. In addition to that, EGCG attenuated cisplatin induced apoptotic cell death and mitochondrial reactive oxygen species (ROS) generation in human kidney tubular cell line HK-2. Thus, our data suggest that EGCG may represent new promising adjunct candidate for

  1. Renal perfusion scintiscan

    Science.gov (United States)

    ... Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion Images Kidney anatomy Kidney - blood and urine flow Intravenous pyelogram References Rottenberg G, Andi AC. Renal ...

  2. The cholinergic pathway alleviates acute oxygen and glucose deprivation induced renal tubular cell injury by reducing the secretion of inflammatory medium of macrophages

    Directory of Open Access Journals (Sweden)

    Ming WU

    2017-10-01

    Full Text Available Objective To investigate the effects of cholinergic pathway on acute renal tubular cell injury induced by acute oxygen and glucose deprivation. Methods Rat kidney macrophages were isolated and cultured for constructing macrophages and renal epithelial cells co-cultivating model of oxygen-glucose deprivation (OGD, and the model cells were divided into three groups: OGD alone group, acetylcholine (ACh 100μmol/L+OGD group and ACh + galantamine (Gal 10μmol/L+OGD group. The cells underwent OGD treatment for 1 hour, and normally cultured for 24 hours. The expressions of TNF alpha, IL-1 beta, and IL-10 in supernatant fluid were detected by ELISA, the renal tubular cell viability was determined by MTT assay, the expression of acetylcholine esterase (AChE mRNA and protein were determined by RT-qPCR and Western blotting. The activity of AChE was determined by colorimetric method. Results The expressions of TNF alpha (pg/ml in OGD, Ach+OGD group, Ach+Gal+OGD groups were 140.2±44.81, 119.46±4.42 and 103.31±1.62 respectively (P0.05; The values of renal tubular cell proliferation were 55.02%±6.28%, 66.65%±6.47%, and 79.75%±4.22% respectively (P0.05; those of AchE protein were 0.66±0.07, 0.74±0.04 and 0.67±0.06 respectively (P>0.05; The activity of AChE (kU/L was 0.51±0.02, 0.35±0.05 and 0.32±0.04 respectively (P=0.001, 0.001 and 0.368. Conclusions ACh and Gal could inhibit the secretion of inflammatory mediators and cholinesterase activity and can reduce the acute hypoxic renal tubular cell injury. The modulation of the cholinergic pathway in macrophages may be the important treatment method for acute renal injury in the future. DOI: 10.11855/j.issn.0577-7402.2017.08.01

  3. Specific estrogen-induced cell proliferation of cultured Syrian hamster renal proximal tubular cells in serum-free chemically defined media

    International Nuclear Information System (INIS)

    Oberley, T.D.; Lauchner, L.J.; Pugh, T.D.; Gonzalez, A.; Goldfarb, S.; Li, S.A.; Li, J.J.

    1989-01-01

    It has long been recognized that the renal proximal tubular epithelium of the hamster is a bona fide estrogen target tissue. The effect of estrogens on the growth of proximal tubule cell explants and dissociated single cells derived from these explant outgrowths has been studied in culture. Renal tubular cells were grown on a PF-HR-9 basement membrane under serum-free chemically defined culture conditions. At 7-14 days in culture, cell number was enhanced 3-fold in the presence of either 17β-estradiol or diethylstilbestrol. A similar 3-fold increase in cell number was also seen at 1 nM 17β-estradiol in subcultured dissociated single tubular cells derived from hamster renal tubular explant outgrowths at 21 days in culture. Concomitant exposure of tamoxifen at 3-fold molar excess in culture completely abolished the increase in cell number seen with 17β-estradiol. The proliferation effect of estrogens on proximal tubular cell growth appears to be species specific since 17β-estradiol did not alter the growth of either rat or guinea pig proximal tubules in culture. In addition, at 7-10 days in culture in the presence of 17β-estradiol, [ 3 H]thymidine labeling of hamster tubular cells was enhanced 3-fold. These results clearly indicate that estrogens can directly induce primary epithelial cell proliferation at physiologic concentrations and provide strong additional evidence for an important hormonal role in the neoplastic transformation of the hamster kidney

  4. Early Conversion from Tacrolimus to Belatacept in a Highly Sensitized Renal Allograft Recipient with Calcineurin Inhibitor-Induced de novo Post-Transplant Hemolytic Uremic Syndrome

    Directory of Open Access Journals (Sweden)

    Vasishta S. Tatapudi

    2018-01-01

    Full Text Available Background: Kidney transplantation is the first-line therapy for patients with end-stage renal disease since it offers greater long-term survival and improved quality of life when compared to dialysis. The advent of calcineurin inhibitor (CNI-based maintenance immunosuppression has led to a clinically significant decline in the rate of acute rejection and better short-term graft survival rates. However, these gains have not translated into improvement in long-term graft survival. CNI-related nephrotoxicity and metabolic side effects are thought to be partly responsible for this. Case Presentation: Here, we report the conversion of a highly sensitized renal transplant recipient with pretransplant donor-specific antibodies from tacrolimus to belatacept within 1 week of transplantation. This substitution was necessitated by the diagnosis of CNI-induced de novo post-transplant hemolytic uremic syndrome. Conclusion: Belatacept is a novel costimulation blocker that is devoid of the nephrotoxic properties of CNIs and has been shown to positively impact long-term graft survival and preserve renal allograft function in low-immunologic-risk kidney transplant recipients. Data regarding its use in patients who are broadly sensitized to human leukocyte antigens are scarce, and the increased risk of rejection associated with belatacept has been a deterrent to more widespread use of this immunosuppressive agent. This case serves as an example of a highly sensitized patient that has been successfully converted to a belatacept-based CNI-free regimen.

  5. Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure.

    Science.gov (United States)

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT2R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT1aR)/AT2R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT2R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT2R might mediate the developmental origin of adult glomerulosclerosis. Copyright © 2015. Published by Elsevier Inc.

  6. Sphingosine 1-phosphate (S1P) induces COX-2 expression and PGE2 formation via S1P receptor 2 in renal mesangial cells.

    Science.gov (United States)

    Völzke, Anja; Koch, Alexander; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

    2014-01-01

    Understanding the mechanisms of sphingosine 1-phosphate (S1P)-induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) formation in renal mesangial cells may provide potential therapeutic targets to treat inflammatory glomerular diseases. Thus, we evaluated the S1P-dependent signaling mechanisms which are responsible for enhanced COX-2 expression and PGE2 formation in rat mesangial cells under basal conditions. Furthermore, we investigated whether these mechanisms are operative in the presence of angiotensin II (Ang II) and of the pro-inflammatory cytokine interleukin-1β (IL-1β). Treatment of rat and human mesangial cells with S1P led to concentration-dependent enhanced expression of COX-2. Pharmacological and molecular biology approaches revealed that the S1P-dependent increase of COX-2 mRNA and protein expression was mediated via activation of S1P receptor 2 (S1P2). Further, inhibition of Gi and p42/p44 MAPK signaling, both downstream of S1P2, abolished the S1P-induced COX-2 expression. In addition, S1P/S1P2-dependent upregulation of COX-2 led to significantly elevated PGE2 levels, which were further potentiated in the presence of Ang II and IL-1β. A functional consequence downstream of S1P/S1P2 signaling is mesangial cell migration that is stimulated by S1P. Interestingly, inhibition of COX-2 by celecoxib and SC-236 completely abolished the migratory response. Overall, our results demonstrate that extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. Thus, targeting S1P/S1P2 signaling pathways might be a novel strategy to treat renal inflammatory diseases. © 2013.

  7. [Effects of the renal blood flow at different levels by transcutaneous electrical acupoint stimulation combined general anesthesia induced controlled hypotension].

    Science.gov (United States)

    Fang, Jian-Qiao; Zhang, Le-Le; Shao, Xiao-Mei

    2012-11-01

    To observe the intervention of transcutaneous electrical acupoint stimulation (TEAS) on the renal blood flow at different levels of mean arterial pressure (MAP) in controlled hypotension. Forty-two male beagle dogs were randomly divided into seven groups, i. e., the general anesthesia group, the 50% controlled group, the 40% controlled group, the 30% controlled group, the 50% experimental group, the 40% experimental group, and the 30% experimental group, 6 in each group. Beagles in the general anesthesia group were not treated with controlled hypotension, and the target MAP was achieved in those of the rest groups and maintained for 60 min. In the experimental groups, TEAS was applied to bilateral Hegu (LI4), Zusanli (ST36), Sanyinjiao (SP6), and Quchi (LI11) at 2/100 Hz with the stimulation strength of (4 +/- 1) mA starting from the stability of their physiological conditions to 60 min of maintaining the target MAP level. The changes of the renal blood flow were monitored at different time points using laser Doppler. From starting pressure control to the target MAP level, the renal blood flow was significantly lower in the 30% controlled group than in the general anesthesia group and the basic level of the same group (P blood pressure, the renal blood flow was significantly lower in the 50% controlled group, the 40% controlled group, the 30% controlled group, and the 30% experimental group than in the general anesthesia group (P blood pressure recovery, the renal blood flow restored to the basic level in the 50% controlled group, the 50% experimental group, and the 40% experimental group (P > 0.05), while it was not restored to the basic level in the 40% controlled group, the 30% controlled group, and the 30% experimental group (P renal blood flow, thus protecting the kidney.

  8. Hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis presenting with a vasculitic syndrome, acute nephritis and a puzzling skin rash: a case report

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    Keasberry Justin

    2013-01-01

    Full Text Available Abstract Introduction Anti-neutrophil cytoplasmic antibody-associated vasculitis has been associated with many drugs and it is a relatively rare side effect of the antihypertensive drug hydralazine. The diagnosis and management of patients who have anti-neutrophil cytoplasmic antibody-associated vasculitis may be challenging because of its relative infrequency, variability of clinical expression and changing nomenclature. The spectrum of anti-neutrophil cytoplasmic antibody-associated vasculitis is wide and can be fatal. This case documents a 62-year-old woman who presented with hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis with a puzzling cutaneous rash. Case presentation We report a rare case of hydralazine-induced anti-neutrophil cytoplasmic antibody-associated vasculitis in a 62-year-old Caucasian woman who presented with a vasculitic syndrome with a sore throat, mouth ulcers and otalgia after several months of constitutional symptoms. She then proceeded to develop a rash over her right lower limb. Clinically, the rash had features to suggest Sweet’s syndrome, but also had some appearances consistent with embolic phenomena and did not have the appearance of palpable purpure usually associated with cutaneous vasculitis. Differential diagnoses were hydralazine-associated Sweet’s syndrome, streptococcal-induced cutaneous eruption or an unrelated contact dermatitis. A midstream urine sample detected glomerular blood cells in the setting of anti-neutrophil cytoplasmic antibody-positive renal vasculitis and Streptococcus pyogenes bacteremia. A renal biopsy revealed a pauci-immune, focally necrotizing glomerulonephritis with small crescents. Her skin biopsy revealed a heavy neutrophil infiltrate involving the full thickness of the dermis with no evidence of a leucocytoclastic vasculitis, but was non-specific. She was initially commenced on intravenous lincomycin for her bloodstream infection and subsequently

  9. Nephrogenic systemic fibrosis versus contrast-induced nephropathy: risks and benefits of contrast-enhanced MR and CT in renally impaired patients

    DEFF Research Database (Denmark)

    Martin, Diego R; Semelka, Richard C; Chapman, Arlene

    2009-01-01

    -sectional imaging modality. Factors to consider include the relative risks of the contrast agent. Other factors include the relative procedural risks, including radiation risks and the relative expected diagnostic yield of the examination technique (12). In this review we describe both nephrogenic systemic fibrosis...... and contrast-induced nephropathy to compare the implications with regard to relative risks and benefits of contrast-enhanced MRI or CT in patients with impaired renal function. J. Magn. Reson. Imaging 2009;30:1350-1356. (c) 2009 Wiley-Liss, Inc....

