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.

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.

Chemical renal denervation in the rat.

Science.gov (United States)

Consigny, Paul M; Davalian, Dariush; Donn, Rosy; Hu, Jie; Rieser, Matthew; Stolarik, Deanne

2014-02-01

The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose-response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography-mass spectrometry. Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10(-5) M through 10(-2) M paclitaxel. We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

Tumor-promoting phorbol esters effect alkalinization of canine renal proximal tubular cells

International Nuclear Information System (INIS)

Mellas, J.; Hammerman, M.R.

1986-01-01

We have demonstrated the presence of specific receptors for tumor-promoting phorbol esters in the plasma membrane of the canine renal proximal tubular cell. These compounds affect proximal tubular metabolism in vitro. For example, we have shown that they inhibit gluconeogenesis in canine renal proximal tubular segments. Tumor-promoting phorbol esters have been shown to effect alkalinization of non-renal cells, by enhancing Na + -H + exchange across the plasma membrane. To determine whether the actions of tumor-promoting phorbol esters in proximal tubular segments might be mediated by a similar process, we incubated suspensions of segments from dog kidney with these compounds and measured changes in intracellular pH using [ 14 C]-5,5-dimethoxazoladine-2-4-dione (DMO) and flow dialysis. Incubation of segments with phorbol 12,13 dibutyrate, but not inactive phorbol ester, 4 γ phorbol, effected alkalinization of cells within the segments in a concentration-dependent manner. Alkalinization was dependent upon the presence of extracellular [Na + ] > intracellular [Na + ], was prevented by amiloride and was demonstrable in the presence of SITS. Our findings suggest that tumor-promoting esters stimulate the Na + -H + exchanger known to be present in the brush border membrane of the renal proximal tubular cell. It is possible that the stimulation reflects a mechanism by which phorbol esters affect metabolic processes in these cells

Dynamic autoregulation and renal injury in Dahl rats

DEFF Research Database (Denmark)

Karlsen, F M; Andersen, C B; Leyssac, P P

1997-01-01

of hypertension, a gradual impairment of autoregulatory control of renal blood flow might expose the glomerular circulation to periods of elevated pressure, resulting in renal injuries in Dahl S rats. Dynamic autoregulatory capacity was assessed in Dahl S and Dahl salt-resistant (Dahl R) rats, SHR, and Sprague......-Dawley rats by inducing broad-band fluctuations in the arterial blood pressure and simultaneously measuring renal blood flow. Dynamic autoregulation was estimated by the transfer function using blood pressure as the input and renal blood flow as the output. Renal morphological injuries were evaluated in Dahl......The Dahl salt-sensitive (Dahl S) rat develops hypertension and renal injuries when challenged with a high salt diet and has been considered to be a model of chronic renal failure. Renal injuries appear very early in life compared with the spontaneously hypertensive rat (SHR). During the course...

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

Chemical Renal Denervation in the Rat

Energy Technology Data Exchange (ETDEWEB)

Consigny, Paul M., E-mail: paul.consigny@av.abbott.com; Davalian, Dariush, E-mail: dariush.davalian@av.abbott.com [Abbott Vascular, Innovation Incubator (United States); Donn, Rosy, E-mail: rosy.donn@av.abbott.com; Hu, Jie, E-mail: jie.hu@av.abbott.com [Abbott Vascular, Bioanalytical and Material Characterization (United States); Rieser, Matthew, E-mail: matthew.j.rieser@abbvie.com; Stolarik, DeAnne, E-mail: deanne.f.stolarik@abbvie.com [Abbvie, Analytical Pharmacology (United States)

2013-12-03

Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10{sup −5} M through 10{sup −2} M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

Chemical Renal Denervation in the Rat

International Nuclear Information System (INIS)

Consigny, Paul M.; Davalian, Dariush; Donn, Rosy; Hu, Jie; Rieser, Matthew; Stolarik, DeAnne

2014-01-01

Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10 −5  M through 10 −2  M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel

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

Renal function in streptozotocin-diabetic rats

DEFF Research Database (Denmark)

Jensen, P K; Christiansen, J S; Steven, K

1981-01-01

to the rise in kidney glomerular filtration rate (diabetic rats: 37.0 nl/min; control rats: 27.9 nl/min). Likewise renal plasma flow was significantly higher in the diabetic rats (4.1 ml/min) than in the control group (3.0 ml/min). Glomerular capillary pressure was identical in both groups (56.0 and 56.0 mm......-1mmHg-1). Kidney weight was significantly higher in the diabetic rats (1.15 g; control rats: 0.96 g) while body weight was similar in both groups (diabetic rats: 232 g; control rats: 238 g). Calculations indicate that the increases in transglomerular hydraulic pressure, renal plasma flow......Renal function was examined with micropuncture methods in the insulin-treated streptozotocin-diabetic rat. Kidney glomerular filtration rate was significantly higher in the diabetic rats (1.21 ml/min) than in the control group (0.84 ml/min) Nephron glomerular filtration rate increased in proportion...

Local pH domains regulate NHE3-mediated Na+ reabsorption in the renal proximal tubule

Science.gov (United States)

Burford, James L.; McDonough, Alicia A.; Holstein-Rathlou, Niels-Henrik; Peti-Peterdi, Janos

2014-01-01

The proximal tubule Na+/H+ exchanger 3 (NHE3), located in the apical dense microvilli (brush border), plays a major role in the reabsorption of NaCl and water in the renal proximal tubule. In response to a rise in blood pressure NHE3 redistributes in the plane of the plasma membrane to the base of the brush border, where NHE3 activity is reduced. This NHE3 redistribution is assumed to provoke pressure natriuresis; however, it is unclear how NHE3 redistribution per se reduces NHE3 activity. To investigate if the distribution of NHE3 in the brush border can change the reabsorption rate, we constructed a spatiotemporal mathematical model of NHE3-mediated Na+ reabsorption across a proximal tubule cell and compared the model results with in vivo experiments in rats. The model predicts that when NHE3 is localized exclusively at the base of the brush border, it creates local pH microdomains that reduce NHE3 activity by >30%. We tested the model's prediction experimentally: the rat kidney cortex was loaded with the pH-sensitive fluorescent dye BCECF, and cells of the proximal tubule were imaged in vivo using confocal fluorescence microscopy before and after an increase of blood pressure by ∼50 mmHg. The experimental results supported the model by demonstrating that a rise of blood pressure induces the development of pH microdomains near the bottom of the brush border. These local changes in pH reduce NHE3 activity, which may explain the pressure natriuresis response to NHE3 redistribution. PMID:25298526

Detection of acute renal allograft rejection by analysis of Renal TissueProteomics in rat models of renal transplantation

International Nuclear Information System (INIS)

Dai, Y.; Lv, T.; Wang, K.; Li, D.; Huang, Y.; Liu, J.

2008-01-01

At present, the diagnosis of renal allograft rejection requires a renalbiopsy. Clinical management of renal transplant patients would be improved ifrapid, noninvasive and reliable biomarkers of rejection were available. Thisstudy is designed to determine whether such protein biomarkers can be foundin renal graft tissue proteomic approach. Orthotopic kidney transplantationswere performed using Fisher (F344) or Lewis rats as donors and Lewis rats asrecipients. Hence, there were two groups of renal transplant models: one isallograft (from F344 to Lewis rats); another is syngrafts (from Lewis toLewis rats) serving as control. Renal tissues were collected 3, 7 and 14 daysafter transplantation. As many 18 samples were analyzed by 2-DElectrophoresis and mass spectrometry (MALDI-TOF-TOF-MS). Elevendifferentially expressed proteins were identified between groups. Inconclusion, proteomic technology can detect renal tissue proteins associatedwith acute renal allograft rejection. Identification of these proteins asdiagnostic markers for rejection in patient's urine or sera may be useful andnon-invasive, and these proteins might serve as novel therapeutic targetsthat also help to improve the understanding of mechanisms of renal rejection.(author)

Detection of acute renal allograft rejection by analysis of renal tissue proteomics in rat models of renal transplantation

Directory of Open Access Journals (Sweden)

Dai Yong

2008-01-01

Full Text Available At present, the diagnosis of renal allograft rejection requires a renal biopsy. Clinical management of renal transplant patients would be improved if rapid, noninvasive and reliable biomarkers of rejection were available. This study is designed to determine whether such protein biomarkers can be found in renal-graft tissue proteomic approach. Orthotopic kidney transplantations were performed using Fisher (F344 or Lewis rats as donors and Lewis rats as recipients. Hence, there were two groups of renal transplant models: one is allograft (from F344 to Lewis rats; another is syngrafts (from Lewis to Lewis rats serving as control. Renal tissues were collected 3, 7 and 14 days after transplantation. As many as 18 samples were analyzed by 2-D Electrophoresis and mass spectrometry (MALDI-TOF-TOF-MS. Eleven differentially expressed proteins were identified between groups. In conclusion, proteomic technology can detect renal tissue proteins associated with acute renal allograft rejection. Identification of these proteins as diagnostic markers for rejection in patients′ urine or sera may be useful and non-invasive, and these proteins might serve as novel therapeutic targets that also help to improve the understanding of mechanism of renal rejection.

Mechanism of petroleum-induced sex-specific protein droplet nephropathy and renal cell proliferation in Fischer-344 rats: relevance to humans

International Nuclear Information System (INIS)

Charbonneau, M.; Short, B.G.; Lock, E.A.; Swenberg, J.A.

1987-01-01

Acute inhalation exposure of male rats to vaporized unleaded gasoline causes a protein droplet-nephropathy syndrome, whereas chronic exposure produces a significant increase renal tumor incidence. The renal lesions produced by chronic or acute exposure to UG have not been observed in kidneys of female rats, or either sex of mice. The assessment of the genotoxic properties of unleaded gasoline by a battery of tests has shown that unleaded gasoline is non-genotoxic. A 21-day histoautoradiographic study in male rats exposed to inhaled unleaded gasoline or gavaged with 2,2,4-trimethylpentane (TMP), a nephrotoxic component of unleaded gasoline selected as a model compound, has shown a dose-dependent increase in cell proliferation specifically in the proximal tubule, segments that have an increased protein droplet formation. A disposition study in male and female rats showed that after a single dose of [ 14 C]-TMP, TMP-derived radiolabel was retained in kidneys of male rats. An increase in the renal α2u-globulin concentration was concomitantly observed in male but not female rats

Quantitative analysis of the renal aging in rats. Stereological study.

Science.gov (United States)

Melchioretto, Eduardo Felippe; Zeni, Marcelo; Veronez, Djanira Aparecida da Luz; Martins, Eduardo Lopes; Fraga, Rogério de

2016-05-01

To evaluate the renal function and the renal histological alterations through the stereology and morphometrics in rats submitted to the natural process of aging. Seventy two Wistar rats, divided in six groups. Each group was sacrificed in a different age: 3, 6, 9, 12, 18 and 24 months. It was performed right nephrectomy, stereological and morphometric analysis of the renal tissue (renal volume and weight, density of volume (Vv[glom]) and numerical density (Nv[glom]) of the renal glomeruli and average glomerular volume (Vol[glom])) and also it was evaluated the renal function for the dosage of serum creatinine and urea. There was significant decrease of the renal function in the oldest rats. The renal volume presented gradual increase during the development of the rats with the biggest values registered in the group of animals at 12 months of age and significant progressive decrease in older animals. Vv[glom] presented statistically significant gradual reduction between the groups and the Nv[glom] also decreased significantly. The renal function proved to be inferior in senile rats when compared to the young rats. The morphometric and stereological analysis evidenced renal atrophy, gradual reduction of the volume density and numerical density of the renal glomeruli associated to the aging process.

Characterization of renal hyperemia in portal hypertensive rats

International Nuclear Information System (INIS)

Premen, A.J.; Banchs, V.; Go, V.L.W.; Benoit, J.N.; Granger, D.N.

1986-01-01

In anesthetized sham-operated control (C) and portal vein stenosed (PVS) rats, renal blood flow (RBF) was measured with radioactive microspheres on days 2, 4, 6, 8, and 10 following surgery. On day 2, only a small increase in RBF (19%) was produced in PVS versus C rats. However, by day 4, a significant increase in RBF (35%) was observed in PVS versus C animals. By day 6, the renal hyperemia in PVS rats reached a maximal value that was 42% higher than in C rats. Thereafter (on days 8 and 10), the renal hyperemia remained at the maximal value. In a separate group of 10-day PVS rats, glucagon antiserum failed to attenuate the 44% increase in RBF observed in PVS versus C rats. Radioimmunoassay of C and PVS plasma (10-day samples) revealed that vasoactive intestinal polypeptide, substance P, cholecystokinin/gastrin, neurotensin, pancreatic polypeptide, beta-endorphin, and peptide histidine-isoleucine amide are not elevated in arterial plasma of PVS rats. These data indicate that the renal hyperemia induced by chronic portal hypertension is manifested within 4 days after the hypertensive insult. Our studies also suggest that at least 9 blood-borne gastrointestinal peptides are not directly involved in the renal response to portal vein stenosis

Characterization of renal hyperemia in portal hypertensive rats

Energy Technology Data Exchange (ETDEWEB)

Premen, A.J.; Banchs, V.; Go, V.L.W.; Benoit, J.N.; Granger, D.N.

1986-03-01

In anesthetized sham-operated control (C) and portal vein stenosed (PVS) rats, renal blood flow (RBF) was measured with radioactive microspheres on days 2, 4, 6, 8, and 10 following surgery. On day 2, only a small increase in RBF (19%) was produced in PVS versus C rats. However, by day 4, a significant increase in RBF (35%) was observed in PVS versus C animals. By day 6, the renal hyperemia in PVS rats reached a maximal value that was 42% higher than in C rats. Thereafter (on days 8 and 10), the renal hyperemia remained at the maximal value. In a separate group of 10-day PVS rats, glucagon antiserum failed to attenuate the 44% increase in RBF observed in PVS versus C rats. Radioimmunoassay of C and PVS plasma (10-day samples) revealed that vasoactive intestinal polypeptide, substance P, cholecystokinin/gastrin, neurotensin, pancreatic polypeptide, beta-endorphin, and peptide histidine-isoleucine amide are not elevated in arterial plasma of PVS rats. These data indicate that the renal hyperemia induced by chronic portal hypertension is manifested within 4 days after the hypertensive insult. Our studies also suggest that at least 9 blood-borne gastrointestinal peptides are not directly involved in the renal response to portal vein stenosis.

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.

Cordyceps sinensis protects against renal ischemia/reperfusion injury in rats.

Science.gov (United States)

Wang, Hua-Pin; Liu, Ching-Wen; Chang, Hsueh-Wen; Tsai, Jen-Wei; Sung, Ya-Zhu; Chang, Li-Ching

2013-03-01

Cordyceps sinensis (CS) is an entomogenous fungus used as a tonic food and Chinese medicine to replenish health. This study investigated the protective effects of CS in rats post-renal ischemia-reperfusion (I/R) sequence by analyzing the influence on stromal cell-derived factor-1α (SDF-1α and chemokine (C-X-C motif) receptor 4 (CXCR4) expressions and senescence during recovery. Chemokine SDF-1 [now called chemokine C-X-C motif ligand 12 (CXCL12)] and its receptor CXCR4 are crucial in kidney repair after ischemic acute renal failure. CS treatment significantly alleviated I/R-induced renal damage assessed by creatinine levels (p < 0.05) and abated renal tubular damages assessed by periodic acid-Schiff with diastase (PASD) staining. CS induced early SDF-1α expression and increased CXCR4 expression 1-6 h post-reperfusion. Histology studies have revealed that CS induced SDF-1α in squamous cells of Bowman's capsule, mesangial cells, distal convoluted tubules (DCT), and proximal convoluted tubules (PCT). CS also improved renal repair in I/R-induced injury by increasing Ki-67 staining. I/R induced renal senescence after 3 and 6 h of reperfusion. However, CS alleviated I/R-induced senescence at early stage (1 and 3 h). We conclude that CS protects against I/R injury via the SDF-1/CXCR4-signaling axis and alleviates senescence.

Functional characterization of apical transporters expressed in rat proximal tubular cells (PTCs) in primary culture.

Science.gov (United States)

Nakanishi, Takeo; Fukushi, Akimasa; Sato, Masanobu; Yoshifuji, Mayuko; Gose, Tomoka; Shirasaka, Yoshiyuki; Ohe, Kazuyo; Kobayashi, Masato; Kawai, Keiichi; Tamai, Ikumi

2011-12-05

Since in vitro cell culture models often show altered apical transporter expression, they are not necessarily suitable for the analysis of renal transport processes. Therefore, we aimed here to investigate the usefulness of primary-cultured rat proximal tubular cells (PTCs) for this purpose. After isolation of renal cortical cells from rat kidneys, PTCs were enriched and the gene expression and function of apical transporters were analyzed by means of microarray, RT-PCR and uptake experiments. RT-PCR confirmed that the major apical transporters were expressed in rat PTCs. Na(+)-dependent uptake of α-methyl-d-glucopyranoside (αMG), ergothioneine and carnitine by the PTCs suggests functional expression of Sglts, Octn1 and Octn2, respectively. Inhibition of pH-dependent glycylsarcosine uptake by low concentration of cephalexin, which is a β-lactam antibiotics recognized by Pepts, indicates a predominant role of high affinity type Pept2, but not low affinity type Pept1, in the PTCs. Moreover, the permeability ratio of [(14)C]αMG (apical to basolateral/basolateral to apical) across PTCs was 4.3, suggesting that Sglt-mediated reabsorptive transport is characterized. In conclusion, our results indicate that rat PTCs in primary culture are found to be a promising in vitro model to evaluate reabsorption processes mediated at least by Sglts, Pept2, Octn1 and Octn2.

Common iliac vein thrombosis as a result of proximal venous stenosis following renal transplantation: A case report

Directory of Open Access Journals (Sweden)

Atish Chopra

2016-12-01

Full Text Available Proximal iliac vein stenosis resulting in iliac vein thrombus and venous outflow obstruction in renal transplant patients is an exceedingly rare occurrence. We present a case of a 63-year-old male who underwent deceased donor renal transplantation and presented 12 days later with ipsilateral lower extremity swelling and plateauing serum creatinine. Further work-up demonstrated proximal iliac vein deep venous thrombosis and anticoagulation was initiated. However, propagation of the thrombus developed despite receiving therapeutic anticoagulation. Subsequent venography demonstrated proximal iliac venous stenosis and the patient underwent successful catheter-directed alteplase thrombolysis, inferior vena cava filter placement and iliac vein stenting with salvage of the renal allograft. A diagnostic strategy and management algorithm for iliac vein stenosis and thrombosis in a renal transplant recipient is proposed.

Inhibition of renal Na+/H+ exchange in cadmium-intoxicated rats

International Nuclear Information System (INIS)

Ahn, Do Whan; Chung, Jin Mo; Kim, Jee Yeun; Kim, Kyoung Ryong; Park, Yang Saeng

2005-01-01

Chronic exposure to cadmium (Cd) results in bicarbonaturia, leading to metabolic acidosis. To elucidate the mechanism(s) by which renal bicarbonate reabsorption is inhibited, we investigated changes in renal transporters and enzymes associated with bicarbonate reabsorption in Cd-intoxicated rats. Cd intoxication was induced by subcutaneous injections of CdCl 2 (2 mg Cd/kg per day) for 3 weeks. Cd intoxication resulted in a significant reduction in V max of Na + /H + antiport with no changes in K Na in the renal cortical brush-border membrane vesicles (BBMV). Western blotting of BBM proteins and indirect immunohistochemistry in renal tissue sections, using an antibody against Na + /H + exchange-3 (NHE3), showed a diminished expression of NHE3 protein in the BBM. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that NHE3 mRNA expression was reduced in the renal cortex. The activity of carbonic anhydrase IV (CA IV) in BBM was not changed. The protein abundance of Na + -HCO 3 - cotransporter-1 (NBC1) in whole kidney membrane fractions was slightly attenuated, whereas that of the Na + -K + -ATPase α-subunit was markedly elevated in Cd-intoxicated animals. These results indicate that Cd intoxication impairs NHE3 expression in the proximal tubule, thereby reducing the capacity for bicarbonate reabsorption, leading to bicarbonaturia in an intact animal

Renal ornithine decarboxylase activity, polyamines, and compensatory renal hypertrophy in the rat

International Nuclear Information System (INIS)

Humphreys, M.H.; Etheredge, S.B.; Lin, Shanyan; Ribstein, J.; Marton, L.J.

1988-01-01

The authors determined the role of ornithine decarboxylase (ODC) in compensatory renal hypertrophy (CRH) by relating renal ODC activity and polyamine content to kidney size, expressed as a percent of body weight, 1 wk after unilateral nephrectomy (UN). In normal rats, renal ODC activity increased after UN; 1 wk later the remaining kidney weight had increased. Renal concentration of putrescine, the product of ODC's decarboxylation of ornithine, was increased 3, 8, and 48 h after UN, but concentrations of polyamines synthesized later in the pathway, spermidine and spermine, were not appreciably affected. Pretreatment with difluoromethylornithine (DFMO), an irreversible inhibitor of ODC inhibited both base-line renal ODC activity and putrescine concentration as well as increases stimulated by UN, although concentrations of spermidine and spermine were not decreased. In hypophysectomized rats, both increased renal ODC activity and CRH occurred as well, indicating that these two consequences of UN do not require intact pituitary function. Thus stimulation of renal ODC activity and putrescine content do not appear critical to the process of CRH after UN

Brown Norway chromosome 1 congenic reduces symptoms of renal disease in fatty Zucker rats.

Directory of Open Access Journals (Sweden)

Craig H Warden

Full Text Available We previously reported that a congenic rat with Brown Norway (BN alleles on chromosome 1 reduces renal disease of 15-week old fatty Zucker rats (ZUC. Development of renal disease in fatty BN congenic and fatty ZUC rats from 9 through 28 weeks is now examined. Analysis of urine metabolites by (1H nuclear magnetic resonance (NMR spectroscopy revealed a significantly increased urinary loss of glucose, myo-inositol, urea, creatine, and valine in ZUC. Food intake was lower in the BN congenic rats at weeks 9-24, but they weighed significantly more at 28 weeks compared with the ZUC group. Fasting glucose was significantly higher in ZUC than congenic and adiponectin levels were significantly lower in ZUC, but there was no significant genotype effect on Insulin levels. Glucose tolerance tests exhibited no significant differences between ZUC and congenic when values were normalized to basal glucose levels. Quantitative PCR on livers revealed evidence for higher gluconeogenesis in congenics than ZUC at 9 weeks. Plasma urea nitrogen and creatinine were more than 2-fold higher in 28-week ZUC. Twelve urine protein markers of glomerular, proximal and distal tubule disease were assayed at three ages. Several proteins that indicate glomerular and proximal tubular disease increased with age in both congenic and ZUC. Epidermal growth factor (EGF level, a marker whose levels decrease with distal tubule disease, was significantly higher in congenics. Quantitative histology of 28 week old animals revealed the most significant genotype effect was for tubular dilation and intratubular protein. The congenic donor region is protective of kidney disease, and effects on Type 2 diabetes are likely limited to fasting glucose and adiponectin. The loss of urea together with a small increase of food intake in ZUC support the hypothesis that nitrogen balance is altered in ZUC from an early age.

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

X radiation effect in the proximal contorted renal tubules of mice

International Nuclear Information System (INIS)

Pacheco, I.P.

1977-01-01

Exposing C 57B1, 100 days old, mice to X-ray radiation in doses of 150, 300 and 400 R was observed in the proximal contorted renal tubules. An early appearance of unspecific alterations which are peculiar to ageing [pt

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.

Localisation and mechanism of renal retention of radiolabelled somatostatin analogues

Energy Technology Data Exchange (ETDEWEB)

Melis, Marleen; Krenning, Eric P.; Bernard, Bert F.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Barone, Raffaella [UCL, Centre of Nuclear Medicine and Laboratory of PET, Brussels (Belgium); Visser, Theo J. [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

2005-10-01

Radiolabelled somatostatin analogues, such as octreotide and octreotate, are used for tumour scintigraphy and radionuclide therapy. The kidney is the most important critical organ during such therapy owing to the reabsorption and retention of radiolabelled peptides. The aim of this study was to investigate in a rat model both the localisation and the mechanism of renal uptake after intravenous injection of radiolabelled somatostatin analogues. The multi-ligand megalin/cubilin receptor complex, responsible for reabsorption of many peptides and proteins in the kidney, is an interesting candidate for renal endocytosis of these peptide analogues. For localisation studies, ex vivo autoradiography and micro-autoradiography of rat kidneys were performed 1-24 h after injection of radiolabelled somatostatin analogues and compared with the renal anti-megalin immunohistochemical staining pattern. To confirm a role of megalin in the mechanism of renal retention of [{sup 111}In-DTPA]octreotide, the effects of three inhibitory substances were explored in rats. Renal ex vivo autoradiography showed high cortical radioactivity and lower radioactivity in the outer medulla. The distribution of cortical radioactivity was inhomogeneous. Micro-autoradiography indicated that radioactivity was only retained in the proximal tubules. The anti-megalin immunohistochemical staining pattern showed a strong similarity with the renal [{sup 111}In-DTPA]octreotide ex vivo autoradiograms. Biodistribution studies showed that co-injection of positively charged d-lysine reduced renal uptake to 60% of control. Sodium maleate reduced renal [{sup 111}In-DTPA]octreotide uptake to 15% of control. Finally, cisplatin pre-treatment of rats reduced kidney uptake to 70% of control. Renal retention of [{sup 111}In-DTPA]octreotide is confined to proximal tubules in the rat kidney, in which megalin-mediated endocytosis may play an important part. (orig.)

Methylmercury inhibits gap junctional intercellular communication in primary cultures of rat proximal tubular cells

Energy Technology Data Exchange (ETDEWEB)

Yoshida, Minoru; Sumi, Yawara [Department of Chemistry, St. Marianna University School of Medicine, Kawasagi (Japan); Kujiraoka, Toru [Department of Physiology, St. Marianna University School of Medicine, Kawasagi (Japan); Hara, Masayuki [Department of Anatomy, St. Marianna University School of Medicine, Kawasagi (Japan); Nakazawa, Hirokazu [Department of Chemistry, Faculty of Sciences, Meisei University (Japan)

1998-03-01

Methylmercury (MeHg) causes renal injury in addition to central and peripheral neuropathy. To clarify the mechanism of nephrotoxicity by MeHg, we investigated the effect of this compound on intercellular communication through gap junction channels in primary cultures of rat renal proximal tubular cells. Twenty minutes after exposure to 30 {mu}M MeHg, gap junctional intercellular communication (GJIC), which was assessed by dye coupling, was markedly inhibited before appearance of cytotoxicity. When the medium containing MeHg was exchanged with MeHg-free medium, dye coupling recovered abruptly. However, the dye-coupling was abolished again 30 min after replacement with control medium, and the cells were damaged. Intracellular calcium concentration, [Ca{sup 2+}]{sub i}, which modulates the function of gap junctions, significantly increased following exposure of the cells to 30 {mu}M MeHg and returned to control level following replacement with MeHg-free medium. These results suggest that the inhibiting effect of MeHg on GJIC is related to the change in [Ca{sup 2+}]{sub i}, and may be involved in the pathogenesis of renal dysfunction. (orig.) With 5 figs., 23 refs.

SGLT2 Inhibitors: Glucotoxicity and Tumorigenesis Downstream the Renal Proximal Tubule?

Science.gov (United States)

Bertinat, Romina; Nualart, Francisco; Yáñez, Alejandro J

2016-08-01

At present, diabetes mellitus is the main cause of end-stage renal disease. Effective glycaemic management is the most powerful tool to delay the establishment of diabetic complications, such as diabetic kidney disease. Together with reducing blood glucose levels, new anti-diabetic agents are expected not only to control the progression but also to restore known defects of the diabetic kidney. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are promising anti-diabetic agents that reduce hyperglycaemia by impairing glucose reabsorption in proximal tubule of the kidney and increasing glucosuria. SGLT2 inhibitors have shown to reduce glucotoxicity in isolated proximal tubule cells and also to attenuate expression of markers of overall kidney damage in experimental animal models of diabetes, but the actual renoprotective effect for downstream nephron segments is still unknown and deserves further attention. Here, we briefly discuss possible undesired effects of enhanced glucosuria and albuminuria in nephron segments beyond the proximal tubule after SGLT2 inhibitor treatment, offering new lines of research to further understand the renoprotective action of these anti-diabetic agents. Strategies blocking glucose reabsorption by renal proximal tubule epithelial cells (RPTEC) may be protective for RPTEC, but downstream nephron segments will still be exposed to high glucose and albumin levels through the luminal face. The actual effect of constant enhanced glucosuria over distal nephron segments remains to be established. J. Cell. Physiol. 231: 1635-1637, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

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

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.

Quantitative analysis of the renal aging in rats. Stereological study

OpenAIRE

Melchioretto, Eduardo Felippe; Zeni, Marcelo; Veronez, Djanira Aparecida da Luz; Martins Filho, Eduardo Lopes; Fraga, Rogério de

2016-01-01

ABSTRACT PURPOSE: To evaluate the renal function and the renal histological alterations through the stereology and morphometrics in rats submitted to the natural process of aging. METHODS: Seventy two Wistar rats, divided in six groups. Each group was sacrificed in a different age: 3, 6, 9, 12, 18 and 24 months. It was performed right nephrectomy, stereological and morphometric analysis of the renal tissue (renal volume and weight, density of volume (Vv[glom]) and numerical density (Nv[glo...

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

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

The effect of two different renal denervation strategies on blood pressure in resistant hypertension: Comparison of full-length versus proximal renal artery ablation.

Science.gov (United States)

Chen, Weijie; Ling, Zhiyu; Du, Huaan; Song, Wenxin; Xu, Yanping; Liu, Zengzhang; Su, Li; Xiao, Peilin; Yuan, Yuelong; Lu, Jiayi; Zhang, Jianhong; Li, Zhifeng; Shao, Jiang; Zhong, Bin; Zhou, Bei; Woo, Kamsang; Yin, Yuehui

2016-11-01

Renal denervation (RDN) is used to manage blood pressure (BP) in patients with resistant hypertension (rHT), but effectiveness is still a concern, and key arterial portion for successful RDN is not clear. The aim of this study was to investigate the efficacy and safety of proximal versus full-length renal artery ablation in patients with resistant hypertension (rHT). Forty-seven patients with rHT were randomly assigned to receive full-length ablation (n = 23) or proximal ablation (n = 24) of the renal arteries. All lesions were treated with radiofrequency energy via a saline-irrigated catheter. Office BP was measured during 12 months of follow-up and ambulatory BP at baseline and 6 months (n = 15 in each group). Compared with full-length ablation, proximal ablation reduced the number of ablation points in both the right (6.1 ± 0.7 vs. 3.3 ± 0.6, P renal arteries (6.2 ± 0.7 vs. 3.3 ± 0.8, P  0.5). Similar office BPs was reduced by -39.4 ± 11.5/-20.9 ± 7.1 mm Hg at 6 months and -38.2 ± 10.3/-21.5 ± 5.8 mm Hg at 12 months in the full-length group (P efficacy and safety profile compared with full-length RDN, and propose the proximal artery as the key portion for RDN. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Exogenous and endogenous angiotensin‐II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow

Science.gov (United States)

Emans, Tonja W.; Janssen, Ben J.; Pinkham, Maximilian I.; Ow, Connie P. C.; Evans, Roger G.; Joles, Jaap A.; Malpas, Simon C.; Krediet, C. T. Paul

2016-01-01

Key points Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary.We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats.This method provides stable and continuous measurements of cortical tissue oxygen tension (PO2) for more than 2 weeks and can reproducibly detect acute changes in cortical oxygenation.Exogenous angiotensin‐II reduced renal cortical tissue PO2 more than equi‐pressor doses of phenylephrine, probably because it reduced renal oxygen delivery more than did phenylephrine.Activation of the endogenous renin–angiotensin system in transgenic Cyp1a1Ren2 rats reduced cortical tissue PO2; in this model renal hypoxia precedes the development of structural pathology and can be reversed acutely by an angiotensin‐II receptor type 1 antagonist.Angiotensin‐II promotes renal hypoxia, which may in turn contribute to its pathological effects during development of chronic kidney disease. Abstract We hypothesised that both exogenous and endogenous angiotensin‐II (AngII) can decrease the partial pressure of oxygen (PO2) in the renal cortex of unrestrained rats, which might in turn contribute to the progression of chronic kidney disease. Rats were instrumented with telemeters equipped with a carbon paste electrode for continuous measurement of renal cortical tissue PO2. The method reproducibly detected acute changes in cortical oxygenation induced by systemic hyperoxia and hypoxia. In conscious rats, renal cortical PO2 was dose‐dependently reduced by intravenous AngII. Reductions in PO2 were significantly greater than those induced by equi‐pressor doses of phenylephrine. In anaesthetised rats, renal oxygen consumption was not affected, and filtration fraction was increased only in the AngII infused animals. Oxygen delivery decreased by 50% after infusion of AngII and renal blood flow (RBF) fell by 3.3 ml min−1

Renal expression of FGF23 in progressive renal disease of diabetes and the effect of ACE inhibitor.

Directory of Open Access Journals (Sweden)

Cristina Zanchi

Full Text Available Fibroblast growth factor 23 (FGF23 is a phosphaturic hormone mainly produced by bone that acts in the kidney through FGF receptors and Klotho. Here we investigated whether the kidney was an additional source of FGF23 during renal disease using a model of type 2 diabetic nephropathy. Renal expression of FGF23 and Klotho was assessed in Zucker diabetic fatty (ZDF and control lean rats at 2, 4, 6, 8 months of age. To evaluate whether the renoprotective effect of angiotensin converting enzyme (ACE inhibitor in this model was associated with changes in FGF23 and Klotho, ZDF rats received ramipril from 4, when proteinuric, to 8 months of age. FGF23 mRNA was not detectable in the kidney of lean rats, nor of ZDF rats at 2 months of age. FGF23 became measurable in the kidney of diabetic rats at 4 months and significantly increased thereafter. FGF23 protein localized in proximal and distal tubules. Renal Klotho mRNA and protein decreased during time in ZDF rats. As renal disease progressed, serum phosphate levels increased in parallel with decline of fractional phosphorus excretion. Ramipril limited proteinuria and renal injury, attenuated renal FGF23 upregulation and ameliorated Klotho expression. Ramipril normalized serum phosphate levels and tended to increase fractional phosphorus excretion. These data indicate that during progressive renal disease the kidney is a site of FGF23 production which is limited by ACE inhibition. Interfering pharmacologically with the delicate balance of FGF23 and phosphorus in diabetes may have implications in clinics.

Early life stress sensitizes the renal and systemic sympathetic system in rats.

Science.gov (United States)

Loria, Analia S; Brands, Michael W; Pollock, David M; Pollock, Jennifer S

2013-08-01

We hypothesized that maternal separation (MS), an early life stress model, induces a sensitization of the sympathetic system. To test this hypothesis, we evaluated the renal and systemic sympathetic system in 12- to 14-wk-old male control or MS rats with the following parameters: 1) effect of renal denervation on conscious renal filtration capacity, 2) norepinephrine (NE) content in key organs involved in blood pressure control, and 3) acute systemic pressor responses to adrenergic stimulation or ganglion blockade. MS was performed by separating pups from their mothers for 3 h/day from day 2 to 14; controls were nonhandled littermates. Glomerular filtration rate (GFR) was examined in renal denervated (DnX; within 2 wk) or sham rats using I¹²⁵-iothalamate plasma clearance. MS-DnX rats showed significantly increased GFR compared with MS-SHAM rats (3.8 ± 0.4 vs. 2.4 ± 0.2 ml/min, respectively, P renal nerves regulate GFR in MS rats. NE content was significantly increased in organ tissues from MS rats (P renal and systemic sympathetic system. Conscious MS rats displayed a significantly greater increase in mean arterial pressure (MAP) in response to NE (2 μg/kg ip) and a greater reduction in MAP in response to mecamylamine (2 mg/kg ip, P renal and systemic sympathetic system ultimately impairing blood pressure regulation.

Application of physiologically-based pharmacokinetic modeling to explore the role of kidney transporters in renal reabsorption of perfluorooctanoic acid in the rat

Energy Technology Data Exchange (ETDEWEB)

Worley, Rachel Rogers, E-mail: idz7@cdc.gov [Agency for Toxic Substances and Disease Registry, Division of Community Health Investigations, 4770 Buford Highway, Atlanta, GA 30341 (United States); Interdisciplinary Toxicology Program, University of Georgia, 341 Pharmacy South, Athens, GA 30602 (United States); Fisher, Jeffrey [Interdisciplinary Toxicology Program, University of Georgia, 341 Pharmacy South, Athens, GA 30602 (United States); Food and Drug Administration, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079 (United States)

2015-12-15

ABSTRACT: Renal elimination and the resulting clearance of perfluorooctanoic acid (PFOA) from the serum exhibit pronounced sex differences in the adult rat. The literature suggests that this is largely due to hormonally regulated expression of organic anion transporters (OATs) on the apical and basolateral membranes of the proximal tubule cells that facilitate excretion and reabsorption of PFOA from the filtrate into the blood. Previously developed PBPK models of PFOA exposure in the rat have not been parameterized to specifically account for transporter-mediated renal elimination. We developed a PBPK model for PFOA in male and female rats to explore the role of Oat1, Oat3, and Oatp1a1 in sex-specific renal reabsorption and excretion of PFOA. Descriptions of the kinetic behavior of these transporters were extrapolated from in vitro studies and the model was used to simulate time-course serum, liver, and urine data for intravenous (IV) and oral exposures in both sexes. Model predicted concentrations of PFOA in the liver, serum, and urine showed good agreement with experimental data for both male and female rats indicating that in vitro derived physiological descriptions of transporter-mediated renal reabsorption can successfully predict sex-dependent excretion of PFOA in the rat. This study supports the hypothesis that sex-specific serum half-lives for PFOA are largely driven by expression of transporters in the kidney and contribute to the development of PBPK modeling as a tool for evaluating the role of transporters in renal clearance. - Highlights: • The PBPK model for PFOA in the rat explores the role of OATs in sex-specific clearance. • Descriptions of OAT kinetics were extrapolated from in vitro studies. • Model predictions showed good fit with experimental data for male and female rats.

Application of physiologically-based pharmacokinetic modeling to explore the role of kidney transporters in renal reabsorption of perfluorooctanoic acid in the rat

International Nuclear Information System (INIS)

Worley, Rachel Rogers; Fisher, Jeffrey

2015-01-01

ABSTRACT: Renal elimination and the resulting clearance of perfluorooctanoic acid (PFOA) from the serum exhibit pronounced sex differences in the adult rat. The literature suggests that this is largely due to hormonally regulated expression of organic anion transporters (OATs) on the apical and basolateral membranes of the proximal tubule cells that facilitate excretion and reabsorption of PFOA from the filtrate into the blood. Previously developed PBPK models of PFOA exposure in the rat have not been parameterized to specifically account for transporter-mediated renal elimination. We developed a PBPK model for PFOA in male and female rats to explore the role of Oat1, Oat3, and Oatp1a1 in sex-specific renal reabsorption and excretion of PFOA. Descriptions of the kinetic behavior of these transporters were extrapolated from in vitro studies and the model was used to simulate time-course serum, liver, and urine data for intravenous (IV) and oral exposures in both sexes. Model predicted concentrations of PFOA in the liver, serum, and urine showed good agreement with experimental data for both male and female rats indicating that in vitro derived physiological descriptions of transporter-mediated renal reabsorption can successfully predict sex-dependent excretion of PFOA in the rat. This study supports the hypothesis that sex-specific serum half-lives for PFOA are largely driven by expression of transporters in the kidney and contribute to the development of PBPK modeling as a tool for evaluating the role of transporters in renal clearance. - Highlights: • The PBPK model for PFOA in the rat explores the role of OATs in sex-specific clearance. • Descriptions of OAT kinetics were extrapolated from in vitro studies. • Model predictions showed good fit with experimental data for male and female rats.

Active lithium transport by rat renal proximal tubule: a micropuncture study

DEFF Research Database (Denmark)

Leyssac, P P; Frederiksen, O; Holstein-Rathlou, N H

1994-01-01

We tested the hypothesis that proximal tubular Li+ reabsorption is due to passive transport. Clearances of [14C]inulin (CIn) and Li+ (CLi), proximal transepithelial electrical potential difference (PD), and tubular fluid-to-plasma Li+ concentration ratios [(TF/P)Li] were measured in anesthetized ...

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.

Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

Science.gov (United States)

Baba, Asuka; Tachi, Masahiro; Ejima, Yutaka; Endo, Yasuhiro; Toyama, Hiroaki; Saito, Kazutomo; Abe, Nozomu; Yamauchi, Masanori; Miura, Chieko; Kazama, Itsuro

2017-02-01

Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF. © 2016 Asian Pacific Society of Nephrology.

Effects of lead intoxication on intercellular junctions and biochemical alterations of the renal proximal tubule cells.

Science.gov (United States)

Navarro-Moreno, L G; Quintanar-Escorza, M A; González, S; Mondragón, R; Cerbón-Solorzáno, J; Valdés, J; Calderón-Salinas, J V

2009-10-01

Lead intoxication is a worldwide health problem which frequently affects the kidney. In this work, we studied the effects of chronic lead intoxication (500 ppm of Pb in drinking water during seven months) on the structure, function and biochemical properties of rat proximal tubule cells. Lead-exposed animals showed increased lead concentration in kidney, reduction of calcium and amino acids uptake, oxidative damage and glucosuria, proteinuria, hematuria and reduced urinary pH. These biochemical and physiological alterations were related to striking morphological modifications in the structure of tubule epithelial cells and in the morphology of their mitochondria, nuclei, lysosomes, basal and apical membranes. Interestingly, in addition to the nuclei, inclusion bodies were found in the cytoplasm and in mitochondria. The epithelial cell structure modifications included an early loss of the apical microvillae, followed by a decrement of the luminal space and the respective apposition and proximity of apical membranes, resulting in the formation of atypical intercellular contacts and adhesion structures. Similar but less marked alterations were observed in subacute lead intoxication as well. Our work contributes in the understanding of the physiopathology of lead intoxication on the structure of renal tubular epithelial cell-cell contacts in vivo.