  10. 17β-estradiol induces non-genomic effects in renal intercalated cells through the G-protein coupled estrogen receptor 1

    DEFF Research Database (Denmark)

    Hofmeister, Marlene Vind; Damkier, Helle Hasager; Christensen, Birgitte Mønster

    2012-01-01

    Steroid hormones such as 17β-estradiol (E2) are known to modulate ion transporter expression in the kidney through classic intracellular receptors. Steroid hormones are also known to cause rapid nongenomic responses in a variety of nonrenal tissues. However, little is known about renal short......-term effects of steroid hormones. Here, we studied the acute actions of E2 on intracellular Ca(2+) signaling in isolated distal convoluted tubules (DCT2), connecting tubules (CNT), and initial cortical collecting ducts (iCCD) by fluo 4 fluorometry. Physiological concentrations of E2 induced transient increases...

  11. Osteomalacia-inducing renal clear cell carcinoma uncovered by 99mTc-Hydrazinonicotinyl-Tyr3-octreotide (99mTc-HYNIC-TOC) scintigraphy.

    Science.gov (United States)

    Jin, Xiaona; Jing, Hongli; Li, Fang; Zhuang, Hongming

    2013-11-01

    Most osteomalacia-causing tumors are small, benign mesenchymal neoplasms, which are commonly located in the extremities or craniofacial regions. An 18-year-old male patient with suspicion of tumor-induced osteomalacia underwent (99m)Tc-HYNIC-TOC scintigraphy to search potential culprit tumor. The images showed a large activity in the region of the left kidney. The lesion was resected and a clear cell renal cell carcinoma was found. One year after the left nephrectomy, the patient was tumor-free without symptoms of osteomalacia.

  12. Podocyte-specific deletion of Rac1 leads to aggravation of renal injury in STZ-induced diabetic mice

    International Nuclear Information System (INIS)

    Ishizaka, Masanori; Gohda, Tomohito; Takagi, Miyuki; Omote, Keisuke; Sonoda, Yuji; Oliva Trejo, Juan Alejandro; Asao, Rin; Hidaka, Teruo; Asanuma, Katsuhiko; Horikoshi, Satoshi; Tomino, Yasuhiko

    2015-01-01

    Rac1, a GTPase of the Rho subfamily, has a crucial role in cytoskeletal architecture, as well as the regulation of cell migration and growth. However, renal injury in mice with podocyte-specific deletion of Rac1 has yet to be elucidated fully due to conflicting findings. Herein, we identified a possible role for Rac1 in podocytes of streptozotocin- (STZ) induced diabetic mice. The urinary albumin/creatinine ratio (ACR) in the knockout (KO) group was significantly higher than that in the wild type (WT) group at any week of age. A more marked ACR increase was observed in STZ/KO group than STZ/WT group, although ACR did increase with weeks of age in both diabetic groups. The kidney sections from diabetic mice revealed a glomerular hypertrophy with mesangial expansion, but there was no appreciable difference in glomerular findings under a light microscope between STZ/WT and STZ/KO mice. However, an electron microscopy analysis revealed that regardless of the presence or absence of diabetes, both KO (KO and STZ/KO) groups had a higher rate of foot process effacement compared with both WT (WT and STZ/WT) groups. The expression levels of the slit diaphragm protein, podocin, was reduced with the induction of diabetes, and the levels in the STZ/KO group experienced a further reduction compared with the STZ/WT group. The number of WT1-positive cells in the STZ/KO group was more significantly decreased than that in the other three groups. In contrast, the numbers of cleaved caspase 3- and TUNEL-positive cells in the glomeruli of the STZ/KO group were more increased than those in the STZ/WT group. Thus, this study provides evidence that podocyte-specific deletion of Rac1 results in morphological alteration in podocytes, and that the induction of apoptosis or decreased expression of the slit diaphragm proteins by hyperglycemic stimuli are associated with the progression of diabetic nephropathy.

  13. Podocyte-specific deletion of Rac1 leads to aggravation of renal injury in STZ-induced diabetic mice

    Energy Technology Data Exchange (ETDEWEB)

    Ishizaka, Masanori [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Gohda, Tomohito, E-mail: goda@juntendo.ac.jp [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Takagi, Miyuki; Omote, Keisuke; Sonoda, Yuji [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Oliva Trejo, Juan Alejandro [Laboratory for Kidney Research (TMK Project), Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-8397 (Japan); Asao, Rin; Hidaka, Teruo [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Asanuma, Katsuhiko [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Laboratory for Kidney Research (TMK Project), Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-8397 (Japan); Horikoshi, Satoshi [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Tomino, Yasuhiko [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Medical Corporation SHOWAKAI, 3-12-12 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023 (Japan)

    2015-11-20

    Rac1, a GTPase of the Rho subfamily, has a crucial role in cytoskeletal architecture, as well as the regulation of cell migration and growth. However, renal injury in mice with podocyte-specific deletion of Rac1 has yet to be elucidated fully due to conflicting findings. Herein, we identified a possible role for Rac1 in podocytes of streptozotocin- (STZ) induced diabetic mice. The urinary albumin/creatinine ratio (ACR) in the knockout (KO) group was significantly higher than that in the wild type (WT) group at any week of age. A more marked ACR increase was observed in STZ/KO group than STZ/WT group, although ACR did increase with weeks of age in both diabetic groups. The kidney sections from diabetic mice revealed a glomerular hypertrophy with mesangial expansion, but there was no appreciable difference in glomerular findings under a light microscope between STZ/WT and STZ/KO mice. However, an electron microscopy analysis revealed that regardless of the presence or absence of diabetes, both KO (KO and STZ/KO) groups had a higher rate of foot process effacement compared with both WT (WT and STZ/WT) groups. The expression levels of the slit diaphragm protein, podocin, was reduced with the induction of diabetes, and the levels in the STZ/KO group experienced a further reduction compared with the STZ/WT group. The number of WT1-positive cells in the STZ/KO group was more significantly decreased than that in the other three groups. In contrast, the numbers of cleaved caspase 3- and TUNEL-positive cells in the glomeruli of the STZ/KO group were more increased than those in the STZ/WT group. Thus, this study provides evidence that podocyte-specific deletion of Rac1 results in morphological alteration in podocytes, and that the induction of apoptosis or decreased expression of the slit diaphragm proteins by hyperglycemic stimuli are associated with the progression of diabetic nephropathy.

  14. OBSTETRIC RENAL FAILURE

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    Rajeshwari

    2015-11-01

    Full Text Available Renal failure in obstetrics is rare but important complication, associated with significant mortality and long term morbidity.1,2 It includes acute renal failure due to obstetrical complications or due to deterioration of existing renal disease. AIMS AND OBJECTIVES: To evaluate the etiology and outcome of renal failure in obstetric patients. METHODS: We prospectively analyzed 30 pregnant and puerperal women with acute renal failure or pre-existing renal disease developing renal failure during pregnancy between November 2007 to sep-2009. Patients who presented/developed ARF during the hospital stay were included in this study. RESULTS: Among 30 patients, mean age was 23 years and 33 years age group. 12 cases (40% patients were primigravidae and 9(30% patients were multigravidae and 9 cases (30% presented in post-partum period. Eighteen cases (60% with ARF were seen in third trimester, followed by in postpartum period 9 cases (30%. Most common contributing factors to ARF were Pre-eclampsia, eclampsia and HELLP syndrome 60%, sepsis 56.6%, post abortal ARF 10%. DIC 40%. Haemorrhage as the aetiology for ARF was present 46%, APH in 20% and PPH in 26.6%. The type of ARF was renal in (63% and prerenal (36%; Oliguric seen in 10 patients (33% and high mortality (30%. Among the 20 pregnant patients with ARF, The average period of gestation was 33±2 weeks (30 -36 weeks, 5 cases (25% presented with intrauterine fetal demise and 18 cases (66% had preterm vaginal delivery and 2 cases (10% had induced abortion. And the average birth weight was 2±0.5 kg (1.5 kg. Eight cases (26% required dialysis. 80% of patients recovered completely of renal functions. 63% patients recovered without renal replacement therapy whereas 17% required dialysis. the maternal mortality was 20%, the main reason for mortality was septic shock and multi organ dysfunction (66%. CONCLUSION: ARF related pregnancy was seen commonly in the primigravidae and in the third trimester, the most

  15. Renal Dysfunction Induced by Kidney-Specific Gene Deletion of Hsd11b2 as a Primary Cause of Salt-Dependent Hypertension.