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...

Exogenous and endogenous angiotensin-II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow.

Science.gov (United States)

Emans, Tonja W; Janssen, Ben J; Pinkham, Maximilian I; Ow, Connie P C; Evans, Roger G; Joles, Jaap A; Malpas, Simon C; Krediet, C T Paul; Koeners, Maarten P

2016-11-01

Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary. We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats. This method provides stable and continuous measurements of cortical tissue oxygen tension (PO2) for more than 2 weeks and can reproducibly detect acute changes in cortical oxygenation. Exogenous angiotensin-II reduced renal cortical tissue PO2 more than equi-pressor doses of phenylephrine, probably because it reduced renal oxygen delivery more than did phenylephrine. Activation of the endogenous renin-angiotensin system in transgenic Cyp1a1Ren2 rats reduced cortical tissue PO2; in this model renal hypoxia precedes the development of structural pathology and can be reversed acutely by an angiotensin-II receptor type 1 antagonist. Angiotensin-II promotes renal hypoxia, which may in turn contribute to its pathological effects during development of chronic kidney disease. We hypothesised that both exogenous and endogenous angiotensin-II (AngII) can decrease the partial pressure of oxygen (PO2) in the renal cortex of unrestrained rats, which might in turn contribute to the progression of chronic kidney disease. Rats were instrumented with telemeters equipped with a carbon paste electrode for continuous measurement of renal cortical tissue PO2. The method reproducibly detected acute changes in cortical oxygenation induced by systemic hyperoxia and hypoxia. In conscious rats, renal cortical PO2 was dose-dependently reduced by intravenous AngII. Reductions in PO2 were significantly greater than those induced by equi-pressor doses of phenylephrine. In anaesthetised rats, renal oxygen consumption was not affected, and filtration fraction was increased only in the AngII infused animals. Oxygen delivery decreased by 50% after infusion of AngII and renal blood flow (RBF) fell by 3.3 ml min -1 . Equi-pressor infusion of

Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips

Science.gov (United States)

Homan, Kimberly A.; Kolesky, David B.; Skylar-Scott, Mark A.; Herrmann, Jessica; Obuobi, Humphrey; Moisan, Annie; Lewis, Jennifer A.

2016-10-01

Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand.

Aging aggravates long-term renal ischemia-reperfusion injury in a rat model.

Science.gov (United States)

Xu, Xianlin; Fan, Min; He, Xiaozhou; Liu, Jipu; Qin, Jiandi; Ye, Jianan

2014-03-01

Ischemia-reperfusion injury (IRI) has been considered as the major cause of acute kidney injury and can result in poor long-term graft function. Functional recovery after IRI is impaired in the elderly. In the present study, we aimed to compare kidney morphology, function, oxidative stress, inflammation, and development of renal fibrosis in young and aged rats after renal IRI. Rat models of warm renal IRI were established by clamping left pedicles for 45 min after right nephrectomy, then the clamp was removed, and kidneys were reperfused for up to 12 wk. Biochemical and histologic renal damage were assessed at 12 wk after reperfusion. The immunohistochemical staining of monocyte macrophage antigen-1 (ED-1) and transforming growth factor beta 1 (TGF-β1) and messenger RNA level of TGF-β1 in the kidney were analyzed. Renal IRI caused significant increases of malondialdehyde and 8-hydroxydeoxyguanosine levels and a decrease of superoxide dismutase activity in young and aged IRI rats; however, these changes were more obvious in the aged rats. IRI resulted in severe inflammation and tubulointerstitial fibrosis with decreased creatinine (Cr) clearance and increased histologic damage in aged rats compared with young rats. Moreover, we measured the ratio of Cr clearance between young and aged IRI rats. It demonstrated that aged IRI rats did have poor Cr clearance compared with the young IRI rats. ED-1 and TGF-β1 expression levels in the kidney were significantly higher in aged rats than in young rats after IRI. Aged rats are more susceptible to IRI-induced renal failure, which may associate with the increased oxidative stress, increased histologic damage, and increased inflammation and tubulointerstitial fibrosis. Targeting oxidative stress and inflammatory response should improve the kidney recovery after IRI. Copyright © 2014 Elsevier Inc. All rights reserved.

Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

International Nuclear Information System (INIS)

Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

2009-01-01

Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

Review of Surgical Techniques of Experimental Renal Transplantation in Rats.

Science.gov (United States)

Shrestha, Badri; Haylor, John

2017-08-01

Microvascular surgical techniques of renal transplant in rats have evolved over the past 5 decades to achieve successful rat renal transplant; these modifications have included surgical techniques to address the anatomic variations in the renal blood vessels and those to reduce ischemic and operation durations. Here, we review the surgical techniques of renal transplant in rats and evaluate the advantages and disadvantages of individual techniques of vascular and ureteric anastomoses. For this review, we performed a systematic literature search using relevant medical subject heading terms and included appropriate publications in the review. Since the first description of a rat model of renal transplant by Bernard Fisher and his colleagues in 1965, which used end-to-side anastomosis between the renal vein and renal artery to the recipient inferior vena cava and aorta, several vascular and ureteric anastomosis techniques have been modified. Vascular anastomosis techniques now include end-to-end anastomosis, use of donor aortic and inferior vena cava conduits, sleeve and cuff anastomoses, and application of fibrin glue. Likewise, restoration of the urinary tract can now be achieved by direct anastomosis of the donor ureter to the recipient bladder, end-to-end anastomosis between the donor and recipient ureters, and donor bladder cuff to the recipient bladder. There are advantages and disadvantages attributable to individual techniques. The range of vascular and ureteric anastomosis techniques that has emerged reflects the need for mastering more than one technique to suit the vascular anatomy of individual animals and to reduce operating time for achieving successful outcomes after renal transplant.

High-protein diets and renal status in rats

OpenAIRE

Aparicio, V. A.; Nebot, E.; García-del Moral, R.; Machado-Vílchez, M.; Porres, J. M.; Sánchez, C.; Aranda, P.

2013-01-01

Introduction: High-protein (HP) diets might affect renal status. We aimed to examine the effects of a HP diet on plasma, urinary and morphological renal parameters in rats. Material and methods: Twenty Wistar rats were randomly distributed in 2 experimental groups with HP or normal-protein (NP) diets over 12 weeks. Results and discussion: Final body weight was a 10% lower in the HP group (p < 0.05) whereas we have not observed differences on food intake, carcass weight and muscle ashes conten...

Functionally induced changes in water transport in the proximal tubule segment of rat kidneys

DEFF Research Database (Denmark)

Faarup, Poul; von Holstein-Rathlou, Niels-Henrik; Nørgaard, Tove

2011-01-01

To eliminate freezing artifacts in the proximal tubule cells, two cryotechniques were applied to normal rat kidneys, ie, freeze substitution and special freeze drying. In addition, salt depletion and salt loading were applied to groups of rats to evaluate whether the segmental structure of the pr......To eliminate freezing artifacts in the proximal tubule cells, two cryotechniques were applied to normal rat kidneys, ie, freeze substitution and special freeze drying. In addition, salt depletion and salt loading were applied to groups of rats to evaluate whether the segmental structure...... segment, representing a structural background for the essential transport of water from the proximal tubules to the peritubular capillaries....

Proximal-tubule-like epithelium in Bowman's capsule in spontaneously hypertensive rats. Changes with age.

OpenAIRE

Haensly, W. E.; Granger, H. J.; Morris, A. C.; Cioffe, C.

1982-01-01

Kidneys were samples from male spontaneously hypertensive rats (SHR) and normotensive rats (WKY) in four groups. Renal tissues were examined in 64 rats: 6 SHR and 6 WKY rats 8 and 16 weeks of age and 10 SHR and 10 WKY rats 32 and 64 weeks of age. Tissue samples were fixed, processed, and stained by routine histologic procedures. The parietal layer of Bowman's capsule in 100-115 renal corpuscles from right to left kidney sections was classified as squamous or cuboidal epithelium. The cuboidal ...

Morphological characteristics of renal artery and kidney in rats.

Science.gov (United States)

Yoldas, Atilla; Dayan, Mustafa Orhun

2014-01-01

The gross anatomy and morphometry of the kidney and renal arteries were studied in the strains of laboratory rat: Sprague-Dawley (Sp) and Wistar (W) rats. Total of 106 three-dimensional endocasts of the intrarenal arteries of kidney that were prepared using standard injection-corrosion techniques were examined. A single renal artery was observed in 100% of the cases. The renal arteries were divided into a dorsal and a ventral branch. The dorsal and ventral branches were divided into two branches, the cranial and caudal branch. Renal arteries were classified into types I and II, depending on the cranial and caudal branches and their made of branching. The present study also showed that the right kidney was slightly heavier than the left one and that the kidney of the male was generally larger than that of the female. The mean live weights of the Sprague-Dawley and Wistar rats were found to be 258.26 ± 5.9 and 182.4 ± 19.05 g, respectively. The kidney weights were significantly correlated (P kidney weights were not found significantly correlated (P > 0.01) with the length of renal arteries.

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

Novel Hg2+-Induced Nephropathy in Rats and Mice Lacking Mrp2: Evidence of Axial Heterogeneity in the Handling of Hg2+ Along the Proximal Tubule

Science.gov (United States)

Zalups, Rudolfs K.; Joshee, Lucy; Bridges, Christy C.

2014-01-01

The role of the multi-resistance protein 2 (Mrp2) in the nephropathy induced by inorganic mercuric mercury (Hg2+) was studied in rats (TR−) and mice (Mrp2−/−), which lack functional Mrp2, and control animals. Animals were exposed to nephrotoxic doses of HgCl2. Forty-eight or 24 hours after exposure, tissues were harvested and analyzed for Hg content and markers of injury. Histological analyses revealed that the proximal tubular segments affected pathologically by Hg2+ were significantly different between Mrp2-deficient animals and controls. In the absence of Mrp2, cellular injury localized almost exclusively in proximal tubular segments in the subcapsular (S1) to midcortical regions (early S2) of the kidney. In control animals, cellular death occurred mainly in the proximal tubular segments in the inner cortex (late S2) and outer stripe of the outer medulla (S3). These differences in renal pathology indicate that axial heterogeneity exists along the proximal tubule with respect to how mercuric ions are handled. Total renal and hepatic accumulation of mercury was also greater in animals lacking Mrp2 than in controls, indicating that Mrp2 normally plays a significant role in eliminating mercuric ions from within proximal tubular cells and hepatocytes. Analyses of plasma creatinine, BUN, and renal expression of Kim-1 and Ngal tend to support the severity of the nephropathies detected histologically. Collectively, our findings indicate that a fraction of mercuric ions is normally secreted by Mrp2 in early portions of proximal tubules into the lumen and then is absorbed downstream in straight portions, where mercuric species typically induce toxic effects. PMID:25145654

Comparison of renal toxicity after injection of CT contrast medium and MR contrast medium: change of renal function in acute renal failure rat models

International Nuclear Information System (INIS)

Han, Young min; Lee, Young Hwan; Kim, Sang Won; Jin, Kong Young; Kim, Won; Chung, Gyung Ho

2002-01-01

To determine renal toxicity through changes in renal function after the injection of CT and MRI contrast media into rats in which acute renal failure (ARF) was induced. To cause acute renal failure, the abdominal cavity of 110 male rats each weighing 250-300 gm was opened via a midline incision under anesthesia. Microvascular clamps were placed on both renal arteries and veins to completely block renal blood flow for 45 minutes, and were then removed, allowing blood flow to return to the kidneys. ARF, defined as a two-fold difference in the creatinine level before ARF and 48 hours after, was successfully induced in 60 of the rats. These were divided into two groups: one was injected with CT contrast medium and the other with MRI contrast medium. Each CT and MRI group was divided into a low dose (0.5 cc/kg, 0.2 ml/kg), standard dose (2 cc/kg, 0.8 ml/kg), and high dose (8 cc/kg, 3.2 ml/kg) sub-group; thus, there was a total of six groups with ten rats in each. Blood samples were obtained before ARF, 48 hours after, and 48 hours after contrast injection, and CT scanning and MRI were performed after blood sampling at 48 hours. In each group, creatinine levels 48 hours after contrast injection were compared by means of the ANOVA test. There were no significant differences in creatinine levels between the CT and MRI contrast medium groups (p=0.116), nor between the animals to which different doses of CT and MRI contrast medium, were administered. After both standard and high doses, CT and MRI provided good images. In rats in which acute renal failure was induced, renal function did not change according to whether CT or MRI contrast medium was injected. Thus, the two media induce similar levels of toxicity

Renal inflammatory response to urinary tract infection in rat neonates.

Science.gov (United States)

Zarepour, M; Moradpoor, H; Emamghorashi, F; Owji, S M; Roodaki, M; Khamoushi, M

2015-09-01

Urinary tract infection (UTI) is one of the most common bacterial infections. Maternal UTI is a risk factor for neonatal UTI. The aim of the present study was to determine the severity of renal inflammation in neonate rats born from mothers with induced UTI. Twelve pregnant rats (Sprague-Dawley) were included in study. The rats were divided into two groups (six rats in each group). In the first group, pyelonephritis was induced in the third trimester of pregnancy and the second group was used as a control group. After delivery, the neonates were divided into three groups based on days after birth (the 1 st, 3 rd and 7 th days after birth). In each group, two neonates of each mother were killed and a midline abdominal incision was made and both kidneys were aseptically removed. On the 7 th day, rat mothers were killed and their kidneys were removed. The preparations were evaluated with a bright field microscope for inflammatory response. Renal pathology showed inflammation in all UTI-induced mothers, but only two cases of neonates (2.1%) showed inflammation in the renal parenchyma. There was no relation between the positive renal culture and the pathological changes. We conclude that neonates with UTI born to UTI-induced mothers showed a lesser inflammatory response.

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.

Adrenal medullary regulation of rat renal cortical adrenergic receptors

International Nuclear Information System (INIS)

Sundaresan, P.R.; Guarnaccia, M.M.; Izzo, J.L. Jr.

1987-01-01

The role of the adrenal medulla in the regulation of renal cortical adrenergic receptors was investigated in renal cortical particular fractions from control rats and rats 6 wk after adrenal demedullation. The specific binding of [ 3 H]prazosin, [ 3 H]rauwolscine, and [ 125 I]iodocyanopindolol were used to quantitate α 1 -, α 2 -, and β-adrenergic receptors, respectively. Adrenal demedullation increased the concentration of all three groups of renal adrenergic receptors; maximal number of binding sites (B max , per milligram membrane protein) for α 1 -, and α 2 -, and β-adrenergic receptors were increased by 22, 18.5, and 25%, respectively. No differences were found in the equilibrium dissociation constants (K D ) for any of the radioligands. Plasma corticosterone and plasma and renal norepinephrine levels were unchanged, whereas plasma epinephrine was decreased 72% by adrenal demedullation, renal cortical epinephrine was not detectable in control or demedullated animals. The results suggest that, in the physiological state, the adrenal medulla modulates the number of renal cortical adrenergic receptors, presumably through the actions of a circulating factor such as epinephrine

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.

Effects of mercury on lysosomal protein digestion in the kidney proximal tubule

International Nuclear Information System (INIS)

Madsen, K.M.; Christensen, E.I.

1978-01-01

The effect of mercury on renal lysosomal protein digestion was studied after administration of mercury in vitro and in vivo. Mercuric chloride or methylmercury chloride was added in vitro to lysosomal enzymes isolated from normal rats, and subsequently, digestion experiments were carried out using 125 I-labeled lysozyme or cytochrome c as substrate proteins. Both mercury compounds produced a concentration-dependent inhibition of the degradation of the proteins, mercuric chloride being the strongest inhibitor. Mercuric chloride was also administered to rats in vivo for 5 to 8 months. Renal lysosomal enzymes from these animals also had a decreased ability to digest the two substrate proteins. Furthermore, the digestion of lysozyme intravenously injected into mercury-intoxicated rats was decreased in renal cortical slices incubated in vitro. Electron microscope autoradiography showed that intravenously injected labeled lysozyme was located primarily over lysosomes in proximal tubule cells 1 hour after injection in both control animals and mercury-intoxicated rats. These results suggest a decreased catabolism of low molecular weight proteins in the kidney during chronic mercury intoxication

Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis.

Science.gov (United States)

Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting; Larsson, Erik; Wåhlin, Nils; Jensen, Boye L; G Persson, A Erik; Carlström, Mattias

2016-01-01

Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin-aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 ± 3 vs. 87 ± 1 mmHg, P < 0.05) and displayed increased urine production and lower urine osmolality. The blood pressure change in response to salt loading (salt sensitivity) was more pronounced in the PUUO group compared with the control group (15 ± 2 vs. 5 ± 1 mmHg, P < 0.05). Renal denervation in PUUO rats attenuated both hypertension (97 ± 3 mmHg) and salt sensitivity (5 ± 1 mmHg, P < 0.05) and normalized the renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates

Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

DEFF Research Database (Denmark)

Graebe, M.; Brond, L.; Christensen, S.

2004-01-01

The present study investigated sodium balance and renal tubular function in cirrhotic rats with chronic blockade of the nitric oxide (NO) system. Rats were treated with the nonselective NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) starting on the day of common bile duct ligation...... (CBL). Three weeks of daily sodium balance studies showed that CBL rats developed sodium retention compared with sham-operated rats and that l-NAME treatment dose dependently deteriorated cumulative sodium balance by reducing urinary sodium excretion. Five weeks after CBL, renal clearance studies were...

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.

Renal inflammatory response to urinary tract infection in rat neonates

Directory of Open Access Journals (Sweden)

M Zarepour

2015-01-01

Full Text Available Urinary tract infection (UTI is one of the most common bacterial infections. Maternal UTI is a risk factor for neonatal UTI. The aim of the present study was to determine the severity of renal inflammation in neonate rats born from mothers with induced UTI. Twelve pregnant rats (Sprague-Dawley were included in study. The rats were divided into two groups (six rats in each group. In the first group, pyelonephritis was induced in the third trimester of pregnancy and the second group was used as a control group. After delivery, the neonates were divided into three groups based on days after birth (the 1 st, 3 rd and 7 th days after birth. In each group, two neonates of each mother were killed and a midline abdominal incision was made and both kidneys were aseptically removed. On the 7 th day, rat mothers were killed and their kidneys were removed. The preparations were evaluated with a bright field microscope for inflammatory response. Renal pathology showed inflammation in all UTI-induced mothers, but only two cases of neonates (2.1% showed inflammation in the renal parenchyma. There was no relation between the positive renal culture and the pathological changes. We conclude that neonates with UTI born to UTI-induced mothers showed a lesser inflammatory response.

Effects of taurine on oxidative-antioxidative status of renal tissue in diabetic rats

International Nuclear Information System (INIS)

Chen Yingjian; Tu Xiaowen; Yin Qiuxia; Hu Chenjing

2004-01-01

Objective: To investigate the effects of taurine on the oxidative-antioxidative status of renal tissue in diabetic rats. Methods: Diabetic models of rat were induced with streptozotocin. Half of the models (n=7) were treated with taurine for 4 weeks. Blood glucose, uric acid and MDA, 24h urinary albumin and renal cortical homogenate MDA, SOD, GSH-Px contents were determined with appropriate laboratory technics in 1) diabetic rats without taurine treatment, n=7 2) diabetic rats treated with taurine, n=7 and 3) control rats, n=7. Results: There were no significant differences between the blood glucose levels in the two groups of diabetic rats. Blood uric acid and 24h urinary albumin contents in the untreated diabetic rats were significantly higher than those in the controls (P<0.01). However, in the taurine treated rats, the blood uric acid levels approximated to those in the controls, with decreased but still higher than normal 24h urinary albumin contents. In the untreated rats, the renal cortical SOD and GSH-Px activities were about the same as those in control rats but there were significantly higher levels of blood and cortical MDA contents (P<0.01). With taurine treatment, the SOD and GSH-Px activities were significantly higher than those in the two other groups (P<0.05); the MDA contents were lower than those in non-treated rats (P<0.05), but still higher than those in controls (P<0.05). Conclusion: Taurine could enhance the anti-oxidative capability and attenuated the oxidative stress in diabetic rats renal tissue with partial protection of renal function. (authors)

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

The effect of zinc on healing of renal damage in rats.

Science.gov (United States)

Salehipour, Mehdi; Monabbati, Ahmad; Ensafdaran, Mohammad Reza; Adib, Ali; Babaei, Amir Hossein

2017-07-01

Several studies have previously been performed to promote kidney healing after injuries. Objectives: The aim of this study was to investigate the effect of zinc on renal healing after traumatic injury in rats. Forty healthy female rats were selected and one of their kidneys was incised. Half of the incisions were limited only to the cortex (renal injury type I) and the other ones reached the pelvocalyceal system of the kidney (renal injury type II). All the rats in the zinc treated group (case group) received 36.3 mg zinc sulfate (contained 8.25 mg zinc) orally. After 28 days, the damaged kidneys were removed for histopathological studies. In the rats with type I injury, kidney inflammation of the case group was significantly lower than that of the control group. However, the result was not significant in rats with type II injury. Tissue loss and granulation tissue formation were significantly lower in the case group than the control group in both type I and II kidney injuries. Overall, Zinc can contribute to better healing of the rat's kidneys after a traumatic injury.

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.

Renal sodium retention in cirrhotic rats depends on glucocorticoid-mediated activation of mineralocorticoid receptor due to decreased renal 11beta-HSD-2 activity

DEFF Research Database (Denmark)

Thiesson, Helle; Jensen, Boye L; Bistrup, Claus

2007-01-01

Downregulation of the renal glucocorticoid-metabolizing enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD-2) during liver cirrhosis may allow activation of the mineralocorticoid receptor (MR) by glucocorticoids and contribute to sodium retention. We tested this hypothesis in male Wistar...... rats with decompensated liver cirrhosis and ascites 7 wk after bile duct ligation (BDL). Renal 11beta-HSD-2 mRNA, protein, and activity were significantly decreased in decompensated rats. The urinary Na(+)/K(+) ratio was reduced by 40%. Renal epithelial sodium channel (ENaC) mRNA and immunostaining...... were only slightly affected. Complete metabolic studies, including fecal excretion, showed that the BDL rats had avid renal sodium retention. Treatment of the BDL rats with dexamethasone suppressed endogenous glucocorticoid production, normalized total sodium balance and renal sodium excretion...

L-NIL prevents renal microvascular hypoxia and increase of renal oxygen consumption after ischemia-reperfusion in rats

NARCIS (Netherlands)

Legrand, Matthieu; Almac, Emre; Mik, Egbert G.; Johannes, Tanja; Kandil, Asli; Bezemer, Rick; Payen, Didier; Ince, Can

2009-01-01

Legrand M, Almac E, Mik EG, Johannes T, Kandil A, Bezemer R, Payen D, Ince C. L-NIL prevents renal microvascular hypoxia and increase of renal oxygen consumption after ischemia-reperfusion in rats. Am J Physiol Renal Physiol 296: F1109-F1117, 2009. First published February 18, 2009;

Aging and the Disposition and Toxicity of Mercury in Rats

Science.gov (United States)

Bridges, Christy C.; Joshee, Lucy; Zalups, Rudolfs K.

2014-01-01

Progressive loss of functioning nephrons, secondary to age-related glomerular disease, can impair the ability of the kidneys to effectively clear metabolic wastes and toxicants from blood. Additionally, as renal mass is diminished, cellular hypertrophy occurs in functional nephrons that remain. We hypothesize that these nephrons are exposed to greater levels of nephrotoxicants, such as inorganic mercury (Hg2+), and thus are at an increased risk of becoming intoxicated by these compounds. The purpose of the present study was to characterize the effects of aging on the disposition and renal toxicity of Hg2+ in young adult and aged Wistar rats. Paired groups of animals were injected (i.v.) with either a 0.5 μmol • kg−1 non-nephrotoxic or a 2.5 μmol • kg−1 nephrotoxic dose of mercuric chloride (HgCl2). Plasma creatinine and renal biomarkers of proximal tubular injury were greater in both groups of aged rats than in the corresponding groups of young adult rats. Histologically, evidence of glomerular sclerosis, tubular atrophy, interstitial inflammation and fibrosis were significant features of kidneys from aged animals. In addition, proximal tubular necrosis, especially along the straight segments in the inner cortex and outer stripe of the outer medulla was a prominent feature in the renal sections from both aged and young rats treated with the nephrotoxic dose of HgCl2. Our findings indicate 1) that overall renal function is significantly impaired in aged rats, resulting in chronic renal insufficiency and 2) the disposition of HgCl2 in aging rats is significantly altered compared to that of young rats. PMID:24548775

Aging and the disposition and toxicity of mercury in rats.

Science.gov (United States)

Bridges, Christy C; Joshee, Lucy; Zalups, Rudolfs K

2014-05-01

Progressive loss of functioning nephrons, secondary to age-related glomerular disease, can impair the ability of the kidneys to effectively clear metabolic wastes and toxicants from blood. Additionally, as renal mass is diminished, cellular hypertrophy occurs in functional nephrons that remain. We hypothesize that these nephrons are exposed to greater levels of nephrotoxicants, such as inorganic mercury (Hg(2+)), and thus are at an increased risk of becoming intoxicated by these compounds. The purpose of the present study was to characterize the effects of aging on the disposition and renal toxicity of Hg(2+) in young adult and aged Wistar rats. Paired groups of animals were injected (i.v.) with either a 0.5μmol·kg(-1) non-nephrotoxic or a 2.5μmol·kg(-1) nephrotoxic dose of mercuric chloride (HgCl2). Plasma creatinine and renal biomarkers of proximal tubular injury were greater in both groups of aged rats than in the corresponding groups of young adult rats. Histologically, evidence of glomerular sclerosis, tubular atrophy, interstitial inflammation and fibrosis were significant features of kidneys from aged animals. In addition, proximal tubular necrosis, especially along the straight segments in the inner cortex and outer stripe of the outer medulla was a prominent feature in the renal sections from both aged and young rats treated with the nephrotoxic dose of HgCl2. Our findings indicate 1) that overall renal function is significantly impaired in aged rats, resulting in chronic renal insufficiency and 2) the disposition of HgCl2 in aging rats is significantly altered compared to that of young rats. Copyright © 2014 Elsevier Inc. All rights reserved.

Small Renal Masses in Close Proximity to the Collecting System and Renal Sinus Are Enriched for Malignancy and High Fuhrman Grade and Should Be Considered for Early Intervention.

Science.gov (United States)

Correa, Andres F; Toussi, Amir; Amin, Milon; Hrebinko, Ronald L; Gayed, Bishoy A; Parwani, Anil V; Maranchie, Jodi K

2018-02-05

Recent reports show a correlation between renal tumor radiographic characteristics and pathologic features. We hypothesize that a more central location within the relatively hypoxic renal medulla might confer a more aggressive tumor phenotype. To test this, radiographic tumor characteristics were compared with tumor grade and histology. We retrospectively reviewed renal masses anatomic features with incidence of malignancy and high nuclear grade. A total of 334 renal tumors had information available for analysis. Univariate analysis showed that increasing endophycity and proximity to the collecting system (anatomical variable predictive of malignancy (odds ratio [OR], 3.58; 95% confidence interval [CI], 1.06-12.05; P = .04) and high nuclear grade (OR, 2.81; 95% CI, 1.44-5.51; P = .003). Malignancy and high tumor grade occur with much greater frequency when tumors are located deep in the kidney, in close proximity to the collecting system and renal sinus. Ninety-six percent of small renal masses in this region were cancers and nearly half were Fuhrman Grade 3 or 4, suggesting that these small centrally located tumors should be targeted for early intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

Intermittent hypoxia alters dose dependent caffeine effects on renal prostanoids and receptors in neonatal rats.

Science.gov (United States)

Beharry, Kay D; Cai, Charles L; Soontarapornchai, Kultida; Ahmad, Taimur; Valencia, Gloria B; Aranda, Jacob V

2018-01-01

Caffeine, one of the most commonly prescribed drugs in preterm neonates, is given in standard or suprapharmacologic doses. Although known as a diuretic, its effects in the neonatal kidneys are not well studied. We tested the hypothesis that neonatal intermittent hypoxia (IH) and high caffeine doses (HCD) alter renal regulators of vasomotor tone and water balance. Newborn rats were randomized to room air, hyperoxia, or IH and treated with standard or high caffeine doses; or placebo saline. Renal prostanoids; histopathology; and cyclooxygenase (COX), prostanoid receptor, and aquaporin (AQP) immunoreactivity were determined. HCD in IH caused severe pathological changes in the glomeruli and proximal tubules, consistent with acute kidney injury. This was associated with reductions in anthropometric growth, PGI 2, and IP, DP, and AQP-4 immunoreactivity, well as a robust increase in COX-2, suggesting that the use of HCD should be avoided in preterm infants who experience frequent IH episodes. Published by Elsevier Inc.

Dynamics of renal blood flow autoregulation in rats

DEFF Research Database (Denmark)

Holstein-Rathlou, N H; Wagner, A J; Marsh, D J

1991-01-01

Two separate components could be resolved in tests of the dynamic autoregulation of renal blood flow. The slow component corresponds to the frequency at which spontaneous proximal tubular pressure oscillations are found, and are most likely due to the operation of the TGF. The high frequency...

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.

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.

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.

Postnatal early overnutrition causes long-term renal decline in aging male rats.

Science.gov (United States)

Yim, Hyung Eun; Yoo, Kee Hwan; Bae, In Sun; Hong, Young Sook; Lee, Joo Won

2014-02-01

We evaluated the influence of postnatal early overnutrition on renal pathophysiological changes in aging rats. Three or 10 male pups per mother were assigned to either the small litter (SL) or normal litter (control) groups, respectively, during the first 21 d of life. The effects of early postnatal overnutrition were determined at 12 mo. SL rats weighed more than controls between 4 d and 6 mo of age (P renal cortex were higher in SL rats (P aging SL rats (P aging kidney and can lead to systolic hypertension with reduced intrarenal renin activity.

Acid-base transport by the renal proximal tubule.

Science.gov (United States)

Skelton, Lara A; Boron, Walter F; Zhou, Yuehan

2010-01-01

Each day, the kidneys filter 180 L of blood plasma, equating to some 4,300 mmol of the major blood buffer, bicarbonate (HCO3-). The glomerular filtrate enters the lumen of the proximal tubule (PT), and the majority of filtered HCO3- is reclaimed along the early (S1) and convoluted (S2) portions of the PT in a manner coupled to the secretion of H+ into the lumen. The PT also uses the secreted H+ to titrate non-HCO3- buffers in the lumen, in the process creating "new HCO3-" for transport into the blood. Thus, the PT - along with more distal renal segments - is largely responsible for regulating plasma [HCO3-]. In this review we first focus on the milestone discoveries over the past 50+ years that define the mechanism and regulation of acid-base transport by the proximal tubule. Further on in the review, we will summarize research still in progress from our laboratory, work that addresses the problem of how the PT is able to finely adapt to acid-base disturbances by rapidly sensing changes in basolateral levels of HCO3- and CO2 (but not pH), and thereby to exert tight control over the acid-base composition of the blood plasma.

Renal hemodynamics and oxygenation in transient renal artery occluded rats evaluated with iron-oxide particles and oxygenation-sensitive imaging

International Nuclear Information System (INIS)

Pedersen, Michael; Aarhus Univ.; Univ. Victor Segalen Bordeaux 2; Laustsen, Christoffer; Perot, Vincent; Grenier, Nicolas; Basseau, Fabrice; Moonen, Chrit

2010-01-01

Mild or severe renal arterial occlusion is a phenomenon occasionally observed in daily clinical practice, potentially leading to renal ischemia and a general impairment of renal function. Secondly, closing the blood flow to the kidneys can also occur during kidney transplantation procedures. However, the exact physiological effects of these conditions on renal blood perfusion as well as the renal oxygen handling are poorly understood. The objectives of this study were therefore to measure the lateral changes of renal blood perfusion in rats subjected to transient unilateral arterial occlusion (RAS), and in addition, to measure the consequences on the intrarenal oxygenation. Experimental studies were performed using sixteen adolescent rats. The left renal artery was exposed through a flank incision and acute RAS for 45 min was achieved by placing a ligature around the renal artery. MRI was performed 3 days after the surgical procedure, where a blood oxygenation sensitive sequence (BOLD MRI) was performed, followed by a perfusion-weighted imaging sequence using a single bolus of the iron-oxide nanoparticle Sinerem. The renal oxygenation of blood was indirectly measured by the BOLD-parameter R2 * , and perfusion measures include relative renal blood flow, relative renal blood volume and mean transit time. Histopathologic changes through the outer stripe of the outer medulla showing typical histopathologic findings of ischemia. This study demonstrated that rats with transient renal arterial stenosis (for 45 min) showed a reduction in intrarenal oxygenation and intrarenal blood flow three days after the surgical procedure. A decreased R2 * was measured within the ipsilateral medulla in parallel with a decreased medullary blood flow, is probably related to a lower reabsorption load within the ipsilateral kidney. MRI may therefore be a promising tool in long-term evaluation of RAS. (orig.)

Renal hemodynamics and oxygenation in transient renal artery occluded rats evaluated with iron-oxide particles and oxygenation-sensitive imaging

Energy Technology Data Exchange (ETDEWEB)

Pedersen, Michael [Aarhus Univ. Hospital (Denmark). MR Research Centre; Aarhus Univ. (Denmark). Inst. of Experimental Clinical Medicine; Univ. Victor Segalen Bordeaux 2 (France). Lab. Imagerie Moleculaire et Fonctionnelle: de la physiologie a la therapie CNRS UMR 5231; Laustsen, Christoffer [Aarhus Univ. Hospital (Denmark). MR Research Centre; Perot, Vincent; Grenier, Nicolas [Hopital Pellegrin, CHU Bordeaux (France). Service d' Imagerie Diagnostique et Therapeutique de l' Adulte; Basseau, Fabrice; Moonen, Chrit [Univ. Victor Segalen Bordeaux 2 (France). Lab. Imagerie Moleculaire et Fonctionnelle: de la physiologie a la therapie CNRS UMR 5231

2010-07-01

Mild or severe renal arterial occlusion is a phenomenon occasionally observed in daily clinical practice, potentially leading to renal ischemia and a general impairment of renal function. Secondly, closing the blood flow to the kidneys can also occur during kidney transplantation procedures. However, the exact physiological effects of these conditions on renal blood perfusion as well as the renal oxygen handling are poorly understood. The objectives of this study were therefore to measure the lateral changes of renal blood perfusion in rats subjected to transient unilateral arterial occlusion (RAS), and in addition, to measure the consequences on the intrarenal oxygenation. Experimental studies were performed using sixteen adolescent rats. The left renal artery was exposed through a flank incision and acute RAS for 45 min was achieved by placing a ligature around the renal artery. MRI was performed 3 days after the surgical procedure, where a blood oxygenation sensitive sequence (BOLD MRI) was performed, followed by a perfusion-weighted imaging sequence using a single bolus of the iron-oxide nanoparticle Sinerem. The renal oxygenation of blood was indirectly measured by the BOLD-parameter R2{sup *}, and perfusion measures include relative renal blood flow, relative renal blood volume and mean transit time. Histopathologic changes through the outer stripe of the outer medulla showing typical histopathologic findings of ischemia. This study demonstrated that rats with transient renal arterial stenosis (for 45 min) showed a reduction in intrarenal oxygenation and intrarenal blood flow three days after the surgical procedure. A decreased R2{sup *} was measured within the ipsilateral medulla in parallel with a decreased medullary blood flow, is probably related to a lower reabsorption load within the ipsilateral kidney. MRI may therefore be a promising tool in long-term evaluation of RAS. (orig.)

Protective effect of Urtica dioica L. on renal ischemia/reperfusion injury in rat.

Science.gov (United States)

Sayhan, Mustafa Burak; Kanter, Mehmet; Oguz, Serhat; Erboga, Mustafa

2012-12-01

Renal ischemia-reperfusion (I/R) injury may occur after renal transplantation, thoracoabdominal aortic surgery, and renal artery interventions. This study was designed to investigate the effect of Urtica dioica L. (UD), in I/R induced renal injury. A total of 32 male Sprague-Dawley rats were divided into four groups: control, UD alone, I/R and I/R + UD; each group contain 8 animals. A rat model of renal I/R injury was induced by 45-min occlusion of the bilateral renal pedicles and 24-h reperfusion. In the UD group, 3 days before I/R, UD (2 ml/kg/day intraperitoneal) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion and kidney tissues samples were obtained for histopathological investigation in all groups. To date, no more histopathological changes on intestinal I/R injury in rats by UD treatment have been reported. Renal I/R caused severe histopathological injury including tubular damage, atrophy dilatation, loss of brush border and hydropic epithelial cell degenerations, renal corpuscle atrophy, glomerular shrinkage, markedly focal mononuclear cell infiltrations in the kidney. UD treatment significantly attenuated the severity of intestinal I/R injury and significantly lowered tubulointerstitial damage score than the I/R group. The number of PCNA and TUNEL positive cells in the control and UD alone groups was negligible. When kidney sections were PCNA and TUNEL stained, there was a clear increase in the number of positive cells in the I/R group rats in the renal cortical tissues. However, there is a significant reduction in the activity of PCNA and TUNEL in kidney tissue of renal injury induced by renal I/R with UD therapy. Our results suggest that administration of UD attenuates renal I/R injury. These results suggest that UD treatment has a protective effect against renal damage induced by renal I/R. This protective effect is possibly due to its ability to inhibit I/R induced renal damage, apoptosis and cell proliferation.

Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride.

Science.gov (United States)

Adedara, Isaac A; Ojuade, Temini Jesu D; Olabiyi, Bolanle F; Idris, Umar F; Onibiyo, Esther M; Ajeigbe, Olufunke F; Farombi, Ebenezer O

2017-02-01

Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.

Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats.

Science.gov (United States)

Li, Peng; Huang, Pei-Pei; Yang, Yun; Liu, Chi; Lu, Yan; Wang, Fang; Sun, Wei; Kong, Xiang-Qing

2017-01-01

Li P, Huang P, Yang Y, Liu C, Lu Y, Wang F, Sun W, Kong X. Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats. J Appl Physiol 122: 121-129, 2017. First published October 14, 2016; doi:10.1152/japplphysiol.01019.2015-Sympathetic activity is enhanced in patients with essential or secondary hypertension, as well as in various hypertensive animal models. Therapeutic targeting of sympathetic activation is considered an effective antihypertensive strategy. We hypothesized that renal sympathetic denervation (RSD) attenuates hypertension and improves vascular remodeling and renal disease in the 2-kidney, 1-clip (2K1C) rat model. Rats underwent 2K1C modeling or sham surgery; then rats underwent RSD or sham surgery 4 wk later, thus resulting in four groups (normotensive-sham, normotensive-RSD, 2K1C-sham, and 2K1C-RSD). Norepinephrine was measured by ELISA. Echocardiography was used to assess heart function. Fibrosis and apoptosis were assessed by Masson and TUNEL staining. Changes in mean arterial blood pressure in response to hexamethonium and plasma norepinephrine levels were used to evaluate basal sympathetic nerve activity. The 2K1C modeling success rate was 86.8%. RSD reversed the elevated systolic blood pressure induced by 2K1C, but had no effect on body weight. Compared with rats in the 2K1C-sham group, rats in the 2K1C-RSD group showed lower left ventricular mass/body weight ratio, interventricular septal thickness in diastole, left ventricular end-systolic diameter, and left ventricular posterior wall thickness in systole, whereas fractional shortening and ejection fraction were higher. Right kidney apoptosis and left kidney hypertrophy were not changed by RSD. Arterial fibrosis was lower in animals in the 2K1C-RSD group compared with those in the 2K1C-sham group. RSD reduced plasma norepinephrine and basal sympathetic activity in rats in the 2K1C-RSD group compared with rats in the 2K1C-sham group. These

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

P-glycoprotein-deficient mice have proximal tubule dysfunction but are protected against ischemic renal injury

NARCIS (Netherlands)

Huls, M.; Kramers, C.; Levtchenko, E.N.; Wilmer, M.J.G.; Dijkman, H.B.P.M.; Kluijtmans, L.A.J.; Hoorn, J.W.A. van der; Russel, F.G.M.; Masereeuw, R.

2007-01-01

The multidrug resistance gene 1 product, P-glycoprotein (P-gp), is expressed in several excretory organs, including the apical membrane of proximal tubules. After inducing acute renal failure, P-gp expression is upregulated and this might be a protective function by pumping out toxicants and harmful

Mechanisms of blood pressure changes following renal irradiation of intact, adrenalectomized, and adrenal regenerating rats

International Nuclear Information System (INIS)

Rosenblum, M.

1977-01-01

This study was conducted to determine the differences in changes in systolic arterial blood pressure following renal x irradiation (1100 R) in adrenal-intact, adrenalectomized, and adrenal-regenerating rats and to elucidate the involvement or roles of the kidneys and of the adrenal glands in the blood pressure changes. The parameters studied included the following: systolic blood pressure; body weight; food and fluid consumption; urine output; plasma and urine electrolytes; sodium balance; plasma renin activity; plasma corticosterone; renal vascular volume; renal vascular permeability (using 125 I-polyvinylpyrrolidone extravasation rate as an indicator); renal blood flow (using 42 K extraction); kidney weight; hematocrit; and total vascular, plasma, and red cell volumes. Renal x irradiation of intact rats caused polydipsia, polyuria, and reduced urine concentrations of sodium and potassium without significantly affecting blood pressure during the period of study (80 days); plasma renin activity was significantly lowered and had a positive correlation with blood volume; an abnormal blood volume-plasma renin activity relationship is suggested. Adrenalectomy caused prolonged hypotension in saline-maintained rats even though their sodium balance was more positive than that in adrenal-intact or adrenal-regenerating rats with normal or elevated blood pressure. The blood pressure of renally irrradiated, adrenalectomized rats was greater than non-irradiated adrenalectomized rats, but with only borderline significance; it is concluded that the absence of the adrenal glands does not affect the degree or duration of the effects of renal irradiation on blood pressure

Dynamic modeling of renal blood flow in Dahl hypertensive and normotensive rats

DEFF Research Database (Denmark)

Knudsen, Torben; Elmer, Henrik; Knudsen, Morten H

2004-01-01

A method is proposed in this paper which allows characterization of renal autoregulatory dynamics and efficiency using quantitative mathematical methods. Based on data from rat experiments, where arterial blood pressure and renal blood flow are measured, a quantitative model for renal blood flow...