    Science.gov (United States)

    Ueda, Kohei; Nishimoto, Mitsuhiro; Hirohama, Daigoro; Ayuzawa, Nobuhiro; Kawarazaki, Wakako; Watanabe, Atsushi; Shimosawa, Tatsuo; Loffing, Johannes; Zhang, Ming-Zhi; Marumo, Takeshi; Fujita, Toshiro

    2017-07-01

    Genome-wide analysis of renal sodium-transporting system has identified specific variations of Mendelian hypertensive disorders, including HSD11B2 gene variants in apparent mineralocorticoid excess. However, these genetic variations in extrarenal tissue can be involved in developing hypertension, as demonstrated in former studies using global and brain-specific Hsd11b2 knockout rodents. To re-examine the importance of renal dysfunction on developing hypertension, we generated kidney-specific Hsd11b2 knockout mice. The knockout mice exhibited systemic hypertension, which was abolished by reducing salt intake, suggesting its salt-dependency. In addition, we detected an increase in renal membrane expressions of cleaved epithelial sodium channel-α and T53-phosphorylated Na + -Cl - cotransporter in the knockout mice. Acute intraperitoneal administration of amiloride-induced natriuresis and increased urinary sodium/potassium ratio more in the knockout mice compared with those in the wild-type control mice. Chronic administration of amiloride and high-KCl diet significantly decreased mean blood pressure in the knockout mice, which was accompanied with the correction of hypokalemia and the resultant decrease in Na + -Cl - cotransporter phosphorylation. Accordingly, a Na + -Cl - cotransporter blocker hydrochlorothiazide significantly decreased mean blood pressure in the knockout mice. Chronic administration of mineralocorticoid receptor antagonist spironolactone significantly decreased mean blood pressure of the knockout mice along with downregulation of cleaved epithelial sodium channel-α and phosphorylated Na + -Cl - cotransporter expression in the knockout kidney. Our data suggest that kidney-specific deficiency of 11β-HSD2 leads to salt-dependent hypertension, which is attributed to mineralocorticoid receptor-epithelial sodium channel-Na + -Cl - cotransporter activation in the kidney, and provides evidence that renal dysfunction is essential for developing the

  16. RENAL CRYOABLATION

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2012-01-01

    Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

  17. Urotensin II Induces ER Stress and EMT and Increase Extracellular Matrix Production in Renal Tubular Epithelial Cell in Early Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Xin-Xin Pang

    2016-07-01

    Full Text Available Background/Aims: Urotensin II (UII and its receptor are highly expressed in the kidney tissue of patients with diabetic nephropathy (DN. The aim of this study is to examine the roles of UII in the induction of endoplasmic reticulum stress (ER stress and Epithelial-mesenchymal transition (EMT in DN in vivo and in vitro. Methods: Kidney tissues were collected from patients with DN. C57BL/6 mice and mice with UII receptor knock out were injected with two consecutive doses of streptozotocin to induce diabetes and were sacrificed at 3th week for in vivo study. HK-2 cells in vitro were cultured and treated with UII. Markers of ER stress and EMT, fibronectin and type IV collagen were detected by immunohistochemistry, real time PCR and western blot. Results: We found that the expressions of protein of UII, GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were upregulated while E-cadherin protein was downregulated as shown by immunohistochemistry or western blot analysis in kidney of diabetic mice in comparison to normal control; moreover expressions of GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were inhibited while E-caherin expression was enhanced in kidney in diabetic mice with UII receptor knock out in comparison to C57BL/6 diabetic mice. In HK-2 cells, UII induced upregulation of GRP78, CHOP, ALPHA-SMA, fibroblast-specifc protein 1(FSP-1, fibronectin and type collagen and downregulation of E-cadherin. UII receptor antagonist can block UII-induced ER stress and EMT; moreover, 4-PBA can inhibit the mRNA expression of ALPHA-SMA and FSP1 induced by UII in HK-2 cells. Conclusions: We are the first to verify UII induces ER stress and EMT and increase extracellular matrix production in renal tubular epithelial cell in early diabetic mice. Moreover, UII may induce renal tubular epithelial EMT via triggering ER stress pathway in vitro, which might be the new pathogenic pathway for the development of renal fibrosis in DN.

  18. The role of the IGF axis in IGFBP-1 and IGF-I induced renal enlargement in Snell dwarf mice

    NARCIS (Netherlands)

    M. van Kleffens (Marjolein); D.J. Lindenbergh-Kortleve (Dicky); J.G. Koster; J.W. van Neck (Han); A. Flyvbjerg (Allan); R. Rasch; S.L.S. Drop (Stenvert); S.C. van Buul-Offers

    2001-01-01

    textabstractInsulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is generally believed to inhibit IGF action in the circulation. In contrast, IGFBP-1 has been reported to interact with cell surfaces and enhance IGF-I action locally in some tissues. Renal IGFBP-1 levels are

  19. Role of IGFBP7 in Diabetic Nephropathy: TGF-β1 Induces IGFBP7 via Smad2/4 in Human Renal Proximal Tubular Epithelial Cells.

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    Jun Watanabe

    Full Text Available Tubular injury is one of the important determinants of progressive renal failure in diabetic nephropathy (DN, and TGF-β1 has been implicated in the pathogenesis of tubulointerstitial disease that characterizes proteinuric renal disease. The aim of this study was to identify novel therapeutic target molecules that play a role in the tubule damage of DN. We used an LC-MS/MS-based proteomic technique and human renal proximal epithelial cells (HRPTECs. Urine samples from Japanese patients with type 2 diabetes (n = 46 were used to quantify the candidate protein. Several proteins in HRPTECs in cultured media were observed to be driven by TGF-β1, one of which was 33-kDa IGFBP7, which is a member of IGFBP family. TGF-β1 up-regulated the expressions of IGFBP7 mRNA and protein in a dose- and time-dependent fashion via Smad2 and 4, but not MAPK pathways in HRPTECs. In addition, the knockdown of IGFBP7 restored the TGF-β1-induced epithelial to mesenchymal transition (EMT. In the immunohistochemical analysis, IGFBP7 was localized to the cytoplasm of tubular cells but not that of glomerular cells in diabetic kidney. Urinary IGFBP7 levels were significantly higher in the patients with macroalbuminuria and were correlated with age (r = 0.308, p = 0.037, eGFR (r = -0.376, p = 0.01, urinary β2-microglobulin (r = 0.385, p = 0.008, and urinary N-acetyl-beta-D-glucosaminidase (NAG (r = 0.502, p = 0.000. A multivariate regression analysis identified urinary NAG and age as determinants associated with urinary IGFBP7 levels. In conclusion, our data suggest that TGF-β1 enhances IGFBP7 via Smad2/4 pathways, and that IGFBP7 might be involved in the TGF-β1-induced tubular injury in DN.

  20. MRP-1 expression levels determine strain-specific susceptibility to sodium arsenic-induced renal injury between C57BL/6 and BALB/c mice

    International Nuclear Information System (INIS)

    Kimura, Akihiko; Ishida, Yuko; Wada, Takashi; Yokoyama, Hitoshi; Mukaida, Naofumi; Kondo, Toshikazu

    2005-01-01

    To clarify the pathophysiological mechanism underlying acute renal injury caused by acute exposure to arsenic, we subcutaneously injected both BALB/c and C57BL/6 mice with sodium arsenite (NaAs; 13.5 mg/kg). BALB/c mice exhibited exaggerated elevation of serum blood urea nitrogen (BUN) and creatinine (CRE) levels, compared with C57BL/6 mice. Moreover, half of BALB/c mice died by 24 h, whereas all C57BL/6 mice survived. Histopathological examination on kidney revealed severe hemorrhages, acute tubular necrosis, neutrophil infiltration, cast formation, and disappearance of PAS-positive brush borders in BALB/c mice, later than 10 h. These pathological changes were remarkably attenuated in C57BL/6 mice, accompanied with lower intrarenal arsenic concentrations, compared with BALB/c mice. Among heavy metal inducible proteins including multidrug resistance-associated protein (MRP)-1, multidrug resistance gene (MDR)-1, metallothionein (MT)-1, and arsenite inducible, cysteine- and histidine-rich RNA-associated protein (AIRAP), intrarenal MDR-1, MT-1, and AIRAP gene expression was enhanced to a similar extent in both strains, whereas NaAs challenge augmented intrarenal MRP-1 mRNA and protein expression levels in C57BL/6 but not BALB/c mice. Moreover, the administration of a specific inhibitor of MRP-1, MK-571, significantly exaggerated acute renal injury in C57BL/6 mice. Thus, MRP-1 is crucially involved in arsenic efflux and eventually prevention of acute renal injury upon acute exposure to NaAs

  1. Small Molecule Inhibiting Nuclear Factor-kB Ameliorates Oxidative Stress and Suppresses Renal Inflammation in Early Stage of Alloxan-Induced Diabetic Nephropathy in Rat.

    Science.gov (United States)

    Borgohain, Manash P; Lahkar, Mangala; Ahmed, Sahabuddin; Chowdhury, Liakat; Kumar, Saurabh; Pant, Rajat; Choubey, Abhinav

    2017-05-01

    Diabetic nephropathy is one of the major microvascular complications of diabetes mellitus which ultimately gives rise to cardiovascular diseases. Prolonged hyperglycaemia and chronic renal inflammation are the two key players in the development and progression of diabetic nephropathy. Nuclear factor kB (NF-kB)-mediated inflammatory cascade is a strong contributor to the renovascular inflammation in diabetic nephropathy. Here, we studied the effects of piceatannol, a potent NF-kB inhibitor, on various oxidative stress markers and NF-kB dependent diabetic renoinflammatory cascades in rat induced by alloxan (ALX). Experimental diabetes was induced in male Wistar rats by a single intraperitoneal dose, 150 mg/kg body-weight (b.w.) of ALX. Diabetic rats were treated with Piceatannol (PCTNL) at a dose of 30 and 50 mg/kg b.w. After 14 days of oral treatment, PCTNL significantly restored blood sugar level, glomerular filtration rate, serum markers and plasma lipids. PCTNL administration also reversed the declined activity of cellular antioxidant machineries namely superoxide dismutase and glutathione and the elevated levels of malondialdehyde and nitric oxide. Moreover, piceatannol-treated groups showed marked inhibition of renal pro-inflammatory cytokines and NF-kB p65/p50 binding to DNA. Renal histopathological investigations also supported its ameliorative effects against diabetic kidney damage. Importantly, effects were more prominent at a dose of 50 mg/kg, and in terms of body-weight gain, PCTNL failed to effect significantly. However, overall findings clearly demonstrated that PCTNL provides remarkable renoprotection in diabetes by abrogating oxidative stress and NF-kB activation - and might be helpful in early stage of diabetic nephropathy. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  2. Resveratrol prevents high glucose-induced epithelial-mesenchymal transition in renal tubular epithelial cells by inhibiting NADPH oxidase/ROS/ERK pathway.

    Science.gov (United States)

    He, Ting; Guan, Xu; Wang, Song; Xiao, Tangli; Yang, Ke; Xu, Xinli; Wang, Junping; Zhao, Jinghong

    2015-02-15

    Resveratrol (RSV) is reported to have renoprotective activity against diabetic nephropathy, while the mechanisms underlying its function have not been fully elucidated. In this study, we investigate the effect and related mechanism of RSV against high glucose-induced epithelial to mesenchymal transition (EMT) in human tubular epithelial cells (HK-2). A typical EMT is induced by high glucose in HK-2 cells, accompanied by increased levels of reactive oxygen species (ROS). RSV exhibits a strong ability to inhibit high glucose-induced EMT by decreasing intracellular ROS levels via down-regulation of NADPH oxidase subunits NOX1 and NOX4. The activation of extracellular signal-regulated kinase (ERK1/2) is found to be involved in high glucose-induced EMT in HK-2 cells. RSV, like NADPH oxidase inhibitor diphenyleneiodonium, can block ERK1/2 activation induced by high glucose. Our results demonstrate that RSV is a potent agent against high glucose-induced EMT in renal tubular cells via inhibition of NADPH oxidase/ROS/ERK1/2 pathway. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. AMP-Activated Protein Kinase Alleviates Extracellular Matrix Accumulation in High Glucose-Induced Renal Fibroblasts through mTOR Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xia Luo

    2015-01-01

    Full Text Available Background/Aims: Extracellular matrix accumulation contributes significantly to the pathogenesis of diabetic nephropathy. Although AMP-activated protein kinase (AMPK has been found to inhibit extracellular matrix synthesis by experiments in vivo and vitro, its role in alleviating the deposition of extracellular matrix in renal interstitial fibroblasts has not been well defined. Methods: Currently, we conducted this study to investigate the effects of AMPK on high glucose-induced extracellular matrix synthesis and involved intracellular signaling pathway by using western blot in the kidney fibroblast cell line (NRK-49f. Results: Collagen IV protein levels were significantly increased by high glucose in a time-dependent manner. This was associated with a decrease in Thr72 phosphorylation of AMPK and an increase in phosphorylation of mTOR on Ser2448. High glucose-induced extracellular matrix accumulation and mTOR activation were significantly inhibited by the co-treatment of rAAV-AMPKα1312 (encoding constitutively active AMPKα1 whereas activated by r-AAV-AMPKα1D157A (encoding dominant negative AMPKα1. In cultured renal fibroblasts, overexpression of AMPKα1D157A upregulated mTOR signaling and matrix synthesis, which were ameliorated by co-treatment with the inhibitor of mTOR, rapamycin. Conclusion: Collectively, these findings indicate that AMPK exerts renoprotective effects by inhibiting the accumulation of extracellular matrix through mTOR signaling pathway.

  4. Antioxidant activity and protective effect of bee bread (honey and pollen) in aluminum-induced anemia, elevation of inflammatory makers and hepato-renal toxicity.

    Science.gov (United States)

    Bakour, Meryem; Al-Waili, Noori S; El Menyiy, Nawal; Imtara, Hamada; Figuira, Anna Cristina; Al-Waili, Thia; Lyoussi, Badiaa

    2017-12-01

    Aluminum toxicity might be related to oxidative stress, and the antioxidant activity and protective effect of bee bread, which contains pollen, honey and bees' enzymes, on aluminum induced blood and hepato-renal toxicity was investigated in rats. Chemical analysis and antioxidant capacity of bee bread were conducted. The animal experiment in rats included; group 1: received distilled water (10 ml/kg b.wt), group 2: received aluminum chloride (662.2 mg/kg b.wt), group 3: received aluminum chloride (662.2 mg/kg b.wt) and ethanolic extract of the bee bread (500 mg/kg b.wt), and group 4: received aluminum chloride (662.2 mg/kg b.wt) and ethanolic extract of the bee bread (750 mg/kg b.wt). Doses were given once daily via a gavage. C-reactive protein, transaminases, urea, creatinine, creatinine clearance, sodium and potassium and urine sodium and potassium were determined on day 28 of the experiment. Bee bread contained protein, fat, fiber, ash, carbohydrate, phenol and flavonoids and it exhibited antioxidant activity. Aluminum caused a significant elevation of blood urea, transaminase, C-reactive protein and monocyte count and significantly decreased hemoglobin. These changes were significantly ameliorated by the use of bee bread. Bee bread has an antioxidant property, and exhibited a protective effect on aluminum induced blood and hepato-renal toxicity and elevation of inflammatory markers C-reactive protein, leukocyte and monocyte counts.

  5. Fas-Induced Apoptosis of Renal Cell Carcinoma is Mediated by Apoptosis Signal-Regulating Kinase 1 via Mitochondrial Damage-Dependent Caspase-8 Activation

    Directory of Open Access Journals (Sweden)

    Mohamed Hassan

    2009-01-01

    Full Text Available Renal cell carcinoma (RCC is a prototype of a chemo refractory tumour. It remains the most lethal of the common urologic cancers and is highly resistant to conventional therapy. Here, we confirmed the efficiency of anti-Fas monoclonal antibody (CH11 as alternative therapeutic approach for the treatment of RCC and investigated the molecular mechanism(s, whereby CH11 induces apoptosis of RCC cells. The present study shows an essential role for apoptosis signal-regulating kinase 1 (ASK1, together with both c-jun-N-terminal kinase (JNK and p38 pathways, and caspase-8 in this process. Furthermore, CH11-dependent induction of the ASK1–JNK/p38 pathways was found to activate the transcription factors AP-1 and ATF-2, and FADD-caspase-8-Bid signalling, resulting in the translocation of both Bax and Bak proteins, and subsequently mitochondrial dysregulation that is characterized by the loss of mitochondrial membrane potential (ΔΨm, cytochrome c release and cleavage of caspase-9, caspase-3 and PARP. Thus, the described molecular mechanisms of CH11-induced apoptosis suggest the reliability of Fas activation as an alternative therapeutic approach for the treatment of patients with advanced renal cell carcinoma.

  6. Impact of benazepril on contrast-induced acute kidney injury for patients with mild to moderate renal insufficiency undergoing percutaneous coronary intervention.

    Science.gov (United States)

    Li, Xi-ming; Cong, Hong-liang; Li, Ting-ting; He, Li-jun; Zhou, Yu-jie

    2011-07-01

    The role of angiotensin-converting enzyme inhibitors (ACEI) in contrast-induced acute kidney injury (CI-AKI) is controversial. Some studies pointed out that it was effective in the prevention of CI-AKI, while some concluded that it was one risk for CI-AKI, especially for patients with pre-existing renal impairment. The purpose of this study was to assess the influence of benazepril administration on the development of CI-AKI in patients with mild to moderate renal insufficiency undergoing coronary intervention. One hundred and fourteen patients with mild to moderate impairment of renal function were enrolled before coronary angioplasty, who were randomly assigned to benazepril group (n = 52) and control group (n = 62). In the benazepril group, the patients received benazepril tablets 10 mg per day at least for 3 days before procedure. CI-AKI was defined as an increase of ≥ 25% in creatinine over the baseline value or increase of 0.5 mg/L within 72 hours of angioplasty. Patients were well matched with no significant differences at baseline in all measured parameters between two groups. The incidence of CI-AKI was lower by 64% in the benazepril group compared with control group but without statistical significance (3.45% vs. 9.68%, P = 0.506). Compared with benazepril group, estimated glomerular filtration rate (eGFR) level significantly decreased from (70.64 ± 16.38) ml · min⁻¹·1.73 m⁻² to (67.30 ± 11.99) ml · min⁻¹·1.73 m⁻² in control group (P = 0.038). There was no significant difference for the post-procedure decreased eGFR from baseline (ΔeGFR) between two groups (benazepril group (0.67 ± 12.67) ml · min⁻¹·1.73 m⁻² vs. control group (-3.33 ± 12.39) ml · min⁻¹·1.73 m⁻², P = 0.092). In diabetic subgroup analysis, ΔeGFR in benazepril group was slightly lower than that in the control group, but the difference was not statistically significant. Benazepril has a protective effect on mild to moderate impairment of renal function

  7. The purinergic 2X7 receptor participates in renal inflammation and injury induced by high-fat diet: possible role of NLRP3 inflammasome activation.

    Science.gov (United States)

    Solini, Anna; Menini, Stefano; Rossi, Chiara; Ricci, Carlo; Santini, Eleonora; Blasetti Fantauzzi, Claudia; Iacobini, Carla; Pugliese, Giuseppe

    2013-11-01

    Renal disease associated with type 2 diabetes and the metabolic syndrome is characterized by a distinct inflammatory phenotype. The purinergic 2X7 receptor (P2X7 R) and the nucleotide-binding and oligomerization domain-like receptor containing a pyrin domain 3 (NLRP3) inflammasome have been separately shown to play a role in two models of non-metabolic chronic kidney disease. Moreover, the NLRP3 inflammasome has been implicated in chronic low-grade sterile inflammation characterizing metabolic disorders, though the mechanism(s) involved in inflammasome activation under these conditions are still unknown. We investigated the role of P2X7 R (through activation of the NLRP3 inflammasome) in renal inflammation and injury induced by a high-fat diet, an established model of the metabolic syndrome. On a high-fat diet, mice lacking P2X7 R developed attenuated renal functional and structural alterations as well as reduced inflammation, fibrosis, and oxidative/carbonyl stress, as compared with wild-type animals, in the absence of significant differences in metabolic parameters. This was associated with blunted up-regulation of the NLRP3 inflammasome components NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), pro-caspase 1, pro-interleukin (IL)-1β, and pro-IL-18, as well as reduced inflammasome activation, as evidenced by decreased formation of mature caspase 1, whereas mature IL-1β and IL-18 were not detected. Up-regulated expression of NLRP3 and pro-caspase 1, post-translational processing of pro-caspase-1, and release of IL-18 in response to lipopolysaccharide + 2'(3')-O-(4-benzoylbenzoyl)ATP were attenuated by P2X7 R silencing in cultured mouse podocytes. Protein and mRNA expression of P2X7 R, NLRP3, and ASC were also increased in kidneys from subjects with type 2 diabetes and the metabolic syndrome, showing histologically documented renal disease. These data provide evidence of a major role for the purinergic system, at

  8. Renal cancer.

    NARCIS (Netherlands)

    Corgna, E.; Betti, M.; Gatta, G.; Roila, F.; Mulder, P.H.M. de

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  9. Renal cancer

    NARCIS (Netherlands)

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  10. Renal effects and nephroprotection induced by SGLT2 inhibitor Empagliflozin in patients with Diabetes Mellitus: a literature review

    Directory of Open Access Journals (Sweden)

    Luis E. Morales-Buenrostro

    2017-01-01

    Full Text Available Chronic kidney disease is a frequent comorbidity in patients with diabetes mellitus (DM and it increases their cardiovascular risk; chronic hyperglycemia in patients with DM leads to direct and indirect disorders in kidney's structure and function, and it is the principal risk factor for the development of diabetic nephropathy and end-stage renal disease. In the current review, results of studies are exposed in which high tolerability of empagliflozin is exposed in diabetic patients with kidney disease. Empagliflozin by inhibiting SGLT2 provides a novel therapy with benefic effects, not only in glycemic control, but it also has cardiovascular and renal benefits, which they have been demonstrated in the EMPA-REG OUTCOME trial, and continue in evaluation in other studies.