Effect of astragalus and dopamine on changes of blood and renal tissue contents of NO, ET in experimental rat models of acute renal failure

International Nuclear Information System (INIS)

Wu Yajun; Zheng Bingjie; Shi Lan; Fan Yaping

2004-01-01

Objective: To explore the effect of intravenous or intra-renal-capsular administration of astragalus and dopamine on the serum NO and renal tissue NO, ET contents in rat models of acute renal failure. Methods: Experimental rat models of acute renal failure induced by intraperitoneal injection of E. Coli endotoxin (lipo-polysaccharide) were prepared (n=60). Treatment with astragalus and dopamine was administered via either intravenous on intra-renal-capsular route (n=20 in each group). Serum NO and renal tissue NO (with nitric acid reductase method), ET (with RIA) contents were determined at 4, 8, 12, 16h after injection of endotoxin. Twenty shock models were left untreated and additional twenty rats receiving saline injection only served as controls. Results: In the intravenously treated group, the increase of serum NO and renal tissue NO, ET contents were significantly less than those in the untreated group (P<0.05). In the group treated via the intracapsular route , the increase of renal tissue NO and ET contents were much less than those in the intravenous group at 12 and 16h (P<0.05). Conclusion: Combined treatment with astragalus and dopamine could abate the abnormally high renal tissue contents of NO and ET after endotoxin shock in experimental rats and treatment with intra capsular administration seems to be more effective. (authors)

Correlation analysis of alveolar bone loss in buccal/palatal and proximal surfaces in rats

Directory of Open Access Journals (Sweden)

Carolina Barrera de Azambuja

2012-12-01

Full Text Available The aim was to correlate alveolar bone loss in the buccal/palatal and the mesial/distal surfaces of upper molars in rats. Thirty-three, 60-day-old, male Wistar rats were divided in two groups, one treated with alcohol and the other not treated with alcohol. All rats received silk ligatures on the right upper second molars for 4 weeks. The rats were then euthanized and their maxillae were split and defleshed with sodium hypochlorite (9%. The cemento-enamel junction (CEJ was stained with 1% methylene blue and the alveolar bone loss in the buccal/palatal surfaces was measured linearly in 5 points on standardized digital photographs. Measurement of the proximal sites was performed by sectioning the hemimaxillae, restaining the CEJ and measuring the alveolar bone loss linearly in 3 points. A calibrated and blinded examiner performed all the measurements. Intraclass Correlation Coefficient revealed values of 0.96 and 0.89 for buccal/lingual and proximal surfaces, respectively. The Pearson Correlation Coefficient (r between measurements in buccal/palatal and proximal surfaces was 0.35 and 0.05 for the group treated with alcohol, with and without ligatures, respectively. The best correlations between buccal/palatal and proximal surfaces were observed in animals not treated with alcohol, in sites both with and without ligatures (r = 0.59 and 0.65, respectively. A positive correlation was found between alveolar bone loss in buccal/palatal and proximal surfaces. The correlation is stronger in animals that were not treated with alcohol, in sites without ligatures. Areas with and without ligature-induced periodontal destruction allow detection of alveolar bone loss in buccal/palatal and proximal surfaces.

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.

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.

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)

Altered renal expression of angiotensin II receptors, renin receptor, and ACE-2 precede the development of renal fibrosis in aging rats.

Science.gov (United States)

Schulman, Ivonne Hernandez; Zhou, Ming-Sheng; Treuer, Adriana V; Chadipiralla, Kiranmai; Hare, Joshua M; Raij, Leopoldo

2010-01-01

The susceptibility to fibrosis and progression of renal disease is mitigated by inhibition of the renin-angiotensin system (RAS). We hypothesized that activation of the intrarenal RAS predisposes to renal fibrosis in aging. Intrarenal expression of angiotensin II type 1 (AT(1)R), type 2 (AT(2)R), and (pro)renin receptors, ACE and ACE-2, as well as pro- and antioxidant enzymes were measured in 3-month-old (young), 14-month-old (middle-aged), and 24-month-old (old) male Sprague-Dawley rats. Old rats manifested glomerulosclerosis and severe tubulointerstitial fibrosis with increased fibronectin and TGF-β expression (7-fold). AT(1)R /AT(2)R ratios were increased in middle-aged (cortical 1.6-fold, medullary 5-fold) and old rats (cortical 2-fold, medullary 4-fold). Similarly, (pro)renin receptor expression was increased in middle-aged (cortical 2-fold, medullary 3-fold) and old (cortical 5-fold, medullary 3-fold) rats. Cortical ACE was increased (+35%) in old rats, whereas ACE-2 was decreased (-50%) in middle-aged and old rats. NADPH oxidase activity was increased (2-fold), whereas antioxidant capacity and expression of the mitochondrial enzyme manganese superoxide dismutase (cortical -40%, medullary -53%) and medullary endothelial nitric oxide synthase (-48%) were decreased in old rats. Age-related intrarenal activation of the RAS preceded the development of severe renal fibrosis, suggesting that it contributes to the increased susceptibility to renal injury observed in the elderly. Copyright © 2010 S. Karger AG, Basel.

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....

Effect of benazepril on the transdifferentiation of renal tubular epithelial cells from diabetic rats.

Science.gov (United States)

Peng, Tao; Wang, Jie; Zhen, Junhui; Hu, Zhao; Yang, Xiangdong

2014-07-01

The aim of this study was to investigate the effect of benazepril on the transdifferentiation of renal tubular epithelial cells from diabetic rats. Thirty male Sprague-Dawley rats were included in the present study. Eight of the 30 rats were randomly selected and served as the normal control group (N group), while the remaining 22 rats, injected with streptozotocin (STZ), comprised the diabetic rat model. Rats with diabetes were randomly divided into the diabetic (DM group) and benazepril (B group) groups. The total course was conducted over 12 weeks. Blood glucose, body weight, kidney/body weight, 24-h urinary protein, serum creatinine and blood urea nitrogen were measured at the start and end of the study. We observed the tubulointerstitial pathological changes, and applied immunohistochemistry and western blotting to detect the expression of α-smooth muscle actin (α-SMA) in renal tissue. The levels of blood glucose, kidney/body weight, 24-h urinary protein, serum creatinine, blood urea nitrogen and tubulointerstitial damage index (TII) in the DM group were significantly higher than that in the N group (pbenazepril significantly reduced the expression of α-SMA in renal tubular epithelial cells obtained from diabetic rats, inhibited the transdifferentiation of renal tubular epithelial cells and played an important role in kidney protection.

Chaos in blood flow control in genetic and renovascular hypertensive rats

DEFF Research Database (Denmark)

Yip, K P; Holstein-Rathlou, N H; Marsh, D J

1991-01-01

Hydrostatic pressure and flow in renal proximal tubules oscillate at 30-40 mHz in normotensive rats anesthetized with halothane. The oscillations originate in tubuloglomerular feedback, a mechanism that provides local blood flow regulation. Instead of oscillations, spontaneously hypertensive rats...... (SHR) have aperiodic tubular pressure fluctuations; the pattern is suggestive of deterministic chaos. Normal rats made hypertensive by clipping one renal artery had similar aperiodic tubular pressure fluctuations in the unclipped kidney, and the fraction of rats with irregular fluctuations increased...... with time after the application of the renal artery clip. Statistical measures of deterministic chaos were applied to tubular pressure data. The correlation dimension, a measure of the dimension of the phase space attractor generating the time series, indicated the presence of a low-dimension strange...

Cardiac and renal antioxidant enzymes and effects of tempol in hyperthyroid rats.

Science.gov (United States)

Moreno, Juan Manuel; Rodríguez Gómez, Isabel; Wangensteen, Rosemary; Osuna, Antonio; Bueno, Pablo; Vargas, Félix

2005-11-01

This study evaluated the activity of cardiac and renal antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR)] and whether chronic treatment with tempol, a cell membrane-permeable SOD mimetic, ameliorates the hypertension of hyperthyroidism. Two experiments were performed. In experiment I, the following four groups of male Wistar rats were used: control group and three groups that received thyroxine (T4) at 10, 50, or 75 microg x rat(-1) x day(-1). In experiment II, tempol was orally administered (18 mg x kg(-1) x day(-1)) to control and T4-treated (75 microg x rat(-1) x day(-1)) rats. All treatments were maintained for 6 wk. Body weight, tail systolic blood pressure (BP), and heart rate were measured one time a week, and direct BP and morphological, metabolic, plasma, and renal variables were measured at the end of the experiment. Enzymatic activities were measured in renal cortex and medulla and right and left ventricles. In renal cortex, SOD activity was decreased in the T4-75 group, and there was a dose-related increase in CAT activity and decrease in GPX and GR activities in T4-treated groups. Activity of all antioxidant enzymes was reduced in left ventricle in T4-50 and T4-75 groups and in right ventricle in the T4-75 group. Tempol reduced BP, plasma malondialdehyde, and total urinary excretion of F2 isoprostanes in hypertensive hyperthyroid rats but not in controls. Tempol did not improve cardiac hypertrophy, proteinuria, or creatinine clearance in hyperthyroid rats. In conclusion, the results obtained indicate that the activity of SOD, GPX, and GR in renal and cardiac tissues is decreased in hyperthyroidism and that antioxidant treatment with tempol ameliorates T4-induced hypertension.

Exogenous and endogenous angiotensin-II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow

NARCIS (Netherlands)

Emans, Tonja W.; Janssen, Ben J.; Pinkham, Maximilian I.; Ow, Connie P. C.; Evans, Roger G.; Joles, Jaap A.; Malpas, Simon C.; Krediet, C. T. Paul; Koeners, Maarten P.

2016-01-01

Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary. We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats. This method provides stable and continuous

Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney

International Nuclear Information System (INIS)

Graceli, J.B.; Cicilini, M.A.; Bissoli, N.S.; Abreu, G.R.; Moysés, M.R.

2013-01-01

The maintenance of extracellular Na + and Cl - concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na + and Cl - reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg -1 ·day -1 , sc) and progesterone (OVP, 1.7 mg·kg -1 ·day -1 , sc). We assessed Na + and Cl - fractional excretion (FE Na + and FE Cl - , respectively) and renal and plasma catecholamine release concentrations. FE Na + , FE Cl - , water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FE Na + , FE Cl - , water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function

THE NEPHROTOXICITY RISK IN RATS SUBJECTED TO HEAVY MUSCLE ACTIVITY

Directory of Open Access Journals (Sweden)

Gülsen Öner

2009-09-01

Full Text Available When the body is exposed to insults, the kidneys exhibit adaptive changes termed renal cytoresistance, characterized by cholesterol accumulation in the membranes of the tubule cells. However, heavy muscle activity has not yet been accepted as one of the stressors that could lead to cytoresistance. In order to study the renal functional characteristics of animals exposed to heavy muscle activity, rats were subjected to exhaustive treadmill exercise for 5 days and their data was compared to those of sedentary controls. It was found that in exercised rats, blood lactate, muscle citrate synthase and proximal tubule peroxynitrite levels were all elevated, suggesting the presence of oxidative stress in the proximal tubule segments. However, mean arterial pressure, renal blood flow, glomerular filtration rate, fractional excretion of sodium and potassium, and organic anion excretion remained normal. Despite unchanged blood cholesterol levels, cholesterol loading in the proximal tubule segments, especially the free form, and decreased lactate dehydrogenase release from cytoresistant proximal tubule segments indicated the development of renal cytoresistance. However, this resistance did not seem to have protected the kidneys as expected because organic anion accumulation associated with glycosuria and proteinuria, in addition to the elevated urinary cholesterol levels, all imply the presence of an impaired glomerular permeability and reabsorption in the proximal tubule cells. Therefore, we suggest that in response to heavy muscle activity the tubular secretion may remain intact, although cytoresistance in the proximal tubule cells may affect the tubular reabsorptive functions and basolateral uptake of substances. Thus, this differential sensitivity in the cytoresistance should be taken into account during functional evaluation of the kidneys

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.

Regulation of renal NaPi-2 expression and tubular phosphate reabsorption by growth hormone in the juvenile rat.

Science.gov (United States)

Woda, Craig B; Halaihel, Nabil; Wilson, Paul V; Haramati, Aviad; Levi, Moshe; Mulroney, Susan E

2004-07-01

Growth hormone (GH) is an important factor in the developmental adaptation to enhance P(i) reabsorption; however, the nephron sites and mechanisms by which GH regulates renal P(i) uptake remain unclear and are the focus of the present study. Micropuncture experiments were performed after acute thyroparathyroidectomy in the presence and absence of parathyroid hormone (PTH) in adult (14- to 17-wk old), juvenile (4-wk old), and GH-suppressed juvenile male rats. While the phosphaturic effect of PTH was blunted in the juvenile rat compared with the adult, suppression of GH in the juvenile restored fractional P(i) excretion to adult levels. In the presence or absence of PTH, GH suppression in the juvenile rat caused a significant increase in the fractional P(i) delivery to the late proximal convoluted (PCT) and early distal tubule, so that delivery was not different from that in adults. These data were confirmed by P(i) uptake studies into brush-border membrane (BBM) vesicles. Immunofluorescence studies indicate increased BBM type IIa NaP(i) cotransporter (NaPi-2) expression in the juvenile compared with adult rat, and GH suppression reduced NaPi-2 expression to levels observed in the adult. GH replacement in the [N-acetyl-Tyr(1)-d-Arg(2)]-GRF-(1-29)-NH(2)-treated juveniles restored high NaPi-2 expression and P(i) uptake. Together, these novel results demonstrate that the presence of GH in the juvenile animal is crucial for the early developmental upregulation of BBM NaPi-2 and, most importantly, describe the enhanced P(i) reabsorption along the PCT and proximal straight nephron segments in the juvenile rat.

Renal blood flow dynamics in inbred rat strains provides insight into autoregulation.

Science.gov (United States)

A Mitrou, Nicholas G; Cupples, William A

2014-01-01

Renal autoregulation maintains stable renal blood flow in the face of constantly fluctuating blood pressure. Autoregulation is also the only mechanism that protects the delicate glomerular capillaries when blood pressure increases. In order to understand autoregulation, the renal blood flow response to changing blood pressure is studied. The steadystate response of blood flow is informative, but limits investigation of the individual mechanisms of autoregulation. The dynamics of autoregulation can be probed with transfer function analysis. The frequency-domain analysis of autoregulation allows investigators to probe the relative activity of each mechanism of autoregulation. We discuss the methodology and interpretation of transfer function analysis. Autoregulation is routinely studied in the rat, of which there are many inbred strains. There are multiple strains of rat that are either selected or inbred as models of human pathology. We discuss relevant characteristics of Brown Norway, Spontaneously hypertensive, Dahl, and Fawn-Hooded hypertensive rats and explore differences among these strains in blood pressure, dynamic autoregulation, and susceptibility to hypertensive renal injury. Finally we show that the use of transfer function analysis in these rat strains has contributed to our understanding of the physiology and pathophysiology of autoregulation and hypertensive renal disease.Interestingly all these strains demonstrate effective tubuloglomerular feedback suggesting that this mechanism is not sufficient for effective autoregulation. In contrast, obligatory or conditional failure of the myogenic mechanism suggests that this component is both necessary and sufficient for autoregulation.

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.

TGF-beta1 immunohistochemistry and promoter methylation in chronic renal failure rats treated with Uremic Clearance Granules.

Directory of Open Access Journals (Sweden)

Cheng-Bin Chen

2010-08-01

Full Text Available The aim of the study was the explain the mechanism related to therapeutic effects of Uremic Clearance Granules (Niaoduqing Keli in Chinese on adenine-induced Chronic Renal Failure in rats. Thirty 8-week-old male Wistar rats were selected and randomly divided in to 3 groups: Normal Control Group (NCGconsisted of 10 rats, Chronic Renal Failure Pathological Control Group (PCG 10 rats, and Uremic Clearance Granules Treatment Group (UCG 10 rats. Each rat in PCG and UCG was fed with adenine-enriched diets, containing 10 g adenine per kg food for 6 weeks. After fed with adenine, each rat in UCG was administered orally with 2 ml solution of Uremic Clearance Granules for 6 weeks. The concentration of Uremic Clearance Granules solution was 0.42 g/ml which was 10 times of human. On days 42 and 84, the serum levels of creatinine, Blood Urea Nitrogen and homocysteine were determined. The methylation of TGFbeta1 promoter was tested by methylation-specific PCR. TGF-beta1 mRNA and protein expression in rat renal cortex were analyzed by real-time RT-PCR and Immunohistochemistry. (1 Experimented on model of Chronic Renal Failure in rats, the preparation was proved to be able to reduce serum creatinine, Blood Urea Nitrogen, and homocysteine (p<0.05, improve renal function. (2 The expression of TGF-beta1 in mRNA and protein level were down-regulated. (3 TGF-beta1 promoter was demethylated at some loci in PCG, and was recovered in UCG. After treatment with Uremic Clearance Granules, the Chronic Renal Failure Wistar rat's kidney function was recovered. The recovery may be result of the remethylation of TGF-beta1 promoter and then lead to TGF-beta1 be transcripted and translated normally. The experimental study explain the molecular mechanism by which Uremic Clearance Granules treat Chronic Renal Failure.

Subcellular distribution of folate and folate binding protein in renal proximal tubules

International Nuclear Information System (INIS)

Sharkey, C.; Hjelle, J.T.; Selhub, J.

1986-01-01

High affinity folate binding protein (FBP) found in brush border membranes derived from renal cortices is thought to be involved in the renal conservation of folate. To examine the mechanisms of folate recovery, the subcellular distribution of FBP and 3 H-folate in rabbit renal proximal tubules (PT) was examined using analytical cell fractionation techniques. Tubules contain 3.41 +/- 0.32 picomoles FBP/mg protein (X +/- S.D.; n = 5). Postnuclear supernates (PNS) of PT were layered atop Percoll-sucrose gradients, centrifuged, fractions collected and assayed for various marker enzymes and FBP. Pooled fractions from such gradients were subsequently treated with digitonin and centrifuged in a stoichiometric manner with the activity of the microvillar enzyme, alanylaminopeptidase (AAP); excess FBP distributed with more buoyant particles. Infusion of 3 H-folate into rabbit kidneys followed by tubule isolation and fractionation revealed a time dependent shift in distribution of radiolabel from the AAP-rich gradient fractions to a region containing more buoyant particles; radiolevel was not associated with lysosomal markers. EM-radioautography revealed grains over intracellular vesicles. These results are consistent with the hypothesis that folate is recovered by a process involving receptor-mediated endocytosis or transcytosis

Spironolactone ameliorates transplant vasculopathy in renal chronic transplant dysfunction in rats

NARCIS (Netherlands)

Waanders, Femke; Rienstra, Heleen; Boer, Mark Walther; Zandvoort, Andre; Rozing, Jan; Navis, Gerjan; van Goor, Harry; Hillebrands, Jan-Luuk

Waanders F, Rienstra H, Walther Boer M, Zandvoort A, Rozing J, Navis G, van Goor H, Hillebrands JL. Spironolactone ameliorates transplant vasculopathy in renal chronic transplant dysfunction in rats. Am J Physiol Renal Physiol 296: F1072-F1079, 2009. First published February 25, 2009;

Dynamic computed tomography (CT) in the rat kidney and application to acute renal failure models

International Nuclear Information System (INIS)

Ishikawa, Isao; Saito, Tadashi; Ishii, Hirofumi; Bansho, Junichi; Koyama, Yukinori; Tobita, Akira

1995-01-01

Renal dynamic CT scanning is suitable for determining the excretion of contrast medium in the cortex and medulla of the kidney, which is valuable for understanding the pathogenesis of disease processes in various conditions. This form of scanning would be convenient for use, if a method of application to the rat kidney were available. Therefore, we developed a method of applying renal dynamic CT to rats and evaluated the cortical and medullary curves, e.g., the corticomedullary junction time which is correlated to creatinine clearance, in various rat models of acute renal failure. The rat was placed in a 10deg oblique position and a bilateral hilar slice was obtained before and 5, 10, 15, 20, 25, 30, 40, 50, 60, 80, 100, 120, 140, 160 and 180 sec after administering 0.5 ml of contrast medium using Somatom DR. The width of the slice was 4 mm and the scan time was 3 sec. The corticomedullary junction time in normal rats was 23.0±10.5 sec, the peak value of the cortical curve was 286.3±76.7 Hounsfield Unit (HU) and the peak value of the medullary curve was 390.1±66.2 HU. Corticomedullary junction time after exposure of the kidney was prolonged compared to that of the unexposed kidney. In rats with acute renal failure, the excretion pattern of contrast medium was similar in both the glycerol- and HgCl2-induced acute renal failure models. The peak values of the cortical curve were maintained three hours after a clamp was placed at the hilar region of the kidney for one hour, and the peak values of the medullary curve were maintained during the administration of 10μg/kg/min of angiotensin II. Dynamic CT curves in the acute renal failure models examined were slightly different from those in human acute renal failure. These results suggest that rats do not provide an ideal model for human acute renal failure. However, the application of dynamic CT to the rat kidney models was valuable for estimating the pathogenesis of various human kidney diseases. (author)

Effects of an Astragalus Polysaccharide and Rhein Combination on Apoptosis in Rats with Chronic Renal Failure

Directory of Open Access Journals (Sweden)

Yonghong Lian

2014-01-01

Full Text Available Objective. To investigate the effects and to analyze the mechanism of the combination of Astragalus polysaccharide (APS and Rhein on apoptosis in rats with chronic renal failure (CRF. Methods. Thirty-seven male Wistar rats were randomly divided into a control group, a model group, a low-dose APS and Rhein combination group, and a high-dose APS and Rhein combination group. CRF was induced by orogastric gavage with adenine. Rats were observed for renal function, electrolyte, and pathological changes for 7 weeks after administration. Renal tubular cell apoptosis was assessed by TUNEL and protein expressions of IRE1 and CHOP were detected by Western-blotting. Results. The combination of APS and Rhein decreased the kidney weight and index, improved renal pathological injury, maintained the stability of serum electrolytes, and reduced SCr and BUN levels in rat models. Moreover, APS and Rhein combination could effectively inhibit the apoptosis and reduce the protein expressions of IRE1and CHOP of renal tubular cells. Conclusions. The combination of APS and Rhein could improve renal function and reduce renal cell apoptosis to protect against further progression of CRF, whose mechanism may be related to alleviate endoplasmic reticulum stress (ERS in the renal cells.

Toxicogenomic multigene biomarker for predicting the future onset of proximal tubular injury in rats

International Nuclear Information System (INIS)

Minowa, Yohsuke; Kondo, Chiaki; Uehara, Takeki; Morikawa, Yuji; Okuno, Yasushi; Nakatsu, Noriyuki; Ono, Atsushi; Maruyama, Toshiyuki; Kato, Ikuo; Yamate, Jyoji; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro

2012-01-01

Drug-induced renal tubular injury is a major concern in the preclinical safety evaluation of drug candidates. Toxicogenomics is now a generally accepted tool for identifying chemicals with potential safety problems. The specific aim of the present study was to develop a model for use in predicting the future onset of drug-induced proximal tubular injury following repeated dosing with various nephrotoxicants. In total, 41 nephrotoxic and nonnephrotoxic compounds were used for the present analysis. Male Sprague-Dawley rats were dosed orally or intravenously once daily. Animals were exposed to three different doses (low, middle, and high) of each compound, and kidney tissue was collected at 3, 6, 9, and 24 h after single dosing, and on days 4, 8, 15, and 29 after repeated dosing. Gene expression profiles were generated from kidney total RNA using Affymetrix DNA microarrays. Filter-type gene selection and linear classification algorithms were employed to discriminate future onset of proximal tubular injury. We identified genomic biomarkers for use in future onset prediction using the gene expression profiles determined on day 1, when most of the nephrotoxicants had yet to produce detectable histopathological changes. The model was evaluated using a five-fold cross validation, and achieved a sensitivity of 93% and selectivity of 90% with 19 probes. We also found that the prediction accuracy of the optimized model was substantially higher than that produced by any of the single genomic biomarkers or histopathology. The genes included in our model were primarily involved in DNA replication, cell cycle control, apoptosis, and responses to oxidative stress and chemical stimuli. In summary, our toxicogenomic model is particularly useful for predicting the future onset of proximal tubular injury.

Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

Energy Technology Data Exchange (ETDEWEB)

Ahad, Amjid [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Ganai, Ajaz Ahmad [Department of Biotechnology, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Mujeeb, Mohd [Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Siddiqui, Waseem Ahmad, E-mail: was.sid121@gmail.com [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India)

2014-08-15

Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16 weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway.

Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

International Nuclear Information System (INIS)

Ahad, Amjid; Ganai, Ajaz Ahmad; Mujeeb, Mohd; Siddiqui, Waseem Ahmad

2014-01-01

Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16 weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway

Nonlinear system analysis of renal autoregulation in normotensive and hypertensive rats

DEFF Research Database (Denmark)

Chon, K H; Chen, Y M; Holstein-Rathlou, N H

1998-01-01

We compared the dynamic characteristics in renal autoregulation of blood flow of normotensive Sprague-Dawley rats (SDR) and spontaneously hypertensive rats (SHR), using both linear and nonlinear systems analysis. Linear analysis yielded only limited information about the differences in dynamics......, NMSE are significantly higher in SHR than SDR, suggesting a more complex nonlinear system in SHR. The contribution of the third-order kernel in describing the dynamics of renal autoregulation in arterial blood pressure and blood flow was found to be important. Moreover, we have identified the presence...

Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury

Directory of Open Access Journals (Sweden)

B.J. Pereira

2010-08-01

Full Text Available Calcineurin inhibitors exacerbate ischemic injury in transplanted kidneys, but it is not known if sirolimus protects or exacerbates the transplanted kidney from ischemic injury. We determined the effects of sirolimus alone or in combination with cyclosporin A (CsA on oxygenated and hypoxic/reoxygenated rat proximal tubules in the following in vitro groups containing 6-9 rats per group: sirolimus (10, 50, 100, 250, 500, and 1000 ηg/mL; CsA (100 µg/mL; sirolimus (50 and 250 ηg/mL + CsA (100 µg/mL; control; vehicle (20% ethanol. For in vivo studies, 3-week-old Wistar rats (150-250 g were submitted to left nephrectomy and 30-min renal artery clamping. Renal function and histological evaluation were performed 24 h and 7 days after ischemia (I in five groups: sham, I, I + SRL (3 mg·kg-1·day-1, po, I + CsA (3 mg·kg-1·day-1, sc, I + SRL + CsA. Sirolimus did not injure oxygenated or hypoxic/reoxygenated proximal tubules and did not potentiate the tubular toxic effects of CsA. Neither drug affected the glomerular filtration rate (GFR at 24 h. GFR was reduced in CsA-treated rats on day 7 (0.5 ± 0.1 mL/min but not in rats receiving sirolimus + CsA (0.8 ± 0.1 mL/min despite the reduction in renal blood flow (3.9 ± 0.5 mL/min. Acute tubular necrosis regeneration was similar for all groups. Sirolimus alone was not toxic and did not enhance hypoxia/reoxygenation injury or CsA toxicity to proximal tubules. Despite its hemodynamic effects, sirolimus protected post-ischemic kidneys against CsA toxicity.

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.

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.

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

Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

Science.gov (United States)

Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

2016-01-01

Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI. PMID:27034930

Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

Directory of Open Access Journals (Sweden)

Sheila Marques Fernandes

2016-01-01

Full Text Available Iodinated contrast (IC is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI. Chronic kidney disease (CKD and chronic hyperglycemia (CH are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH; Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI.

Histopathological study on the effects of turmeric (Curcuma longa linn. powdwer on renal ischemia-reperfusion injuryin rats

Directory of Open Access Journals (Sweden)

D Mohajeri

2012-05-01

Full Text Available Renal ischemia/reperfusion (I/R injury is a major cause of acute renal failure (ARF, which is faced in many clinical situations. This study was designed to investigate the effect of pre-treatment with turmeric (Curcuma longa linn powder on kidney histopathology and function markers in renal ischemia / reperfusion (IR induced injury in the rats. A total of 80 male Wistar rats were randomly divided into 4 groups: sham, IR model and two I/R+TREE (2%and4% - treated groups (n=20 per group. I/R groups’ kidneys were subjected to 60 min of global ischemia at 37oc followed by 30min of reperfusion. After 24h of reperfusion period, the rats were sacrificed. Kidney function tests and histopathological examination were also performed. Results were compared with a group of rats with sham operation. High serum creatinine, blood urea nitrogen and uric acid were observed in I/R rats compared to the sham rats. Pre-treatment of turmeric powder for 30 days prior to IR operation improved renal function reduced IR induced renal inflammatory and oxidative injury. The results of this study showed that turmeric powder significantly prevented renal I/R-induced functional and histological injuries.

Tubuloglomerular feedback dynamics and renal blood flow autoregulation in rats

DEFF Research Database (Denmark)

Holstein-Rathlou, N H; Wagner, A J; Marsh, D J

1991-01-01

To decide whether tubuloglomerular feedback (TGF) can account for renal autoregulation, we tested predictions of a TGF simulation. Broad-band and single-frequency perturbations were applied to arterial pressure; arterial blood pressure, renal blood flow and proximal tubule pressure were measured....... Data were analyzed by linear systems analysis. Broad-band forcings of arterial pressure were also applied to the model to compare experimental results with simulations. With arterial pressure as the input and tubular pressure, renal blood flow, or renal vascular resistance as outputs, the model...... correctly predicted gain and phase only in the low-frequency range. Experimental results revealed a second component of vascular control active at 100-150 mHz that was not predicted by the simulation. Forcings at single frequencies showed that the system behaves linearly except in the band of 33-50 m...

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)...

Donor dopamine treatment in brain dead rats is associated with an improvement in renal function early after transplantation and a reduction in renal inflammation

NARCIS (Netherlands)

Hoeger, Simone; Reisenbuechler, Anke; Gottmann, Uwe; Doyon, Fabian; Braun, Claude; Kaya, Ziya; Seelen, Marc A.; van Son, Willem J.; Waldherr, Ruediger; Schnuelle, Peter; Yard, Benito A.

Brain death (BD) is associated with tissue inflammation. As dopamine treatment of BD donor rats reduces renal monocyte infiltration, we tested if this treatment affects renal function and inflammation in recipients. BD was induced in F344 rats and was maintained for 6 h in all experiments. Dopamine

Reversible uranyl fluoride nephrotoxicity in the Long Evans rat

International Nuclear Information System (INIS)

Diamond, G.L.; Morrow, P.E.; Panner, B.J.; Gelein, R.M.; Baggs, R.B.

1989-01-01

Severity and duration of renal injury produced by low levels of uranyl fluoride (UO2F2) were examined in the rat. Rats received multiple ip injections of UO2F2 (cumulative dose: 0.66 or 1.32 mg U/kg body wt). Renal injury was characterized histologically by cellular and tubular necrosis of pars recta of proximal tubule (S2 and S3), with less severe cellular injury to thick ascending limb of loop of Henle and collecting tubule. Injury was evident when renal uranium levels were between 0.7 and 1.4 micrograms U/g wet kidney and was most severe when renal uranium burden was between 3.4 and 5.6 micrograms U/g. Repair of injury was rapid, with complete restoration within 35 days after exposure. Associated with injury were abnormalities in renal function, including impaired tubular reabsorption, proteinuria, and enzymuria, which appeared temporally related, to variable degrees, to progression of renal injury. Thus, reversible renal injury occurs in the rat at levels of uranium in kidney below the present Nuclear Regulatory Commission standard of 3 micrograms U/g kidney for renal injury in humans

Renal effects of in utero exposure to mercuric chloride in rats

Energy Technology Data Exchange (ETDEWEB)

Bernard, A.M.; Collette, C.; Lauwerys, R. (Catholic Univ. of Louvain, Industrial Toxicology and Occupational Medicine Unit, Brussels (Belgium))

1992-08-01

The transplacental nephrotoxicity of mercuric chloride has been studied in female Sprague-Dawley rats. Mercuric chloride was injected s.c. to rats at the dose of 1 mg/kg during the last 8 gestational days or the whole pregnancy. Both mothers and newborns developed a transient renal dysfunction resulting in an increased urinary excretion of beta[sub 2]-microglobulin and albumin. In mothers and their female offspring, these effects were completely reversible and did not influence the subsequent evolution of the renal function. In the male offspring, however, transitory changes in protein excretion were again observed a few months later, concomitantly with an enhanced accumulation of alpha[sub 2u]-globulin in the kidney. The transfer of mercury from maternal to fetal tissues was very small. The kidney concentrations of mercury in newborns were more than 300 times lower than in mothers. The barrier role of the placenta is not sufficient to prevent the occurrence of renal effects in the offspring of rats treated with inorganic mercury during pregnancy. (orig.).

Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis

DEFF Research Database (Denmark)

Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting

2016-01-01

Hydronephrosis is associated with development of salt-sensitive hypertension. Studies suggest that increased sympathetic nerve activity (SNA) and oxidative stress play important roles in renovascular hypertension. This study aimed to investigate the link between renal SNA and NADPH oxidase (NOX......) regulation in the development of hypertension in rats with hydronephrosis. Hydronephrosis was induced by partial unilateral ureteral obstruction (PUUO) in young rats. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high and low salt diets. Renal...

Role of Renal Nerves in the Treatment of Renovascular Hypertensive Rats with L-Arginine

Directory of Open Access Journals (Sweden)

Sonia Alves Gouvea

2014-01-01

Full Text Available The purpose was to determine the role of renal nerves in mediating the effects of antihypertensive treatment with L-arginine in a renovascular hypertension model. The 2K1C (two-kidney one-clip model hypertensive rats were submitted to bilateral surgical-pharmacological renal denervation. The animals were subdivided into six experimental groups: normotensive control rats (SHAM, 2K1C rats, 2K1C rats treated with L-arginine (2K1C + L-arg, denervated normotensive (DN rats, denervated 2K1C (2K1C + DN rats, and denervated 2K1C + L-arg (2K1C + DN + L-arg rats. Arterial blood pressure, water intake, urine volume, and sodium excretion were measured. The 2K1C rats exhibited an increase in the mean arterial pressure (MAP (from 106 ± 3 to 183 ± 5.8 mmHg, P<0.01, whereas L-arg treatment induced a reduction in the MAP (143 ± 3.4 mmHg without lowering it to the control level. Renal nerve denervation reduced the MAP to normotensive levels in 2K1C rats with or without chronic L-arg treatment. L-arg and denervation induced increases in water intake and urine volume, and L-arg caused a significant natriuretic effect. Our results suggest that renal sympathetic activity participates in the genesis and the maintenance of the hypertension and also demonstrate that treatment with L-arg alone is incapable of normalizing the MAP and that the effect of such treatment is not additive with the effect of kidney denervation.

Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin

Directory of Open Access Journals (Sweden)

Junghyun Kim

2012-01-01

Full Text Available Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS, which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c, and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury.

Using BOLD imaging to measure renal oxygenation dynamics in rats injected with diuretics

International Nuclear Information System (INIS)

Kusakabe, Yoshinori; Matsushita, Taro; Honda, Saori; Okada, Sakie; Murase, Kenya

2010-01-01

We used blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI) to measure renal oxygenation dynamics in rats injected with diuretics and evaluated diuretic effect on renal oxygenation. We performed BOLD MRI studies in 32 rats using a 1.5-tesla MR imaging system for animal experiments. We intravenously injected rats with saline (n=7), furosemide (n=7), acetazolamide (n=6), or mannitol (n=6). For controls, 6 rats were not injected with drugs. We estimated the apparent transverse relaxation rate (R 2 *) from the apparent transverse relaxation time (T 2 *)-weighted images and measured the time course of R 2 * at 4-min intervals over approximately 30 min. Compared with preadministration values, the R 2 * value did not change significantly in either the cortex or medulla in the control and mannitol groups but decreased significantly in the saline group; the R 2 * value significantly decreased in the medulla but did not change significantly in the cortex in the furosemide group; and the R 2 * value significantly increased in the medulla and significantly decreased in the cortex in the acetazolamide group. Our study results suggest that BOLD MRI is useful for evaluating the dynamics of renal oxygenation in response to various diuretics in the renal cortex and in the medulla. (author)

Polar orientation of renal grafts within the proximal seal zone affects risk of early type IA endoleaks after chimney endovascular aneurysm repair.

Science.gov (United States)

Tran, Kenneth; Ullery, Brant W; Itoga, Nathan; Lee, Jason T

2018-04-01

The objective of this study was to describe the polar orientation of renal chimney grafts within the proximal seal zone and to determine whether graft orientation is associated with early type IA endoleak or renal graft compression after chimney endovascular aneurysm repair (ch-EVAR). Patients who underwent ch-EVAR with at least one renal chimney graft from 2009 to 2015 were included in this analysis. Centerline three-dimensional reconstructions were used to analyze postoperative computed tomography scans. The 12-o'clock polar position was set at the takeoff of the superior mesenteric artery. Relative polar positions of chimney grafts were recorded at the level of the renal artery ostium, at the mid-seal zone, and at the proximal edge of the graft fabric. Early type IA endoleaks were defined as evidence of a perigraft flow channel within the proximal seal zone. There were 62 consecutive patients who underwent ch-EVAR (35 double renal, 27 single renal) for juxtarenal abdominal aortic aneurysms with a mean follow-up of 31.2 months; 18 (29%) early type IA "gutter" endoleaks were identified. During follow-up, the majority of these (n = 13; 72%) resolved without intervention, whereas two patients required reintervention (3.3%). Estimated renal graft patency was 88.9% at 60 months. Left renal chimney grafts were most commonly at the 3-o'clock position (51.1%) at the ostium, traversing posteriorly to the 5- to 7-o'clock positions (55.5%) at the fabric edge. Right renal chimney grafts started most commonly at the 9-o'clock position (n = 17; 33.3%) and tended to traverse both anteriorly (11 to 1 o'clock; 39.2%) and posteriorly (5 to 7 o'clock; 29.4%) at the fabric edge. In the polar plane, the majority of renal chimney grafts (n = 83; 85.6%) traversed 90 degrees were independently associated with early type IA endoleaks (odds ratio, 11.5; 95% confidence interval, 2.1-64.8) even after controlling for other device and anatomic variables. Polar orientation of the chimney

Loss of renal SNX5 results in impaired IDE activity and insulin resistance in mice.

Science.gov (United States)

Li, Fengmin; Yang, Jian; Villar, Van Anthony M; Asico, Laureano D; Ma, Xiaobo; Armando, Ines; Sanada, Hironobu; Yoneda, Minoru; Felder, Robin A; Jose, Pedro A; Wang, Xiaoyan

2018-03-01

We hypothesised that renal sorting nexin 5 (SNX5) regulates the insulin-degrading enzyme (IDE) and, thus, circulating insulin levels. We therefore studied the dynamic interaction between SNX5 and IDE in human renal proximal tubule cells (hRPTCs), as well as in rat and mouse kidneys. The regulation of IDE by SNX5 expressed in the kidney was studied in vitro and in vivo. Snx5 or mock siRNA was added to immortalised hRPTCs (passage <20) in culture or selectively infused, via osmotic mini-pump, into the remnant kidney of uninephrectomised mice and rats. SNX5 co-localised with IDE at the plasma membrane and perinuclear area of hRPTCs and in the brush border membrane of proximal tubules of human, rat, and mouse kidneys. Insulin increased the co-localisation and co-immunoprecipitation of SNX5 and IDE in hRPTCs. Silencing SNX5 in hRPTCs decreased IDE expression and activity. Renal-selective silencing of Snx5 (SNX5 protein: 100 ± 25 vs 29 ± 10, p < 0.05 [% of control]) in C57Bl/6J mice decreased IDE protein (100 ± 13 vs 57 ± 6, p < 0.05 [% of control]) and urinary insulin excretion, impaired the responses to insulin and glucose, and increased blood insulin and glucose levels. Spontaneously hypertensive rats (SHRs) had increased blood insulin and glucose levels and decreased renal SNX5 (100 ± 27 vs 29 ± 6, p < 0.05 [% of control]) and IDE (100 ± 5 vs 75 ± 4, p < 0.05 [% of control]) proteins, compared with normotensive Wistar-Kyoto (WKY) rats. Kidney Snx5-depleted WKY rats also had increased blood insulin and glucose levels. The expression of SNX5 and IDE was decreased in RPTCs from SHRs and hypertensive humans compared with cells from normotensive volunteers, indicating a common cause for hyperinsulinaemia and hypertension. Renal SNX5 positively regulates IDE expression and function. This study is the first to demonstrate the novel and crucial role of renal SNX5 in insulin and glucose metabolism.

On the role of renal alpha-adrenergic receptors in spontaneously hypertensive rats

NARCIS (Netherlands)

Michel, M. C.; Jäger, S.; Casto, R.; Rettig, R.; Graf, C.; Printz, M.; Insel, P. A.; Philipp, T.; Brodde, O. E.

1992-01-01

We tested the hypothesis that a genetically determined increase in renal alpha-adrenergic receptor density might be a pathophysiologically important factor in the spontaneously hypertensive rat model of genetic hypertension. In a first study, we compared renal alpha 1 and alpha 2-adrenergic receptor

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.

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

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.

Differential regulation of renal Klotho and FGFR1 in normal and uremic rats.

Science.gov (United States)

Muñoz-Castañeda, Juan R; Herencia, Carmen; Pendón-Ruiz de Mier, Maria Victoria; Rodriguez-Ortiz, Maria Encarnación; Diaz-Tocados, Juan M; Vergara, Noemi; Martínez-Moreno, Julio M; Salmerón, Maria Dolores; Richards, William G; Felsenfeld, Arnold; Kuro-O, Makoto; Almadén, Yolanda; Rodríguez, Mariano

2017-09-01

In renal failure, hyperphosphatemia occurs despite a marked elevation in serum fibroblast growth factor (FGF)-23. Abnormal regulation of the FGFR1-Klotho receptor complex may cause a resistance to the phosphaturic action of FGF23. The purpose of the present study was to investigate the regulation of renal Klotho and FGF receptor (FEFR)-1 in healthy and uremic rats induced by 5/6 nephrectomy. In normal rats, the infusion of rat recombinant FGF23 enhanced phosphaturia and increased renal FGFR1 expression; however, Klotho expression was reduced. Uremic rats on a high-phosphate (HP) diet presented hyperphosphatemia with marked elevation of FGF23 and an increased fractional excretion of phosphate (P) that was associated with a marked reduction of Klotho expression and an increase in FGFR1. After neutralization of FGF23 by anti-FGF23 administration, phosphaturia was still abundant, Klotho expression remained low, and the FGFR1 level was reduced. These results suggest that the expression of renal Klotho is modulated by phosphaturia, whereas the FGFR1 expression is regulated by FGF23. Calcitriol (CTR) administration prevented a decrease in renal Klotho expression. In HEK293 cells HP produced nuclear translocation of β-catenin, together with a reduction in Klotho. Wnt/β-catenin inhibition with Dkk-1 prevented the P-induced down-regulation of Klotho. The addition of CTR to HP medium was able to recover Klotho expression. In summary, high FGF23 levels increase FGFR1, whereas phosphaturia decreases Klotho expression through the activation of Wnt/β-catenin pathway.-Muñoz-Castañeda, J. R., Herencia, C., Pendón-Ruiz de Mier, M. V., Rodriguez-Ortiz, M. E., Diaz-Tocados, J. M., Vergara, N., Martínez-Moreno, J. M., Salmerón, M. D., Richards, W. G., Felsenfeld, A., Kuro-O, M., Almadén, Y., Rodríguez, M. Differential regulation of renal Klotho and FGFR1 in normal and uremic rats. © FASEB.

The Role of Endothelin System in Renal Structure and Function during the Postnatal Development of the Rat Kidney.

Science.gov (United States)

Albertoni Borghese, María F; Ortiz, María C; Balonga, Sabrina; Moreira Szokalo, Rocío; Majowicz, Mónica P

2016-01-01

Renal development in rodents, unlike in humans, continues during early postnatal period. We aimed to evaluate whether the pharmacological inhibition of Endothelin system during this period affects renal development, both at structural and functional level in male and female rats. Newborn rats were treated orally from postnatal day 1 to 20 with vehicle or bosentan (Actelion, 20 mg/kg/day), a dual endothelin receptor antagonist (ERA). The animals were divided in 4 groups: control males, control females, ERA males and ERA females. At day 21, we evaluated renal function, determined the glomerular number by a maceration method and by morphometric analysis and evaluated possible structural renal alterations by three methods: 〈alpha〉-Smooth muscle actin (α-SMA) immunohistochemistry, Masson's trichrome and Sirius red staining. The pharmacological inhibition of Endothelin system with a dual ERA during the early postnatal period of the rat did not leads to renal damage in the kidneys of male and female rats. However, ERA administration decreased the number of glomeruli, the juxtamedullary filtration surface area and the glomerular filtration rate and increased the proteinuria. These effects could predispose to hypertension or renal diseases in the adulthood. On the other hand, these effects were more pronounced in male rats, suggesting that there are sex differences that could be greater later in life. These results provide evidence that Endothelin has an important role in rat renal postnatal development. However these results do not imply that the same could happen in humans, since human renal development is complete at birth.

Protective effects of Rosmarinic acid against renal ischaemia/reperfusion injury in rats

International Nuclear Information System (INIS)

Ozturk, H.; Ozturk, H.; Terzi, E.H.

2014-01-01

Objective: To investigate the potential protective effects of Rosmarinic acid (RA) on rats exposed to ischaemia/reperfusion renal injury. Methods: The prospective study was conducted at Abant Izzet Baysal University, Turkey, and comprised 21 male Spraque Dawley rats weighing 250-270g each. They were divided into three equal groups. Unilaterally nephrectomised rats were subjected to 60 minutes of left renal ischaemia followed by 60 minutes of reperfusion. Group 1 had shamoperated animals; group 2 had ischaemia/reperfusion untreated animals; and group 3 had ischaemia/reperfusion animals treated with rosmarinic acid. Serum creatinine, blood urea nitrogen, tissue malondialdehyde, glutathione peroxidase, superoxide dismutase and myeloperoxidase (MPO) activities, and light microscopic findings were evaluated. SPSS 17 was used for statistical analysis. Results: Treatment of rats with rosmarinic acid produced a reduction in the serum levels of creatinine and blood urea nitrogen compared to the other groups. However, no statistically significant difference was found. The levels of malondialdehyde and myeloperoxidase were decreased in the renal tissue of group 3, while glutathione peroxidose and superoxide dismutase levels remained unchanged. The injury score decreased in the treatment group rats compared to the untreated group. Rosmarinic acid significantly decreased focal glomerular necrosis, dilatation of Bowman's capsule, degeneration of tubular epithelium, necrosis in tubular epithelium, and tubular dilatation. Conclusions: Rosmarinic acid prevented ischaemia/reperfusion injury in the kidneys by decreasing oxidative stress. (author)

Neuropeptide Y-enhanced diuresis and natriuresis in anaesthetized rats is independent of renal blood flow reduction

NARCIS (Netherlands)

Bischoff, A.; Erdbrügger, W.; Smits, J.; Michel, M. C.

1996-01-01

1. Neuropeptide Y (NPY) has been reported to enhance diuresis and natriuresis in anaesthetized rats although it is a potent renal vasoconstrictor in vitro in vivo in several species. Therefore, we have investigated anaesthetized rats to see whether reduction in renal blood flow (RBF) and enhancement

Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease

NARCIS (Netherlands)

Koppen, A. van; Papazova, D.A.; Oosterhuis, N.R.; Gremmels, H.; Giles, R.H.; Fledderus, J.O.; Joles, J.A.; Verhaar, M.C.

2015-01-01

Introduction: Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported

Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease

NARCIS (Netherlands)

van Koppen, Arianne; Papazova, Diana A.; Oosterhuis, Nynke R.; Gremmels, Hendrik; Giles, Rachel H.; Fledderus, Joost O.; Joles, Jaap A.; Verhaar, Marianne C.

2015-01-01

INTRODUCTION: Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported

Perinatal Na+ Overload Programs Raised Renal Proximal Na+ Transport and Enalapril-Sensitive Alterations of Ang II Signaling Pathways during Adulthood

Science.gov (United States)

Cabral, Edjair V.; Vieira-Filho, Leucio D.; Silva, Paulo A.; Nascimento, Williams S.; Aires, Regina S.; Oliveira, Fabiana S. T.; Luzardo, Ricardo; Vieyra, Adalberto; Paixão, Ana D. O.

2012-01-01

Background High Na+ intake is a reality in nowadays and is frequently accompanied by renal and cardiovascular alterations. In this study, renal mechanisms underlying perinatal Na+ overload-programmed alterations in Na+ transporters and the renin/angiotensin system (RAS) were investigated, together with effects of short-term treatment with enalapril in terms of reprogramming molecular alterations in kidney. Methodology/Principal Findings Male adult Wistar rats were obtained from dams maintained throughout pregnancy and lactation on a standard diet and drinking water (control) or 0.17 M NaCl (saline group). Enalapril (100 mg/l), an angiotensin converting enzyme inhibitor, was administered for three weeks after weaning. Ninety day old offspring from dams that drank saline presented with proximal tubules exhibiting increased (Na++K+)ATPase expression and activity. Ouabain-insensitive Na+-ATPase activity remained unchanged but its response to angiotensin II (Ang II) was lost. PKC, PKA, renal thiobarbituric acid reactive substances (TBARS), macrophage infiltration and collagen deposition markedly increased, and AT2 receptor expression decreased while AT1 expression was unaltered. Early treatment with enalapril reduced expression and activity of (Na++K+)ATPase, partially recovered the response of Na+-ATPase to Ang II, and reduced PKC and PKA activities independently of whether offspring were exposed to high perinatal Na+ or not. In addition, treatment with enalapril per se reduced AT2 receptor expression, and increased TBARS, macrophage infiltration and collagen deposition. The perinatally Na+-overloaded offspring presented high numbers of Ang II-positive cortical cells, and significantly lower circulating Ang I, indicating that programming/reprogramming impacted systemic and local RAS. Conclusions/Significance Maternal Na+ overload programmed alterations in renal Na+ transporters and in its regulation, as well as severe structural lesions in adult offspring. Enalapril

Maternal separation diminishes α-adrenergic receptor density and function in renal vasculature from male Wistar-Kyoto rats.

Science.gov (United States)

Loria, Analia S; Osborn, Jeffrey L

2017-07-01

Adult rats exposed to maternal separation (MatSep) are normotensive but display lower glomerular filtration rate and increased renal neuroadrenergic drive. The aim of this study was to determine the renal α-adrenergic receptor density and the renal vascular responsiveness to adrenergic stimulation in male rats exposed to MatSep. In addition, baroreflex sensitivity was assessed to determine a component of neural control of the vasculature. Using tissue collected from 4-mo-old MatSep and control rats, α 1 -adrenergic receptors (α 1 -ARs) were measured in renal cortex and isolated renal vasculature using receptor binding assay, and the α-AR subtype gene expression was determined by RT-PCR. Renal cortical α 1 -AR density was similar between MatSep and control tissues (B max = 44 ± 1 vs. 42 ± 2 fmol/mg protein, respectively); however, MatSep reduced α 1 -AR density in renal vasculature (B max = 47 ± 4 vs. 62 ± 4 fmol/mg protein, P adrenergic receptor expression and function in the renal vasculature could develop secondary to MatSep-induced overactivation of the renal neuroadrenergic tone. Copyright © 2017 the American Physiological Society.

Vitamin D-dependent rat renal calcium-binding protein: development of a radioimmunoassay, tissue distribution, and immunologic identification

International Nuclear Information System (INIS)

Sonnenberg, J.; Pansini, A.R.; Christakos, S.

1984-01-01

A sensitive double antibody RIA has been developed for the 28,000 mol wt rat renal vitamin D-dependent calcium-binding protein. Using this assay, concentrations of calcium-binding protein (CaBP) as low as 30 ng can be measured. The assay is precise (intraassay variability, 5.0%) and reproductible (interassay variability, 8.2%). Measurements of renal CaBP by RIA showed a good correlation with measurements of CaBP by the chelex resin assay and by polyacrylamide gel analysis by densitometric tracing using a purified CaBP marker. The concentration of CaBP in the vitamin D-replete rat kidney is 7.3 +/- 1.0 (mean +/- SEM) micrograms/mg protein. In vitamin D-deficient rats the level of renal CaBP is 2.6 +/- 0.3 micrograms/mg protein. Tissue distribution of immunoreactive rat renal CaBP showed the highest concentration of CaBP in the rat cerebellum (38.3 +/- 5.1 micrograms/mg protein). Lower concentrations of immunoreactive CaBP were detected in several other rat tissues. No immunoreactive CaBP was detected in rat or human serum. In necropsy human kidney and cerebellum, high levels of immunoreactive CaBP were also detected (1.5 +/- 0.1 and 27.3 +/- 2.1 micrograms/mg protein, respectively). When extracts of rat kidney and brain and human cerebellum and kidney were assayed at several dilutions, immunodisplacement curves parallel to that of pure renal CaBP were observed, indicating immunochemical similarity. Fractionation of extracts of rat cerebellum, human kidney, and human cerebellum on Sephadex G-100 revealed immunoreactivity and calcium-binding activity in the 28,000 mol wt region similar to rat kidney

Nonlinear analysis of renal autoregulation in rats using principal dynamic modes

DEFF Research Database (Denmark)

Marmarelis, V Z; Chon, K H; Holstein-Rathlou, N H

1999-01-01

This article presents results of the use of a novel methodology employing principal dynamic modes (PDM) for modeling the nonlinear dynamics of renal autoregulation in rats. The analyzed experimental data are broadband (0-0.5 Hz) blood pressure-flow data generated by pseudorandom forcing and colle......This article presents results of the use of a novel methodology employing principal dynamic modes (PDM) for modeling the nonlinear dynamics of renal autoregulation in rats. The analyzed experimental data are broadband (0-0.5 Hz) blood pressure-flow data generated by pseudorandom forcing...... and collected in normotensive and hypertensive rats for two levels of pressure forcing (as measured by the standard deviation of the pressure fluctuation). The PDMs are computed from first-order and second-order kernel estimates obtained from the data via the Laguerre expansion technique. The results...

Data on Na,K-ATPase in primary cultures of renal proximal tubule cells treated with catecholamines

Directory of Open Access Journals (Sweden)

Mary Taub

2016-03-01

Full Text Available This data article is concerned with chronic regulation of Na,K-ATPase by catecholamines. After a chronic treatment, inhibition of Na,K-ATPase activity was observed in cultures with dopamine, while a stimulation was observed in cultures treated with norepinephrine. Following a chronic incubation with guanabenz, an α adrenergic agonist, an increase in Na,K-ATPase α and β subunit mRNAs was observed. This data supports the research article entitled, “Renal proximal tubule Na, K-ATPase is controlled by CREB regulated transcriptional coactivators as well as salt inducible kinase 1” (Taub et al. 2015 [1]. Keywords: Catecholamines, Kidney, Proximal tubule, Na,K-ATPase, Chronic

L-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats.

Science.gov (United States)

Rodríguez-Gómez, Isabel; Moliz, Juan N; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Osuna, Antonio; Wangensteen, Rosemary; Vargas, Félix

2016-03-01

This study assessed the effects of thyroid hormones on the enzymes involved in l-arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC). Metabolites studied were l-arginine, l-citrulline, spermidine, spermine, and l-proline. Kidney heart and aorta levels of eNOS and iNOS were augmented and reduced (P hyperthyroid rats and was decreased in kidney and aorta of hypothyroid rats (P hyperthyroid rats and remained unchanged in all organs of hypothyroid rats. The substrate for these enzymes, l-arginine, was reduced (P hyperthyroid rats. Levels of ODC and spermidine, its product, were increased and decreased (P metabolic pathways. The changes recorded in the abundance of eNOS, arginases I and II, and ADC protein in renal and cardiovascular tissues may play a role in the hemodynamic and renal manifestations observed in thyroid disorders. Furthermore, the changes in ODC and spermidine might contribute to the changes in cardiac and renal mass observed in thyroid disorders. © 2015 by the Society for Experimental Biology and Medicine.

Uptake and washout of I-123-MIBG in neuronal and non-neuronal sites in rat hearts. Relationship to renal clearance

International Nuclear Information System (INIS)

Arbab, A.S.; Koizumi, Kiyoshi; Araki, Tsutomu

1996-01-01

We investigated the uptake and washout of I-123-metaiodobenzylguanidine (MIBG) in neuronal (both intra-and extravesicular) and non-neuronal sites in the heart and its relationship to renal clearance. Acute renal failure was induced in rats by ligating the renal vessels, and the findings were compared with those of sham-operated rats. Each group consisted of control, reserpine-treated and 6-hydroxydopamine (6-OHDA)-treated subgroups. Rats were sacrificed at 10 minutes and 4 hours after injection of MIBG. MIBG activity was calculated in specimens of heart, spleen, lung and blood. At 10 minutes, no significant difference in MIBG uptake in the heart was observed among the subgroups or between sham-operated and renal failure rats despite a significantly higher blood MIBG activity in the latter. At 4 hours, however, the hearts of both reserpine-treated and 6-OHDA-treated rats showed significantly lower MIBG uptake than control rats. Furthermore, the hearts of renal failure rats showed higher MIBG uptake in the control and reserpine-treated rats than in the corresponding subgroups in sham-operated rats. Intra and extravesicular neuronal uptake of MIBG in the heart were estimated using control, reserpine-treated and 6-OHDA-treated rats. Vesicular uptake values were similar in both the sham-operated group (0.51% ID/g) and the renal failure group (0.44% ID/g). But extravesicular neuronal uptake values were quite different in the renal failure group (0.86% ID/g) and the sham-operated group (0.19% ID/g). In conclusion, uptake to and washout from extravesicular neuronal sites may depend on the concentration of MIBG in the blood or the state of renal clearance, but vesicular uptake may be independent of these factors. (author)

Effect of Folic Acid Supplementation on Renal Phenotype and Epigenotype in Early Weanling Intrauterine Growth Retarded Rats

Directory of Open Access Journals (Sweden)

Xiaori He

2015-07-01

Full Text Available Background/Aims: The objective of this study was to examine the responses of p53 promoter methylation involved in kidney structure and function of early weaning intrauterine growth retarded (IUGR rats to dietary folic acid supplementation. Method: Sprague-Dawley rats were fed isocaloric diets containing either 21% protein diet (normal feed or 10% protein diet throughout pregnancy and normal feed during lactation. After weaning, Offspring were then fed onto normal feed and normal feed supplemented with 5 mg folic acid/kg feed for a month, this produced 4 dietary groups (maternal diet/ weanling diet: Con, Folic, IUGR and IUGR+Folic. Renal function, renal structure, p53 promoter methylation and protein expression of offspring rats were measured at postnatal 2 months and 3 months. Results: Glomerular volume, blood urea nitrogen, 24 hours urine protein were significantly elevated in IUGR rats compared with Con rats but were decreased by dietary folic acid supplementation. p53 protein expression in IUGR rats were significantly higher than that in Con rats, and p53 promoter methylation status in IUGR rats was reduced significantly compared with Con rats. However, the changes in p53 gene expression and DNA methylation status of IUGR rats were reversed by dietary folic acid supplementation. Conclusions: Our study showed for the first time that folic acid supplementation during early period of life could reverse the abnormality in renal p53 methylation status and protein expression, glomerular volume and renal function of IUGR rats offspring.

Effects of age and caloric restriction in the vascular response of renal arteries to endothelin-1 in rats.

Science.gov (United States)

Amor, Sara; García-Villalón, Angel Luis; Rubio, Carmen; Carrascosa, Jose Ma; Monge, Luis; Fernández, Nuria; Martín-Carro, Beatriz; Granado, Miriam

2017-02-01

Cardiovascular alterations are the most prevalent cause of impaired physiological function in aged individuals with kidney being one the most affected organs. Aging-induced alterations in renal circulation are associated with a decrease in endothelium-derived relaxing factors such as nitric oxide (NO) and with an increase in contracting factors such as endothelin-1(ET-1). As caloric restriction (CR) exerts beneficial effects preventing some of the aging-induced alterations in cardiovascular system, the aim of this study was to analyze the effects of age and caloric restriction in the vascular response of renal arteries to ET-1 in aged rats. Vascular function was studied in renal arteries from 3-month-old Wistar rats fed ad libitum (3m) and in renal arteries from 8-and 24-month-old Wistar rats fed ad libitum (8m and 24m), or subjected to 20% caloric restriction during their three last months of life (8m-CR and 24m-CR). The contractile response to ET-1 was increased in renal arteries from 8m and 24m compared to 3m rats. ET-1-induced contraction was mediated by ET-A receptors in all experimental groups and also by ET-B receptors in 24m rats. Caloric restriction attenuated the increased contraction to ET-1 in renal arteries from 8m but not from 24m rats possibly through NO release proceeding from ET-B endothelial receptors. In 24m rats, CR did not attenuate the aging-increased response of renal arteries to ET-1, but it prevented the aging-induced increase in iNOS mRNA levels and the aging-induced decrease in eNOS mRNA levels in arterial tissue. In conclusion, aging is associated with an increased response to ET-1 in renal arteries that is prevented by CR in 8m but not in 24m rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Blood pressure-renal blood flow relationships in conscious angiotensin II- and phenylephrine-infused rats.

Science.gov (United States)

Polichnowski, Aaron J; Griffin, Karen A; Long, Jianrui; Williamson, Geoffrey A; Bidani, Anil K

2013-10-01

Chronic ANG II infusion in rodents is widely used as an experimental model of hypertension, yet very limited data are available describing the resulting blood pressure-renal blood flow (BP-RBF) relationships in conscious rats. Accordingly, male Sprague-Dawley rats (n = 19) were instrumented for chronic measurements of BP (radiotelemetry) and RBF (Transonic Systems, Ithaca, NY). One week later, two or three separate 2-h recordings of BP and RBF were obtained in conscious rats at 24-h intervals, in addition to separate 24-h BP recordings. Rats were then administered either ANG II (n = 11, 125 ng·kg(-1)·min(-1)) or phenylephrine (PE; n = 8, 50 mg·kg(-1)·day(-1)) as a control, ANG II-independent, pressor agent. Three days later the BP-RBF and 24-h BP recordings were repeated over several days. Despite similar increases in BP, PE led to significantly greater BP lability at the heart beat and very low frequency bandwidths. Conversely, ANG II, but not PE, caused significant renal vasoconstriction (a 62% increase in renal vascular resistance and a 21% decrease in RBF) and increased variability in BP-RBF relationships. Transfer function analysis of BP (input) and RBF (output) were consistent with a significant potentiation of the renal myogenic mechanism during ANG II administration, likely contributing, in part, to the exaggerated reductions in RBF during periods of BP elevations. We conclude that relatively equipressor doses of ANG II and PE lead to greatly different ambient BP profiles and effects on the renal vasculature when assessed in conscious rats. These data may have important implications regarding the pathogenesis of hypertension-induced injury in these models of hypertension.

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.

Renal cysteine conjugate C-S lyase mediated toxicity of halogenated alkenes in primary cultures of human and rat proximal tubular cells.

Science.gov (United States)

McGoldrick, Trevor A; Lock, Edward A; Rodilla, Vicente; Hawksworth, Gabrielle M

2003-07-01

Proximal tubular cells from human (HPT) and rat (RPT) kidneys were isolated, grown to confluence and incubated with S-(1,2-dichlorovinyl)- l-cysteine (DCVC), S-(1,2,2-trichlorovinyl)- l-cysteine (TCVC), S-(1,1,2,2-tetrafluoroethyl)- l-cysteine (TFEC) and S-(2-chloro-1,1-difluorethyl)- l-cysteine (CDFEC), the cysteine conjugates of nephrotoxicants. The cultures were exposed to the conjugates for 12, 24 and 48 h and the toxicity determined using the MTT assay. All four conjugates caused dose-dependent toxicity to RPT cells over the range 50-1,000 microM, the order of toxicity being DCVC>TCVC>TFEC=CDFEC. The inclusion of aminooxyacetic acid (AOAA; 250 microM), an inhibitor of pyridoxal phosphate-dependent enzymes such as C-S lyase, afforded protection, indicating that C-S lyase has a role in the bioactivation of these conjugates. In HPT cultures only DCVC caused significant time- and dose-dependent toxicity. Exposure to DCVC (500 microM) for 48 h decreased cell viability to 7% of control cell values, whereas co-incubation of DCVC (500 microM) with AOAA (250 microM) resulted in cell viability of 71%. Human cultures were also exposed to S-(1,2-dichlorovinyl)-glutathione (DCVG). DCVG was toxic to HPT cells, but the onset of toxicity was delayed compared with the corresponding cysteine conjugate. AOAA afforded almost complete protection from DCVG toxicity. Acivicin (250 microM), an inhibitor of gamma-glutamyl transferase (gamma-GT), partially protected against DCVG (500 microM)-induced toxicity at 48 h (5% viability and 53% viability in the absence and presence of acivicin, respectively). These results suggest that DCVG requires processing by gamma-GT prior to bioactivation by C-S lyase in HPT cells. The activity of C-S lyase, using TFEC as a substrate, and glutamine transaminase K (GTK) was measured in rat and human cells with time in culture. C-S lyase activity in RPT and HPT cells decreased to approximately 30% of fresh cell values by the time the cells reached

Effect of glycation of albumin on its renal clearance in normal and diabetic rats

International Nuclear Information System (INIS)

Layton, G.J.; Jerums, G.

1988-01-01

Two independent techniques have been used to study the renal clearances of nonenzymatically glycated albumin and nonglycated albumin in normal and streptozotocin-induced diabetic rats, 16 to 24 weeks after the onset of diabetes. In the first technique, serum and urinary endogenous glycated and nonglycated albumin were separated using m-aminophenylboronate affinity chromatography and subsequently quantified by radioimmunoassay. Endogenous glycated albumin was cleared approximately twofold faster than nonglycated albumin in normal and diabetic rats. However, no difference was observed in the glycated albumin/nonglycated albumin clearance ratios (Cga/Calb) in normal and diabetic rats, respectively (2.18 +/- 0.39 vs 1.83 +/- 0.22, P greater than 0.05). The second technique measured the renal clearance of injected 125I-labelled glycated albumin and 125I-labelled albumin. The endogenous results were supported by the finding that 125I-labelled glycated albumin was cleared more rapidly than 125I-labelled albumin in normal (P less than 0.01) and diabetic (P less than 0.05) rats. The Cga/Calb ratio calculated for the radiolabelled albumins was 1.4 and 2.0 in normal and diabetic rats, respectively. This evidence suggests that nonenzymatic glycation of albumin increases its renal clearance to a similar degree in normal and diabetic rats

Effect of castration on renal glycosaminoglycans and their urinary excretion in male and female rats with chronic renal failure

International Nuclear Information System (INIS)

Lemos, C.C.S.; Tovar, A.M.F.; Guimarães, M.A.M.; Bregman, R.

2013-01-01

Glycosaminoglycans (GAGs) participate in a variety of processes in the kidney, and evidence suggests that gender-related hormones participate in renal function. The aim of this study was to analyze the relationship of GAGs, gender, and proteinuria in male and female rats with chronic renal failure (CRF). GAGs were analyzed in total kidney tissue and 24-h urine of castrated (c), male (M), and female (F) Wistar control (C) rats (CM, CMc, CF, CFc) and after 30 days of CRF induced by 5/6 nephrectomy (CRFM, CRFMc, CRFF, CRFFc). Total GAG quantification and composition were determined using agarose and polyacrylamide gel electrophoresis, respectively. Renal GAGs were higher in CF compared to CM. CRFM presented an increase in renal GAGs, heparan sulfate (HS), and proteinuria, while castration reduced these parameters. However, CRFF and CRFFc groups showed a decrease in renal GAGs concomitant with an increase in proteinuria. Our results suggest that, in CRFM, sex hormones quantitatively alter GAGs, mainly HS, and possibly the glomerular filtration barrier, leading to proteinuria. The lack of this response in CRFMc, where HS did not increase, corroborates this theory. This pattern was not observed in females. Further studies of CRF are needed to clarify gender-dependent differences in HS synthesis

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

A microfluidic renal proximal tubule with active reabsorptive function.

Directory of Open Access Journals (Sweden)

Else M Vedula

Full Text Available In the kidney, the renal proximal tubule (PT reabsorbs solutes into the peritubular capillaries through active transport. Here, we replicate this reabsorptive function in vitro by engineering a microfluidic PT. The microfluidic PT architecture comprises a porous membrane with user-defined submicron surface topography separating two microchannels representing a PT filtrate lumen and a peritubular capillary lumen. Human PT epithelial cells and microvascular endothelial cells in respective microchannels created a PT-like reabsorptive barrier. Co-culturing epithelial and endothelial cells in the microfluidic architecture enhanced viability, metabolic activity, and compactness of the epithelial layer. The resulting tissue expressed tight junctions, kidney-specific morphology, and polarized expression of kidney markers. The microfluidic PT actively performed sodium-coupled glucose transport, which could be modulated by administration of a sodium-transport inhibiting drug. The microfluidic PT reproduces human physiology at the cellular and tissue levels, and measurable tissue function which can quantify kidney pharmaceutical efficacy and toxicity.

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.

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.

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.

Identification of key metabolic changes in renal interstitial fibrosis rats using metabonomics and pharmacology.

Science.gov (United States)

Zhao, Liangcai; Dong, Minjian; Liao, Shixian; Du, Yao; Zhou, Qi; Zheng, Hong; Chen, Minjiang; Ji, Jiansong; Gao, Hongchang

2016-06-03

Renal fibrosis is one of the important pathways involved in end-stage renal failure. Investigating the metabolic changes in the progression of disease may enhance the understanding of its pathogenesis and therapeutic information. In this study, (1)H-nuclear magnetic resonance (NMR)-based metabonomics was firstly used to screen the metabolic changes in urine and kidney tissues of renal interstitial fibrotic rats induced by unilateral ureteral obstruction (UUO), at 7, 14, 21, and 28 days after operation, respectively. The results revealed that reduced levels of bioenergy synthesis and branched chain amino acids (BCAAs), as well as elevated levels of indoxyl sulfate (IS) are involved in metabolic alterations of renal fibrosis rats. Next, by pharmacological treatment we found that reduction of IS levels could prevent the renal fibrotic symptoms. Therefore, we suggested that urinary IS may be used as a potential biomarker for the diagnosis of renal fibrosis, and a therapeutic target for drugs. Novel attempt combining metabonomics and pharmacology was established that have ability to provide more systematic diagnostic and therapeutic information of diseases.

In vivo tracking of magnetically labeled mesenchmal stem cells injected via renal arteries in kidney failure rat

International Nuclear Information System (INIS)

Sun Junhui; Teng Gaojun; Ju Shenghong; Ma Zhanlong; Mai Xiaoli; Zhang Yu; Ma Ming

2006-01-01

Objective: To evaluate in vivo depiction and tracking for magnetically labeled bone marrow mesenchymal stern cells (MSCs) in a renal failure rat model injected intravascularly using a 1.5 T magnetic resonance imaging (MRI) system. Methods: Rat MSCs were isolated, purified, expanded and then incubated with home synthesized Fe 2 O 3 -PLL. Prussian blue stain was employed for identifying intracellular irons. An acute renal failure in rat was induced by intramuscular injection of glycerol and MSCs were injected into renal arteries of 11 recipients (labeled cells in six, unlabeled cells in five). MR images of kidneys were obtained respectively before injection of MSCs, and immediately, 1, 3, 5, and 8 clays after transplantation. MR imaging findings were analyzed, which were correlated with histological findings. Results: Rat MSCs were successfully labeled, and labeling efficiency was almost 100%. Prussian blue staining of Fe 2 O 3 -PLL labeled cells revealed the presence of iron-containing vesicles or endosomes in the cytoplasm. In the renal failure model of rats, the labeled MSCs were demonstrated as signal intensity loss in renal cortex on T 2 * -weighted MR images. The signal intensity decrease was visualized up to days 8 after transplantation. Histological analyses showed that most Prussian blue staining-positive cells were well correlated with the area where a signal intensity loss was observed in MRI. Signal intensity decrease was not detected after transplantation of unlabeled cells. Conclusion: The rat MSCs can be effectively labeled with Fe 2 O 3 -PLL. 1.5-T MR imaging seems to be a good technique to monitor the magnetically labeled MSCs in vivo in renal failure rat model intravascularly administered, which may have much more potential values for studying the engraftment of stem cells in kidneys. (authors)

Inbred Rats as a Model to Study Persistent Renal Leptospirosis and Associated Cellular Immune Responsiveness

Directory of Open Access Journals (Sweden)

Jarlath E. Nally

2018-03-01

Full Text Available Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Rats are regarded as one of the most significant reservoir hosts of infection for human disease, and in the absence of clinical signs of infection, excrete large numbers of organisms in their urine. A unique biological equilibrium exists between pathogenic leptospires and reservoir hosts of infection, but surprisingly, little is known concerning the host's cellular immune response that facilitates persistent renal colonization. To address this deficiency, we established and applied an immunocompetent inbred rat model of persistent renal colonization; leptospires were detected in urine of experimentally infected rats by 3 weeks post-infection and remained positive until 8 weeks post-infection. However, there was little, if any, evidence of inflammation in colonized renal tubules. At 8 weeks post-infection, a robust antibody response was detected against lipopolysaccharide and protein outer membrane (OM components. Purified B and T cells derived from the spleen of infected and non-infected rats proliferated in response to stimulation with 0.5 μg of OM fractions of Leptospira, including CD4+ T cells, which comprised 40% of proliferating cells, compared to 25% in non-infected controls. However, analysis of gene expression did not determine which immunoregulatory pathways were activated. Lymphocytes purified from the lymph node draining the site of colonization, the renal lymph node, also showed an increase in percentage of proliferating B and T cells. However, in contrast to a phenotype of 40% CD4+ T cells in the spleen, the phenotype of proliferating T cells in the renal lymph node comprised 65% CD4+ T cells. These results confirm that the renal lymph node, the local lymphoid organ, is a dominant site containing Leptospira reactive CD4+ T cells and highlight the need to consider the local, vs

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.

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.

High-NaCl intake impairs dynamic autoregulation of renal blood flow in ANG II-infused rats

DEFF Research Database (Denmark)

Saeed, Aso; Dibona, Gerald F; Marcussen, Niels

2010-01-01

The aim of this study was to investigate dynamic autoregulation of renal blood flow (RBF) in ANG II-infused rats and the influence of high-NaCl intake. Sprague-Dawley rats received ANG II (250 ng·kg(-1)·min(-1) sc) or saline vehicle (sham) for 14 days after which acute renal clearance experiments...

Glucagon-like peptide-1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP-1 receptors

DEFF Research Database (Denmark)

Ronn, Jonas; Jensen, Elisa P; Wewer Albrechtsen, Nicolai J

2017-01-01

to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect......Glucagon-like peptide-1 (GLP-1) is an incretin hormone increasing postprandial insulin release. GLP-1 also induces diuresis and natriuresis in humans and rodents. The GLP-1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP-1 treatment leads...... in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e...

Recombinant human erythropoietin in humans down-regulates proximal renal tubular reabsorption and causes a fall in glomerular filtration rate

DEFF Research Database (Denmark)

Olsen, Niels Vidiendal; Aachmann-Andersen, Niels Jacob; Oturai, Peter

2010-01-01

HuEPO for 28 days in doses raising the hematocrit to 48.3 (4.1) %. Renal clearance studies with urine collections (N = 8) were done at baseline and at days 4, 11, 29, and 42. Glomerular filtration rate (GFR) was measured by (51)Cr-EDTA. Renal clearance of lithium (C(Li)) was used as an index of proximal...... tubular outflow and to assess segmental renal tubular handling of sodium and water. rHuEPO-induced increases in hematocrit occurred from day 10 onwards and was caused by both an increase in red cell volume and a fall in plasma volume. Well before that (from day 2 and throughout the treatment time), r...... and water (APR = GFR - C(Li), P

Non-invasive imaging of acute renal allograft rejection in rats using small animal F-FDG-PET.

Directory of Open Access Journals (Sweden)

Stefan Reuter

Full Text Available BACKGROUND: At present, renal grafts are the most common solid organ transplants world-wide. Given the importance of renal transplantation and the limitation of available donor kidneys, detailed analysis of factors that affect transplant survival are important. Despite the introduction of new and effective immunosuppressive drugs, acute cellular graft rejection (AR is still a major risk for graft survival. Nowadays, AR can only be definitively by renal biopsy. However, biopsies carry a risk of renal transplant injury and loss. Most important, they can not be performed in patients taking anticoagulant drugs. METHODOLOGY/PRINCIPAL FINDINGS: We present a non-invasive, entirely image-based method to assess AR in an allogeneic rat renal transplantation model using small animal positron emission tomography (PET and (18F-fluorodeoxyglucose (FDG. 3 h after i.v. injection of 30 MBq FDG into adult uni-nephrectomized, allogeneically transplanted rats, tissue radioactivity of renal parenchyma was assessed in vivo by a small animal PET-scanner (post operative day (POD 1,2,4, and 7 and post mortem dissection. The mean radioactivity (cps/mm(3 tissue as well as the percent injected dose (%ID was compared between graft and native reference kidney. Results were confirmed by histological and autoradiographic analysis. Healthy rats, rats with acute CSA nephrotoxicity, with acute tubular necrosis, and syngeneically transplanted rats served as controls. FDG-uptake was significantly elevated only in allogeneic grafts from POD 1 on when compared to the native kidney (%ID graft POD 1: 0.54+/-0.06; POD 2: 0.58+/-0.12; POD 4: 0.81+/-0.06; POD 7: 0.77+/-0.1; CTR: 0.22+/-0.01, n = 3-28. Renal FDG-uptake in vivo correlated with the results obtained by micro-autoradiography and the degree of inflammatory infiltrates observed in histology. CONCLUSIONS/SIGNIFICANCE: We propose that graft FDG-PET imaging is a new option to non-invasively, specifically, early detect, and follow

Renal accumulation of [{sup 111}In]DOTATOC in rats: influence of inhibitors of the organic ion transport and diuretics

Energy Technology Data Exchange (ETDEWEB)

Stahl, A.R. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Nuclear Medicine, Munich (Germany); Universitaetsklinikum Essen, Department of Radiology, Essen (Germany); Wagner, B.; Heemann, U.; Lutz, J. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Nephrology, Munich (Germany); Poethko, T.; Perutka, M.; Wester, H.J.; Essler, M.; Schwaiger, M. [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Nuclear Medicine, Munich (Germany)

2007-12-15

Radiation exposure to the kidney limits therapy with radiometal labelled DOTATOC. This study evaluates the organic anion and cation transport (inhibitors: probenecid and cimetidine/dexamethason) as well as diuresis (furosemide and mannitol) regarding renal uptake of [{sup 111}In]DOTATOC. One hundred eight male Fisher rats were injected with [{sup 111}In]DOTATOC via the tail vein. Prior to activity injection a total of 84 rats underwent injection with probenecid vs. sodium chloride 0.9% (48 rats), cimetidine vs. dexamethasone vs. sodium chloride 0.9% (18 rats), and furosemide vs. mannitol vs. sodium chloride 0.9% (18 rats). Rats were sacrificed at predetermined time points up to 48 h after activity injection. Kidneys, adrenal glands, pancreas, spleen, blood, liver, and muscle were harvested and injected activity per gram tissue was determined. Autoradiographic images of the kidneys were acquired in a total of 24 rats. Probenecid led to a reduction in renal uptake by up to 30% while not significantly changing the activity accumulation in the other organs investigated. This reduction was attributable to the renal cortex (ratio cortex/medulla 1.72 vs. 1.99; p = 0.006). Cimetidine and dexamethasone had no effect in any of the organs. Furosemide led to a 44% increase in renal activity accumulation attributable to enhanced renal medullary uptake (ratio cortex/medulla 1.44 versus 1.69; p = 0.006). Mannitol had no effect on renal activity uptake. Inhibition of the organic anion transport by probenecid may help reduce renal uptake regarding therapy with radiometal labelled DOTATOC. The enhancing effect of furosemide may be unfavourable for therapy. The results must be confirmed by human studies. (orig.)

Renal Pathology in a Nontraditional Aging Model: The Naked Mole-Rat (Heterocephalus glaber).

Science.gov (United States)

Delaney, M A; Kinsel, M J; Treuting, P M

2016-03-01

The naked mole-rat (NMR; Heterocephalus glaber) is growing in popularity as a model for aging research due to its extreme longevity (up to 30 years), highly adapted physiology, and resistance to cancer, particularly when compared with traditional aging models such as laboratory mice and rats. Despite the NMR's seemingly lengthy health span, several age-related lesions have been documented. During a 15-year retrospective evaluation of a zoo-housed population, histologic changes in the kidneys were reported in 127 of 138 (92%) adult NMRs. Of these, renal tubular mineralization was very common (115 of 127; 90.6%) and found in NMRs without concurrent renal lesions (36 of 127; 28.3%). Many of the other described lesions were considered progressive stages of a single process, generally referred to as chronic nephritis or nephropathy, and diagnosed in 73 of 127 (57.5%), while end-stage renal disease was reported in only 12 (9.4%) NMRs. Renal lesions of these NMRs were comparable to disease entities reported in laboratory rats and certain strains of inbred and noninbred mice. Although many lesions of NMR kidneys were similar to those found in aged laboratory rodents, some common urinary diseases were not represented in the examined colonies. The goal of this study was to describe renal lesions in NMRs from a zoologic setting to familiarize investigators and pathologists with an apparently common and presumably age-related disease in this nontraditional model. © The Author(s) 2015.

The effect of L-cysteine on the portion-selective uptake of cadmium in the renal proximal tubule

International Nuclear Information System (INIS)

Murakami, Masataka; Sano, Kenichi; Webb, M.

1987-01-01

Cadmium (Cd), co-administered with an excess of L-cysteine, accumulates rapidly in the kidneys of the rat. After subcutaneous (s.c.) injection of 3 μmol CdCl 2 /kg body wt the concentrations of Cd in the blood and kidneys increase with the dose of cysteine over the range 0.06-5.0 mmol/kg body wt. At cysteine doses of less than 1.5 mmol/kg body wt the ratio of the concentrations of Cd in the outer medulla and cortex of the kidney remains the same as that after the injection of Cd alone. This ratio, however, is more than doubled at dose levels of 5-10 mmol cysteine/kg body wt. Hepatic uptake of Cd is unaffected by doses of cysteine below 1.5 mmol/kg body wt but decreases markedly at higher doses. In animals that are dosed simultaneously with 5 mmol cysteine/kg body wt, renal uptake of 109 Cd is known to occur in the straight segments of the proximal tubules. At a dose level of less than 1.5 mmol cysteine/kg body wt the present autoradiographical studies show that 109 Cd is taken up predominantly by the proximal convoluted tubules of the kidney cortex. At the critical dose level (1.5 mmol/kg body wt), cysteine decreases the retention of Cd at the s.c. injection site, but probably has little effect on the distribution of Cd between protein and other carrier molecules in the blood. This distribution, however, is altered at higher cysteine dose levels. It is suggested that, under the latter conditions, stable Cd-cysteine complexes are formed in the blood and are filtered readily through the glomeruli. These complexes are taken up in the kidney at the sites of cysteine reabsorption which, by studies with L-[ 35 S]-cysteine, are identified as the straight segments of the proximal tubules. (orig.)