  11. Omega-3 attenuates high fat diet-induced kidney injury of female rats and renal programming of their offsprings.

    Science.gov (United States)

    Shamseldeen, Asmaa Mohammed; Ali Eshra, Mohammed; Ahmed Rashed, Laila; Fathy Amer, Marwa; Elham Fares, Amal; Samir Kamar, Samaa

    2018-05-09

    Maternal diet composition could influence fetal organogenesis. We investigated effects of high fat diet (HFD) intake alone or combined with omega 3 during pregnancy, lactation and early days of weaning on nephrogenesis of pups and maternal renal function and morphology. Mothers and their pups included in each group were supplied with the same diet composition. Rats were divided into group I, II and III supplied with chow of either 10 kcal%, 45 kcal% or 45 kcal% from fat together with omega-3 respectively. Group II showed increased serum urea and creatinine, renal TNF-α, IL1β. Structural injury was observed in mothers and their pups as Bowman's capsule and tubular dilatation and increased expression of PCNA that were decreased following omega-3 supplementation added to down regulation of Wnt4, Pax2 gene and podocin expression. Omega-3 supplementation improves lipid nephrotoxicity observed in mothers and their pups.

  12. Ex Vivo Normothermic Perfusion Induces Donor-Derived Leukocyte Mobilization and Removal Prior to Renal Transplantation

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    John P. Stone

    2016-11-01

    Discussion: We demonstrate that ex vivo normothermic perfusion initiates an inflammatory cytokine storm and release of mitochondrial and genomic DNA. This is likely to be responsible for immune cell activation and mobilization into the circuit prior to transplantation. Interestingly this did not have an impact on renal function. These data therefore suggest that normothermic perfusion can be used to immunodeplete and to saturate the pro-inflammatory capacity of donor kidneys prior to transplantation.

  13. Sunitinib-induced hypertension, neutropenia and thrombocytopenia as predictors of good prognosis in metastatic renal cell carcinoma patients

    DEFF Research Database (Denmark)

    Rautiola, Juhana; Donskov, Frede; Peltola, Katriina

    2016-01-01

    OBJECTIVES: To evaluate the clinical significance of hypertension, neutropenia and thrombocytopenia as possible new biomarkers of sunitinib efficacy in non-trial metastatic renal cell carcinoma (mRCC) patients. MATERIALS AND METHODS: 181 consecutive mRCC patients were treated with sunitinib. Thir...... of sunitinib efficacy patients with mRCC. Our results may help to individualize sunitinib dosing during therapy based on these common sunitinib-related AEs....

  14. A High Fat Diet During Pregnancy and Lactation Induces Cardiac and Renal Abnormalities in GLUT4 +/- Male Mice

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    Michael Kruse

    2017-07-01

    Full Text Available Background/Aims: Altered nutrients during the in utero (IU and/or lactation (L period predispose offspring to cardio-renal diseases in adulthood. This study investigates the effect of a high fat diet (HFD fed to female mice during IU/L on gene expression patterns associated with heart and kidney failure and hypertension in male offspring. Methods: Female wild type (WT mice were fed either a HFD or control chow (C prior to mating with males with a genetic heterozygous deletion of GLUT4 (G4+/-, a model of peripheral insulin resistance and hypertension and throughout IU/L. After weaning male offspring were placed on a standard rodent chow until 24 weeks of age. Results: All offspring exposed to a maternal HFD showed increased heart and kidney weight and reduced cardiac insulin responsiveness. G4+/- offspring on a HFD displayed early hypertension associated with increased renal gene expression of renin and the AT1- receptors compared to G4+/- on a C diet. This group showed decreased cardiac expression of key genes involved in fatty acid oxidation compared to WT on a C diet. Conclusions: These results indicate an interaction between a HFD diet and genotype during early life development that can enhance susceptibility to cardio-renal diseases later in life.

  15. ANCA Associated Vasculitis and Renal Failure Related to Propylthiouracil and Hyperthyroidism Induced Cholestasis in the Same Case

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    Mehmet Tuncay

    2014-01-01

    Full Text Available Introduction. Liver involvement due to hyperthyroidism and also ANCA positive vasculitis related renal failure cases were reported separately several times before. However, to our knowledge, these two complications together in the same case had never been observed before. Case Presentation. The case of an ANCA positive 71-year-old Caucasian male with renal failure and lung involvement, subclinical hyperthyroidism, and intrahepatic cholestatic jaundice was presented in this paper. After exclusion of all of the other possibilities, cholestatic hepatitis was explained by subclinical hyperthyroidism; renal failure and lung involvement were interpreted as ANCA related vasculitis which might be a side effect of propylthiouracil use. Conclusion. The coexistence of these rare conditions in the same patient deserves emphasis and it is worth reporting. This case demonstrates that following the clinical course of the patient is essential after prescribing any medications to see whether any complication occurs or not. If the complications of this case were noticed earlier, it would be possible to treat and to prevent the permanent damages.

  16. Crosstalk between Smad and Mitogen-Activated Protein Kinases for the Regulation of Apoptosis in Cyclosporine A- Induced Renal Tubular Injury

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    Hideyuki Iwayama

    2011-10-01

    Full Text Available Background/Aims: It remains elusive whether there is a crosstalk between Smad and mitogen-activated protein kinases (MAPKs and whether it regulates cyclosporine A (CyA-induced apoptosis in renal proximal tubular cells (RPTCs. Methods: The effect of CyA on nuclear translocation of Smad2/3 and MAPKs (measured by Western blotting or immunofluorescence and apoptosis (determined by Hoechst 33258 staining was examined in HK-2 cells. Results: CyA induced apoptosis at 24 h and nuclear translocation of phosphorylated (p-Smad2/3 at 3 h, which was continued till 24 h. CyA enhanced the expression of p-ERK at 1 h, which was continued till 24 h, and of p-p38MAPK at 1–6 h, which returned to control level at 12 h. CyA did not affect JNK. An inhibitor of ERK, PD98059, prevented CyA-induced nuclear translocation of Smad2/3 and apoptosis. An inhibitor of p38MAPK, SB202190, deteriorated CyA-induced nuclear translocation of p-Smad2/3. Epidermal growth factor (EGF activated ERK and p38MAPK but not JNK. EGF-induced activation of MAPKs ameliorated CyA-induced nuclear translocation of p-Smad2/3 and apoptosis. Inhibition of p38MAPK but not of ERK abolished the protective effect of EGF on CyA-induced nuclear translocation of p-Smad2/3 and apoptosis. Conclusion: Crosstalk between R-Smad and p38MAPK/ERK, but not JNK differentially regulates apoptosis in CyA-induced RPTC injury.

  17. SIRT1 overexpression decreases cisplatin-induced acetylation of NF-κB p65 subunit and cytotoxicity in renal proximal tubule cells

    International Nuclear Information System (INIS)

    Jung, Yu Jin; Lee, Jung Eun; Lee, Ae Sin; Kang, Kyung Pyo; Lee, Sik; Park, Sung Kwang; Lee, Sang Yong; Han, Myung Kwan; Kim, Duk Hoon; Kim, Won

    2012-01-01

    Highlights: ► Cisplatin increases acetylation of NF-κB p65 subunit in HK2 cells. ► SIRT1 overexpression decreases cisplatin-induced p65 acetylation and -cytotoxicity. ► Resveratrol decreased cisplatin-induced cell viability through deacetylation of p65. -- Abstract: As the increased acetylation of p65 is linked to nuclear factor-κB (NF-κB) activation, the regulation of p65 acetylation can be a potential target for the treatment of inflammatory injury. Cisplatin-induced nephrotoxicity is an important issue in chemotherapy of cancer patients. SIRT1, nicotinamide adenine dinucleotide (NAD + )-dependent protein deacetylase, has been implicated in a variety of cellular processes such as inflammatory injury and the control of multidrug resistance in cancer. However, there is no report on the effect of SIRT1 overexpression on cisplatin-induced acetylation of p65 subunit of NF-κB and cell injury. To investigate the effect of SIRT1 in on cisplatin-induced acetylation of p65 subunit of NF-κB and cell injury, HK2 cells were exposed with SIRT1 overexpression, LacZ adenovirus or dominant negative adenovirus after treatment with cisplatin. While protein expression of SIRT1 was decreased by cisplatin treatment compared with control buffer treatment, acetylation of NF-κB p65 subunit was significantly increased after treatment with cisplatin. Overexpression of SIRT1 ameliorated the increased acetylation of p65 of NF-κB during cisplatin treatment and cisplatin-induced cytotoxicity. Further, treatment of cisplatin-treated HK2 cells with resveratrol, a SIRT1 activator, also decreased acetylation of NF-κB p65 subunit and cisplatin-induced increase of the cell viability in HK2 cells. Our findings suggests that the regulation of acetylation of p65 of NF-κB through SIRT1 can be a possible target to attenuate cisplatin-induced renal cell damage.

  18. Induction and regulation of tumor necrosis factor-related apoptosis-inducing ligand/Apo-2 ligand-mediated apoptosis in renal cell carcinoma.

    Science.gov (United States)

    Griffith, Thomas S; Fialkov, Jonathan M; Scott, David L; Azuhata, Takeo; Williams, Richard D; Wall, Nathan R; Altieri, Dario C; Sandler, Anthony D

    2002-06-01

    The lack of effective therapy for disseminated renal cell carcinoma (RCC) has stimulated the search for novel treatments including immunotherapeutic strategies. However, poor therapeutic responses and marked toxicity associated with immunological agents has limited their use. The tumor necrosis factor family member tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo-2 ligand induces apoptosis in a variety of tumor cell types, while having little cytotoxic activity against normal cells. In this study the activation and regulation of TRAIL-induced apoptosis and TRAIL receptor expression in human RCC cell lines and pathologic specimens was examined. TRAIL induced caspase-mediated apoptotic death of RCC cells with variable sensitivities among the cell lines tested. Compared with TRAIL-sensitive RCC cell lines (A-498, ACHN, and 769-P), the TRAIL-resistant RCC cell line (786-O) expressed lesser amounts of the death-inducing TRAIL receptors, and greater amounts of survivin, an inhibitor of apoptosis. Incubation of 786-O with actinomycin D increased the expression of the death-inducing TRAIL receptors and, concomitantly, decreased the intracellular levels of survivin, resulting in TRAIL-induced apoptotic death. The link between survivin and TRAIL regulation was confirmed when an increase in TRAIL resistance was observed after overexpression of survivin in the TRAIL-sensitive, survivin-negative RCC line A-498. These findings, along with our observation that TRAIL receptors are expressed in RCC tumor tissue, suggest that TRAIL may be useful as a therapeutic agent for RCC and that survivin may partially regulate TRAIL-induced cell death.