Receptor-mediated endocytosis of lysozyme in renal proximal tubules of the frog Rana temporaria

Directory of Open Access Journals (Sweden)

E.V. Seliverstova

2015-04-01

Full Text Available The mechanism of protein reabsorption in the kidney of lower vertebrates remains insufficiently investigated in spite of raising interest to the amphibian and fish kidneys as a useful model for physiological and pathophysiological examinations. In the present study, we examined the renal tubular uptake and the internalization rote of lysozyme after its intravenous injection in the wintering frog Rana temporaria using immunohisto- and immunocytochemistry and specific markers for some endocytic compartments. The distinct expression of megalin and cubilin in the proximal tubule cells of lysozyme-injected frogs was revealed whereas kidney tissue of control animals showed no positive immunoreactivity. Lysozyme was detected in the apical endocytic compartment of the tubular cells and colocalized with clathrin 10 min after injection. After 20 min, lysozyme was located in the subapical compartment negative to clathrin (endosomes, and intracellular trafficking of lysozyme was coincided with the distribution of megalin and cubilin. However, internalized protein was retained in the endosomes and did not reach lysosomes within 30 min after treatment that may indicate the inhibition of intracellular trafficking in hibernating frogs. For the first time, we provided the evidence that lysozyme is filtered through the glomeruli and absorbed by receptor-mediated clathrin-dependent endocytosis in the frog proximal tubule cells. Thus, the protein uptake in the amphibian mesonephros is mediated by megalin and cubilin that confirms a critical role of endocytic receptors in the renal reabsorption of proteins in amphibians as in mammals.

Effects of Human Umbilical Cord Mesenchymal Stem Cells on Renal Ischaemia-reperfusion Injury in Rats

Directory of Open Access Journals (Sweden)

Zhenyu Qiu

2014-08-01

Full Text Available Objective This study aims to observe the function of umbilical cord-mesenchymal stem cells (UC-MSCs labelled with enhanced green fluorescent protein (eGFP in the repair of renal ischaemia-reperfusion (I/R injury, to determine the effects on inflammatory cascade in an established rat model and to explore possible pathogenesis. Materials and Methods Sixty rats were randomly divided into three groups: the sham-operated, I/R and UC-MSC treatment groups. All rats underwent right nephrectomy. Ischaemia was induced in the left kidney by occlusion of the renal artery and vein for 1hour, followed by reperfusion for 24 hours or 48 hours. Kidney samples were collected to observe morphological changes. Immunohistochemistry was performed to assess the expression of intercellular adhesion molecule 1 (ICAM-1 in the renal tissue sample, as well as the number of infiltrating polymorphonuclear neutrophils (PMNLs and UC-MSCs with positive eGFP. Results Renal histopathological damages and the expression of ICAM-1 and PMNL increased significantly in the I/R group compared with those in the sham-operated group, whereas the damages were less conspicuous in the UC-MSC treatment group. Conclusions Renal ICAM-1, which mediated PMNL infiltration and contributed to renal damage, was significantly up-regulated in the I/R group. UC-MSCs were identified to inhibit these pathological processes and protect the kidney from I/R injury.

Experimental selective elevation of renal medullary blood flow in hypertensive rats: evidence against short-term hypotensive effect.

Science.gov (United States)

Bądzyńska, B; Sadowski, J

2012-08-01

Renal medullary blood flow (MBF) can be selectively increased by intrarenal or systemic infusion of bradykinin (Bk) in anaesthetized normotensive rats. We reproduced this effect in a number of rat models of arterial hypertension and examined whether increased perfusion of the renal medulla can cause a short-term decrease in blood pressure (BP) that is not mediated by increased renal excretion and depletion of body fluids. In uninephrectomized Sprague-Dawley rats, BP was elevated to approx. 145 mmHg by acute i.v. infusion of noradrenaline (NA) or angiotensin II (Ang II) (groups 1, 2), 2-week exposure to high-salt diet (3), high-salt diet + chronic low-dose infusion of Ang II using osmotic minipumps (4) or chronic high-dose Ang II infusion on normal diet (5). Uninephrectomized spontaneous hypertensive rats (SHR) were also examined (6,7). To selectively increase medullary perfusion, in anaesthetized rats, bradykinin was infused during 30-75 min into the renal medullary interstitium or intravenously. Bradykinin increased outer- and inner-medullary blood flow (laser-Doppler fluxes) by 10-20% in groups (1, 2), by 30-50% in groups (3, 4, 5) and approx. 20% in SHR (6, 7). The concurrent increase in total renal blood flow (Transonic probe) was < 3%. A minor (<3%) decrease in BP was seen only in rats acutely rendered hypertensive by NA or Ang II infusions; however, the decreases in BP and increases in medullary perfusion were not correlated. Thus, there was no evidence that in hypertensive rats, substantial selective increases in medullary perfusion can cause a short-term decrease in BP. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

Reactive Oxygen Species Modulation of Na/K-ATPase Regulates Fibrosis and Renal Proximal Tubular Sodium Handling

Directory of Open Access Journals (Sweden)

Jiang Liu

2012-01-01

Full Text Available The Na/K-ATPase is the primary force regulating renal sodium handling and plays a key role in both ion homeostasis and blood pressure regulation. Recently, cardiotonic steroids (CTS-mediated Na/K-ATPase signaling has been shown to regulate fibrosis, renal proximal tubule (RPT sodium reabsorption, and experimental Dahl salt-sensitive hypertension in response to a high-salt diet. Reactive oxygen species (ROS are an important modulator of nephron ion transport. As there is limited knowledge regarding the role of ROS-mediated fibrosis and RPT sodium reabsorption through the Na/K-ATPase, the focus of this review is to examine the possible role of ROS in the regulation of Na/K-ATPase activity, its signaling, fibrosis, and RPT sodium reabsorption.

Interaction of renal failure and dyslipidaemia in the development of calcific aortic valve disease in rats.

Science.gov (United States)

Gillis, Kris; Roosens, Bram; Bala, Gezim; Remory, Isabel; Hernot, Sophie; Delvenne, Philippe; Mestrez, Fabienne; Droogmans, Steven; Cosyns, Bernard

2017-10-01

Calcific aortic valve disease (CAVD) is currently the most common heart valve disease worldwide and is known to be an active process. Both renal failure and dyslipidaemia are considered to be promoting factors for the development of valvular calcifications. The aim of this study is to prospectively evaluate the respective contribution and interaction of renal failure and dyslipidaemia on CAVD in a rat model, using echocardiography and compared with histology. Sixty-eight male Wistar rats were prospectively divided in eight groups, each fed a different diet to induce renal failure alone and combined with hyperlipidaemia or hypercholesterolemia. CAVD was detected and quantified by calibrated integrated backscatter of ultrasound (cIB) and compared with the histological calcium score. The study follow-up was 20 weeks. At the end of the study, the cIB value and the calcium score of the aortic valve were significantly increased in the group with isolated renal failure but not with dyslipidaemia. The combination of renal failure with high cholesterol or high-fat diet did not significantly increase calcifications further. Renal failure alone does induce aortic valve calcifications in a rat model of CAVD, whereas dyslipidaemia alone does not. The combination of renal failure with dyslipidaemia does not increase calcification further. These findings suggest that a combination of atherosclerotic and calcifying factors is not required to induce aortic valve calcifications in this model.

Effects of anesthesia on renal function and metabolism in rats assessed by hyperpolarized MRI

DEFF Research Database (Denmark)

Qi, Haiyun; Mariager, Christian Østergaard; Lindhardt, Jakob

2018-01-01

. In the present study, we aimed to investigate the renal functional and metabolic consequences of 3 typical rodent anesthetics used in preclinical MRI: sevoflurane, inaction, and a mixture of fentanyl, fluanisone, and midazolam (FFM). METHODS: The renal effects of 3 different classes of anesthetics (inactin......, servoflurane, and FFM) were investigated using functional and metabolic MRI. The renal glucose metabolism and hemodynamics was characterized with hyperpolarized [1-13C]pyruvate MRI and by DCE imaging. RESULTS: Rats receiving sevoflurane or FFM had blood glucose levels that were 1.3-fold to 1.4-fold higher than...... rats receiving inactin. A 2.9-fold and 4.8-fold increased13C-lactate/13C-pyruvate ratio was found in the FFM mixture anesthetized group compared with the sevoflurane and the inactin anesthetized groups. The FFM anesthesia resulted in a 50% lower renal plasma flow compared with the sevoflurane...

Glucagon-like peptide-1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP-1 receptors.

Science.gov (United States)

Ronn, Jonas; Jensen, Elisa P; Wewer Albrechtsen, Nicolai J; Holst, Jens Juul; Sorensen, Charlotte M

2017-12-01

Glucagon-like peptide-1 (GLP-1) is an incretin hormone increasing postprandial insulin release. GLP-1 also induces diuresis and natriuresis in humans and rodents. The GLP-1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP-1 treatment leads to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect of acute intrarenal infusion of GLP-1. We hypothesized that GLP-1 would increase diuresis and natriuresis and reduce MAP in SHR. Immunohistochemical staining and in situ hybridization for the GLP-1 receptor were used to localize GLP-1 receptors in the kidney. Sevoflurane-anesthetized normotensive Sprague-Dawley rats and SHR received a 20 min intrarenal infusion of GLP-1 and changes in MAP, RBF, heart rate, dieresis, and natriuresis were measured. The vasodilatory effect of GLP-1 was assessed in isolated interlobar arteries from normo- and hypertensive rats. We found no expression of GLP-1 receptors in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e.g., insulin) to induce the renal changes observed or possibly by an alternative renal GLP-1 receptor. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Megalin and cubilin are endocytic receptors involved in renal clearance of hemoglobin

DEFF Research Database (Denmark)

Gburek, Jakub; Verroust, Pierre J; Willnow, Thomas E

2002-01-01

-Sepharose affinity chromatography of solubilized renal brush-border membranes. Apparent dissociation constants of 1.7 microM for megalin and 4.1 microM for cubilin were determined by surface plasmon resonance analysis. The binding was calcium dependent in both cases. Uptake of fluorescence-labeled hemoglobin by BN......The kidney is the main site of hemoglobin clearance and degradation in conditions of severe hemolysis. Herein it is reported that megalin and cubilin, two epithelial endocytic receptors, mediate the uptake of hemoglobin in renal proximal tubules. Both receptors were purified by use of hemoglobin...... not affect the uptake. By use of immunohistochemistry, it was demonstrated that uptake of hemoglobin in proximal tubules of rat, mouse, and dog kidneys occurs under physiologic conditions. Studies on normal and megalin knockout mouse kidney sections showed that megalin is responsible for physiologic...

The protective effects of tadalafil on renal damage following ischemia reperfusion injury in rats

Directory of Open Access Journals (Sweden)

Bulent Erol

2015-09-01

Full Text Available Ischemia-reperfusion injury can cause renal damage, and phosphodiesterase inhibitors are reported to regulate antioxidant activity. We investigated the prevention of renal damage using tadalafil after renal ischemia reperfusion (I/R injury in rats. A total of 21 adult male Wistar albino rats were randomly divided into three groups of seven, including Group 1-control, Group 2-I/R, and Group 3-tadalafil + I/R group (I/R-T group received tadalafil intraperitoneally at 30 minutes before ischemia. Inducible nitric oxide synthase, endothelial nitric oxide synthase, malondialdehyde, and total antioxidant capacity levels were evaluated, and histopathological changes and apoptosis in the groups were examined. Tadalafil decreased malondialdehyde levels in the I/R group and increased the total antioxidant capacity level. Histopathological and immunohistochemical findings revealed that tadalafil decreased renal injury scores and the ratios of injured cells, as measured through apoptotic protease activating factor 1, inducible nitric oxide synthase, and endothelial nitric oxide synthase levels. We suggest that tadalafil has protective effects against I/R-related renal tissue injury.

CYTOCHROME P450-DEPENDENT METABOLISM OF TRICHLOROETHYLENE IN THE RAT KIDNEY

Science.gov (United States)

The metabolism of trichloroethylene (Tri) by cytochrome P450 (P450) was studied in microsomes from liver and kidney homogenates and from isolated renal proximal tubular (PT) and distal tubular (DT) cells from male Fischer 344 rats. Chloral hydrate (CH) was the only metabolite con...

Renal response to L-arginine in diabetic rats. A possible link between nitric oxide system and aquaporin-2.

Directory of Open Access Journals (Sweden)

María C Ortiz

Full Text Available The aim of this study was to evaluate whether L-Arginine (L-Arg supplementation modifies nitric oxide (NO system and consequently aquaporin-2 (AQP2 expression in the renal outer medulla of streptozotocin-diabetic rats at an early time point after induction of diabetes. Male Wistar rats were divided in four groups: Control, Diabetic, Diabetic treated with L-Arginine and Control treated with L-Arginine. Nitric oxide synthase (NOS activity was estimated by [14C] L-citrulline production in homogenates of the renal outer medulla and by NADPH-diaphorase staining in renal outer medullary tubules. Western blot was used to detect the expression of AQP2 and NOS types I and III; real time PCR was used to quantify AQP2 mRNA. The expression of both NOS isoforms, NOS I and NOS III, was decreased in the renal outer medulla of diabetic rats and L-Arg failed to prevent these decreases. However, L-Arg improved NO production, NADPH-diaphorase activity in collecting ducts and other tubular structures, and NOS activity in renal homogenates from diabetic rats. AQP2 protein and mRNA were decreased in the renal outer medulla of diabetic rats and L-Arg administration prevented these decreases. These results suggest that the decreased NOS activity in collecting ducts of the renal outer medulla may cause, at least in part, the decreased expression of AQP2 in this model of diabetes and constitute additional evidence supporting a role for NO in contributing to renal water reabsorption through the modulation of AQP2 expression in this pathological condition. However, we cannot discard that another pathway different from NOS also exists that links L-Arg to AQP2 expression.

Effects of dietary lipids on renal function of aged rats

Directory of Open Access Journals (Sweden)

Valente Gamba C.

2001-01-01

Full Text Available Normal aging is accompanied by renal functional and morphological deterioration and dietetic manipulation has been used to delay this age-related decline. We examined the effects of chronic administration of diets containing 5% lipid-enriched diet (LD, w/w on renal function of rats at different ages. Three types of LD were tested: canola oil, fish oil and butter. Mean systemic tail-cuff blood pressure and glycemia remained within the normal range whatever the age and the diet of the animals. Proteinuria began to rise from the 8th month in the groups ingesting LD, while in the control group it increased significantly (above 10 mg/24 h only after the 10th month. With age, a significant and progressive decline in glomerular filtration rate (GFR and renal plasma flow was observed in the LD groups but after 6 months of lipid supplementation, the decline in these parameters was more marked in the butter and fish oil groups. By the 18th month, the lowest GFR level was observed in the group ingesting the butter diet (2.93 ± 0.22 vs 5.01 ± 0.21 ml min-1 kg-1 in control, P<0.05. Net acid excretion, evaluated in 9- and 18-month-old rats, was stimulated in the fish oil group when compared both to control and to the other two LD groups. These results suggest that even low levels of LD in a chronic nutritional regimen can modify the age-related changes in renal function and that the impact of different types of lipid-supplemented diets on renal function depends on the kind of lipid present in the diet.

Serum metabonomic analysis of protective effects of Curcuma aromatica oil on renal fibrosis rats.

Science.gov (United States)

Zhao, Liangcai; Zhang, Haiyan; Yang, Yunjun; Zheng, Yongquan; Dong, Minjian; Wang, Yaqiang; Bai, Guanghui; Ye, Xinjian; Yan, Zhihan; Gao, Hongchang

2014-01-01

Curcuma aromatica oil is a traditional herbal medicine demonstrating protective and anti-fibrosis activities in renal fibrosis patients. However, study of its mechanism of action is challenged by its multiple components and multiple targets that its active agent acts on. Nuclear magnetic resonance (NMR)-based metabonomics combined with clinical chemistry and histopathology examination were performed to evaluate intervening effects of Curcuma aromatica oil on renal interstitial fibrosis rats induced by unilateral ureteral obstruction. The metabolite levels were compared based on integral values of serum 1H NMR spectra from rats on 3, 7, 14, and 28 days after the medicine administration. Time trajectory analysis demonstrated that metabolic profiles of the agent-treated rats were restored to control levels after 7 days of dosage. The results confirmed that the agent would be an effective anti-fibrosis medicine in a time-dependent manner, especially in early renal fibrosis stage. Targeted metabolite analysis showed that the medicine could lower levels of lipid, acetoacetate, glucose, phosphorylcholine/choline, trimethylamine oxide and raise levels of pyruvate, glycine in the serum of the rats. Serum clinical chemistry and kidney histopathology examination dovetailed well with the metabonomics data. The results substantiated that Curcuma aromatica oil administration can ameliorate renal fibrosis symptoms by inhibiting some metabolic pathways, including lipids metabolism, glycolysis and methylamine metabolism, which are dominating targets of the agent working in vivo. This study further strengthens the novel analytical approach for evaluating the effect of traditional herbal medicine and elucidating its molecular mechanism.

Systemic calciphylaxis presenting as a painful, proximal myopathy.

OpenAIRE

Edelstein, C. L.; Wickham, M. K.; Kirby, P. A.

1992-01-01

A renal transplant patient who presented with a painful, proximal myopathy due to systemic calciphylaxis is described. The myopathy preceded the characteristic skin and soft tissue necrosis. Systemic calciphylaxis should be considered in a dialysis or a renal transplant patient presenting with a painful proximal myopathy even in the absence of necrotic skin lesions.

Early segmental changes in ischemic acute tubular necrosis of the rat kidney

DEFF Research Database (Denmark)

Faarup, Poul; Nørgaard, Tove; Hegedüs, Viktor

2004-01-01

The background and mechanisms of ischemic acute tubular necrosis are still essentially unclarified. Therefore a quantitative morphological technique was applied for evaluation of the early structural changes in different fractions of the proximal convoluted tubule in the rat renal cortex. In male...

Exaggerated natriuresis and lithium clearance in spontaneously hypertensive rats

DEFF Research Database (Denmark)

Holstein-Rathlou, N H; Kanters, J K; Leyssac, P P

1988-01-01

Since hypertension is associated with changes in the handling of various cations (including sodium and lithium) across the cell membrane, the present study investigated the validity of the lithium clearance method in hypertension by comparing two measures of proximal reabsorption. Thus, fractional...... lithium excretion and transit time (TT)-occlusion time (OT; e-TT/T) were determined successively in the same spontaneously hypertensive rat (SHR, Okamoto strain). The rats were examined both before and after an acute saline load. The results show that the lithium clearance method can be used...... for the determination of proximal reabsorption in SHR. Utilizing the lithium clearance method, the changes in renal sodium handling underlying the exaggerated natriuresis were investigated in unanaesthetized catheterized rats. It was found that the exaggerated natriuresis was associated with an increased output from...

Elemental imaging of kidneys of adult rats exposed to uranium acetate

Energy Technology Data Exchange (ETDEWEB)

Homma-Takeda, S. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)], E-mail: shino_ht@nirs.go.jp; Terada, Y. [Japan Synchrotron Radiation Research Institute, Mikazuki, Hyogo 679-5198 (Japan); Nakata, A.; Sahoo, S.K.; Yoshida, S. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Ueno, S. [School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628 (Japan); Inoue, M. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Iso, H.; Ishikawa, T.; Konishi, T.; Imaseki, H. [Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Shimada, Y. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

2009-06-15

Concern about the toxicity of depleted uranium for military use has increased recently. Renal toxicity is the hallmark effect of uranium exposure. However, the dynamics and distribution of uranium in the kidney are not well understood. Here, we determined the precise distribution of uranium and essential elements in the rat kidney using microbeam scanning particle-induced X-ray emission (micro-PIXE) and synchrotron radiation X-ray fluorescence (SR-XRF). Uranium accumulation in the rat kidney reached a maximum at 1 day after the subcutaneous (s.c.) administration of 2 mg U/kg of uranium acetate and then gradually decreased. At 3 h after administration, uranium was distributed mainly in the proximal tubules of the inner zone of the cortex and in the outer stripe of the outer medulla, and absorbed by the proximal tubule epithelium. Iron was localized more in the inside of the outer medulla than uranium, while phosphorus, potassium, sulfur and zinc were equally distributed in the cortex and the outer stripe of the outer medulla. At 3 days after administration, the number of apoptotic cells increased and cells were lost from the proximal tubules. Uranium was detectable mainly in the outer stripe of the outer medulla at 15 days, suggesting that the renal distribution of uranium is site-selective and causes site-specific renal lesions.

Surgical Anatomy and Microvascular Surgical Technique Relevant to Experimental Renal Transplant in Rat Employing Aortic and Inferior Venacaval Conduits.

Science.gov (United States)

Shrestha, Badri Man; Haylor, John

2017-11-15

Rat models of renal transplant are used to investigate immunologic processes and responses to therapeutic agents before their translation into routine clinical practice. In this study, we have described details of rat surgical anatomy and our experiences with the microvascular surgical technique relevant to renal transplant by employing donor inferior vena cava and aortic conduits. For this study, 175 rats (151 Lewis and 24 Fisher) were used to establish the Fisher-Lewis rat model of chronic allograft injury at our institution. Anatomic and technical details were recorded during the period of training and establishment of the model. A final group of 12 transplanted rats were studied for an average duration of 51 weeks for the Lewis-to-Lewis isografts (5 rats) and 42 weeks for the Fisher-to-Lewis allografts (7 rats). Functional measurements and histology confirmed the diagnosis of chronic allograft injury. Mastering the anatomic details and microvascular surgical techniques can lead to the successful establishment of an experimental renal transplant model.

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.

Renal cortical calcification in syngeneic intact rats and those receiving an infrarenal thoracic aortic graft: possible etiological roles of endothelin, nitrate and minerals, and different preventive effects of long-term oral treatment with magnesium, citrate and alkali-containing preparations.

Science.gov (United States)

Schmiedl, A; Schmiedl, P O; Bonucci, E; Seitz, T; Schwille, R M; Manoharan, M

2001-08-01

Renal cortical nephrocalcinosis (C-NC) is a rare disorder of uncertain etiology. Using highly inbred (syngeneic) male Lewis rats, we describe the spontaneous occurrence of histologically detectable C-NC in sham operated control rats (Sham; n=12), its aggravation following grafting of the ascending thoracic aorta from a donor rat to the infrarenal aorta of a recipient (ATx; n=12), and differences in C-NC inhibition after 12 weeks of oral administration of magnesium (Mg), citrate and alkali. C-NC is characterized by Kossa-positive areas located in cells of the proximal tubule close to blood vessels and also, to a lesser extent, within glomeruli. After ATx there was vascular overproduction of endothelin (ET-1) but decreased production of nitrate; in renal cortical tissue there was an excess of calcium over Mg and phosphorus and oxalate over citrate. In plasma there was an increase in calcium and creatinine within the normal range. Calcification of tubular cells was eliminated by a preparation containing potassium, sodium and bases (from citrate degradation and bicarbonate) in addition to Mg. Less effective than the latter was Mg-potassium citrate and least effective, Mg citrate. The former treatment also normalized calcemia and urinary nitrate, but only incompletely suppressed ET-1 and had no significant effect on glomerular calcification or tissue and urinary oxalate. Urinary ET-1 excess appeared directly related to the cortical tissue calcium/Mg ratio, and urinary excretion of Mg, citrate and total protein appeared to be inversely related to the severity of C-NC. It was concluded that (1) the highly inbred rat is prone to precipitation of calcium phosphate in the renal cortex; (2) this type of C-NC occurs in close proximity to and within renal vascular tissue and is associated with an imbalance of vasoconstrictors and vasodilators of endothelial origin; (3) effective inhibition of C-NC can be achieved by an alkalinizing combination of Mg, potassium, sodium and

The Renal Protective Effects of Corn Silk and Feijoa by using in situ Rat Renal System

Directory of Open Access Journals (Sweden)

Mohammad Karami

2014-06-01

Full Text Available Background: Corn silk (CS is widely used in Iranian traditional medicine. Feijoa sellowiana (FS, on the other hand, is a non-native plant widespread in the southern part of Iran. The aim of the present study was to examine the renal protective activity of CS and FS against dosage-induced ecstasy (MDMA by in situ rat renal perfusion (IRRP system. Methods: Hydro-alcoholic extracts of CS and FS (10, 20, 40 and 100 mg/ kg were studied for their renal protective activities by IRRP system. In this study, the kidneys were perfused with Kerbs-Henseleit buffer, containing different concentrations of hydro-alcoholic (HA extracts of CS and FS (10, 20, 40, 50, and 100mg/kg added to the buffer and perfused for two hours. During the perfusion, many factors, including urea, creatinine and GSH levels assessed as indicator of renal viability. Consequently, sections of renal tissue were examined for any histopathological changes. Results: The results showed that histopathological changes in renal tissue related to HA extract of CS AND FS concentrations dose-dependently. Doses of 50, 100 mg/kg caused significant histopathological changes (P<0.05. Glutathione (GSH levels of samples perfused by HA extract of CS and FS increased compared with the positive control group. Conclusion: Renal protective effects of CS and FS decrease lipid peroxidation, although other mechanisms may also be involved.

The entire miR-200 seed family is strongly deregulated in clear cell renal cell cancer compared to the proximal tubular epithelial cells of the kidney

NARCIS (Netherlands)

Duns, Gerben; van den Berg, Anke; van Dijk, Marcory C. R. F.; van Duivenbode, Inge; Giezen, Cor; Kluiver, Joost; van Goor, Harry; Hofstra, Robert M. W.; van den Berg, Eva; Kok, Klaas

Despite numerous studies reporting deregulated microRNA (miRNA) and gene expression patterns in clear cell renal cell carcinoma (ccRCC), no direct comparisons have been made to its presumed normal counterpart: the renal proximal tubular epithelial cells (PTECs). The aim of this study was to

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

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

Effect of indomethacin and salt depletion on renal proton MR imaging; An experimental study in the rat

Energy Technology Data Exchange (ETDEWEB)

Heyman, S.N.; Mammen, M. (Harvard Medical School, Boston, MA (United States). Charles A Dana Research Inst. Beth Israel Hospital, Boston, MA (United States))

1991-11-01

Blockade of the synthesis of vasodilating prostaglandins with non-steroidal anti-inflammatory drugs (NSAID) renders the renal medulla susceptible to hypoxic injury with reduced renal function, especially in clinical conditions characterized by volume depletion. Alterations in renal hemodynamics and urine production may effect renal MR imaging under these circumstances. We injected salt-depleted and control rats undergoing proton MR imaging with indomethacin 10 mg/kg. Indomethacin abolished the cortico-medullary T2-gradient and markedly diminished the overall renal signal in salt-depleted rats only. These changes, which progressed over a period of 40 min after indomethacin was injected, probably result from renal oligemia and decreased urine production, with an associated decrease in T2-values. We suggest that a history of consumption of non-steroidal anti-inflammatory drugs should be obtained and taken into account in the evaluation of renal proton MR imaging, especially in the presence of salt and volume depletion. (orig.).

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.

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.

Absence of functional renal effects of uro-angiographic contrast media on post-ischemic rat kidneys

International Nuclear Information System (INIS)

Verbaeys, A.; Maele, G. van; Sy, W. de; Ringoir, S.; Lameire, N.; University Hospital, Ghent; University Hospital, Ghent

1991-01-01

Water soluble ionic contrast media (CM) and glucose 5% were administered to Sprague-Dawley rats 36 hours after bilateral warm renal ischemia for 45 min. In all animals (n=28) the renal ischemia caused a decrease of the absolute urinary creatinine output. Intraarterial injection of glucose 5% or CM did not produce different patterns of absolute urinary creatinine output. The serum creatinine increased after 36 hours of reflow. When compared by means of a Mann-Whitney U-test to a normal median serum creatinine obtained in a separate group of 22 normal rats, the increase was statistically significant (p≤0.01). The serum creatinine medians returned to a normal level after 24 hours. It seems therefore that 45 min of warm renal ischemia and 36 hours of reflow is an insufficient challenge to the rat kidney for the detection of the nephrotoxic properties of CM as opposed to when CM are injected during ischemia. (orig.)

Effects of water deprivation on renal hydroelectrolytic excretion in chronically Trypanosoma cruzi-infected rats

Directory of Open Access Journals (Sweden)

T.T. Rosa

1995-03-01

Full Text Available The effect of an 8 hour-period of water deprivation on fluid and electrolyte renal excretion was investigated in male Wistar rats infected with the strain São Felipe (12SF of Trypanosoma cruzi, in comparison with age and sex matched non-infected controls. The median percent reductions in the urinary flow (-40% v -63% and excretion ofsodium (-57% v-79% were smaller in chagasic than in control rats, respectively. So, chagasic rats excreted more than controls. On the other hand, the median percent decrement in the clearance of creatinine was higher in chagasic (-51% than in controls (-39%. Thus, chagasic rats showed some disturbed renal hydroelectrolytic responses to water deprivation, expressed by smaller conservation, or higher excretion of water and sodium in association with smaller glomerularfiltration rate. This fact denoted an elevation in the fractional excretion of sodium and water.

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.

Plasticity and constraints on social evolution in African mole-rats: ultimate and proximate factors.

Science.gov (United States)

Faulkes, Chris G; Bennett, Nigel C

2013-05-19

Here, we review comparative studies of African mole-rats (family Bathyergidae) to explain how constraints acting at the ultimate (environmental) and proximate (organismal) levels have led to convergent gains and losses of sociality within this extensive adaptive radiation of subterranean rodents endemic to sub-Saharan Africa. At the ultimate level, living in environments that range from mesic through to arid has led to both variation and flexibility in social organization among species, culminating in the pinnacle of social evolution in the eusocial naked and Damaraland mole-rats (Heterocephalus glaber and Fukomys damarensis). The common mole-rat (Cryptomys hottentotus) provides a model example of how plasticity in social traits exists within a single species inhabiting areas with different ecological constraint. At the proximate level, reproductive strategies and cooperative breeding may be constrained by the correlated evolution of a suite of traits including physiological suppression of reproduction, the development of physiological and morphological castes, and the mode of ovulatory control and seasonality in breeding. Furthermore, recent neurobiological advances indicate that differential patterns of neurotransmitter expression within the forebrain may underpin (and limit) either a solitary or group living/cooperative lifestyle not only in mole-rats, but also more widely among disparate mammalian taxa.

Kefir administration reduced progression of renal injury in STZ-diabetic rats by lowering oxidative stress.

Science.gov (United States)

Punaro, Giovana R; Maciel, Fabiane R; Rodrigues, Adelson M; Rogero, Marcelo M; Bogsan, Cristina S B; Oliveira, Marice N; Ihara, Silvia S M; Araujo, Sergio R R; Sanches, Talita R C; Andrade, Lucia C; Higa, Elisa M S

2014-02-15

This study aimed at assessing the effects of Kefir, a probiotic fermented milk, on oxidative stress in diabetic animals. The induction of diabetes was achieved in adult male Wistar rats using streptozotocin (STZ). The animals were distributed into four groups as follows: control (CTL); control Kefir (CTLK); diabetic (DM) and diabetic Kefir (DMK). Starting on the 5th day of diabetes, Kefir was administered by daily gavage at a dose of 1.8 mL/day for 8 weeks. Before and after Kefir treatment, the rats were placed in individual metabolic cages to obtain blood and urine samples to evaluate urea, creatinine, proteinuria, nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and C-reactive protein (CRP). After sacrificing the animals, the renal cortex was removed for histology, oxidative stress and NOS evaluation. When compared to CTL rats, DM rats showed increased levels of glycemia, plasmatic urea, proteinuria, renal NO, superoxide anion, TBARS, and plasmatic CRP; also demonstrated a reduction in urinary urea, creatinine, and NO. However, DMK rats showed a significant improvement in most of these parameters. Despite the lack of differences observed in the expression of endothelial NO synthase (eNOS), the expression of inducible NO synthase (iNOS) was significantly lower in the DMK group when compared to DM rats, as assessed by Western blot analysis. Moreover, the DMK group presented a significant reduction of glycogen accumulation within the renal tubules when compared to the DM group. These results indicate that Kefir treatment may contribute to better control of glycemia and oxidative stress, which is associated with the amelioration of renal function, suggesting its use as a non-pharmacological adjuvant to delay the progression of diabetic complications. Copyright © 2014 Elsevier Inc. All rights reserved.

The plasma carnitine concentration regulates renal OCTN2 expression and carnitine transport in rats

OpenAIRE

Schürch, R; Todesco, L; Novakova, K; Mevissen, M; Stieger, B; Krähenbühl, S

2010-01-01

Previous findings in rats and in human vegetarians suggest that the plasma carnitine concentration and/or carnitine ingestion may influence the renal reabsorption of carnitine. We tested this hypothesis in rats with secondary carnitine deficiency following treatment with N-trimethyl-hydrazine-3-propionate (THP) for 2 weeks and rats treated with excess L-carnitine for 2 weeks. Compared to untreated control rats, treatment with THP was associated with an approximately 70% decrease in plasma car...

The 6-hydroxychromanol derivative SUL-109 ameliorates renal injury after deep hypothermia and rewarming in rats.

Science.gov (United States)

Vogelaar, Pieter C; Roorda, Maurits; de Vrij, Edwin L; Houwertjes, Martin C; Goris, Maaike; Bouma, Hjalmar; van der Graaf, Adrianus C; Krenning, Guido; Henning, Robert H

2018-04-11

Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats. Human proximal tubule cell viability was assessed following exposure to H/R for 48/4 h in the presence of various 6-hydroxychromanols. Selected compounds (SUL-109, SUL-121) or vehicle were administered to ketamine-anaesthetized male Wistar rats (IV 135 µg/kg/h) undergoing H/R at 15°C for 3 h followed by rewarming and normothermia for 1 h. Metabolic parameters and body temperature were measured throughout. In addition, renal function, renal injury, histopathology and mitochondrial fitness were assessed. H/R injury in vitro lowered cell viability by 94 ± 1%, which was counteracted dose-dependently by multiple 6-hydroxychomanols derivatives. In vivo, H/R in rats showed kidney injury molecule 1 expression in the kidney and tubular dilation, accompanied by double-strand DNA breaks and protein nitrosylation. SUL-109 and SUL-121 ameliorated tubular kidney damage, preserved mitochondrial mass and maintained cortical adenosine 5'-triphosphate (ATP) levels, although SUL-121 did not reduce protein nitrosylation. The substituted 6-hydroxychromanols SUL-109 and SUL-121 ameliorate kidney injury during in vivo H/R by preserving mitochondrial mass, function and ATP levels. In addition, both 6-hydroxychromanols

Novel resveratrol analogues attenuate renal ischemic injury in rats

Science.gov (United States)

Khader, Adam; Yang, Weng-Lang; Kuncewitch, Michael; Prince, Jose M.; Marambaud, Philippe; Nicastro, Jeffrey; Coppa, Gene F.; Wang, Ping

2014-01-01

Background Renal ischemia-reperfusion (I/R) is a severe clinical complication with no specific treatment. Resveratrol has been shown as a promising experimental agent in renal I/R due to its effect on cellular energy metabolism, oxidative stress, and inflammation. Recently, we identified two biologically active resveratrol analogues (RSVAs), RSVA405 and RSVA314. We hypothesized that both RSAVs would attenuate I/R-induced renal injury. Methods Adult male rats were subjected to renal I/R through bilateral renal pedicle clamping for 60 min, followed by reperfusion. RSVA405 (3 mg/kg BW), RSVA314 (3 mg/kg BW), or vehicle (10% DMSO and 33% Solutol in PBS) was administered by intraperitoneal injection 1 h prior to ischemia. Blood and renal tissues were collected 24 h after I/R for evaluation. Results Administration of RSVA405 and RSVA314 significantly reduced the serum levels of renal dysfunction and injury markers, including creatinine, blood urea nitrogen, aspartate aminotransferase, and lactate dehydrogenase, compared to vehicle. The protective effect of RSVA405 and RSVA314 was also reflected on histologic evaluation. Both RSVAs reduced the number of apoptotic cells by more than 60% as determined by TUNEL assay, compared to vehicle. The renal ATP levels of the vehicle group was decreased to 52.4% of control, while those of the RSVA405 and RSVA314 groups were restored to 72.3% and 79.6% of control, respectively. Both RSVAs significantly reduced the protein expression of inducible nitric oxide synthase and nitrotyrosine, and the mRNA levels of TNF-α, IL-6 and IL-1β. Conclusions RSVA405 and RSVA314 attenuate I/R-induced renal injury through the modulation of energy metabolism, oxidative stress, and inflammation. PMID:25214260

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...

Noninvasive measurement of renal blood flow by magnetic resonance imaging in rats.

Science.gov (United States)

Romero, Cesar A; Cabral, Glauber; Knight, Robert A; Ding, Guangliang; Peterson, Edward L; Carretero, Oscar A

2018-01-01

Renal blood flow (RBF) provides important information regarding renal physiology and nephropathies. Arterial spin labeling-magnetic resonance imaging (ASL-MRI) is a noninvasive method of measuring blood flow without exogenous contrast media. However, low signal-to-noise ratio and respiratory motion artifacts are challenges for RBF measurements in small animals. Our objective was to evaluate the feasibility and reproducibility of RBF measurements by ASL-MRI using respiratory-gating and navigator correction methods to reduce motion artifacts. ASL-MRI images were obtained from the kidneys of Sprague-Dawley (SD) rats on a 7-Tesla Varian MRI system with a spin-echo imaging sequence. After 4 days, the study was repeated to evaluate its reproducibility. RBF was also measured in animals under unilateral nephrectomy and in renal artery stenosis (RST) to evaluate the sensitivity in high and low RBF models, respectively. RBF was also evaluated in Dahl salt-sensitive (SS) rats and spontaneous hypertensive rats (SHR). In SD rats, the cortical RBFs (cRBF) were 305 ± 59 and 271.8 ± 39 ml·min -1 ·100 g tissue -1 in the right and left kidneys, respectively. Retest analysis revealed no differences ( P = 0.2). The test-retest reliability coefficient was 92 ± 5%. The cRBFs before and after the nephrectomy were 296.8 ± 30 and 428.2 ± 45 ml·min -1 ·100 g tissue -1 ( P = 0.02), respectively. The kidneys with RST exhibited a cRBF decrease compared with sham animals (86 ± 17.6 vs. 198 ± 33.7 ml·min -1 ·100 g tissue -1 ; P < 0.01). The cRBFs in SD, Dahl-SS, and SHR rats were not different ( P = 0.35). We conclude that ASL-MRI performed with navigator correction and respiratory gating is a feasible and reliable noninvasive method for measuring RBF in rats.

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.

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.

Effect of tempol and tempol plus catalase on intra-renal haemodynamics in spontaneously hypertensive stroke-prone (SHSP) and Wistar rats.

Science.gov (United States)

Ahmeda, Ahmad F; Rae, Mark G; Al Otaibi, Mohammed F; Anweigi, Lamyia M; Johns, Edward J

2017-05-01

Vasoconstriction within the renal medulla contributes to the development of hypertension. This study investigated the role of reactive oxygen species (ROS) in regulating renal medullary and cortical blood perfusion (MBP and CBP respectively) in both stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar rats. CBP and MBP were measured using a laser-Doppler flow meter before and after intra-renal infusion of tempol, the superoxide dismutase (SOD) mimetic or tempol plus catalase, the hydrogen peroxide-degrading enzyme. Tempol infusion significantly elevated blood perfusion within the renal medulla (MBP) in both SHRSP (by 43 ± 7%, P catalase and tempol were co-infused, MBP was again significantly increased in SHRSP (by 57 ± 6%, P < 0.001) and Wistar rats (by 33 ± 6%, P < 0.001), with a significantly greater increase in perfusion being induced in the SHRSP relative to the Wistar rats (P < 0.01). Notably, this increase was significantly greater than in those animals infused with tempol alone (P < 0.01). These results suggest that ROS plays a proportionally greater role in reducing renal vascular compliance, particularly within the renal medulla, in normotensive and hypertensive animals, with effects being greater in the hypertensive animals. This supports the hypothesis that SHRSP renal vasculature might be subjected to elevated level of oxidative stress relative to normotensive animals.

Reversal of Proximal Renal Tubular Dysfunction after Nucleotide Analogue Withdrawal in Chronic Hepatitis B

Directory of Open Access Journals (Sweden)

Abhasnee Sobhonslidsuk

2017-01-01

Full Text Available Aims. Proximal renal tubular dysfunction (PRTD is an infrequent complication after nucleotide analogue therapy. We evaluated the outcomes of PRTD and nephrotoxicity after nucleotide analogue withdrawal in chronic hepatitis B (CHB. Methods. A longitudinal follow-up study was performed in patients with PRTD after nucleotide analogue discontinuation. Serum and urine were collected at baseline and every 3 months for one year. The fractional excretion of phosphate (PO4, uric acid (UA, and potassium and tubular maximal reabsorption rate of PO4 to glomerular filtration rate (TmPO4/GFR were calculated. Renal losses were defined based on the criteria of substance losses. Subclinical PRTD and overt PRTD were diagnosed when 2 and ≥3 criteria were identified. Results. Eight subclinical and eight overt PRTD patients were enrolled. After nucleotide analogue withdrawal, there were overall improvements in GFR, serum PO4, and UA. Renal loss of PO4, UA, protein, and β2-microglobulin reduced over time. At one year, complete reversal of PRTD was seen in 13 patients (81.2%. Improvements in PRTD were seen in all but one patient. Conclusion. One year after nucleotide analogue withdrawal, PRTD was resolved in most patients. Changes in TmPO4/GFR, urinary protein, and β2-microglobulin indicate that urinary biomarkers may represent an early sign of PRTD recovery.

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.

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.

Online feedback-controlled renal constant infusion clearances in rats.

Science.gov (United States)

Schock-Kusch, Daniel; Shulhevich, Yury; Xie, Qing; Hesser, Juergen; Stsepankou, Dzmitry; Neudecker, Sabine; Friedemann, Jochen; Koenig, Stefan; Heinrich, Ralf; Hoecklin, Friederike; Pill, Johannes; Gretz, Norbert

2012-08-01

Constant infusion clearance techniques using exogenous renal markers are considered the gold standard for assessing the glomerular filtration rate. Here we describe a constant infusion clearance method in rats allowing the real-time monitoring of steady-state conditions using an automated closed-loop approach based on the transcutaneous measurement of the renal marker FITC-sinistrin. In order to optimize parameters to reach steady-state conditions as fast as possible, a Matlab-based simulation tool was established. Based on this, a real-time feedback-regulated approach for constant infusion clearance monitoring was developed. This was validated by determining hourly FITC-sinistrin plasma concentrations and the glomerular filtration rate in healthy and unilaterally nephrectomized rats. The transcutaneously assessed FITC-sinistrin fluorescence signal was found to reflect the plasma concentration. Our method allows the precise determination of the onset of steady-state marker concentration. Moreover, the steady state can be monitored and controlled in real time for several hours. This procedure is simple to perform since no urine samples and only one blood sample are required. Thus, we developed a real-time feedback-based system for optimal regulation and monitoring of a constant infusion clearance technique.

The effects of angiotensin II receptor antagonist (candesartan on rat renal vascular resistance

Directory of Open Access Journals (Sweden)

Supatraviwat, J

2004-05-01

Full Text Available The present study aimed to investigate the action of angiotensin II (AII on renal perfusion pressure and renal vascular resistance using noncompetitive AT1-receptor antagonist (candesartan or CV 11974. Experiments were performed in isolated kidney of adult male Wistar rats. Kreb's Henseleit solution was perfused into the renal artery at the rate of 3.5 ml/min. This flow rate was designed in order to maintain renal perfusion pressure between 80-120 mm Hg. Dose-response relationship between perfusion flow rate and AII concentration were studied. Renal perfusion pressure in response to 1, 10 and 100 nM AII were increased from basal perfusion pressure of 94±8 mm Hg to 127±6, 157±12 and 190±16 mm Hg, respectively. Administration of perfusate containing 11.4 μM candesartan for 30 min had no effect on the basal perfusion pressure. However, this significantly reduced renal perfusion pressure in the presence of AII (1, 10 and 100 nM by 39%, 47% and 61%, (n=7, P<0.05 respectively. At the basal perfusion pressure, calculated renal vascular resistance was 27±2 mm Hg · min · ml-1. However, the vascular resistance were found to be 41±1, 45±2 and 47±2 mm Hg · min · ml-1 when 1, 10 and 100 nM AII were added. Moreover, this dose of candesartan also showed a significant decrease in renal vascular resistance at the corresponding doses of AII by 38%, 48% and 43%, (n=7, P<0.05 respectively. The higher dose of candesartan (22.7 μM completely inhibited the action of 1, 10 and 100 nM AII on renal vasoconstriction. These results may indicate that the action of AII on renal vascular resistance is via AT1-receptor, at least in rat isolated perfusion kidney.

Toxicological significance of renal Bcrp: Another potential transporter in the elimination of mercuric ions from proximal tubular cells

Energy Technology Data Exchange (ETDEWEB)

Bridges, Christy C., E-mail: bridges_cc@mercer.edu; Zalups, Rudolfs K.; Joshee, Lucy

2015-06-01

Secretion of inorganic mercury (Hg{sup 2+}) from proximal tubular cells into the tubular lumen has been shown to involve the multidrug resistance-associated protein 2 (Mrp2). Considering similarities in localization and substrate specificity between Mrp2 and the breast cancer resistance protein (Bcrp), we hypothesize that Bcrp may also play a role in the proximal tubular secretion of mercuric species. In order to test this hypothesis, the uptake of Hg{sup 2+} was examined initially using inside-out membrane vesicles containing Bcrp. The results of these studies suggest that Bcrp may be capable of transporting certain conjugates of Hg{sup 2+}. To further characterize the role of Bcrp in the handling of mercuric ions and in the induction of Hg{sup 2+}-induced nephropathy, Sprague–Dawley and Bcrp knockout (bcrp{sup −/−}) rats were exposed intravenously to a non-nephrotoxic (0.5 μmol·kg{sup −1}), a moderately nephrotoxic (1.5 μmol·kg{sup −1}) or a significantly nephrotoxic (2.0 μmol·kg{sup −1}) dose of HgCl{sub 2}. In general, the accumulation of Hg{sup 2+} was greater in organs of bcrp{sup −/−} rats than in Sprague–Dawley rats, suggesting that Bcrp may play a role in the export of Hg{sup 2+} from target cells. Within the kidney, cellular injury and necrosis was more severe in bcrp{sup −/−} rats than in controls. The pattern of necrosis, which was localized in the inner cortex and the outer stripe of the outer medulla, was significantly different from that observed in Mrp2-deficient animals. These findings suggest that Bcrp may be involved in the cellular export of select mercuric species and that its role in this export may differ from that of Mrp2. - Highlights: • Bcrp may mediate transport of mercury out of proximal tubular cells. • Hg-induced nephropathy was more severe in Bcrp knockout rats. • Bcrp and Mrp2 may differ in their ability to transport Hg.

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.

Perivascular radiofrequency renal denervation lowers blood pressure and ameliorates cardiorenal fibrosis in spontaneously hypertensive rats

Science.gov (United States)

Zhang, Yan; Su, Linan; Zhang, Yunrong; Wang, Qiang; Yang, Dachun; Li, De; Yang, Yongjian; Ma, Shuangtao

2017-01-01

Background Catheter-based renal denervation (RDN) is a promising approach to treat hypertension, but innervation patterns limit the response to endovascular RDN and the post-procedural renal artery narrowing or stenosis questions the endovascular ablation strategy. This study was performed to investigate the anti-hypertensive and target organ protective effects of perivascular RDN in spontaneously hypertensive rats (SHR). Methods SHR and normotensive Wistar-Kyoto (WKY) rats were divided into sham group (n = 10), radiofrequency ablation group (n = 20) in which rats received bilateral perivascular ablation with radiofrequency energy (2 watts), and chemical (10% phenol in 95% ethanol) ablation group (n = 12). The tail-cuff blood pressure was measured before the ablation and on day 14 and day 28 after the procedure. The plasma levels of creatinine, urea nitrogen, and catecholamines, urinary excretion of electrolytes and protein, and myocardial and glomerular fibrosis were analyzed and compared among the groups on day 28 after the procedure. Results We identified that 2-watt is the optimal radiofrequency power for perivascular RDN in rats. Perivascular radiofrequency and chemical ablation achieved roughly comparable blood pressure reduction in SHR but not in WKY on day 14 and day 28 following the procedure. Radiofrequency-mediated ablation substantially destroyed the renal nerves surrounding the renal arteries of both SHR and WKY without damaging the renal arteries and diminished the expression of tyrosine hydroxylase, the enzyme marker for postganglionic sympathetic nerves. Additionally, perivascular radiofrequency ablation also decreased the plasma catecholamines of SHR. Interestingly, both radiofrequency and chemical ablation decreased the myocardial and glomerular fibrosis of SHR, while neither increased the plasma creatinine and blood urea nitrogen nor affected the urinary excretion of electrolytes and protein when compared to sham group. Conclusions Radiofrequency

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.

Tranilast prevents renal interstitial fibrosis by blocking mast cell infiltration in a rat model of diabetic kidney disease.

Science.gov (United States)

Yin, Dan-Dan; Luo, Jun-Hui; Zhao, Zhu-Ye; Liao, Ying-Jun; Li, Ying

2018-05-01

Renal interstitial fibrosis is a final pathway that is observed in various types of kidney diseases, including diabetic kidney disease (DKD). The present study investigated the effect of tranilast on renal interstitial fibrosis and the association between its role and mast cell infiltration in a rat model of DKD. A total of 30 healthy 6‑week‑old male Sprague‑Dawley rats were randomly divided into the following four groups: Normal control group; DKD model group; low‑dose tranilast group (200 mg/kg/day); and high‑dose tranilast group (400 mg/kg/day). The morphological alterations of tubulointerstitial fibrosis were evaluated by Masson's trichrome staining, while mast cell infiltration into the renal tubular interstitium was measured by toluidine blue staining and complement C3a receptor 1 (C3aR) immunohistochemical staining (IHC). The expression of fibronectin (FN), collagen I (Col‑I), stem cell factor (SCF) and proto‑oncogene c‑kit (c‑kit) was detected by IHC, western blotting and reverse transcription‑quantitative‑polymerase chain reaction. The results demonstrated that tubulointerstitial fibrosis and mast cell infiltration were observed in DKD model rats, and this was improved dose‑dependently in the tranilast treatment groups. The expression of FN, Col‑I, SCF and c‑kit mRNA and protein was upregulated in the tubulointerstitium of DKD model rats compared with the normal control rats, and tranilast inhibited the upregulated expression of these markers. Furthermore, the degree of SCF and c‑kit expression demonstrated a significant positive correlation with C3aR‑positive mast cells and the markers of renal interstitial fibrosis. The results of the present study indicate that mast cell infiltration may promote renal interstitial fibrosis via the SCF/c‑kit signaling pathway. Tranilast may prevent renal interstitial fibrosis through inhibition of mast cell infiltration mediated through the SCF/c-kit signaling pathway.

Transient renal impairment in rats after oral exposure to diethylene glycol.

Science.gov (United States)

Freundt, K J; Weis, N

1989-10-01

Volume, specific gravity, creatinine, lactate dehydrogenase (LDH), leucine aminopeptidase (LAP), beta-galactosidase (GAL), leucocytes, erythrocytes, nitrite, protein (albumin), glucose, ketone, urobilinogen, bilirubin and pH were estimated in urine of rats after single (by gavage) or repeated (via drinking water) oral administration of diethylene glycol (DEG). Following single or repetitive doses (daily over 90 days) of 0.2 g DEG kg-1 body weight, no change in renal function was observed (no effect level). In urine of rats treated once with 0.7 g DEG kg-1 body weight, LDH activity was significantly enhanced one day after treatment. A single dose of 2.0 g DEG kg-1 body weight resulted in an additional rise in urinary GAL activity two days after treatment, a significant rise of urinary volume and a decrease in creatinine concentration and pH on the first day. One day following a single dose of 8.0 g DEG kg-1 body weight, in addition to the changes mentioned before, LAP activity was significantly elevated and the specific gravity decreased. However, in all experiments the wet weight of the kidneys remained normal as compared to controls. The results thus show dose-dependent changes in several renal parameters, indicating a slight-to-moderate and reversible renal impairment.

Changes in renal uptake of Tc-99m methylene diphosphonate (MDP) in stone-forming rats

International Nuclear Information System (INIS)

McAfee, J.G.; Thomas, F.D.; Roskopf, M.; Ritter, K.; Lyons, B.; Lilien, O.M.; Schoonmaker, J.E.

1984-01-01

A pyridoxine (vitamin B6)-deficient diet in rats was used as a model of early renal lithiasis to find out if stone-formers could be identified from control animals by differences in the biodistribution of Tc-99m MDP. The mean renal uptake of this agent at 3 hours was about 70% higher in test animals than in controls, but there was considerable overlap between the upper limits of the normal range and lower values in stone-formers. If these results were valid for humans, the metabolic abnormality in males with early stone-forming disease could not be identified with certainty by in vivo measurements of Tc-99m MDP renal uptake alone. However, the skeletal uptake of MDP in the stone-forming animals was depressed by 28 to 35%, compared with control rats. Consequently, the renal to skeletal MDP concentration ratio was invariably elevated in stone-formers beyond the 95 percentile normal range. Unexpectedly, 76% of the pyridoxine-deficient animals had a higher accumulation of MDP in the myocardium than the upper limit of the normal range. The pyridoxine-deficient diet induced no remarkable early changes in the biodistribution or renal clearance of I-131 Hippuran

Dynamic renal scintigraphic estimation of deceased donor kidneys in a rat model

Directory of Open Access Journals (Sweden)

Huseyin Aydin Mitil

2017-01-01

Full Text Available At present a large number of the renal transplantations are being performed from the deceased donors. The success of these transplantations depends on the viability of the deceased donor kidneys. The aim of this study was to investigate the reliability of scintigraphic estimation of function of deceased donor kidneys by comparing the histopathologic and scintigraphic findings. Ten rats were included in the study (2–3 months old, 250–300 g, all male. Control scintigraphy was performed to all the rats by injection of 37 MBq Tc-99m DTPA from the tail vein in a dynamic manner. Brain death of the rats was achieved by inflation of a Fogartys catheter in the cranial cavity. Immediately, after brain death confirmation, dynamic renal scintigraphy was performed with the same parameters of control scintigraphy. In the comparison of scintigraphies obtained in the before and just after brain death period, there was impairment of tubular functions, concentration and excretion functions in the postbrain death period. In the immediate postbrain death period, there was a significant elevation in the glomerular filtration rate and time to maximum concentration values. In the histopathological evaluation of the kidney samples in the postbrain death period, there were definitive findings of tubular impairment. Dynamic renal scintigraphy also demonstrated definite impairment of tubular system and tubular functions in the deceased donor kidneys. This could explain the reason of the increased frequency of acute tubular necrosis seen among deceased donor kidneys.

Dynamic 18F-fluoride small animal PET to noninvasively assess renal function in rats

International Nuclear Information System (INIS)

Schnoeckel, Uta; Stegger, Lars; Schaefers, Klaus P.; Hermann, Sven; Schober, Otmar; Schaefers, Michael; Reuter, Stefan; Schlatter, Eberhard; Gabriels, Gert

2008-01-01

Renal function can be quantified by both laboratory and scintigraphic methods. In the case of small animal diagnostics, scintigraphic image-based methods are ideal since they can assess split renal function, work noninvasively, and can be repeated. The aim of this study is to validate a 18 F-PET-based method to quantify renal function in rats. Fluoride clearance was calculated from a dynamic whole body listmode acquisition of 60 min length in a small animal PET scanner following an i.v. injection of 15 MBq 18 F-fluoride. Volumes of interest (VOIs) were placed in the left ventricle and the bladder as well as traced around the kidney contours. The respective time-activity curves (TAC) were calculated. The renal 18 F-clearance was calculated by the ratio of the total renal excreted activity (bladder VOI) and the integral of the blood TAC. PET-derived renal function was validated by intraindividual measurements of creatinine clearance (n=23), urea clearance (n=23), and tubular excretion rate (TER-MAG3). The split renal function was derived from the injection of the clinically available radionuclide 99m Tc-mercaptotriglycine by blood sampling and planar renography (n=8). In all animals studied, PET revealed high-quality TACs. PET-derived renal fluoride clearance was linearly correlated with intraindividual laboratory measures (PET vs. creatinine: r=0.78; PET vs. urea: r=0.73; PET vs. TER-MAG3: r=0.73). Split function was comparable ( 18 F-PET vs. MAG3-renography: r=0.98). PET-derived measures were highly reproducible. 18 F-PET is able to noninvasively assess renal function in rats and provides a significant potential for serial studies in different experimental scenarios. (orig.)

Renal denervation decreases blood pressure and renal tyrosine hydroxylase but does not augment the effect of hypotensive drugs.

Science.gov (United States)

Skrzypecki, Janusz; Gawlak, Maciej; Huc, Tomasz; Szulczyk, Paweł; Ufnal, Marcin

2017-01-01

The effect of renal denervation on the efficacy of antihypertensive drugs has not yet been elucidated. Twenty-week-old spontaneously hypertensive rats were treated with metoprolol, losartan, indapamide, or saline (controls) and assigned to renal denervation or a sham procedure. Acute hemodynamic measurements were performed ten days later. Series showing a significant interaction between renal denervation and the drugs were repeated with chronic telemetry measurements. In the saline series, denervated rats showed a significantly lower mean arterial blood pressure (blood pressure) than the sham-operated rats. In contrast, in the metoprolol series denervated rats showed a significantly higher blood pressure than sham rats. There were no differences in blood pressure between denervated and sham rats in the losartan and indapamide series. In chronic studies, a 4-week treatment with metoprolol caused a decrease in blood pressure. Renal denervation and sham denervation performed 10 days after the onset of metoprolol treatment did not affect blood pressure. Denervated rats showed markedly reduced renal nerve tyrosine hydroxylase levels. In conclusion, renal denervation decreases blood pressure in hypertensive rats. The hypotensive action of metoprolol, indapamide, and losartan is not augmented by renal denervation, suggesting the absence of synergy between renal denervation and the drugs investigated in this study.

Influence of fluid resuscitation on renal microvascular PO2 in a normotensive rat model of endotoxemia

NARCIS (Netherlands)

Johannes, Tanja; Mik, Egbert G.; Nohé, Boris; Raat, Nicolaas J. H.; Unertl, Klaus E.; Ince, Can

2006-01-01

INTRODUCTION: Septic renal failure is often seen in the intensive care unit but its pathogenesis is only partly understood. This study, performed in a normotensive rat model of endotoxemia, tests the hypotheses that endotoxemia impairs renal microvascular PO2 (microPO2) and oxygen consumption

Cardiovascular-renal and metabolic characterization of a rat model of polycystic ovary syndrome.

Science.gov (United States)

Yanes, Licy L; Romero, Damian G; Moulana, Mohaddetheh; Lima, Roberta; Davis, Deborah D; Zhang, Huimin; Lockhart, Rachel; Racusen, Lorraine C; Reckelhoff, Jane F

2011-04-01

Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is also associated with increased risk of cardiovascular disease when PCOS first occurs and later in life. Hypertension, a common finding in women with PCOS, is a leading risk factor for cardiovascular disease. The mechanisms responsible for hypertension in women with PCOS have not been elucidated. This study characterized the cardiovascular-renal consequences of hyperandrogenemia in a female rat model. Female Sprague-Dawley rats (aged 4-6 weeks) were implanted with dihydrotestosterone or placebo pellets lasting 90 days. After 10 to 12 weeks, blood pressure (by radiotelemetry), renal function (glomerular filtration rate, morphology, protein, and albumin excretion), metabolic parameters (plasma insulin, glucose, leptin, cholesterol, and oral glucose tolerance test), inflammation (plasma tumor necrosis factor-α), oxidative stress (mRNA expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, p22(phox), p47(phox), gp91(phox), and NOX4), nitrate/nitrite excretion and mRNA expression of components of the renin-angiotensin system (angiotensinogen, angiotensin-I-converting enzyme [ACE], and AT1 receptor) were determined. Plasma dihydrotestosterone increased 3-fold in hyperandrogenemic female (HAF) rats, whereas plasma estradiol levels did not differ compared with control females. HAF rats exhibited estrus cycle dysfunction. They also had increased food intake and body weight, increased visceral fat, glomerular filtration rate, renal injury, insulin resistance and metabolic dysfunction, oxidative stress, and increased expression of angiotensinogen and ACE and reduced AT1 receptor expression. The HAF rat is a unique model that exhibits many of the characteristics of PCOS in women and is a useful model to study the mechanisms responsible for PCOS-mediated hypertension. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

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.

Urinary loss of glucose, phosphate, and protein by diffusion into proximal straight tubules injured by D-serine and maleic acid

International Nuclear Information System (INIS)

Carone, F.A.; Nakamura, S.; Goldman, B.

1985-01-01

In several models of acute renal failure leakage of glomerular filtrate out of the tubule is an important pathogenetic mechanism; however, bidirectional diffusion of solute to account for certain pathophysiologic features of acute renal failure has received meager attention. Using micropuncture and clearance methods, the authors assessed sequentially leakage of solutes and inulin across proximal straight tubules (PST) injured by two nephrotoxins. In d-serine-treated rats with extensive necrosis of PST, the basis for glucosuria and tubular leakage of inulin was studied. Glucose absorption by the proximal convoluted tubule and glucose delivery to the PST were normal, but glucose delivery to the distal tubule was increased nearly 8-fold, indicating diffusion of glucose from interstitial to tubular luminal fluid across the necrotic PST. Total kidney inulin clearance was greatly reduced, but single nephron glomerular filtration rate, based on proximal convoluted tubule samples, was normal, indicating tubular loss of inulin. Urinary recovery of [ 14 C]inulin infused into tubular lumina revealed that proximal convoluted tubule and distal tubule were impermeable to inulin and that inulin diffused out of the necrotic PST. The progressive return over 6 days of tubular impermeability for inulin correlated with relining of PST with new cells. In maleic acid-treated rats the site and extent of tubular necrosis and the nature of urinary loss of solutes were studied. Microdissection revealed that maleic acid caused limited necrosis of PST which averaged 7.4% of total proximal tubular length. Increased urinary excretion of protein, phosphate, and glucose and increased tubular permeability to microinfused [ 14 C]inulin occurred with the onset of PST necrosis, and return of these abnormalities to normal correlated with the degree of cellular repair of the PST

Expression profiles of genes involved in xenobiotic metabolism and disposition in human renal tissues and renal cell models

Energy Technology Data Exchange (ETDEWEB)

Van der Hauwaert, Cynthia; Savary, Grégoire [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Buob, David [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Leroy, Xavier; Aubert, Sébastien [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); Flamand, Vincent [Service d' Urologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Hennino, Marie-Flore [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Service de Néphrologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Perrais, Michaël [Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); and others

2014-09-15

Numerous xenobiotics have been shown to be harmful for the kidney. Thus, to improve our knowledge of the cellular processing of these nephrotoxic compounds, we evaluated, by real-time PCR, the mRNA expression level of 377 genes encoding xenobiotic-metabolizing enzymes (XMEs), transporters, as well as nuclear receptors and transcription factors that coordinate their expression in eight normal human renal cortical tissues. Additionally, since several renal in vitro models are commonly used in pharmacological and toxicological studies, we investigated their metabolic capacities and compared them with those of renal tissues. The same set of genes was thus investigated in HEK293 and HK2 immortalized cell lines in commercial primary cultures of epithelial renal cells and in proximal tubular cell primary cultures. Altogether, our data offers a comprehensive description of kidney ability to process xenobiotics. Moreover, by hierarchical clustering, we observed large variations in gene expression profiles between renal cell lines and renal tissues. Primary cultures of proximal tubular epithelial cells exhibited the highest similarities with renal tissue in terms of transcript profiling. Moreover, compared to other renal cell models, Tacrolimus dose dependent toxic effects were lower in proximal tubular cell primary cultures that display the highest metabolism and disposition capacity. Therefore, primary cultures appear to be the most relevant in vitro model for investigating the metabolism and bioactivation of nephrotoxic compounds and for toxicological and pharmacological studies. - Highlights: • Renal proximal tubular (PT) cells are highly sensitive to xenobiotics. • Expression of genes involved in xenobiotic disposition was measured. • PT cells exhibited the highest similarities with renal tissue.

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.

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.

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.

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...

Gender Difference in Renal Blood Flow Response to Angiotensin II Administration after Ischemia/Reperfusion in Rats: The Role of AT2 Receptor.

Science.gov (United States)

Maleki, Maryam; Nematbakhsh, Mehdi

2016-01-01

Background. Renal ischemia/reperfusion (I/R) is one of the major causes of kidney failure, and it may interact with renin angiotensin system while angiotensin II (Ang II) type 2 receptor (AT2R) expression is gender dependent. We examined the role of AT2R blockade on vascular response to Ang II after I/R in rats. Methods. Male and female rats were subjected to 30 min renal ischemia followed by reperfusion. Two groups of rats received either vehicle or AT2R antagonist, PD123319. Mean arterial pressure (MAP), and renal blood flow (RBF) responses were assessed during graded Ang II (100, 300, and 1000 ng/kg/min, i.v.) infusion at controlled renal perfusion pressure (RPP). Results. Vehicle or antagonist did not alter MAP, RPP, and RBF levels significantly; however, 30 min after reperfusion, RBF decreased insignificantly in female treated with PD123319 (P = 0.07). Ang II reduced RBF and increased renal vascular resistance (RVR) in a dose-related fashion (P dose renal I/R injury appears to be sexually dimorphic. PD123319 infusion promotes these hemodynamic responses in female more than in male rats.

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...

Uranium XAFS analysis of kidney from rats exposed to uranium.

Science.gov (United States)

Kitahara, Keisuke; Numako, Chiya; Terada, Yasuko; Nitta, Kiyohumi; Shimada, Yoshiya; Homma-Takeda, Shino

2017-03-01

The kidney is the critical target of uranium exposure because uranium accumulates in the proximal tubules and causes tubular damage, but the chemical nature of uranium in kidney, such as its chemical status in the toxic target site, is poorly understood. Micro-X-ray absorption fine-structure (µXAFS) analysis was used to examine renal thin sections of rats exposed to uranyl acetate. The U L III -edge X-ray absorption near-edge structure spectra of bulk renal specimens obtained at various toxicological phases were similar to that of uranyl acetate: their edge position did not shift compared with that of uranyl acetate (17.175 keV) although the peak widths for some kidney specimens were slightly narrowed. µXAFS measurements of spots of concentrated uranium in the micro-regions of the proximal tubules showed that the edge jump slightly shifted to lower energy. The results suggest that most uranium accumulated in kidney was uranium (VI) but a portion might have been biotransformed in rats exposed to uranyl acetate.

Arctigenin suppresses renal interstitial fibrosis in a rat model of obstructive nephropathy.

Science.gov (United States)

Li, Ao; Zhang, Xiaoxun; Shu, Mao; Wu, Mingjun; Wang, Jun; Zhang, Jingyao; Wang, Rui; Li, Peng; Wang, Yitao

2017-07-01

Renal tubulointerstitial fibrosis (TIF) is commonly the final result of a variety of progressive injuries and leads to end-stage renal disease. There are few therapeutic agents currently available for retarding the development of renal TIF. The aim of the present study is to evaluate the role of arctigenin (ATG), a lignan component derived from dried burdock (Arctium lappa L.) fruits, in protecting the kidney against injury by unilateral ureteral obstruction (UUO) in rats. Rats were subjected to UUO and then administered with vehicle, ATG (1 and 3mg/kg/d), or losartan (20mg/kg/d) for 11 consecutive days. The renoprotective effects of ATG were evaluated by histological examination and multiple biochemical assays. Our results suggest that ATG significantly protected the kidney from injury by reducing tubular dilatation, epithelial atrophy, collagen deposition, and tubulointerstitial compartment expansion. ATG administration dramatically decreased macrophage (CD68-positive cell) infiltration. Meanwhile, ATG down-regulated the mRNA levels of pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) and cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interferon-γ (IFN-γ), in the obstructed kidneys. This was associated with decreased activation of nuclear factor κB (NF-κB). ATG attenuated UUO-induced oxidative stress by increasing the activity of renal manganese superoxide dismutase (SOD2), leading to reduced levels of lipid peroxidation. Furthermore, ATG inhibited the epithelial-mesenchymal transition (EMT) of renal tubules by reducing the abundance of transforming growth factor-β1 (TGF-β1) and its type I receptor, suppressing Smad2/3 phosphorylation and nuclear translocation, and up-regulating Smad7 expression. Notably, the efficacy of ATG in renal protection was comparable or even superior to losartan. ATG could protect the kidney from UUO-induced injury and fibrogenesis by suppressing inflammation, oxidative

Role of Mas receptor in renal blood flow response to angiotensin-(1-7) in ovariectomized estradiol treated rats.

Science.gov (United States)

Saberi, Shadan; Dehghani, Aghdas; Nematbakhsh, Mehdi

2016-01-01

The angiotensin 1-7 (Ang 1-7), is abundantly produced in kidneys and antagonizes the function of angiotensin II through Mas receptor (MasR) or other unknown mechanisms. In the current study, the role of MasR and steroid hormone estrogen on renal blood flow response to Ang 1-7 administration was investigated in ovariectomized (OV) female rats. OV female Wistar-rats received estradiol (500 μg/kg/week) or vehicle for two weeks. In the day of the experiment, the animals were anesthetized, cannulated, and the responses including mean arterial pressure, renal blood flow (RBF), and renal vascular resistance at the constant level of renal perfusion pressure to graded infusion of Ang 1-7 at 0, 100 and 300 ng/kg/min were determined in OV and OV estradiol-treated (OVE) rats, treated with vehicle or MasR antagonist; A779. RBF response to Ang 1-7 infusion increased dose-dependently in vehicle (Pdose <0.001) and A779-treated (Pdose <0.01) animals. However, when MasR was blocked, the RBF response to Ang 1-7 significantly increased in OV animals compared with OVE rats (P<0.05). When estradiol was limited by ovariectomy, A779 increased RBF response to Ang 1-7 administration, while this response was attenuated in OVE animals.

Renovascular hypertension in spontaneous hypertensive rats: an experimental model of renal artery stenosis superimposed on essential hypertension.

Science.gov (United States)

Rosenthal, T; Bass, A; Grossman, E; Shani, M; Griffel, B; Adar, R

1987-09-01

Renovascular hypertension superimposed on essential hypertension, a condition encountered in the elderly, was studied. An experimental animal model consisting of a two-kidney one-clip Goldblatt preparation in the spontaneous hypertensive (SHR) rat, that would simulate this condition, was designed. A 0.25 mm silver clip was placed on the left renal artery of SHR male rats. The same procedure performed on WKY rats served as control. All experiments were performed on low, normal, and rich sodium diet. Systolic blood pressure (BP) was measured by tail-cuff method. Plasma renin concentration (PRC) was determined before and after clipping of the renal artery. Results were as follows: Mean systolic BP increased significantly in clipped rats fed with normal and rich sodium diets. SHR showed an increase from 144 +/- 3 (mean + s.e.m.) to 168 +/- 3 mmHg, and WKY rats showed an increase from 120 +/- 2 to 139 +/- 5 mmHg. There was a two- to threefold rise in PRC. A low-salt diet given prior to clipping prevented the appearance of renovascular hypertension despite a significant rise in PRC. We concluded that renal artery narrowing plays a significant role in the rise of BP in the basically essential type of hypertension.

Fluid resuscitation does not improve renal oxygenation during hemorrhagic shock in rats

OpenAIRE

Legrand, Matthieu; Mik, Egbert; Balestra, Gianmarco; Lutter, Rene; Pirracchio, Romain; Payen, Didier; Ince, Can

2010-01-01

textabstractBackground: The resuscitation strategy for hemorrhagic shock remains controversial, with the kidney being especially prone to hypoxia. Methods: The authors used a three-phase hemorrhagic shock model to investigate the effects of fluid resuscitation on renal oxygenation. After a 1-h shock phase, rats were randomized into four groups to receive either normal saline or hypertonic saline targeting a mean arterial pressure (MAP) of either 40 or 80 mmHg. After such resuscitation, rats w...

The effect of bacterial lipopolysaccharide on gastric emptying in rats suffering from moderate renal insufficiency

Directory of Open Access Journals (Sweden)

Rigatto S.Z.P.

1998-01-01

Full Text Available The objective of the present study was to evaluate the response of rats suffering from moderate renal insufficiency to bacterial lipopolysaccharide (LPS, or endotoxin. The study involved 48 eight-week-old male SPF Wistar rats (175-220 g divided into two groups of 24 animals each. One group underwent 5/6 nephrectomy while the other was sham-operated. Two weeks after surgery, the animals were further divided into two subgroups of 12 animals each and were fasted for 20 h but with access to water ad libitum. One nephrectomized and one sham-treated subgroup received E. coli LPS (25 µg/kg, iv while the other received a sterile, pyrogen-free saline solution. Gastric retention (GR was determined 10 min after the orogastric infusion of a standard saline test meal labeled with phenol red (6 mg/dl. The gastric emptying of the saline test meal was studied after 2 h. Renal function was evaluated by measuring the plasma levels of urea and creatinine. The levels of urea and creatinine in 5/6 nephrectomized animals were two-fold higher than those observed in the sham-operated rats. Although renal insufficiency did not change gastric emptying (median %GR = 26.6 for the nephrectomized subgroup and 29.3 for the sham subgroup, LPS significantly retarded the gastric emptying of the sham and nephretomized groups (median %GR = 42.0 and 61.0, respectively, and was significantly greater (P<0.01 in the nephrectomized rats. We conclude that gastric emptying in animals suffering from moderate renal insufficiency is more sensitive to the action of LPS than in sham animals

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

Energy Technology Data Exchange (ETDEWEB)

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.

Contrasting Nephropathic Responses to Oral Administration of Extract of Cultured Penicillium polonicum in Rat and Primate

Directory of Open Access Journals (Sweden)

John E. Fincham

2010-08-01

Full Text Available Liquid- or solid substrate-cultured Penicillium polonicum administered in feed to rats over several days evokes a histopathological response in kidney involving apoptosis and abnormal mitosis in proximal tubules. The amphoteric toxin is yet only partly characterized, but can be isolated from cultured sporulating biomass in a fraction that is soluble in water and ethanol, and exchangeable on either anion- or cation-exchange resins. After several weeks of treatment renal proximal tubule distortion became striking on account of karyocytomegaly, but even treatment for nearly two years remained asymptomatic. Extract from a batch of solid substrate fermentation of P. polonicum on shredded wheat was incorporated into feed for rats during four consecutive days, and also given as an aqueous solution by oral gavage to a vervet monkey daily for 10 days. Treatment was asymptomatic for both types of animal. Rat response was evident as the typical renal apoptosis and karyomegaly. In contrast there was no such response in the primate; and neither creatinine clearance nor any haematological characteristic or serum component concentration deviated from a control or from historical data for this primate. The contrast is discussed concerning other negative findings for P. polonicum in pigs and hamsters. Renal karyomegaly, as a common rat response to persistent exposure to ochratoxin A, is not known in humans suspected as being exposed to more than the usual trace amounts of dietary ochratoxin A. Therefore the present findings question assumptions that human response to ochratoxin A conforms to that in the rat.

The effects of valproic acid on renal corpuscle of pregnant rats and ...

African Journals Online (AJOL)

The effects of valproic acid on renal corpuscle of pregnant rats and protective role of folic acid and vitamin E. Ayfer Aktas, Yusuf Nergız, Yusuf Nergız, Murat Akkus, Murat Akkus, Yasemin Nasır, Yasemin Nasır ...

Effect of kefir and low-dose aspirin on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet.

Science.gov (United States)

Kanbak, Güngör; Uzuner, Kubilay; Kuşat Ol, Kevser; Oğlakçı, Ayşegül; Kartkaya, Kazım; Şentürk, Hakan

2014-01-01

Abstract We aim to study the effect of low-dose aspirin and kefir on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet. Forty adult male Sprague-Dawley rats were divided into five groups: control, high-salt (HS) (8.0% NaCl), HS+aspirin (10 mg/kg), HS+kefir (10.0%w/v), HS+aspirin +kefir. We measured sistolic blood pressure (SBP), mean arterial pressure (MAP), diastolic pressure, pulse pressure in the rats. Cathepsin B, L, DNA fragmentation and caspase-3 activities were determined from rat kidney tissues and rats clearance of creatinine calculated. Although HS diet increased significantly SBP, MAP, diastolic pressure, pulse pressure parameters compared the control values. They were not as high as accepted hypertension levels. When compared to HS groups, kefir groups significantly decrease Cathepsin B and DNA fragmentation levels. Caspase levels were elevated slightly in other groups according to control group. While, we also found that creatinine clearance was higher in HS+kefir and HS+low-dose aspirin than HS group. Thus, using low-dose aspirin had been approximately decreased of renal function damage. Kefir decreased renal function damage playing as Angiotensin-converting enzyme inhibitor. But, low-dose aspirin together with kefir worsened rat renal function damage. Cathepsin B might play role both apoptosis and prorenin-processing enzyme. But not caspase pathway may be involved in the present HS diet induced apoptosis. In conclusion, kefir and low-dose aspirin used independently protect renal function and renal damage induced by HS diet in rats.

Effect of thyroparathyroidectomy on urinary acidification in diabetic rats

Directory of Open Access Journals (Sweden)

Zaladek-Gil F.

1999-01-01

Full Text Available In previous studies we have shown stimulation of renal acid excretion in the proximal tubules of rats with diabetes of short duration, with no important alterations in glomerular hemodynamics; on the other hand, in thyroparathyroidectomized rats (TPTX model, a significant decrease in renal acid excretion, glomerular filtration rate (GFR and renal plasma flow (RPF was detected. Since important changes in the parathyroid hormone-vitamin D-Ca axis are observed in the diabetic state, the present study was undertaken to investigate the renal repercussions of thyroparathyroidectomy in rats previously made diabetic by streptozotocin (45 mg/kg. Four to 6 days after the induction of diabetes (DM, a group of rats were thyroparathyroidectomized (DM + TPTX. Renal functional parameters were evaluated by measuring the inulin and sodium para-aminohippurate clearance on the tenth day. The decrease in the GFR and RPF observed in TPTX was not reversed by diabetes since the same alterations were observed in DM + TPTX. Net acid (NA excretion was unchanged in DM (6.19 ± 0.54, decreased in TPTX (3.76 ± 0.25 and returned to normal levels in DM + TPTX (5.54 ± 0.72 when compared to the control group (6.34 ± 0.14 µmol min-1 kg-1. The results suggest that PTH plays an important vasodilator role regarding glomerular hemodynamics, since in its absence the impairment in GFR and RPF was not reversed by the diabetic state. However, with respect to acid excretion, the presence of diabetes was able to overcome the negative stimulus represented by TPTX.

Valsartan attenuates cardiac and renal hypertrophy in rats with experimental cardiorenal syndrome possibly through down-regulating galectin-3 signaling.

Science.gov (United States)

Zhang, M-J; Gu, Y; Wang, H; Zhu, P-F; Liu, X-Y; Wu, J

2016-01-01

Aortocaval fistula (AV) induced chronic volume overload in rats with preexisting mild renal dysfunction (right kidney remove: UNX) could mimic the type 4 cardiorenal syndrome (CRS): chronic renocardiac syndrome. Galectin-3, a β-galactoside binding lectin, is an emerging biomarker in cardiovascular as well as renal diseases. We observed the impact of valsartan on cardiac and renal hypertrophy and galectin-3 changes in this model. Adult male Sprague-Dawley (SD) rats (200-250 g) were divided into S (Sham, n = 7), M (UNX+AV, n = 7) and M+V (UNX+AV+valsartan, n = 7) groups. Eight weeks later, cardiac function was measured by echocardiography. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, renal blood flow and 24 hours albuminuria. Immunohistochemistry and real-time PCR were used to evaluate the expressions of galectin-3 in heart and renal. Cardiac hypertrophy and renal hypertrophy as well as cardiac enlargement were evidenced in this AV shunt induced chronic volume overload rat model with preexisting mild renal dysfunction. Cardiac and renal hypertrophy were significantly attenuated but cardiac enlargement was unaffected by valsartan independent of its blood pressure lowering effect. 24 hours urine albumin was significantly increased, which was significantly reduced by valsartan in this model. Immunohistochemistry and real-time PCR evidenced significantly up-regulated galectin-3 expression in heart and kidney and borderline increased myocardial collagen I expression, which tended to be lower post valsartan treatment. Up-regulated galectin-3 signaling might also be involved in the pathogenesis in this CRS model. The beneficial effects of valsartan in terms of attenuating cardiac and renal hypertrophy and reducing 24 hours albumin in this model might partly be mediated through down-regulating galectin-3 signal pathway.

Protective effects of regular aerobic exercise on renal tissue injury following creatine monohydrate supplementation in rats

Directory of Open Access Journals (Sweden)

Davoud Rahimi

2017-01-01

Full Text Available Creatine is one of the most common supplements for improvement of athletic performance which is used by athletes. The most important debate about creatine consumption is its adverse effect on kidneys due to increased protein load. This study was performed to evaluate the protective effects of aerobic exercise on renal tissue injury following consumption of creatine monohydrate in the rat. For this purpose, 30 male Wistar rats were randomly divided into 3 groups of 10 animals each. Group 1, as control, received only standard food. Group 2 received 5 g/kg b.w. creatine monohydrate supplement daily for 8 weeks through gavage and group 3 received creatine monohydrate supplementation in the same manner30 minutes before aerobic exercise. Aerobic exercise was performed 5 times per week on treadmill at speed of 10-25m/min for 10-30 minutes with the slope of 5 degrees. At the end of 8 weeks, water intake and urinary excretion of rats were measured and blood samples were collected for measurement of serum renal function biomarkers including urea, uric acid and creatinine. Finally, the rats were euthanized for renal histopathology. In group 3, by doing regular aerobic exercise, water intake and urinary excretion rates were significantly (p

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

Science.gov (United States)

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.

N-acetylcysteine protects rats with chronic renal failure from gadolinium-chelate nephrotoxicity.

Directory of Open Access Journals (Sweden)

Leonardo Victor Barbosa Pereira

Full Text Available The aim of this study was to evaluate the effect of Gd-chelate on renal function, iron parameters and oxidative stress in rats with CRF and a possible protective effect of the antioxidant N-Acetylcysteine (NAC. Male Wistar rats were submitted to 5/6 nephrectomy (Nx to induced CRF. An ionic-cyclic Gd (Gadoterate Meglumine was administrated (1.5 mM/KgBW, intravenously 21 days after Nx. Clearance studies were performed in 4 groups of anesthetized animals 48 hours following Gd- chelate administration: 1--Nx (n = 7; 2--Nx+NAC (n = 6; 3--Nx+Gd (n = 7; 4--Nx+NAC+Gd (4.8 g/L in drinking water, initiated 2 days before Gd-chelate administration and maintained during 4 days (n = 6. This group was compared with a control. We measured glomerular filtration rate, GFR (inulin clearance, ml/min/kg BW, proteinuria (mg/24 hs, serum iron (µg/dL; serum ferritin (ng/mL; transferrin saturation (%, TIBC (µg/dL and TBARS (nmles/ml. Normal rats treated with the same dose of Gd-chelate presented similar GFR and proteinuria when compared with normal controls, indicating that at this dose Gd-chelate is not nephrotoxic to normal rats. Gd-chelate administration to Nx-rats results in a decrease of GFR and increased proteinuria associated with a decrease in TIBC, elevation of ferritin serum levels, transferrin oversaturation and plasmatic TBARS compared with Nx-rats. The prophylactic treatment with NAC reversed the decrease in GFR and the increase in proteinuria and all alterations in iron parameters and TBARS induced by Gd-chelate. NAC administration to Nx rat did not modify the inulin clearance and iron kinetics, indicating that the ameliorating effect of NAC was specific to Gd-chelate. These results suggest that NAC can prevent Gd-chelate nephrotoxicity in patients with chronic renal failure.

Effect of magnesium deficiency on renal magnesium and calcium transport in the rat.