  19. Oxidative stress by monosodium urate crystals promotes renal cell apoptosis through mitochondrial caspase-dependent pathway in human embryonic kidney 293 cells: mechanism for urate-induced nephropathy.

    Science.gov (United States)

    Choe, Jung-Yoon; Park, Ki-Yeun; Kim, Seong-Kyu

    2015-01-01

    The aim of this study is to clarify the effect of oxidative stress on monosodium urate (MSU)-mediated apoptosis of renal cells. Quantitative real-time polymerase chain reaction and immunoblotting for Bcl-2, caspase-9, caspase-3, iNOS, cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), IL-18, TNF receptor-associated factor-6 (TRAF-6), and mitogen-activated protein kinases were performed on human embryonic kidney 293 (HEK293) cells, which were stimulated by MSU crystals. Fluorescence-activated cell sorting was performed using annexin V for assessment of apoptosis. Reactive oxygen species (ROS) were measured. IL-1β siRNA was used for blocking IL-1β expression. MSU crystals promoted ROS, iNOS, and COX-2 expression and also increased TRAF-6 and IL-1β expression in HEK293 cells, which was inhibited by an antioxidant ascorbic acid. Caspase-dependent renal cell apoptosis was induced through attenuation of Bcl-2 and enhanced caspase-3 and caspase-9 expression by MSU crystals, which was significantly reversed by ascorbic acid and transfection of IL-1β siRNA to HEK293 cells. Ascorbic acid inhibited phosphorylation of extracellular signal-regulated kinase and Jun N-terminal protein kinase stimulated by MSU crystals. ROS accumulation and iNOS and COX-2 mRNA expression by MSU crystals was also suppressed by transfection with IL-1β siRNA. Oxidative stress generated by MSU crystals promotes renal apoptosis through the mitochondrial caspase-dependent apoptosis pathway.

  20. Role of TLR4/NADPH oxidase/ROS-activated p38 MAPK in VCAM-1 expression induced by lipopolysaccharide in human renal mesangial cells

    Directory of Open Access Journals (Sweden)

    Lee I-Ta

    2012-11-01

    Full Text Available Abstract Background In bacteria-induced glomerulonephritis, Toll-like receptor 4 (TLR4 activation by lipopolysaccharide (LPS, a key component of the outer membranes of Gram-negative bacteria can increase oxidative stress and the expression of vascular cell adhesion molecule-1 (VCAM-1, which recruits leukocytes to the glomerular mesangium. However, the mechanisms underlying VCAM-1 expression induced by LPS are still unclear in human renal mesangial cells (HRMCs. Results We demonstrated that LPS induced VCAM-1 mRNA and protein levels associated with an increase in the promoter activity of VCAM-1, determined by Western blot, RT-PCR, and promoter assay. LPS-induced responses were inhibited by transfection with siRNAs of TLR4, myeloid differentiation factor 88 (MyD88, Nox2, Nox4, p47phox, c-Src, p38 MAPK, activating transcription factor 2 (ATF2, and p300 or pretreatment with the inhibitors of reactive oxygen species (ROS, edaravone, NADPH oxidase [apocynin (APO or diphenyleneiodonium chloride (DPI], c-Src (PP1, p38 MAPK (SB202190, and p300 (GR343. LPS induced NADPH oxidase activation, ROS production, and p47phox translocation from the cytosol to the membrane, which were reduced by PP1 or c-Src siRNA. We observed that LPS induced TLR4, MyD88, c-Src, and p47phox complex formation determined by co-immunoprecipitation and Western blot. We further demonstrated that LPS stimulated ATF2 and p300 phosphorylation and complex formation via a c-Src/NADPH oxidase/ROS/p38 MAPK pathway. Up-regulation of VCAM-1 led to enhancing monocyte adhesion to HRMCs challenged with LPS, which was inhibited by siRNAs of c-Src, p47phox, p38 MAPK, ATF2, and p300 or pretreatment with an anti-VCAM-1 neutralizing antibody. Conclusions In HRMCs, LPS-induced VCAM-1 expression was, at least in part, mediated through a TLR4/MyD88/ c-Src/NADPH oxidase/ROS/p38 MAPK-dependent p300 and ATF2 pathway associated with recruitment of monocyte adhesion to kidney. Blockade of these pathways may

  1. Berberine activates Nrf2 nuclear translocation and inhibits apoptosis induced by high glucose in renal tubular epithelial cells through a phosphatidylinositol 3-kinase/Akt-dependent mechanism.

    Science.gov (United States)

    Zhang, Xiuli; Liang, Dan; Lian, Xu; Jiang, Yan; He, Hui; Liang, Wei; Zhao, Yue; Chi, Zhi-Hong

    2016-06-01

    Apoptosis of tubular epithelial cells is a major feature of diabetic kidney disease, and hyperglycemia triggers the generation of free radicals and oxidant stress in tubular cells. Berberine (BBR) is identified as a potential anti-diabetic herbal medicine due to its beneficial effects on insulin sensitivity, glucose metabolism and glycolysis. In this study, the underlying mechanisms involved in the protective effects of BBR on high glucose-induced apoptosis were explored using cultured renal tubular epithelial cells (NRK-52E cells) and human kidney proximal tubular cell line (HK-2 cells). We identified the pivotal role of phosphatidylinositol 3-kinase (PI3K)/Akt in BBR cellular defense mechanisms and revealed the novel effect of BBR on nuclear factor (erythroid-derived 2)-related factor-2 (Nrf2) and heme oxygenase (HO)-1 in NRK-52E and HK-2 cells. BBR attenuated reactive oxygen species production, antioxidant defense (GSH and SOD) and oxidant-sensitive proteins (Nrf2 and HO-1), which also were blocked by LY294002 (an inhibitor of PI3K) in HG-treated NRK-52E and HK-2 cells. Furthermore, BBR improved mitochondrial function by increasing mitochondrial membrane potential. BBR-induced anti-apoptotic function was demonstrated by decreasing apoptotic proteins (cytochrome c, Bax, caspase3 and caspase9). All these findings suggest that BBR exerts the anti-apoptosis effects through activation of PI3K/Akt signal pathways and leads to activation of Nrf2 and induction of Nrf2 target genes, and consequently protecting the renal tubular epithelial cells from HG-induced apoptosis.

  2. The Protective Effect of γ-aminobutyric Acid on Kidney Injury Induced by Renal Ischemia-reperfusion in Ovariectomized Estradiol-treated Rats.

    Science.gov (United States)

    Talebi, Nahid; Nematbakhsh, Mehdi; Monajemi, Ramesh; Mazaheri, Safoora; Talebi, Ardeshir; Vafapour, Marzieh

    2016-01-01

    Renal ischemia-reperfusion injury (IRI) is one of the most important causes of kidney injury, which is possibly gender-related. This study was designed to investigate the role of γ-aminobutyric acid (GABA) against IRI in ovariectomized estradiol-treated rats. Thirty-five ovariectomized Wistar rats were used in six experimental groups. The first three groups did not subject to estradiol treatment and assigned as sham-operated, control, and GABA-treated groups. GABA (50 μmol/kg) and saline were injected in the treated and control groups 30 min before the surgery, respectively. The second three groups received the same treatments but received estradiol valerate (500 μg/kg, intramuscularly) 3 days prior to the surgery. The IRI was induced in the control and treated groups by clamping the renal artery for 45 min and then 24 h of reperfusion. All animals were sacrificed for the measurements. The serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score significantly increased in the IRI rats (P GABA significantly decreased the aforementioned parameters (P levels of nitrite (nitric oxide metabolite) did not alter significantly. Serum level of malondialdehyde increased significantly in the ovariectomized rats exposed to IRI (P GABA improved IRI in ovariectomized rats. Estradiol was also nephroprotective against IRI. However, co-administration of estradiol and GABA could not protect the kidney against IRI.

  3. Antioxidative effects of fermented sesame sauce against hydrogen peroxide-induced oxidative damage in LLC-PK1 porcine renal tubule cells

    Science.gov (United States)

    Song, Jia-Le; Choi, Jung-Ho; Seo, Jae-Hoon; Kil, Jeung-Ha

    2014-01-01

    BACKGROUND/OBJECTIVES This study was performed to investigate the in vitro antioxidant and cytoprotective effects of fermented sesame sauce (FSeS) against hydrogen peroxide (H2O2)-induced oxidative damage in renal proximal tubule LLC-PK1 cells. MATERIALS/METHODS 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical (•OH), and H2O2 scavenging assay was used to evaluate the in vitro antioxidant activity of FSeS. To investigate the cytoprotective effect of FSeS against H2O2-induced oxidative damage in LLC-PK1 cells, the cellular levels of reactive oxygen species (ROS), lipid peroxidation, and endogenous antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) were measured. RESULTS The ability of FSeS to scavenge DPPH, •OH and H2O2 was greater than that of FSS and AHSS. FSeS also significantly inhibited H2O2-induced (500 µM) oxidative damage in the LLC-PK1 cells compared to FSS and AHSS (P sauces, FSeS also significantly increased cellular CAT, SOD, and GSH-px activities and mRNA expression (P < 0.05). CONCULUSIONS These results from the present study suggest that FSeS is an effective radical scavenger and protects against H2O2-induced oxidative damage in LLC-PK1 cells by reducing ROS levels, inhibiting lipid peroxidation, and stimulating antioxidant enzyme activity. PMID:24741396

  4. Renal scan

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003790.htm Renal scan To use the sharing features on this ... anaphylaxis . Alternative Names Renogram; Kidney scan Images Kidney anatomy Kidney - blood and urine flow References Chernecky CC, ...

  5. Mercury exposure induces cytoskeleton disruption and loss of renal function through epigenetic modulation of MMP9 expression.