OpenAIRE

Carney, S L; Wong, N L; Quamme, G A; Dirks, J H

1980-01-01

Recollection of micropuncture experiments were performed on acutely thyroparathyroidectomized rats rendered magnesium deficient by dietary deprivation. Urinary magnesium excretion fell from a control of 15 to 3% of the filtered load after magnesium restriction. The loop of Henle, presumably the thick ascending limb, was the major modulator for renal magnesium homeostasis. The transport capacity for magnesium, however, was less in deficient rats than control animals. Absolute magnesium reabsor...

Spontaneous renal tumors suspected of being familial in sprague-dawley rats.

Science.gov (United States)

Kudo, Kayoko; Hoshiya, Toru; Nakazawa, Tomomi; Saito, Tsubasa; Shimoyama, Natsumi; Suzuki, Isamu; Tamura, Kazutoshi; Seely, John Curtis

2012-12-01

Spontaneous renal tubule tumors (RTTs), with a distinctive morphological phenotype, were present in three Sprague-Dawley rats, 1 male and 2 females, out a total of 120 animals of each sex from untreated and placebo control groups in a 2-year carcinogenicity study. One female had one carcinoma, adenoma and hyperplasia, and the other female had five adenomas and many hyperplastic lesions; the male case had one carcinoma. From these cases, a biological continuum of hyperplasia, adenoma and carcinoma could be recognized. The tumors were present in the renal cortex and appeared as solid lobulated growths with occasional central necrosis. The lobules were divided by a small amount of fibrovascular tissue. Occasionally the larger tumors contained a cystic area. Tumor cells appeared distinctive and exhibited variable amounts of eosinophilic/amphophilic and vacuolated cytoplasm. Nuclei were round to oval with a prominent nucleolus. Mitotic figures were uncommon, and no distant metastasis was noted. The tumors were seen as multiple and bilateral lesions in two animals and had no apparent relationship to chronic progressive nephropathy (CPN). Foci of tubule hyperplasia were also noted to contain the same type of cellular morphology. The morphological and biological features of these 3 cases resembled the amphophilic-vacuolar (AV) variant of RTT that has been posited to be of familial origin. This is a report of spontaneous familial renal tumors in Sprague-Dawley rats from Japan.

Gender difference and sex hormone production in rodent renal ischemia reperfusion injury and repair

Directory of Open Access Journals (Sweden)

Ghazali Daniel

2011-06-01

Full Text Available Abstract Background Several lines of evidence suggest a protective effect of female sex hormones in several organs subjected to ischemia-reperfusion injury. The aim of the study was to investigate sex hormone production in male rats after a renal ischemia-reperfusion sequence and analyze the influence of gender differences on tissue remodelling during the recovery process. Method Age-matched sexually mature male and female rats were subjected to 60 min of renal unilateral ischemia by pedicle clamping with contralateral nephrectomy and followed for 1 or 5 days after reperfusion. Plasma creatinine, systemic testosterone, progesterone and estradiol levels were determined. Tubular injury, cell proliferation and inflammation, were evaluated as well as proliferating cell nuclear antigen, vimentin and translocator protein (TSPO expressions by immunohistochemistry. Results After 1 and 5 days of reperfusion, plasma creatinine was significantly higher in males than in females, supporting the high mortality in this group. After reperfusion, plasma testosterone levels decreased whereas estradiol significantly increased in male rats. Alterations of renal function, associated with tubular injury and inflammation persisted during the 5 days post-ischemia-reperfusion, and a significant improvement was observed in females at 5 days of reperfusion. Proliferating cell nuclear antigen and vimentin expression were upregulated in kidneys from males and attenuated in females, in parallel to injury development. TSPO expression was transiently increased in proximal tubules in male rats. Conclusions After ischemia, renal function recovery and tissue injury is gender-dependent. These differences are associated with a modulation of sex hormone production and a modification of tissue remodeling and proliferative cell processes.

Anatomic Patterns of Renal Arterial Sympathetic Innervation: New Aspects for Renal Denervation.

Science.gov (United States)

Imnadze, Guram; Balzer, Stefan; Meyer, Baerbel; Neumann, Joerg; Krech, Rainer Horst; Thale, Joachim; Franz, Norbert; Warnecke, Henning; Awad, Khaled; Hayek, Salim S; Devireddy, Chandan

2016-12-01

Initial studies of catheter-based renal arterial sympathetic denervation to lower blood pressure in resistant hypertensive patients renewed interest in the sympathetic nervous system's role in the pathogenesis of hypertension. However, the SYMPLICITY HTN-3 study failed to meet its prespecified blood pressure lowering efficacy endpoint. To date, only a limited number of studies have described the microanatomy of renal nerves, of which, only two involve humans. Renal arteries were harvested from 15 cadavers from the Klinikum Osnabruck and Schuchtermann Klinik, Bad Rothenfelde. Each artery was divided longitudinally in equal thirds (proximal, middle, and distal), with each section then divided into equal superior, inferior, anterior, and posterior quadrants, which were then stained. Segments containing no renal nerves were given a score value = 0, 1-2 nerves with diameter 4 nerves or nerve diameter ≥600 µm a score = 3. A total of 22 renal arteries (9 right-sided, 13 left-sided) were suitable for examination. Overall, 691 sections of 5 mm thickness were prepared. Right renal arteries had significantly higher mean innervation grade (1.56 ± 0.85) compared to left renal arteries (1.09 ± 0.87) (P renal artery has significantly higher innervation scores than the left. The anterior and superior quadrants of the renal arteries scored higher in innervation than the posterior and inferior quadrants did. The distal third of the renal arteries are more innervated than the more proximal segments. These findings warrant further evaluation of the spatial innervation patterns of the renal artery in order to understand how it may enhance catheter-based renal arterial denervation procedural strategy and outcomes. The SYMPLICITY HTN-3 study dealt a blow to the idea of the catheter-based renal arterial sympathetic denervation. We investigated the location and patterns of periarterial renal nerves in cadaveric human renal arteries. To quantify the density of the

Urinary aminopeptidase activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats.

Directory of Open Access Journals (Sweden)

Andrés Quesada

Full Text Available This study analyzes the fluorimetric determination of alanyl- (Ala, glutamyl- (Glu, leucyl-cystinyl- (Cys and aspartyl-aminopeptidase (AspAp urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG, albumin, and neutrophil gelatinase-associated lipocalin (NGAL. Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p0.259 with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.

Fetal development and renal function in adult rats prenatally subjected to sodium overload.

Science.gov (United States)

Cardoso, Henriqueta D; Cabral, Edjair V; Vieira-Filho, Leucio D; Vieyra, Adalberto; Paixão, Ana D O

2009-10-01

The aims of this study were (1) to evaluate two factors that affect fetal development--placental oxidative stress (Ox) and plasma volume (PV)--in dams with sodium overload and (2) to correlate possible alterations in these factors with subsequent modifications in the renal function of adult offspring. Wistar dams were maintained on 0.17 M NaCl instead of water from 20 days before mating until either the twentieth pregnancy day/parturition or weaning. Colorimetric methods were used to measure Ox in maternal and offspring tissues, PV, 24-h urinary protein (U(Prot24 h)) and serum triacylglycerols (TG) and cholesterol (Chol). Renal hemodynamics was evaluated in the offspring at 90 days of age using a blood pressure transducer, a flow probe and inulin clearance to measure mean arterial pressure (MAP), renal blood flow and glomerular filtration rate (GFR), respectively. The number of nephrons (NN) was counted in kidney suspensions. Dams showed unchanged PV, placental Ox and fetal weight but increased U(Prot24 h) (150%, P sodium-overloaded pups showed increased U(Prot24 h) (45%, P sodium-overloaded rats showed increased U(Prot24 h) (27%, P sodium-overloaded group. We conclude that salt overload from the prenatal stage until weaning leads to alterations in lipid metabolism and in the renal function of the pups, which are additional to those alterations seen in rats only overloaded prenatally.

Analysis of accumulation of 99mTc-octreotide and 99mTc-EDDA/HYNIC-Tyr3-octreotide in the rat kidneys.

Science.gov (United States)

Kopecky, Martin; Semecky, Vladimir; Trejtnar, Frantisek; Laznicek, Milan; Laznickova, Alice; Nachtigal, Petr; Decristoforo, Clemens; Mather, Stephen J; Mäcke, Helmut R

2004-02-01

The aim of this study was to compare renal handling and distribution of (99m)Tc-octreotide and (99m)Tc-EDDA/HYNIC-Tyr(3)-octreotide (HYNIC-TOC) in rats. In kidney perfusion experiments, the renal clearance value of (99m)Tc-octreotide was three times lower than that of (99m)Tc-EDDA/HYNIC-TOC. The predominant renal excretion of (99m)Tc-EDDA/HYNIC-TOC was associated with a high and long-term renal accumulation up to 48 hrs. Microautoradiographic results indicated that (99m)Tc-EDDA/HYNIC-TOC was retained mainly in the renal medulla within the cells of the collecting ducts and in the surrounding tissue. Lower positivity was found in the proximal and distal tubular cells. We conclude that the mechanism of renal accumulation of somatostatin analogues renal accumulation is complex and that proximal tubular reabsorption is probably not the main mechanism for uptake of (99m)Tc-EDDA/HYNIC-TOC in the kidneys. The presence of the somatostatin receptors, differences in the tonicity level within kidneys and other possible mechanisms could participate in their renal accumulation.

Analysis of accumulation of 99mTc-octreotide and 99mTc-EDDA/HYNIC-Tyr3-octreotide in the rat kidneys

International Nuclear Information System (INIS)

Kopecky, Martin; Semecky, Vladimir; Trejtnar, Frantisek; Laznicek, Milan; Laznickova, Alice; Nachtigal, Petr; Decristoforo, Clemens; Mather, Stephen J.; Maecke, Helmut R.

2004-01-01

The aim of this study was to compare renal handling and distribution of 99m Tc-octreotide and 99m Tc-EDDA/HYNIC-Tyr 3 -octreotide (HYNIC-TOC) in rats. In kidney perfusion experiments, the renal clearance value of 99m Tc-octreotide was three times lower than that of 99m Tc-EDDA/HYNIC-TOC. The predominant renal excretion of 99m Tc-EDDA/HYNIC-TOC was associated with a high and long-term renal accumulation up to 48 hrs. Microautoradiographic results indicated that 99m Tc-EDDA/HYNIC-TOC was retained mainly in the renal medulla within the cells of the collecting ducts and in the surrounding tissue. Lower positivity was found in the proximal and distal tubular cells. We conclude that the mechanism of renal accumulation of somatostatin analogues renal accumulation is complex and that proximal tubular reabsorption is probably not the main mechanism for uptake of 99m Tc-EDDA/HYNIC-TOC in the kidneys. The presence of the somatostatin receptors, differences in the tonicity level within kidneys and other possible mechanisms could participate in their renal accumulation

Quantitative arterial spin labelling perfusion measurements in rat models of renal transplantation and acute kidney injury at 3 T

Energy Technology Data Exchange (ETDEWEB)

Zimmer, Fabian; Schad, Lothar R.; Zoellner, Frank G. [Heidelberg Univ., Mannheim (Germany). Computer Assisted Clinical Medicine; Klotz, Sarah; Hoeger, Simone; Yard, Benito A.; Kraemer, Bernhard K. [Heidelberg Univ., Mannheim (Germany). Dept. of Medicine V

2017-05-01

To employ ASL for the measurement of renal cortical perfusion in particular renal disorders typically associated with graft loss and to investigate its potential to detect and differentiate the related functional deterioration i.e., in a setting of acute kidney injury (AKI) as well as in renal grafts showing acute and chronic transplant rejection. 14 Lewis rats with unilateral ischaemic AKI and 43 Lewis rats with renal grafts showing acute or chronic rejections were used. All ASL measurements in this study were performed on a 3 T MR scanner using a FAIR True-FISP approach to assess renal blood flow (RBF). Perfusion maps were calculated and the cortical blood flow was determined using a region-of-interest based analysis. RBF of healthy and AKI kidneys as well as of both rejection models, were compared. In a subsample of 20 rats, creatinine clearance was measured and correlated with cortical perfusion. RBF differs significantly between healthy and AKI kidneys (P < 0.001) with a mean difference of 213 ± 80 ml/100 g/min. Renal grafts with chronic rejections show a significantly higher (P < 0.001) mean cortical perfusion (346 ± 112 ml/100 g/min) than grafts with acute rejection (240 ± 66 ml/100 g/min). Both transplantation models have a significantly (P < 0.001) lower perfusion than healthy kidneys. Renal creatinine clearance is significantly correlated (R = 0.85, P < 0.001) with cortical blood flow. Perfusion measurements with ASL have the potential to become a valuable diagnostic tool, regarding the detection of renal impairment and the differentiation of disorders that lead to a loss of renal function and that are typically associated with graft loss.

Quantitative arterial spin labelling perfusion measurements in rat models of renal transplantation and acute kidney injury at 3 T

International Nuclear Information System (INIS)

Zimmer, Fabian; Schad, Lothar R.; Zoellner, Frank G.; Klotz, Sarah; Hoeger, Simone; Yard, Benito A.; Kraemer, Bernhard K.

2017-01-01

To employ ASL for the measurement of renal cortical perfusion in particular renal disorders typically associated with graft loss and to investigate its potential to detect and differentiate the related functional deterioration i.e., in a setting of acute kidney injury (AKI) as well as in renal grafts showing acute and chronic transplant rejection. 14 Lewis rats with unilateral ischaemic AKI and 43 Lewis rats with renal grafts showing acute or chronic rejections were used. All ASL measurements in this study were performed on a 3 T MR scanner using a FAIR True-FISP approach to assess renal blood flow (RBF). Perfusion maps were calculated and the cortical blood flow was determined using a region-of-interest based analysis. RBF of healthy and AKI kidneys as well as of both rejection models, were compared. In a subsample of 20 rats, creatinine clearance was measured and correlated with cortical perfusion. RBF differs significantly between healthy and AKI kidneys (P < 0.001) with a mean difference of 213 ± 80 ml/100 g/min. Renal grafts with chronic rejections show a significantly higher (P < 0.001) mean cortical perfusion (346 ± 112 ml/100 g/min) than grafts with acute rejection (240 ± 66 ml/100 g/min). Both transplantation models have a significantly (P < 0.001) lower perfusion than healthy kidneys. Renal creatinine clearance is significantly correlated (R = 0.85, P < 0.001) with cortical blood flow. Perfusion measurements with ASL have the potential to become a valuable diagnostic tool, regarding the detection of renal impairment and the differentiation of disorders that lead to a loss of renal function and that are typically associated with graft loss.

Dynamic {sup 18}F-fluoride small animal PET to noninvasively assess renal function in rats

Energy Technology Data Exchange (ETDEWEB)

Schnoeckel, Uta; Stegger, Lars; Schaefers, Klaus P.; Hermann, Sven; Schober, Otmar; Schaefers, Michael [Klinik und Poliklinik fuer Nuklearmedizin, Muenster (Germany); Reuter, Stefan; Schlatter, Eberhard; Gabriels, Gert [Universitaetsklinikum Muenster, Medizinische Klinik und Poliklinik D, Experimentelle Nephrologie, Muenster (Germany)

2008-12-15

Renal function can be quantified by both laboratory and scintigraphic methods. In the case of small animal diagnostics, scintigraphic image-based methods are ideal since they can assess split renal function, work noninvasively, and can be repeated. The aim of this study is to validate a {sup 18}F-PET-based method to quantify renal function in rats. Fluoride clearance was calculated from a dynamic whole body listmode acquisition of 60 min length in a small animal PET scanner following an i.v. injection of 15 MBq {sup 18}F-fluoride. Volumes of interest (VOIs) were placed in the left ventricle and the bladder as well as traced around the kidney contours. The respective time-activity curves (TAC) were calculated. The renal {sup 18}F-clearance was calculated by the ratio of the total renal excreted activity (bladder VOI) and the integral of the blood TAC. PET-derived renal function was validated by intraindividual measurements of creatinine clearance (n=23), urea clearance (n=23), and tubular excretion rate (TER-MAG3). The split renal function was derived from the injection of the clinically available radionuclide {sup 99m}Tc-mercaptotriglycine by blood sampling and planar renography (n=8). In all animals studied, PET revealed high-quality TACs. PET-derived renal fluoride clearance was linearly correlated with intraindividual laboratory measures (PET vs. creatinine: r=0.78; PET vs. urea: r=0.73; PET vs. TER-MAG3: r=0.73). Split function was comparable ({sup 18}F-PET vs. MAG3-renography: r=0.98). PET-derived measures were highly reproducible. {sup 18}F-PET is able to noninvasively assess renal function in rats and provides a significant potential for serial studies in different experimental scenarios. (orig.)

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.

Renal origin of rat urinary epidermal growth factor

DEFF Research Database (Denmark)

Nexø, Ebba; Poulsen, Steen Seier

1984-01-01

The origin of rat urinary epidermal growth factor (EGF) has been investigated. Unilateral nephrectomy decreased the concentration, total output of EGF and EGF/creatinine ratio by approximately 50%, while the output of creatinine was unchanged. Removal of the submandibular glands and duodenal...... Brunner's glands, organs known to produce EGF, had no influence on the output of EGF in urine. Renal clearance of EGF exceeded that of creatinine, and after bilateral nephrectomy or bilateral ligation of the ureters, the concentration of creatinine in serum increased, while the concentration of EGF...

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

Accelerated recovery of renal mitochondrial and tubule homeostasis with SIRT1/PGC-1α activation following ischemia–reperfusion injury

Energy Technology Data Exchange (ETDEWEB)

Funk, Jason A., E-mail: funkj@musc.edu [Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Schnellmann, Rick G., E-mail: schnell@musc.edu [Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Ralph H. Johnson VA Medical Center, Charleston, SC 29401 (United States)

2013-12-01

Kidney ischemia–reperfusion (I/R) injury elicits cellular injury in the proximal tubule, and mitochondrial dysfunction is a pathological consequence of I/R. Promoting mitochondrial biogenesis (MB) as a repair mechanism after injury may offer a unique strategy to restore both mitochondrial and organ function. Rats subjected to bilateral renal pedicle ligation for 22 min were treated once daily with the SIRT1 activator SRT1720 (5 mg/kg) starting 24 h after reperfusion until 72 h–144 h. SIRT1 expression was elevated in the renal cortex of rats after I/R + vehicle treatment (IRV), but was associated with less nuclear localization. SIRT1 expression was even further augmented and nuclear localization was restored in the kidneys of rats after I/R + SRT1720 treatment (IRS). PGC-1α was elevated at 72 h–144 h in IRV and IRS kidneys; however, SRT1720 treatment induced deacetylation of PGC-1α, a marker of activation. Mitochondrial proteins ATP synthase β, COX I, and NDUFB8, as well as mitochondrial respiration, were diminished 24 h–144 h in IRV rats, but were partially or fully restored in IRS rats. Urinary kidney injury molecule-1 (KIM-1) was persistently elevated in both IRV and IRS rats; however, KIM-1 tissue expression was attenuated in IRS rats. Additionally, sustained loss of Na{sup +},K{sup +}–ATPase expression and basolateral localization and elevated vimentin in IRV rats was normalized in IRS rats, suggesting restoration of a differentiated, polarized tubule epithelium. The results suggest that SRT1720 treatment expedited recovery of mitochondrial protein expression and function by enhancing MB, which was associated with faster proximal tubule repair. Targeting MB may offer unique therapeutic strategy following ischemic injury. - Highlights: • We examined recovery of mitochondrial and renal function after ischemia–reperfusion. • SRT1720 treatment after I/R induced mitochondrial biogenesis via SIRT1/PGC-1α. • Recovery of mitochondrial function was

Efficacy of lycopene on modulation of renal antioxidant enzymes, ACE and ACE gene expression in hyperlipidaemic rats.

Science.gov (United States)

Khan, Nazish Iqbal; Noori, Shafaq; Mahboob, Tabassum

2016-07-01

We aimed to evaluate the efficacy of lycopene on renal tissue antioxidant enzymes and angiotensin converting enzyme (ACE) gene expression and serum activity in diet-induced hyperlipidaemia. Thirty-two female Wistar albino rats (200-250 g weight), 5-6 months of age, were randomly selected and divided into four groups. Group I received normal diet; group II received 24 g high fat diet/100 g of daily diet; group III received 24 g high fat diet/100 g daily diet and 200 ml of lycopene extract (twice a week) for 8 weeks; and group IV received 200 ml oral lycopene extract twice a week for 8 weeks. A marked increase was observed in plasma urea and creatinine levels, serum C-reactive protein, kidney weight, tissue renal malonyldialdehyde level, ACE gene expression and serum level, while a decrease catalase level among hyperlipidaemic rats was observed. Histologically, interstitial inflammation and proliferation was seen. Lycopene supplementation significantly decreased plasma urea and creatinine, serum ACE, renal tissue malonyldialdehyde level and C-reactive protein level, while it increased tissue antioxidant enzymes level and total protein. Tissue inflammation and proliferation was improved. This finding suggests that supplementation of lycopene is effective for renal antioxidant enzymes, ACE gene expression and ACE serum level in hyperlipidaemic rats. © The Author(s) 2016.

The effect of exposure of rats during prenatal period to radiation spreading from mobile phones on renal development.

Science.gov (United States)

Bedir, Recep; Tumkaya, Levent; Şehitoğlu, İbrahim; Kalkan, Yıldıray; Yilmaz, Adnan; Şahin, Osman Zikrullah

2015-03-01

The aim of this study was to investigate the effects of exposure to a 900-MHz electromagnetic field (EMF) produced by mobile phones on the renal development of prenatal rats. Histopathological changes and apoptosis in the kidneys, together with levels of urea, creatinine and electrolyte in serum were determined. A total of 14 Sprague-Dawley rats were studied. Pregnant rats were divided into two equal groups: a control group and an EMF-exposed group. The study group was exposed to 900-MHz of EMF during the first 20 days of pregnancy, while the control group was unexposed to EMF. Sections obtained from paraffin blocks were stained for caspase-3 by immunohistochemistry, hematoxylin-eosin and Masson's trichrome. Mild congestion and tubular defects, and dilatation of Bowman's capsule were observed in the kidney tissues of rats in the exposed group. Apoptosis was evaluated using anti-caspase-3; stronger positive staining was observed in the renal tubular cells in the study group than those of the control group. Although there was a significant difference between the study and control groups in terms of K+ level (p0.05). Our study shows that the electromagnetic waves propagated from mobile phones have harmful effects on the renal development of prenatal rats.

Role of Mas receptor in renal blood flow response to angiotensin (1-7) in male and female rats.

Science.gov (United States)

Nematbakhsh, Mehdi; Safari, Tahereh

2014-01-01

Epidemiologic and clinical studies have shown that progression of renal disease in male is faster than that in female. However, the exact mechanisms are not well recognized. Angiotensin (1-7) (Ang 1-7) receptor, called "Mas", is an element in the depressor arm of renin angiotensin system (RAS), and its expression is enhanced in females. We test the hypothesis that Mas receptor (MasR) blockade (A779) attenuates renal blood flow (RBF) in response to infusion of graded doses of Ang 1-7 in female rats. Male and female Wistar rats were anesthetized and catheterized. Then, the mean arterial pressure (MAP), RBF, and controlled renal perfusion pressure (RPP) responses to infusion of graded doses of Ang 1-7 (100-1000 ng/kg/min i.v.) with and without A779 were measured in the animals. Basal MAP, RPP, RBF, and renal vascular resistance (RVR) were not significantly different between the two groups. After Ang 1-7 administration, RPP was controlled at a constant level. However, RBF increased in a dose-related manner in response to Ang 1-7 infusion in both male and female rats (Pdoserenal diseases.

Effects of aqueous extract of Hibiscus sabdariffa on renal Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in Wistar rats.

Science.gov (United States)

Olatunji, Lawrence A; Usman, Taofeek O; Adebayo, Joseph O; Olatunji, Victoria A

2012-09-01

To investigate the effects of oral administration of aqueous extract of Hibiscus sabdariffa on renal Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in rats. The 25 and 50 mg/(kg·d) of aqueous extracts of H. sabdariffa were respectively given to rats in the experimental groups for 28 d, and rats in the control group received an appropriate volume of distilled water as vehicle. Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in the kidney were assayed by spectrophotometric method. Administrations of 25 and 50 mg/(kg·d) of aqueous extract of H. sabdariffa significantly decreased the Ca(2+)-Mg(2+)-ATPase activity in the kidney of rats (Psabdariffa may preserve the renal function despite a decreased renal Ca(2+)-Mg(2+)-ATPase activity.

Cordyceps sinensis attenuates renal fibrosis and suppresses BAG3 induction in obstructed rat kidney.

Science.gov (United States)

Du, Feng; Li, Si; Wang, Tian; Zhang, Hai-Yan; Zong, Zhi-Hong; Du, Zhen-Xian; Li, De-Tian; Wang, Hua-Qin; Liu, Bo; Miao, Jia-Ning; Bian, Xiao-Hui

2015-01-01

BAG3 regulates a number of cellular processes, including cell proliferation, apoptosis, adhesion and migration, and epithelial-mesenchymal transition (EMT). However, the role of BAG3 in renal tubular EMT and renal interstitial fibrosis remains elusive. This study aimed to examine the dynamic expression of BAG3 during renal fibrosis, and to investigate the efficacy of Cordyceps sinensis (C. sinensis) on renal fibrosis. A rat model of unilateral ureteral obstruction (UUO) was established, and the expression of BAG3 and α-SMA, and the efficacy of C. sinensis on renal fibrosis induced by UUO were examined. The results showed that UUO led to collagen accumulation, which was significantly suppressed by C. sinensis. UUO increased the expression of BAG3 and α-SMA, a mesenchymal marker, while UUO induced BAG3 and α-SMA expression was significantly inhibited by C. sinensis. In addition, immunohistochemical staining demonstrated that BAG3 immunoreactivity was restricted to tubular epithelium. In conclusion, BAG3 is a potential target for the prevention and/or treatment of renal fibrosis, and C. Sinensis is a promising agent for renal fibrosis.

Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane.

Science.gov (United States)

Chichger, Havovi; Cleasby, Mark E; Srai, Surjit K; Unwin, Robert J; Debnam, Edward S; Marks, Joanne

2016-06-01

What is the central question of this study? Although SGLT2 inhibitors represent a promising treatment for patients suffering from diabetic nephropathy, the influence of metabolic disruption on the expression and function of glucose transporters is largely unknown. What is the main finding and its importance? In vivo models of metabolic disruption (Goto-Kakizaki type II diabetic rat and junk-food diet) demonstrate increased expression of SGLT1, SGLT2 and GLUT2 in the proximal tubule brush border. In the type II diabetic model, this is accompanied by increased SGLT- and GLUT-mediated glucose uptake. A fasted model of metabolic disruption (high-fat diet) demonstrated increased GLUT2 expression only. The differential alterations of glucose transporters in response to varying metabolic stress offer insight into the therapeutic value of inhibitors. SGLT2 inhibitors are now in clinical use to reduce hyperglycaemia in type II diabetes. However, renal glucose reabsorption across the brush border membrane (BBM) is not completely understood in diabetes. Increased consumption of a Western diet is strongly linked to type II diabetes. This study aimed to investigate the adaptations that occur in renal glucose transporters in response to experimental models of diet-induced insulin resistance. The study used Goto-Kakizaki type II diabetic rats and normal rats rendered insulin resistant using junk-food or high-fat diets. Levels of protein kinase C-βI (PKC-βI), GLUT2, SGLT1 and SGLT2 were determined by Western blotting of purified renal BBM. GLUT- and SGLT-mediated d-[(3) H]glucose uptake by BBM vesicles was measured in the presence and absence of the SGLT inhibitor phlorizin. GLUT- and SGLT-mediated glucose transport was elevated in type II diabetic rats, accompanied by increased expression of GLUT2, its upstream regulator PKC-βI and SGLT1 protein. Junk-food and high-fat diet feeding also caused higher membrane expression of GLUT2 and its upstream regulator PKC

Interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway in renal carcinogenesis of uninephrectomized rats.

Science.gov (United States)

Yang, Ke-Ke; Sui, Yi; Zhou, Hui-Rong; Zhao, Hai-Lu

2017-05-01

Renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway both play important roles in carcinogenesis, but the interplay of renin-angiotensin system and adenosine monophosphate-activated protein kinase in carcinogenesis is not clear. In this study, we researched the interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase in renal carcinogenesis of uninephrectomized rats. A total of 96 rats were stratified into four groups: sham, uninephrectomized, and uninephrectomized treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Renal adenosine monophosphate-activated protein kinase and its downstream molecule acetyl coenzyme A carboxylase were detected by immunohistochemistry and western blot at 10 months after uninephrectomy. Meanwhile, we examined renal carcinogenesis by histological transformation and expressions of Ki67 and mutant p53. During the study, fasting lipid profiles were detected dynamically at 3, 6, 8, and 10 months. The results indicated that adenosine monophosphate-activated protein kinase expression in uninephrectomized rats showed 36.8% reduction by immunohistochemistry and 89.73% reduction by western blot. Inversely, acetyl coenzyme A carboxylase expression increased 83.3% and 19.07% in parallel to hyperlipidemia at 6, 8, and 10 months. The histopathology of carcinogenesis in remnant kidneys was manifested by atypical proliferation and carcinoma in situ, as well as increased expressions of Ki67 and mutant p53. Intervention with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker significantly prevented the inhibition of adenosine monophosphate-activated protein kinase signaling pathway and renal carcinogenesis in uninephrectomized rats. In conclusion, the novel findings suggest that uninephrectomy-induced disturbance in adenosine monophosphate-activated protein kinase signaling pathway resulted in hyperlipidemia and

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.

Renal toxicological evaluations of sulphonated nanocellulose from Khaya sengalensis seed in Wistar rats.

Science.gov (United States)

Adewuyi, Adewale; Otuechere, Chiagoziem A; Adebayo, Olusegun L; Anazodo, Chibuzo; Pereira, Fabiano V

2018-03-25

Nanocellulose is currently gaining attention due to its unique properties. This attention includes its application as building blocks for developing novel functional materials, plant drug and also in drug delivery systems. However, its safety remains largely untested or less understood. Thus, sulphonated nanocellulose (KSS) was prepared from cellulose (KSC) isolated from Khaya senegalensis seed (KS). KS, KSC and KSS were characterized using Fourier transformed infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TG), particle size distribution (PSD), zeta potential and scanning electron microscopy (SEM). The impact of KSS on selected renal markers of oxidative stress, inflammation and apoptosis in Wistar rats was also investigated. Thus, male rats were randomly assigned to four groups of five animals each and were treated with KSS (0, 50, 75 and 100 mg/kg BW) for 14 days. Thereafter, biomarkers of renal oxidative damage, inflammation and immunohistochemical expressions of iNOS, COX-2, Bcl-2 and p53 were evaluated. The results revealed KSS to have crystallinity of 70.40%, it was monomodal and has a flaky surface with agglomerations. KSS had no effect on markers of kidney function and oxidative damage, although there was a generalized hypernatremia after 14 days of exposure. Lastly, KSS enhanced the antioxidant status and immunohistochemical expressions of iNOS and COX-2 in the kidney of the rats. While the biomedical applications of KSS may appear plausible, our data suggests that it could induce renal toxicity via the combined impacts of electrolyte imbalance and inflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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.

Characterization of Organic Anion Transporter 2 (SLC22A7): A Highly Efficient Transporter for Creatinine and Species-Dependent Renal Tubular Expression.

Science.gov (United States)

Shen, Hong; Liu, Tongtong; Morse, Bridget L; Zhao, Yue; Zhang, Yueping; Qiu, Xi; Chen, Cliff; Lewin, Anne C; Wang, Xi-Tao; Liu, Guowen; Christopher, Lisa J; Marathe, Punit; Lai, Yurong

2015-07-01

The contribution of organic anion transporter OAT2 (SLC22A7) to the renal tubular secretion of creatinine and its exact localization in the kidney are reportedly controversial. In the present investigation, the transport of creatinine was assessed in human embryonic kidney (HEK) cells that stably expressed human OAT2 (OAT2-HEK) and isolated human renal proximal tubule cells (HRPTCs). The tubular localization of OAT2 in human, monkey, and rat kidney was characterized. The overexpression of OAT2 significantly enhanced the uptake of creatinine in OAT2-HEK cells. Under physiologic conditions (creatinine concentrations of 41.2 and 123.5 µM), the initial rate of OAT2-mediated creatinine transport was approximately 11-, 80-, and 80-fold higher than OCT2, multidrug and toxin extrusion protein (MATE)1, and MATE2K, respectively, resulting in approximately 37-, 1850-, and 80-fold increase of the intrinsic transport clearance when normalized to the transporter protein concentrations. Creatinine intracellular uptake and transcellular transport in HRPTCs were decreased in the presence of 50 µM bromosulfophthalein and 100 µM indomethacin, which inhibited OAT2 more potently than other known creatinine transporters, OCT2 and multidrug and toxin extrusion proteins MATE1 and MATE2K (IC50: 1.3 µM vs. > 100 µM and 2.1 µM vs. > 200 µM for bromosulfophthalein and indomethacin, respectively) Immunohistochemistry analysis showed that OAT2 protein was localized to both basolateral and apical membranes of human and cynomolgus monkey renal proximal tubules, but appeared only on the apical membrane of rat proximal tubules. Collectively, the findings revealed the important role of OAT2 in renal secretion and possible reabsorption of creatinine and suggested a molecular basis for potential species difference in the transporter handling of creatinine. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Cellular transport of l-arginine determines renal medullary blood flow in control rats, but not in diabetic rats despite enhanced cellular uptake capacity.

Science.gov (United States)

Persson, Patrik; Fasching, Angelica; Teerlink, Tom; Hansell, Peter; Palm, Fredrik

2017-02-01

Diabetes mellitus is associated with decreased nitric oxide bioavailability thereby affecting renal blood flow regulation. Previous reports have demonstrated that cellular uptake of l-arginine is rate limiting for nitric oxide production and that plasma l-arginine concentration is decreased in diabetes. We therefore investigated whether regional renal blood flow regulation is affected by cellular l-arginine uptake in streptozotocin-induced diabetic rats. Rats were anesthetized with thiobutabarbital, and the left kidney was exposed. Total, cortical, and medullary renal blood flow was investigated before and after renal artery infusion of increasing doses of either l-homoarginine to inhibit cellular uptake of l-arginine or N ω -nitro- l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase. l-Homoarginine infusion did not affect total or cortical blood flow in any of the groups, but caused a dose-dependent reduction in medullary blood flow. l-NAME decreased total, cortical and medullary blood flow in both groups. However, the reductions in medullary blood flow in response to both l-homoarginine and l-NAME were more pronounced in the control groups compared with the diabetic groups. Isolated cortical tubular cells displayed similar l-arginine uptake capacity whereas medullary tubular cells isolated from diabetic rats had increased l-arginine uptake capacity. Diabetics had reduced l-arginine concentrations in plasma and medullary tissue but increased l-arginine concentration in cortical tissue. In conclusion, the reduced l-arginine availability in plasma and medullary tissue in diabetes results in reduced nitric oxide-mediated regulation of renal medullary hemodynamics. Cortical blood flow regulation displays less dependency on extracellular l-arginine and the upregulated cortical tissue l-arginine may protect cortical hemodynamics in diabetes. Copyright © 2017 the American Physiological Society.

Effect of strenuous maternal exercise before and during pregnancy on rat progeny renal function

Directory of Open Access Journals (Sweden)

Oliveira A.O.

2004-01-01

Full Text Available The effects of strenuous exercise before and during pregnancy on the renal function and morphological alterations of the progeny were determined in a study on female Wistar rats. This research was done based on a previous study carried out in our laboratory, which showed morphological alterations in rats submitted to this kind of exercise. As the form is related to the function, the physiological relevance of submitting a pregnant female to a high-intensity exercise training regimen could be explained by the fact that morphological alterations can influence kidney function. The animals were assigned to one of two groups: control animals that did not exercise during pregnancy and trained animals that swam for 120 min 5 days a week for 8 weeks before pregnancy and daily for 60 min over a period of 8 weeks starting on the second day of pregnancy. Seven rats of each group were analyzed for morphological alterations and for renal function. The progeny of the rats used for morphological evaluation were born by cesarean section and the progeny of the animals used to evaluate renal function were born normally. The progeny were two months old when renal function was evaluated. Fertility and morbidity were the same for both groups. Strenuous maternal exercise had no significant influence on glomerular filtration rate (GFR but renal plasma flow was lower in the progeny of the trained group (mean ± SD, 16.65 ± 3.77 ml min-1 kg-1 compared to the progeny of the control group (33.42 ± 2.56 ml min-1 kg-1. Antidiuretic and antinatriuretic effects on the progeny of the trained group were observed, since urine flow as percentage of GFR and the fraction of urinary sodium excretion were lower in this group (1.38 ± 0.10 and 0.60 ± 0.04%, respectively compared to the progeny of the control group (2.36 ± 0.11 and 1.55 ± 0.20%, respectively. Moreover, in this exercise program, fetuses from trained animals were small-sized (2.45 ± 0.19 vs 4.66 ± 2.45 g for

Comparison of the effects of dexmedetomidine administered at two different times on renal ischemia/reperfusion injury in rats

Directory of Open Access Journals (Sweden)

Edip Gonullu

2014-05-01

Full Text Available Background and objectives: We investigated the effect of dexmedetomidine on ischemic renal failure in rats. Methods: In the present study, 26 male adult Wistar albino rats weighting 230–300 g were randomly separated into four groups: sham-operated (n = 5, ischemia reperfusion (IR (IR group, n = 7, IR/reperfusion treatment with dexmedetomidine (Dex. R group, n = 7 and IR/pre-ischemic treatment with dexmedetomidine (Dex. I group, n = 7. In the first group, sham operation was achieved and renal clamps were not applied. For the IR group, renal ischemia was induced by occlusion of the bilateral renal arteries and veins for 60 min followed by reperfusion for 24 h. For the Dex. R and Dex. I groups, the same surgical procedure as in the IR group was performed, and dexmedetomidine (100 mcg/kg intraperitoneal was administrated at the 5th min after reperfusion and before ischemia. At the end of reperfusion, blood samples were drawn, the rats were sacrificed, and the left kidney was processed for histopathology. Results: The blood urea nitrogen (BUN levels in groups Dex. R and Dex. I were significantly lower than in the IR group (p = 0.015, p = 0.043, although urine flow was significantly higher in group Dex. R (p = 0.003. The renal histopathological score in the IR group was significantly higher than in the other groups. There was no significant difference between the Dex. R and Dex. I groups. Conclusions: The results were shown that administration of dexmedetomidine reduced the renal IR injury histomorphologically. Administration of dexmedetomidine in the reperfusion period was considered as more effective due to increase in urinary output and decrease in BUN levels. Keywords: Kidney, Ischemia/reperfusion, Dexmedetomidine, Acute renal failure

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

Directory of Open Access Journals (Sweden)

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.

Acute Urinary Bladder Distension Triggers ICAM-1-mediated Renal Oxidative Injury via the Norepinephrine–renin–angiotensin II System in Rats

Directory of Open Access Journals (Sweden)

Show-Shing Chen

2009-08-01

Conclusion: Acute urinary retention enhances renal sympathetic activity, which causes renal vasoconstriction and increases oxidative stress, adhesion-molecule expression and leukocyte infiltration in the rat kidney via the angiotensin II type 1 receptor pathway.

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.

Morphological and cytohistochemical evaluation of renal effects of cadmium-doped silica nanoparticles given intratracheally to rat

International Nuclear Information System (INIS)

Coccini, T; Roda, E; Manzo, L; Barni, S

2013-01-01

Renal morphological parameters were determined in rats intratracheally instilled with model cadmium-containing silica nanoparticles (Cd-SiNPs, 1mg/rat), also exploring whether their potential modifications would be associated with toxicogenomic changes. Cd-SiNP effects, evaluated 7 and 30 days post-exposure, were assessed by (i) histopathology (Haematoxylin/Eosin Staining), (ii) characterization of apoptotic features by TUNEL staining. Data were compared with those obtained by CdCl 2 (400μg/rat), SiNPs (600μg/rat), 0.1 ml saline. Area-specific cell apoptosis was observed in all treatment groups: cortex and inner medulla were the most affected regions. Apoptotic changes were apparent at 7 days post-exposure in both areas, and were still observable in inner medulla 30 days after treatment. Increase in apoptotic frequency was more pronounced in Cd-SiNP-treated animals compared to either CdCl 2 or SiNPs. Histological findings showed comparable alterations in the renal glomerular (cortex) architecture occurring in all treatment groups at both time-points considered. The glomeruli appeared often collapsed, showing condensed, packed mesangial and endothelial cells. Oedematous haemorrhagic glomeruli were also observed in Cd-SiNPs-treated animals. Bare SiNPs caused morphological and apoptotic changes without modifying the renal gene expression profile. These findings support the concept that multiple assays and an integrated testing strategy should be recommended to characterize toxicological responses to nanoparticles in mammalian systems.

Morphological and cytohistochemical evaluation of renal effects of cadmium-doped silica nanoparticles given intratracheally to rat

Science.gov (United States)

Coccini, T.; Roda, E.; Barni, S.; Manzo, L.

2013-04-01

Renal morphological parameters were determined in rats intratracheally instilled with model cadmium-containing silica nanoparticles (Cd-SiNPs, 1mg/rat), also exploring whether their potential modifications would be associated with toxicogenomic changes. Cd-SiNP effects, evaluated 7 and 30 days post-exposure, were assessed by (i) histopathology (Haematoxylin/Eosin Staining), (ii) characterization of apoptotic features by TUNEL staining. Data were compared with those obtained by CdCl2 (400μg/rat), SiNPs (600μg/rat), 0.1 ml saline. Area-specific cell apoptosis was observed in all treatment groups: cortex and inner medulla were the most affected regions. Apoptotic changes were apparent at 7 days post-exposure in both areas, and were still observable in inner medulla 30 days after treatment. Increase in apoptotic frequency was more pronounced in Cd-SiNP-treated animals compared to either CdCl2 or SiNPs. Histological findings showed comparable alterations in the renal glomerular (cortex) architecture occurring in all treatment groups at both time-points considered. The glomeruli appeared often collapsed, showing condensed, packed mesangial and endothelial cells. Oedematous haemorrhagic glomeruli were also observed in Cd-SiNPs-treated animals. Bare SiNPs caused morphological and apoptotic changes without modifying the renal gene expression profile. These findings support the concept that multiple assays and an integrated testing strategy should be recommended to characterize toxicological responses to nanoparticles in mammalian systems.