    Science.gov (United States)

    Khan, Hafizurrahman; Singh, Radha Dutt; Tiwari, Ratnakar; Gangopadhyay, Siddhartha; Roy, Somendu Kumar; Singh, Dhirendra; Srivastava, Vikas

    2017-07-01

    Mercury is one of the major heavy metal pollutants occurring in elemental, inorganic and organic forms. Due to ban on most inorganic mercury containing products, human exposure to mercury generally occurs as methylmercury (MeHg) by consumption of contaminated fish and other sea food. Animal and epidemiological studies indicate that MeHg affects neural and renal function. Our study is focused on nephrotoxic potential of MeHg. In this study, we have shown for the first time how MeHg could epigenetically modulate matrix metalloproteinase 9(MMP9) to promote nephrotoxicity using an animal model of sub chronic MeHg exposure. MeHg caused renal toxicity as was seen by increased levels of serum creatinine and expression of early nephrotoxicity markers (KIM-1, Clusterin, IP-10, and TIMP). MeHg exposure also correlated strongly with induction of MMP9 mRNA and protein in a dose dependent manner. Further, while induction of MMP9 promoted cytoskeleton disruption and loss of cell-cell adhesion (loss of F-actin, Vimentin and Fibronectin), inhibition of MMP9 was found to reduce these disruptions. Mechanistic studies by ChIP analysis showed that MeHg modulated MMP9 by promoting demethylation of its regulatory region to increase its expression. Bisulfite sequencing identified critical CpGs in the first exon of MMP9 which were demethylated following MeHg exposure. ChIP studies also showed loss of methyl binding protein, MeCP2 and transcription factor PEA3 at the demethylated site confirming decreased CpG methylation. Our studies thus show how MeHg could epigenetically modulate MMP9 to promote cytoskeleton disruption leading to loss of renal function. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Acute renal failure after rifampicin

    Directory of Open Access Journals (Sweden)

    Adriana Weinberg

    1984-12-01

    Full Text Available A patient with miliary tuberculosis and a chronic urogenital focus is described, who had a borderline renal function at diagnosis and developed overt renal failure upon daily treatment with rifampin (RMP, isoniazid (INH and ethambutol (EMB. This is the first Brazilian report of BMP induced renal damage. A renal biopsy taken on the third day of oliguria showed recent tubular necrosis with acute interstitial inflammation and granuloma formation. The aspect of the granulomatous lesion hightly suggested drug etiology because of the lack of palisading, high incidence of neutrophils and absence of facid-fast bacilli. This is the first presentation of an acute granulomatous interstitial nephritis probably due to RMP. Furthermore the pathogenesis of the renal damage caused by tuberculosis and RMP are discussed.

  7. Pazopanib-Induced Hypertension in Patients With Renal Cell Carcinoma Is Associated With Low Urine Excretion of NO Metabolites

    DEFF Research Database (Denmark)

    Tinning, Anne Robdrup; Bengtsen, Camilla; Jensen, Niels Viggo

    2018-01-01

    -NAME or by impaired endothelin-1 leads to hypertension. The present study was designed to test the hypothesis that VEGF receptor inhibitor treatment leads to hypertension through decreased renal medullary formation of NO and endothelin-1. With a single-center prospective observational design, patients with metastatic...... increased, whereas heart rate decreased significantly; urine protein/creatinine ratio increased significantly, whereas estimated glomerular filtration rate was unchanged. Urine nitrite/nitrate (NOx) and cGMP/creatinine ratios decreased significantly, whereas urine endothelin-1/creatinine ratio and FENa...

  8. Renal Hemangiopericytoma

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    İbrahim Halil Bozkurt

    2015-03-01

    Full Text Available Hemangiopericytoma is an uncommon perivascular tumor originating from pericytes in the pelvis, head and tneck, and the meninges; extremely rarely in the urinary system. We report a case of incidentally detected renal mass in which radiologic evaluation was suggestive of renal cell carcinoma. First, we performed partial nephrectomy, and then, radical nephrectomy because of positive surgical margins and the pathological examination of the surgical specimen that revealed a hemangiopericytoma. No additional treatment was administered.

  9. Sodium intake modifies the negative prognostic value of renal damage prior to treatment with ACE inhibitors on proteinuria induced by adriamycin

    NARCIS (Netherlands)

    Kramer, Andrea B.; Bos, Hendrik; van Goor, Harry; Navis, Gerjan J.

    2006-01-01

    Background: Antiproteinuric treatment by ACE inhibition (ACEi) provides renoprotection. However, resistance to antiproteinuric intervention occurs frequently, resulting in progressive renal damage. The extent of renal damage prior to treatment with ACEi reversely correlates with the antiproteinuric

  10. High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels

    DEFF Research Database (Denmark)

    Kashioulis, Pavlos; Hammarsten, Ola; Marcussen, Niels

    2016-01-01

    AIMS: To examine the effects of 2 weeks of high-NaCl diet on left ventricular (LV) morphology and serum levels of cardiac troponin T (cTnT) in rats with adenine-induced chronic renal failure (ACRF). METHODS: Male Sprague-Dawley rats either received chow containing adenine or were pair......-fed an identical diet without adenine [controls (C)]. Approximately 10 weeks after the beginning of the study, the rats were randomized to either remain on a normal NaCl diet (NNa; 0.6%) or to be switched to high-NaCl chow (HNa; 4%) for 2 weeks, after which acute experiments were performed. RESULTS: Rats with ACRF...... showed statistically significant increases (p rats (p

  11. Lenalidomide-induced myelosuppression is associated with renal dysfunction: adverse events evaluation of treatment-naïve patients undergoing front-line lenalidomide and dexamethasone therapy.

    Science.gov (United States)

    Niesvizky, Ruben; Naib, Tara; Christos, Paul J; Jayabalan, David; Furst, Jessica R; Jalbrzikowski, Jessica; Zafar, Faiza; Mark, Tomer; Lent, Richard; Pearse, Roger N; Ely, Scott; Leonard, John P; Mazumdar, Madhu; Chen-Kiang, Selina; Coleman, Morton

    2007-09-01

    Data on 72 patients receiving lenalidomide/dexamethasone for multiple myeloma (MM) was used to determine the factors that are associated with lenalidomide-induced myelosuppression. Eight of 14 patients with grade > or =3 myelosuppression had baseline creatinine clearance (CrCl) < or =0.67 ml/s. Kaplan-Meier analysis by log-rank test demonstrated a significant association (P < 0.0001) between renal insufficiency and time to myelosuppression (hazard ratio = 8.4; 95% confidence interval 2.9-24.7, P = 0.0001). Therefore, CrCl is inversely associated with significant myelosuppression. Caution should be exercised when lenalidomide therapy is commenced and CrCl should be incorporated as a determinant of the initial dosing of lenalidomide in MM patients.

  12. Tacrolimus Modulates TGF-β Signaling to Induce Epithelial-Mesenchymal Transition in Human Renal Proximal Tubule Epithelial Cells

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    Jason Bennett

    2016-04-01

    Full Text Available Epithelial-mesenchymal transition (EMT, a process which describes the trans-differentiation of epithelial cells into motile mesenchymal cells, is pivotal in stem cell behavior, development and wound healing, as well as contributing to disease processes including fibrosis and cancer progression. Maintenance immunosuppression with calcineurin inhibitors (CNIs has become routine management for renal transplant patient, but unfortunately the nephrotoxicity of these drugs has been well documented. HK-2 cells were exposed to Tacrolimus (FK506 and EMT markers were assessed by RT PCR and western blot. FK506 effects on TGF-β mRNA were assessed by RT PCR and TGF-β secretion was measured by ELISA. The impact of increased TGF-β secretion on Smad signaling pathways was investigated. The impact of inhibition of TGF-β signaling on EMT processes was assessed by scratch-wound assay. The results presented in this study suggest that FK506 initiates EMT processes in the HK-2 cell line, with altered expression of epithelial and myofibroblast markers evident. Additionally, the study demonstrates that FK506 activation of the TGF-β/ SMAD pathways is an essential step in the EMT process. Overall the results demonstrate that EMT is heavily involved in renal fibrosis associated with CNI nephrotoxicity.

  13. Comparison of the therapeutic effects of thymoquinone and methotrexate on renal injury in pristane induced arthritis in rats

    International Nuclear Information System (INIS)

    Faisal, R.

    2015-01-01

    To determine the effect of thymoquinone and methotrexate on blood urea and serum creatinine in arthritic rats. Study Design:Experimental, comparative study. Place and Duration of Study: Postgraduate Medical Institute, Lahore, from March to August 2013. Methodology: Thirty two female Sprague-Dawley rats were randomized into four equal groups (n=8); group A(healthy control), group B (positive control), group C (Thymoquinone treated) and group D (Methotrexate treated). Arthritis developed within two weeks after a single pristane injection. Total leukocyte count, blood urea and serum creatinine were taken at day 0, 15 and 30. While clinical score of inflammation was taken at day 0 and then on every alternate day. Results: Development of arthritis and renal involvement was accompanied by significant raise in total leukocyte count, clinical score of inflammation, blood urea and serum creatinine as compared to healthy control rats (group A) till day 15 (p < 0.001). From day 15 to day 30 both thymoquinone (group C) and methotrexate (group D) significantly lowered the total leukocyte count, clinical score of inflammation and improved blood urea and serum creatinine as compared to arthritic rats (group B) (p < 0.001). Methotrexate was found a bit more effective than thymoquinone. Conclusion: Evaluation of results supported the beneficial effects of thymoquinone in renal injury produced by rheumatoid arthritis. (author)

  14. Role of the renin-angiotensin system, renal sympathetic nerve system, and oxidative stress in chronic foot shock-induced hypertension in rats.

    Science.gov (United States)

    Dong, Tao; Chen, Jing-Wei; Tian, Li-Li; Wang, Lin-Hui; Jiang, Ren-Di; Zhang, Zhe; Xu, Jian-Bing; Zhao, Xiao-Dong; Zhu, Wei; Wang, Guo-Qing; Sun, Wan-Ping; Zhang, Guo-Xing

    2015-01-01

    The renin-angiotensin system (RAS) and renal sympathetic nerve system (RSNS) are involved in the development of hypertension. The present study is designed to explore the possible roles of the RAS and the RSNS in foot shock-induced hypertension. Male Sprague-Dawley rats were divided into six groups: control, foot shock, RSNS denervation, denervation plus foot shock, Captopril (angiotensin I converting enzyme inhibitor, ACE inhibitor) plus foot shock, and Tempol (superoxide dismutase mimetic) plus foot shock. Rats received foot shock for 14 days. We measured the quantity of thiobarbituric acid reactive substances (TBARS), corticosterone, renin, and angiotensin II (Ang II) in plasma, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and renal noradrenaline content. RAS component mRNA and protein levels were quantified in the cerebral cortex and hypothalamus. The two week foot shock treatment significantly increased systolic blood pressure, which was accompanied by an increase in angiotensinogen, renin, ACE1, and AT1a mRNA and protein expression in the cerebral cortex and hypothalamus, an increase of the plasma concentrations of renin, Ang II, corticosterone, and TBARS, as well as a decrease in plasma SOD and GSH-Px activities. Systolic blood pressure increase was suppressed by denervation of the RSNS or treatment with Captopril or Tempol. Interestingly, denervation or Tempol treatment both decreased main RAS components not only in the circulatory system, but also in the central nervous system. In addition, decreased antioxidant levels and increased TBARS and corticosterone levels were also partially restored by denervation or treatment with Tempol or Captopril. RAS, RSNS and oxidative stress reciprocally potentiate to play important roles in the development of foot shock-induced hypertension.

  15. Effect of exogenous leptin on serum levels of lipids, glucose, renal and hepatic variables in both genders of obese and streptozotocin-induced diabetic rats

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    Parichehr Hayatdavoudi

    2015-11-01

    Full Text Available Objective(s: Leptin exerts various effects on appetite and body weight. Disruption of the obesitygene is precedent to fatness. Insulin or glucose elevates leptin, but streptozotocin reduces it. However, controversial data exist for the effects of leptin on diabetes and leptin level in each gender. Leptin can damage the kidney function but little evidence exists for its hepatic effects. The aim of this study was to investigate the probable sex-dependent differences in blood sugar levels, lipid profile, and renal and hepatic biochemical factors in the obesity and streptozotocin-induced diabetic rats after leptin administration. Materials and Methods: Wistar rats of both sexes were randomly divided into two groups, namely obese and diabetic rats. Each group was further divided into male and female subgroups. Extra fat and carbohydrate was added to the diet to induce obesity. Furthermore, streptozotocin (55 mg/kg, IP was injected to induce diabetes. The treatment groups received leptin (0.1 mg/kg SC for 10 days, and then, blood samples were taken from the orbital sinus for laboratory evaluations. Results: Leptin resulted in a significant weight loss in both sexes (P

  16. Calcium oxalate crystals induces tight junction disruption in distal renal tubular epithelial cells by activating ROS/Akt/p38 MAPK signaling pathway.

    Science.gov (United States)

    Yu, Lei; Gan, Xiuguo; Liu, Xukun; An, Ruihua

    2017-11-01

    Tight junction plays important roles in regulating paracellular transports and maintaining cell polarity. Calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stones, have been demonstrated to be able to cause tight junction disruption to accelerate renal cell injury. However, the cellular signaling involved in COM crystal-induced tight junction disruption remains largely to be investigated. In the present study, we proved that COM crystals induced tight junction disruption by activating ROS/Akt/p38 MAPK pathway. Treating Madin-Darby canine kidney (MDCK) cells with COM crystals induced a substantial increasing of ROS generation and activation of Akt that triggered subsequential activation of ASK1 and p38 mitogen-activated protein kinase (MAPK). Western blot revealed a significantly decreased expression of ZO-1 and occludin, two important structural proteins of tight junction. Besides, redistribution and dissociation of ZO-1 were observed by COM crystals treatment. Inhibition of ROS by N-acetyl-l-cysteine (NAC) attenuated the activation of Akt, ASK1, p38 MAPK, and down-regulation of ZO-1 and occludin. The redistribution and dissociation of ZO-1 were also alleviated by NAC treatment. These results indicated that ROS were involved in the regulation of tight junction disruption induced by COM crystals. In addition, the down-regulation of ZO-1 and occludin, the phosphorylation of ASK1 and p38 MAPK were also attenuated by MK-2206, an inhibitor of Akt kinase, implying Akt was involved in the disruption of tight junction upstream of p38 MAPK. Thus, these results suggested that ROS-Akt-p38 MAPK signaling pathway was activated in COM crystal-induced disruption of tight junction in MDCK cells.

  17. Gender difference following high cholesterol diet induced renal injury and the protective role of rutin and ascorbic acid combination in Wistar albino rats

    Science.gov (United States)

    2012-01-01

    Background An increased interest is given to the impact of high fat diet on health worldwide. Abnormalities in lipid metabolism induced by high cholesterol diet (HCD) were reported to exacerbate renal diseases via oxidative stress pathways. Rutin and ascorbic acid showed a protective role against oxidative stress-mediated diseases. Furthermore, both lipid metabolism and tissue response to oxidative stress damage was found to vary according to animal gender. Thus, the objective of this work was to examine possible gender-related differences and the possible protective effects of rutin and ascorbic acid supplementation on high cholesterol diet induced nephrotoxicity. Methods 96 young male and female Wistar albino rats were used. HCD supplemented animals were treated with rutin alone or in combination with ascorbic acid for 6 weeks. Creatinine plasma level was estimated. Furthermore, kidney levels of nucleic acids, total protein, malondialdehyde (MDA), reduced glutathione (GSH), total cholesterol, and triglycerides were determined. Finally, kidney tissues were used for histopathological examination. Results HCD supplementation decreased kidney level of nucleic acids, which was more prominent in female animals. Both vitamin combination significantly attenuated HCD induced decrease in nucleic acids. Moreover, kidney level of MDA was significantly altered by HCD in both genders, which was inhibited by rutin and ascorbic acid alone or in combination in male groups and by both vitamins in female groups. There was a reduction in kidney level of GSH by HCD, especially in male groups, which was attenuated by rutin and ascorbic acid combination. Kidney levels of total cholesterol and triglycerides were significantly increased by HCD supplementation in both genders. Coadministration with rutin and/or ascorbic acid protected from such increase, which was more obvious in both vitamins combination. Histopathological investigation supported vitamins protective effect, which was

  18. Gender difference following high cholesterol diet induced renal injury and the protective role of rutin and ascorbic acid combination in Wistar albino rats.

    Science.gov (United States)

    Al-Rejaie, Salim Salih; Abuohashish, Hatem Mustafa; Alkhamees, Osama Abdelrahman; Aleisa, Abdulaziz Mohammed; Alroujayee, Abdulaziz S

    2012-03-16

    An increased interest is given to the impact of high fat diet on health worldwide. Abnormalities in lipid metabolism induced by high cholesterol diet (HCD) were reported to exacerbate renal diseases via oxidative stress pathways. Rutin and ascorbic acid showed a protective role against oxidative stress-mediated diseases. Furthermore, both lipid metabolism and tissue response to oxidative stress damage was found to vary according to animal gender. Thus, the objective of this work was to examine possible gender-related differences and the possible protective effects of rutin and ascorbic acid supplementation on high cholesterol diet induced nephrotoxicity. 96 young male and female Wistar albino rats were used. HCD supplemented animals were treated with rutin alone or in combination with ascorbic acid for 6 weeks. Creatinine plasma level was estimated. Furthermore, kidney levels of nucleic acids, total protein, malondialdehyde (MDA), reduced glutathione (GSH), total cholesterol, and triglycerides were determined. Finally, kidney tissues were used for histopathological examination. HCD supplementation decreased kidney level of nucleic acids, which was more prominent in female animals. Both vitamin combination significantly attenuated HCD induced decrease in nucleic acids. Moreover, kidney level of MDA was significantly altered by HCD in both genders, which was inhibited by rutin and ascorbic acid alone or in combination in male groups and by both vitamins in female groups. There was a reduction in kidney level of GSH by HCD, especially in male groups, which was attenuated by rutin and ascorbic acid combination. Kidney levels of total cholesterol and triglycerides were significantly increased by HCD supplementation in both genders. Coadministration with rutin and/or ascorbic acid protected from such increase, which was more obvious in both vitamins combination. Histopathological investigation supported vitamins protective effect, which was more prominent in male

  19. Gender difference following high cholesterol diet induced renal injury and the protective role of rutin and ascorbic acid combination in Wistar albino rats

    Directory of Open Access Journals (Sweden)

    Al-Rejaie Salim

    2012-03-01

    Full Text Available Abstract Background An increased interest is given to the impact of high fat diet on health worldwide. Abnormalities in lipid metabolism induced by high cholesterol diet (HCD were reported to exacerbate renal diseases via oxidative stress pathways. Rutin and ascorbic acid showed a protective role against oxidative stress-mediated diseases. Furthermore, both lipid metabolism and tissue response to oxidative stress damage was found to vary according to animal gender. Thus, the objective of this work was to examine possible gender-related differences and the possible protective effects of rutin and ascorbic acid supplementation on high cholesterol diet induced nephrotoxicity. Methods 96 young male and female Wistar albino rats were used. HCD supplemented animals were treated with rutin alone or in combination with ascorbic acid for 6 weeks. Creatinine plasma level was estimated. Furthermore, kidney levels of nucleic acids, total protein, malondialdehyde (MDA, reduced glutathione (GSH, total cholesterol, and triglycerides were determined. Finally, kidney tissues were used for histopathological examination. Results HCD supplementation decreased kidney level of nucleic acids, which was more prominent in female animals. Both vitamin combination significantly attenuated HCD induced decrease in nucleic acids. Moreover, kidney level of MDA was significantly altered by HCD in both genders, which was inhibited by rutin and ascorbic acid alone or in combination in male groups and by both vitamins in female groups. There was a reduction in kidney level of GSH by HCD, especially in male groups, which was attenuated by rutin and ascorbic acid combination. Kidney levels of total cholesterol and triglycerides were significantly increased by HCD supplementation in both genders. Coadministration with rutin and/or ascorbic acid protected from such increase, which was more obvious in both vitamins combination. Histopathological investigation supported vitamins

  20. The Protective Roles of Zinc and Magnesium in Cadmium-Induced Renal Toxicity in Male Wistar Rats

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    Nasim Babaknejad

    2014-12-01

    Full Text Available Background: Cadmium (Cd is a heavy metal that has widespread use. It enters the food chain in different ways, including soil and water. Cadmium can cause dysfunction of different body organs. Zinc (Zn and magnesium (Mg supplementation can have protective effects against cadmium toxicity due to their antagonistic and antioxidants properties. This study examines the influence of supplemental Zn and Mg on Cd renal toxicity. Methods: Young male Wistar rats were divided into six groups of five. The Cd group received 1 mg Cd/kg and the control group received 0.5 mg/kg normal saline (i.p.. The other four groups were administered 1 mg/kg Cd+0.5 mg/kg Zn, 1 mg/kg Cd+1.5 mg/kg Zn, 1 mg/kg Cd+ 0.5 mg/kg Mg, and 1 mg/kg Cd+ 1.5 mg/kg Mg (i.p. for 21 days. Then, serum sodium, potassium, urea, creatinine, and protein levels were measured. Results: The results indicated that creatinine and protein levels decreased while urea, sodium, and potassium levels increased as a result of Cd exposure. Co-administered Cd and Zn and Mg decreased urea and increased sodium serum level in comparison to the cadmium group. Treatment by Mg, contrary to co-administered Cd and Zn, reduced serum protein level compared to the cadmium group. Compared to the cadmium treated group, Zn and Mg treatment enhanced serum creatinine level and reduced serum potassium level. Conclusion: The findings seem to suggest that zinc and magnesium compounds, due to their antagonistic and antioxidant activities, can protect Cd renal toxic effects in a dose-dependent manner.