A Mechanism for the induction of renal tumours in male Fischer 344 rats by short-chain chlorinated paraffins.

Science.gov (United States)

Warnasuriya, Gayathri D; Elcombe, Barbara M; Foster, John R; Elcombe, Clifford R

2010-03-01

Short-chain chlorinated paraffins (SCCPs) cause kidney tumours in male rats, but not in female rats or mice of either sex. Male rat-specific tumours also occur in rats dosed with a range of compounds including 1,4- dichlorobenzene (DCB) and d-limonene (DL). These compounds bind to a male rat-specific hepatic protein, alpha-2-urinary globulin (α2u), and form degradationresistant complexes in the kidney. The resulting accumulation of α2u causes cell death and sustained regenerative cell proliferation, which in turn leads to the formation of renal tumours. To investigate whether the SCCP, Chlorowax 500C (C500C), causes tumours via the accumulation of α2u male rats were orally dosed with either C500C (625 mg/kg of body weight), DCB (300 mg/kg of body weight), or DL (150 mg/kg of body weight) for 28 consecutive days. An increase in renal α2u and cell proliferation was observed in DCB- and DL-treated rats but not in C500C-treated rats. C500C caused peroxisome proliferation and a down-regulation of α2u synthesis in male rat liver. This down-regulation occurred at the transcriptional level. Since less α2u was produced in C500C-treated rats, there was less available for accumulation in the kidney hence a typical α2u nephropathy did not appear. However, the administration of a radiolabelled SCCP, [14C]polychlorotridecane (PCTD), to male rats demonstrated its binding to renal α2u. Thus, it is possible that SCCPs bind to α2u and cause a slow accumulation of the protein in the kidney followed by delayed onset of α2u nephropathy. As a consequence of these findings in the current experiments, while evidence exists implicating α2u-globulin in the molecular mechanism of action of the C500C, the classic profile of a α2u-globulin nephropathy seen with other chemicals such as DCB and DL was not reproduced during this experimental protocol.

Renal hypertension prevents run training modification of cardiomyocyte diastolic Ca2+ regulation in male rats.

Science.gov (United States)

Palmer, B M; Lynch, J M; Snyder, S M; Moore, R L

2001-06-01

The combined effects of endurance run training and renal hypertension on cytosolic Ca2+ concentration ([Ca2+]c) dynamics and Na+-dependent Ca2+ regulation in rat left ventricular cardiomyocytes were examined. Male Fischer 344 rats underwent stenosis of the left renal artery [hypertensive (Ht), n = 18] or a sham operation [normotensive (Nt), n = 20]. One-half of the rats from each group were treadmill trained for >16 wk. Cardiomyocyte fura 2 fluorescence ratio transients were recorded for 7 min during electrical pacing at 0.5 Hz, 2 mM extracellular Ca2+ concentration, and 29 degrees C. The rate of [Ca2+]c decline was not changed by run training in the Nt group but was reduced in the Ht group. At 7 min, cardiomyocytes were exposed to 10 mM caffeine in the absence of Na+ and Ca2+, which triggered sarcoplasmic reticular Ca2+ release and suppressed Ca2+ efflux via Na+/Ca2+ exchanger. External Na+ was then added, and Na+-dependent Ca2+ efflux rate was recorded. Treadmill training significantly enhanced Na+-dependent Ca2+ efflux rate under these conditions in the Nt group but not in the Ht group. These data provide evidence that renal hypertension prevents the normal run training-induced modifications in diastolic [Ca2+]c regulation mechanisms, including Na+/Ca2+ exchanger.

Generation of Urinary Albumin Fragments Does Not Require Proximal Tubular Uptake

OpenAIRE

Weyer, K.; Nielsen, R.; Christensen, E. I.; Birn, H.

2012-01-01

Urinary albumin excretion is an important diagnostic and prognostic marker of renal function. Both animal and human urine contain large amounts of albumin fragments, but whether these fragments originate from renal tubular degradation of filtered albumin is unknown. Here, we used mice with kidneys lacking megalin and cubilin, the coreceptors that mediate proximal tubular endocytosis of albumin, to determine whether proximal tubular degradation of albumin forms the detectable urinary albumin f...

Prevention of Renal Injury After Induction of Ozone Tolerance in Rats Submitted to Warm Ischaemia

Directory of Open Access Journals (Sweden)

E. Barber

1999-01-01

Full Text Available On the basis that ozone (O3 can upregulate cellular antioxidant enzymes, a morphological, biochemical and functional renal study was performed in rats undergoing a prolonged treatment with O3 before renal ischaemia. Rats were divided into four groups: (1 control, a medial abdominal incision was performed to expose the kidneys; (2 ischaemia, in animals undergoing a bilateral renal ischaemia (30 min, with subsequent reperfusion (3 h; (3 O3 + ischaemia, as group 2, but with previous treatment with O3 (0.5 mg/kg per day given in 2.5 ml O2 via rectal administration for 15 treatments; (4 O2 + ischaemia, as group 3, but using oxygen (O2 alone. Biochemical parameters as fructosamine level, phospholipase A, and superoxide dismutases (SOD activities, as well as renal plasma flow (RPF and glomerular filtration rate (GFR, were measured by means of plasma clearance of p-amino-hippurate and inulin, respectively. In comparison with groups 1 and 3, the RPF and GFR were significantly decreased in groups 2 and 4. Interestingly, renal homogenates of the latter groups yielded significantly higher values of phospholipase A activity and fructosamine level in comparison with either the control (1 and the O3 (3 treated groups. Moreover renal SOD activity showed a significant increase in group 3 without significant differences among groups 1, 2 and 4. Morphological alterations of the kidney were present in 100%, 88% and 30% of the animals in groups 2, 4 and 3, respectively. It is proposed that the O3 protective effect can be ascribed to the substantial possibility of upregulating the antioxidant defence system capable of counteracting the damaging effect of ischaemia. These findings suggest that, whenever possible, ozone preconditioning may represent a prophylactic approach for minimizing renal damage before transplantation.

Segmental heterogeneity of enzymatic response during compensatory renal growth

International Nuclear Information System (INIS)

Hoang, T.; Bergeron, M.

1985-01-01

The activities of DNA polymerase α and key enzymes of gluconeogenesis and glycolysis were measured in different segments of the rat nephron at various times (up to 96 hrs) following a unilateral nephrectomy (UNx). Tubule fragments were obtained after collagenase treatment followed by centrifugation on a Percoll gradient. The DNA polymerase α activity in control rats showed moderate and similar values in different segmental extracts as well as in the whole kidney extract (1700-1800 μμmole[ 3 H] dAMP/mg DNA). In Unx rats, activity in proximal tubules (PT) measured at 24, 48, 72 and 96 hrs after nephrectomy represented an increase of 60%, 200%, 420% and 370% respectively over control values. Distal tubule fragments (DT) showed only minor increases. The results demonstrate that the proximal tubule accounts for most of the compensatory renal growth (CRG) in the remaining kidney. The gluconeogenic and glycolytic enzymes were confined to the PT and those of glycolysis to the DT fragments. Following UNx, the specific activities of these enzymes were not modified in the remaining kidney; however, the overall activity of gluconeogenesis was increased as a result of the cell hyperplasia occurring in the PT. The work also illustrates that biochemical studies of CRG on the whole organ may provide misleading information due to the presence of heterogeneous cell populations in the mammalian kidney and to their uneven response in CRG

Comparison of the effects of dexmedetomidine administered at two different times on renal ischemia/reperfusion injury in rats

Directory of Open Access Journals (Sweden)

Edip Gonullu

2014-06-01

Full Text Available Background and objectives: We investigated the effect of dexmedetomidine on ischemic renal failure in rats. Methods: In the present study, 26 male adult Wistar albino rats weighting 230-300 g were randomly separated into four groups: sham-operated (n = 5, ischemia reperfusion (IR (IR group, n = 7, IR/reperfusion treatment with dexmedetomidine (Dex. R group, n = 7 and IR/pre-ischemic treatment with dexmedetomidine (Dex. I group, n = 7. In the first group, sham operation was achieved and renal clamps were not applied. For the IR group, renal ischemia was induced by occlusion of the bilateral renal arteries and veins for 60 min followed by reperfusion for 24 h. For the Dex. R and Dex. I groups, the same surgical procedure as in the IR group was performed, and dexmedetomidine (100 mcg/kg intraperitoneal was administrated at the 5th min after reperfusion and before ischemia. At the end of reperfusion, blood samples were drawn, the rats were sacrificed, and the left kidney was processed for histopathology. Results: The blood urea nitrogen (BUN levels in groups Dex. R and Dex. I were significantly lower than in the IR group (p = 0.015, p = 0.043, although urine flow was significantly higher in group Dex. R (p = 0.003. The renal histopathological score in the IR group was significantly higher than in the other groups. There was no significant difference between the Dex. R and Dex. I groups. Conclusions: The results were shown that administration of dexmedetomidine reduced the renal IR injury histomorphologically. Administration of dexmedetomidine in the reperfusion period was considered as more effective due to increase in urinary output and decrease in BUN levels.

Effect of high saturated free fatty acids feeding on progression of renal failure in rat model of experimental nephrotoxicity

Directory of Open Access Journals (Sweden)

Zaid O. Ibraheem

2012-02-01

Full Text Available The current study evaluates the impact of high saturated fat feeding in rat model of experimental nephrotoxicity induced by gentamicin. Sprague-Dawley rats weighing 200 g were randomized into four groups; the first one received the standard rodents chow for 8 weeks and was treated as control, the second group (HFDreceived an experimental high fat diet rich in palm kernel oil (40% of Calories as fat for the same period. The third group (HFDG was given 80 mg/kg (body weight/day gentamicin sulphate intraperitoneally during the last 24 days of the feeding period while the fourth group was given gentamicin as above along with the standard rodents chow. Renal function was assessed through measuring serum creatinine, creatinine clearance and absolute and fractional excretion of both sodium and potassium. At the end, rats underwent a surgical procedure for blood pressure measurement. Renal function study showed a stronger nephrotoxicity for HFDG group. Hypertension was observed in HFD group while the pressure declined after gentamicin co-administration. Overall, changing the feeding behavior toward using more SAFFAs for rats injected with gentamicin promotes the progression of renal failure.

Comparison of para-aminophenol cytotoxicity in rat renal epithelial cells and hepatocytes.

Science.gov (United States)

Li, Ying; Bentzley, Catherine M; Tarloff, Joan B

2005-04-01

Several chemicals, including para-aminophenol (PAP), produce kidney damage in the absence of hepatic damage. Selective nephrotoxicity may be related to the ability of the kidney to reabsorb filtered water, thereby raising the intraluminal concentration of toxicants and exposing tubular epithelial cells to higher concentrations than would be present in other tissues. The present experiments tested the hypothesis that hepatocytes and renal epithelial cells exposed to equivalent concentrations of PAP would be equally susceptible to toxicity. Hepatocytes and renal epithelial cells were prepared by collagenase digestion of tissues obtained from female Sprague-Dawley rats. Toxicity was monitored using trypan blue exclusion, oxygen consumption and ATP content. We measured the rate of PAP clearance and formation of PAP-glutathione conjugate by HPLC. We found that renal epithelial cells accumulated trypan blue and showed declines in oxygen consumption and ATP content at significantly lower concentrations of PAP and at earlier time points than hepatocytes. The half-life of PAP in hepatocyte incubations was significantly shorter (0.71+/-0.07 h) than in renal epithelial cell incubations (1.33+/-0.23 h), suggesting that renal epithelial cells were exposed to PAP for longer time periods than hepatocytes. Renal epithelial cells formed significantly less glutathione conjugates of PAP (PAP-SG) than did hepatocytes, consistent with less efficient detoxification of reactive PAP intermediates by renal epithelial cells. Finally, hepatocytes contained significant more reduced glutathione (NPSH) than did renal epithelial cells, possibly explaining the enhanced formation of PAP-SG by this cell population. In conclusion, our data indicates that renal epithelial cells are intrinsically more susceptible to PAP cytotoxicity than are hepatocytes. This enhanced cytotoxicity may be due to longer exposure to PAP and/or reduced detoxification of reactive intermediates due to lower concentrations

Mathematical Model of Ammonia Handling in the Rat Renal Medulla

Science.gov (United States)

Noiret, Lorette; Baigent, Stephen; Jalan, Rajiv; Thomas, S. Randall

2015-01-01

The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney. Mechanisms regulating the balance between urinary excretion and renal vein release are not fully understood. We developed a mathematical model that reflects current thinking about renal ammonia handling in order to investigate the role of each tubular segment and identify some of the components which might control this balance. The model treats the movements of water, sodium chloride, urea, NH3 and NH4+, and non-reabsorbable solute in an idealized renal medulla of the rat at steady state. A parameter study was performed to identify the transport parameters and microenvironmental conditions that most affect the rate of urinary ammonia excretion. Our results suggest that urinary ammonia excretion is mainly determined by those parameters that affect ammonia recycling in the loops of Henle. In particular, our results suggest a critical role for interstitial pH in the outer medulla and for luminal pH along the inner medullary collecting ducts. PMID:26280830

Maternal drugs and neonatal renal failure

Directory of Open Access Journals (Sweden)

M Sahay

2014-01-01

Full Text Available Maternal use of drugs during pregnancy may cause irreversible renal failure in the newborn. This report highlights the adverse effect of telmisartan during the last trimester of pregnancy. The neonate presented with oliguric renal failure and the renal histology showed proximal tubular dysgenesis.

Cytochrome P450-2C11 mRNA is not expressed in endothelial cells dissected from rat renal arterioles.

Science.gov (United States)

Heil, Sandra G; De Vriese, An S; Kluijtmans, Leo A J; Dijkman, Henry; van Strien, Denise; Akkers, Robert; Blom, Henk J

2005-01-01

Cytochrome P450 (CYP) isoenzymes (CYP2C and CYP2J) are involved in the production of epoxyeicosatrienoic acids, which are postulated as endothelium-derived hyperpolarizing factors (EDHFs). We hypothesized that if CYP2C11 is involved in the EDHF-mediated responses, its mRNA should be expressed in endothelial cells. We, therefore, examined the mRNA expression of CYP2C11 in endothelial cells of renal arterioles. Laser microdissection was applied to isolate endothelial cells from the renal arterioles of 4 male and 4 female Wistar rats. As a positive control of CYP2C11 expression, hepatocytes were also dissected from these rats. RNA was isolated and real-time quantitative polymerase chain reaction (Q-PCR) analysis was applied. Q-PCR analysis showed that CYP2C11 mRNA was not expressed in laser microdissected endothelial cells of renal arterioles of male and female rats. CYP2C11 mRNA expression was highly abundant in hepatocytes dissected from male livers, but in female livers hardly any CYP2C11 mRNA was detected. We have shown that endothelial cells can be dissected from small renal arterioles by laser microdissection to study the mRNA expression of specific genes by Q-PCR. Using this novel tool, we demonstrated that the CYP2C11 mRNA was not expressed in the endothelial cells of renal arterioles. Therefore, we speculate that CYP2C11 does not contribute to the EDHF-mediated responses in renal arterioles. Copyright (c) 2005 S. Karger AG, Basel.

NMR-based urine analysis in rats: prediction of proximal tubule kidney toxicity and phospholipidosis.

Science.gov (United States)

Lienemann, Kai; Plötz, Thomas; Pestel, Sabine

2008-01-01

The aim of safety pharmacology is early detection of compound-induced side-effects. NMR-based urine analysis followed by multivariate data analysis (metabonomics) identifies efficiently differences between toxic and non-toxic compounds; but in most cases multiple administrations of the test compound are necessary. We tested the feasibility of detecting proximal tubule kidney toxicity and phospholipidosis with metabonomics techniques after single compound administration as an early safety pharmacology approach. Rats were treated orally, intravenously, inhalatively or intraperitoneally with different test compounds. Urine was collected at 0-8 h and 8-24 h after compound administration, and (1)H NMR-patterns were recorded from the samples. Variation of post-processing and feature extraction methods led to different views on the data. Support Vector Machines were trained on these different data sets and then aggregated as experts in an Ensemble. Finally, validity was monitored with a cross-validation study using a training, validation, and test data set. Proximal tubule kidney toxicity could be predicted with reasonable total classification accuracy (85%), specificity (88%) and sensitivity (78%). In comparison to alternative histological studies, results were obtained quicker, compound need was reduced, and very importantly fewer animals were needed. In contrast, the induction of phospholipidosis by the test compounds could not be predicted using NMR-based urine analysis or the previously published biomarker PAG. NMR-based urine analysis was shown to effectively predict proximal tubule kidney toxicity after single compound administration in rats. Thus, this experimental design allows early detection of toxicity risks with relatively low amounts of compound in a reasonably short period of time.

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

Directory of Open Access Journals (Sweden)

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.

Proximal tubular hypertrophy and enlarged glomerular and proximal tubular urinary space in obese subjects with proteinuria.

Directory of Open Access Journals (Sweden)

Ana Tobar

Full Text Available BACKGROUND: Obesity is associated with glomerular hyperfiltration, increased proximal tubular sodium reabsorption, glomerular enlargement and renal hypertrophy. A single experimental study reported an increased glomerular urinary space in obese dogs. Whether proximal tubular volume is increased in obese subjects and whether their glomerular and tubular urinary spaces are enlarged is unknown. OBJECTIVE: To determine whether proximal tubules and glomerular and tubular urinary space are enlarged in obese subjects with proteinuria and glomerular hyperfiltration. METHODS: Kidney biopsies from 11 non-diabetic obese with proteinuria and 14 non-diabetic lean patients with a creatinine clearance above 50 ml/min and with mild or no interstitial fibrosis were retrospectively analyzed using morphometric methods. The cross-sectional area of the proximal tubular epithelium and lumen, the volume of the glomerular tuft and of Bowman's space and the nuclei number per tubular profile were estimated. RESULTS: Creatinine clearance was higher in the obese than in the lean group (P=0.03. Proteinuria was similarly increased in both groups. Compared to the lean group, the obese group displayed a 104% higher glomerular tuft volume (P=0.001, a 94% higher Bowman's space volume (P=0.003, a 33% higher cross-sectional area of the proximal tubular epithelium (P=0.02 and a 54% higher cross-sectional area of the proximal tubular lumen (P=0.01. The nuclei number per proximal tubular profile was similar in both groups, suggesting that the increase in tubular volume is due to hypertrophy and not to hyperplasia. CONCLUSIONS: Obesity-related glomerular hyperfiltration is associated with proximal tubular epithelial hypertrophy and increased glomerular and tubular urinary space volume in subjects with proteinuria. The expanded glomerular and urinary space is probably a direct consequence of glomerular hyperfiltration. These effects may be involved in the pathogenesis of obesity

A case of huge colon carcinoma and right renal angiomyolipoma accompanied by proximal deep venous thrombosis, pulmonary embolism and tumor thrombus in the renal vein.

Science.gov (United States)

Ban, Daisuke; Yamamoto, Seiichiro; Kuno, Hirofumi; Fujimoto, Hiroyuki; Fujita, Shin; Akasu, Takayuki; Moriya, Yoshihiro

2008-10-01

A preoperative inferior vena cava (IVC) filter is reported to be effective in surgical cases with proximal deep venous thrombosis (DVT) or in which pulmonary embolism (PE) has already developed, and considered to be at high risk of developing secondary fatal PE during or after surgery. However, guidelines for using an IVC filter have yet to be established. The patient in the present report had two huge tumors, ascending colon cancer and renal angiomyolipoma, which occupied the entire right half of the abdomen, coexisting PE, DVT and tumor thrombus in the right renal vein. Secondary PE is fatal in the perioperative period, therefore, the vena cava filters were preoperatively inserted into the supra- and the infrarenal IVC. We successfully removed the tumors without complications. The patient is alive without tumor recurrence and PE or recurrent DVT 1 year and 6 months after surgery. The coexistence of two huge abdominal tumors as potential causes of PE and DVT is extremely rare, and we could have safely undergone the operation, using two vena cava filters in the supra- and infrarenal IVC.

Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

Directory of Open Access Journals (Sweden)

Ding F

2014-09-01

Full Text Available Fengan Ding,1 Yiping Li,1 Jing Liu,1 Lei Liu,1 Wenmin Yu,1 Zhi Wang,1 Haifeng Ni,2 Bicheng Liu,2 Pingsheng Chen1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Institute of Nephrology, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China Background: Gold nanoparticles (GNPs can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells.Results: Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM to human renal proximal tubular cells (HK-2 by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the

Diclofenac causes anastomotic leakage in the proximal colon but not in the distal colon of the rat

NARCIS (Netherlands)

Yauw, S.T.; Lomme, R.M.; Vijver, R.J. van der; Hendriks, T.; Laarhoven, K.J. van; Goor, H. van

2015-01-01

BACKGROUND: Nonsteroidal anti-inflammatory drugs have been associated with anastomotic leakage. It was studied if diclofenac affects anastomoses differently depending on the location in the gut. METHODS: Ninety-five rats were randomized to 6 groups with an anastomosis in either ileum (IL), proximal

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

Directory of Open Access Journals (Sweden)

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.

Role of Bone Morphogenetic Proteins-7 (BMP-7 in the Renal Improvement Effect of DangGui (Angelica sinensis in Type-1 Diabetic Rats

Directory of Open Access Journals (Sweden)

Ching-Hua Yeh

2011-01-01

Full Text Available Hyperglycemia induced reactive oxygen species (ROS generation is believed as major factors leading to diabetic nephropathy (DN. DangGui (Angelica sinensis is mentioned to show renal protective effect in combination with other herbs. Bone morphogenetic proteins-7 (BMP-7 is produced merit in protection of DN. The role of BMP-7 in DangGui-induced renal improvement is not clear. The present study investigated the effects of DangGui on renal functions, BMP-7 expression and the levels of ROS in streptozotocin (STZ-induced diabetic rats and high glucose-exposed rat mesangial cells (RMCs. After 1- or 4-week treatment, DangGui improved renal functions and increased renal BMP-7 expression in diabetic rats. The BMP-7 expression in RMCs was reduced by high glucose treatment and this could be reversed by DangGui. Moreover, RMCs exposed to high glucose were expired by BMP-7 RNAi transfection but those cells remained alive by scramble transfection. Thus, we employed regular RMCs to knock down BMP-7 with RNAi and we found that DangGui increased BMP-7 expression in these RMCs. Direct activation of BMP-7 expression by DangGui could be considered. The results of DPPH assay, DHE stain and lucigenin assay indicated that DangGui could inhibit high glucose-induced ROS in RMCs. These results suggest that DangGui has an ability to improve renal functions in STZ-diabetic rats through increasing endogenous BMP-7 expression and decreasing oxidative stress in kidney. The present study suggest that DangGui could be applied to improve renal functions in diabetic disorders.

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.

Inhibition of plasma kallikrein-kinin system to alleviate renal injury and arthritis symptoms in rats with adjuvant-induced arthritis.

Science.gov (United States)

Zhu, Jie; Wang, Hui; Chen, Jingyu; Wei, Wei

2018-04-01

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Impairment of kidney functions in RA was observed. However, the mechanism of kidney injury of RA has not been clear. Plasma kallikrein-kinin system (KKS) was involved in inflammatory processes in kidney disease. This study aimed to explore the role of plasma KKS in immune reactions and kidney injury of RA. The paw of AA rats appeared to be swelling and redness, the arthritis index was significantly increased on the 18, 21 and 24 d after injection and secondary inflammation in multi-sites was observed. Kidney dysfunction accompanied with inflammatory cell infiltration, tubular epithelial cell mitochondrial swelling and vacuolar degeneration, renal glomerular foot process fusions and glomerular basement membrane thickening were observed in AA rats. The expressions of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) in kidney of AA rats were increased. In addition, expressions of BK, PK, B1R and B2R in the renal tissue of AA rats were up-regulated. Pro-inflammatory cytokines IL-2, IFN-γ and TNF-α were increased and anti-inflammatory cytokines IL-4 and IL-10 were low in kidney. Plasma kallikrein (PK) inhibitor PKSI-527 attenuated arthritis signs and renal damage, and inhibited BK, PK, B1R and B2R expressions. The protein expressions of P38, p-P38 and p-JNK and IFN-γ and TNF-α were inhibited by PKSI-527. These findings demonstrate that plasma KKS activation contributed to the renal injury of AA rats through MAPK signaling pathway. Plasma KKS might be a potential target for RA therapy.

Glutamyl aminopeptidase in microvesicular and exosomal fractions of urine is related with renal dysfunction in cisplatin-treated rats.

Directory of Open Access Journals (Sweden)

Andrés Quesada

Full Text Available The aim of this work was to investigate if the content of glutamyl aminopeptidase (GluAp in microvesicular and exosomal fractions of urine is related with renal dysfunction in cisplatin-treated rats.Urine samples were collected 24 hours after injection of cisplatin (7 mg/kg, n = 10 or saline serum (n = 10, and they were subjected to differential centrifugation at 1.000, 17.000 and 200.000 g to obtain microvesicular and exosomal fractions. GluAp was measured with a commercial ELISA kit in both fractions. Serum creatinine (SCr and body weight were measured 15 days after treatment. We analyzed if early excretion of GluAp in microsomal and exosomal fractions was correlated with final SCr and body weight increase. In a second experiment, enzymatic activities of GluAp and alanyl aminopeptidase (AlaAp in urine, microvesicular and exosomal fractions were measured three days after injection. We analyzed the correlation of both markers with SCr determined at this point. Finally, we studied the expression of GluAp and extracellular vesicles markers Alix and tumor susceptibility gene (TSG101 in both fractions by immunoblotting.GluAp excretion was increased in all fractions of urine after cisplatin treatment, even if data were normalized per mg of creatinine, per body weight or per total protein content of each fraction. We found significant predictive correlations with SCr concentration, and inverse correlations with body weight increase determined 15 days later. Three days after injection, aminopeptidasic activities were markedly increased in all fractions of urine in cisplatin-treated rats. The highest correlation coefficient with SCr was found for GluAp in microvesicular fraction. Increase of GluAp in microvesicular and exosomal fractions from cisplatin-treated rats was confirmed by immunoblotting. Alix and TSG101 showed different patterns of expression in each fraction.Determination of GluAp content or its enzymatic activity in microvesicular and

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.

Proximal tubule Na transporter responses are the same during acute and chronic hypertension

DEFF Research Database (Denmark)

Magyar, C E; Zhang, Y; Holstein-Rathlou, N H

2000-01-01

Acute hypertension in Sprague-Dawley rats (SD) provokes a decrease in renal proximal tubule (PT) salt and fluid reabsorption, redistribution of apical Na/H exchanger isoform 3 (NHE3) and Na-P(i) cotransporter type 2 (NaPi2) out of the brush border into higher density membranes, and inhibition...... to persistent adaptive changes in NHE3 and NaPi2 distribution and/or NKA activity. Renal cortex Na transporter protein density distributions and activities were compared by subcellular fractionation in 1) adult SHR with an acute increase or decrease in arterial pressure and 2) young SD (YSD) and young SHR (YSHR......) vs. adult SD and SHR. In adult hypertensive SHR NHE3 was shifted to membranes of higher densities, analogous to SD with acute hypertension, and there were no further changes with a further increase or decrease in arterial pressure. There was no change in total pool size of NHE3 in cortex in YSHR vs...

Oxidative damage parameters in renal tissues of aged and young rats based on gender

Directory of Open Access Journals (Sweden)

Uzun D

2013-06-01

Full Text Available Duygu Uzun,1 Gülcan Güntas Korkmaz,2 Mustafa Erinç Sitar,3 Tamer Cebe,4 Karolin Yanar,3 Ufuk Çakatay,3 Seval Aydin3 1Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey; 2Kirklareli University, School of Health, Kirklareli, Turkey; 3Istanbul University, Cerrahpasa Faculty of Medicine, Department of Medical Biochemistry, Istanbul, Turkey; 4Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey Purpose: Aging is characterized by a gradual functional decrease of all systems including the kidneys. Growing evidence links altered lipid protein redox-homeostasis with renal dysfunction. The effect of sexual dimorphism on the lipid protein redox-homeostasis mechanisms in the aging kidney is obscure. In the current study, we aimed to investigate redox homeostasis as it related to sexual dimorphism on protein oxidation and lipid peroxidation parameters, as protein carbonyl (PCO, total thiol (T-SH, advanced oxidation protein products (AOPP, malondialdehyde, glutathione (GSH, and superoxide dismutase (SOD activity, as potential aging biomarkers, which may contribute to an analysis of the free radical theory of aging. Materials and methods: The study was carried out with 16 naturally aged rats (24 months old; eight males and eight females and their corresponding young rat groups as controls (6 months old; eight males and eight females. All of the aforementioned parameters (PCO, T-SH, AOPP, MDA, GSH, SOD were measured manually instead of automated devices or ELISA kits. Results: PCO, AOPP, and malondialdehyde levels in aged rats were significantly higher in the older rat group than in the younger rat group, whereas SOD activities were significantly lower in old rats. T-SH levels were not significantly different in male groups; however, T-SH levels were lower in the aged female group than in the young female control group. In addition, GSH levels were significantly different between the aged rat group and the corresponding

Simultaneous characterization of metabolic, cardiac, vascular and renal phenotypes of lean and obese SHHF rats.

Science.gov (United States)

Youcef, Gina; Olivier, Arnaud; L'Huillier, Clément P J; Labat, Carlos; Fay, Renaud; Tabcheh, Lina; Toupance, Simon; Rodriguez-Guéant, Rosa-Maria; Bergerot, Damien; Jaisser, Frédéric; Lacolley, Patrick; Zannad, Faiez; Laurent Vallar; Pizard, Anne

2014-01-01

Individuals with metabolic syndrome (MetS) are prone to develop heart failure (HF). However, the deleterious effects of MetS on the continuum of events leading to cardiac remodeling and subsequently to HF are not fully understood. This study characterized simultaneously MetS and cardiac, vascular and renal phenotypes in aging Spontaneously Hypertensive Heart Failure lean (SHHF(+/?) regrouping (+/+) and (+/cp) rats) and obese (SHHF(cp/cp), "cp" defective mutant allele of the leptin receptor gene) rats. We aimed to refine the milestones and their onset during the progression from MetS to HF in this experimental model. We found that SHHF(cp/cp )but not SHHF(+/?) rats developed dyslipidemia, as early as 1.5 months of age. This early alteration in the lipidic profile was detectable concomitantly to impaired renal function (polyuria, proteinuria but no glycosuria) and reduced carotid distensibility as compared to SHHF(+/?) rats. By 3 months of age SHHFcp/cp animals developed severe obesity associated with dislipidemia and hypertension defining the onset of MetS. From 6 months of age, SHHF(+/?) rats developed concentric left ventricular hypertrophy (LVH) while SHHF(cp/cp) rats developed eccentric LVH apparent from progressive dilation of the LV dimensions. By 14 months of age only SHHF(cp/cp) rats showed significantly higher central systolic blood pressure and a reduced ejection fraction resulting in systolic dysfunction as compared to SHHF(+/?). In summary, the metabolic and hemodynamic mechanisms participating in the faster decline of cardiac functions in SHHF(cp/cp) rats are established long before their physiological consequences are detectable. Our results suggest that the molecular mechanisms triggered within the first three months after birth of SHHF(cp/cp) rats should be targeted preferentially by therapeutic interventions in order to mitigate the later HF development.

In Vivo MR Imaging of Magnetically Labeled Mesenchymal Stem Cells in a Rat Model of Renal Ischemia

Energy Technology Data Exchange (ETDEWEB)

Jung, Sung Il [Konkuk University Medical Center, Seoul (Korea, Republic of); Kim, Seung Hyup [Seoul National University Medical Research Center, Seoul (Korea, Republic of); Kim, Hyo Cheol; Chung, Se Young; Moon, Woo Kyung; Kim, Hoe Suk [Seoul National University Hospital, Seoul (Korea, Republic of); Choi, Jong Sun [Dongguk University International Hospital, Goyang (Korea, Republic of); Moon, Min Hoan [Cheil General Hospital and Women' s Healthcare Center, Seoul (Korea, Republic of); Son, Kyu Ri; Sung, Chang Kyu [Seoul National University Boramae Hospital, Seoul (Korea, Republic of)

2009-06-15

This study was designed to evaluate in vivo MR imaging for the depiction of intraarterially injected superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) in an experimental rat model of renal ischemia. Left renal ischemia was induced in 12 male Sprague- Dawley rats by use of the catheter lodging method. In vivo MR signal intensity variations depicted on T2*-weighted sequences were evaluated in both the left and right kidneys prior to injection (n = 2), two hours (n = 4), 15 hours (n = 2), 30 hours (n = 2) and 72 hours (n = 2) after injection of SPIO-labeled MSCs in both kidneys. Signal intensity variations were correlated with the number of Prussian blue stain-positive cells as visualized in histological specimens. In an in vivo study, it was determined that there was a significant difference in signal intensity variation for both the left and right cortex (40.8 {+-} 4.12 and 26.4 {+-} 7.92, respectively) and for both the left and right medulla (23.2 {+-} 3.32 and 15.2 {+-} 3.31, respectively) until two hours after injection (p < 0.05). In addition, signal intensity variation in the left renal cortex was well correlated with the number of Prussian blue stain-positive cells per high power field (r = 0.98, p < 0.05). Intraarterial injected SPIO-labeled MSCs in an experimental rat model of renal ischemia can be detected with the use of in vivo MR imaging immediately after injection.

Microinjection studies of phosphate permeability in rats during mild saline diuresis: influence of acute thyroparathyroidectomy and parathormone administration

International Nuclear Information System (INIS)

Poujeol, P.; Rouffignac, C. de.

1975-01-01

The tubular permeability to phosphate of the different segments of the rat nephron and the influence of parathyroid hormone on such a permeability were investigated. Tracer microinjections of 32 P and 3 H inulin were performed in control, acutely thyroparathyroidectomized (TPTX) and TPTX + PTH animals undergoing saline diuresis. In order to estimate the 32 P reabsorption capacity of the proximal convoluted tubule (PCT), the loop of Henle and the terminal part of the nephron, microinjections were performed in early proximal, late proximal and early distal tubules respectively. The results reported confirm that the renal phosphate reabsorption is under PTH control [fr

Pentraxin 3 Activates JNK Signaling and Regulates the Epithelial-To-Mesenchymal Transition in Renal Fibrosis

Directory of Open Access Journals (Sweden)

Tung-Wei Hung

2016-12-01

Full Text Available Background/Aims: Tubulointerstitial fibrosis can lead to end-stage renal disease. Pentraxin 3 (PTX3 is an acute phase protein produced by resident and innate immunity cells. We investigated the effect of PTX3 on cultured human proximal tubular epithelial (HK-2 cells and a rat unilateral ureteral obstruction (UUO model of renal fibrosis. Methods: Gain-of-function experiments were used to examine the effect of recombinant human PTX3 (Rh-PTX3 on HK-2 cells. Cell proliferation (MTT assay and in vitro cell migration were measured. The levels of PTX3, p-JNK, and EMT markers were measured using immunohistochemistry, RT-PCR, and western blotting in UUO rats and HK-2 cells. Results: HK-2 cells treated with Rh PTX3 did not affect cell viability, but significantly increased cell migration. Moreover, Rh-PTX3 increased the expression of snail, slug, N-cadherin, and vimentin, decreased the expression of E-cadherin, and increased the phosphorylation of JNK. SP600126 (a specific JNK inhibitor enhanced the effects of Rh-PTX3. Rats with UUO exhibited time-dependent increased levels of PTX3, p-JNK, and vimentin, and decreased expression of E-cadherin. Conclusions: Our results suggest that PTX3 induces cell migration via upregulation of EMT in a JNK-dependent mechanism, and highlight the role of PTX3 in the pathogenesis renal fibrosis.

Change in iron metabolism in rats after renal ischemia/reperfusion injury.

Directory of Open Access Journals (Sweden)

Guang-Liang Xie

Full Text Available Previous studies have indicated that hepcidin, which can regulate iron efflux by binding to ferroportin-1 (FPN1 and inducing its internalization and degradation, acts as the critical factor in the regulation of iron metabolism. However, it is unknown whether hepcidin is involved in acute renal ischemia/reperfusion injury (IRI. In this study, an IRI rat model was established via right renal excision and blood interruption for 45 min in the left kidney, and iron metabolism indexes were examined to investigate the change in iron metabolism and to analyze the role of hepcidin during IRI. From 1 to 24 h after renal reperfusion, serum creatinine and blood urea nitrogen were found to be time-dependently increased with different degrees of kidney injury. Regular variations in iron metabolism indexes in the blood and kidneys were observed in renal IRI. Renal iron content, serum iron and serum ferritin increased early after reperfusion and then declined. Hepcidin expression in the liver significantly increased early after reperfusion, and its serum concentration increased beginning at 8 h after reperfusion. The splenic iron content decreased significantly in the early stage after reperfusion and then increased time-dependently with increasing reperfusion time, and the hepatic iron content showed a decrease in the early stage after reperfusion. The early decrease of the splenic iron content and hepatic iron content might indicate their contribution to the increase in serum iron in renal IRI. In addition, the duodenal iron content showed time-dependently decreased since 12 h after reperfusion in the IRI groups compared to the control group. Along with the spleen, the duodenum might contribute to the decrease in serum iron in the later stage after reperfusion. The changes in iron metabolism indexes observed in our study demonstrate an iron metabolism disorder in renal IRI, and hepcidin might be involved in maintaining iron homeostasis in renal IRI. These

Antenatal glucocorticoid treatment alters Na+ uptake in renal proximal tubule cells from adult offspring in a sex-specific manner

OpenAIRE

Su, Yixin; Bi, Jianli; Pulgar, Victor M.; Figueroa, Jorge; Chappell, Mark; Rose, James C.

2015-01-01

We have shown a sex-specific effect of fetal programming on Na+ excretion in adult sheep. The site of this effect in the kidney is unknown. Therefore, we tested the hypothesis that renal proximal tubule cells (RPTCs) from adult male sheep exposed to betamethasone (Beta) before birth have greater Na+ uptake than do RPTCs from vehicle-exposed male sheep and that RPTCs from female sheep similarly exposed are not influenced by antenatal Beta. In isolated RPTCs from 1- to 1.5-yr-old male and femal...

Proximal Tubular Cannabinoid-1 Receptor Regulates Obesity-Induced CKD.

Science.gov (United States)

Udi, Shiran; Hinden, Liad; Earley, Brian; Drori, Adi; Reuveni, Noa; Hadar, Rivka; Cinar, Resat; Nemirovski, Alina; Tam, Joseph

2017-12-01

Obesity-related structural and functional changes in the kidney develop early in the course of obesity and occur independently of hypertension, diabetes, and dyslipidemia. Activating the renal cannabinoid-1 receptor (CB 1 R) induces nephropathy, whereas CB 1 R blockade improves kidney function. Whether these effects are mediated via a specific cell type within the kidney remains unknown. Here, we show that specific deletion of CB 1 R in the renal proximal tubule cells did not protect the mice from obesity, but markedly attenuated the obesity-induced lipid accumulation in the kidney and renal dysfunction, injury, inflammation, and fibrosis. These effects associated with increased activation of liver kinase B1 and the energy sensor AMP-activated protein kinase, as well as enhanced fatty acid β -oxidation. Collectively, these findings indicate that renal proximal tubule cell CB 1 R contributes to the pathogenesis of obesity-induced renal lipotoxicity and nephropathy by regulating the liver kinase B1/AMP-activated protein kinase signaling pathway. Copyright © 2017 by the American Society of Nephrology.

Prenatal programming of renal salt wasting resets postnatal salt appetite, which drives food intake in the rat.

Science.gov (United States)

Alwasel, Saleh H; Barker, David J P; Ashton, Nick

2012-03-01

Sodium retention has been proposed as the cause of hypertension in the LP rat (offspring exposed to a maternal low-protein diet in utero) model of developmental programming because of increased renal NKCC2 (Na+/K+/2Cl- co-transporter 2) expression. However, we have shown that LP rats excrete more rather than less sodium than controls, leading us to hypothesize that LP rats ingest more salt in order to maintain sodium balance. Rats were fed on either a 9% (low) or 18% (control) protein diet during pregnancy; male and female offspring were studied at 4 weeks of age. LP rats of both sexes held in metabolism cages excreted more sodium and urine than controls. When given water to drink, LP rats drank more and ate more food than controls, hence sodium intake matched excretion. However, when given a choice between saline and water to drink, the total volume of fluid ingested by LP rats fell to control levels, but the volume of saline taken was significantly larger [3.8±0.1 compared with 8.8±1.3 ml/24 h per 100 g of body weight in control and LP rats respectively; Psodium content and ECF (extracellular fluid) volumes were greater in LP rats. These results show that prenatal programming of renal sodium wasting leads to a compensatory increase in salt appetite in LP rats. We speculate that the need to maintain salt homoeostasis following malnutrition in utero stimulates greater food intake, leading to accelerated growth and raised BP (blood pressure).

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

Directory of Open Access Journals (Sweden)

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.

Hemorheological and metabolic consequences of renal ischemia-reperfusion and their modulation by N,N-dimethyl-tryptamine on a rat model.

Science.gov (United States)

Peto, Katalin; Nemeth, Norbert; Mester, Anita; Magyar, Zsuzsanna; Ghanem, Souleiman; Somogyi, Viktoria; Tanczos, Bence; Deak, Adam; Bidiga, Laszlo; Frecska, Ede; Nemes, Balazs

2018-04-13

Micro-rheological relations of renal ischemia-reperfusion (I/R) have not been completely elucidated yet. Concerning anti-inflammatory agents, it is supposed that sigma-1 receptor agonist N,N-dimethyl-tryptamin (DMT) can be useful to reduce I/R injury. To investigate the micro-rheological and metabolic parameters, and the effects of DMT in renal I/R in rats. In anesthetized rats from median laparotomy both kidneys were exposed. In Control group (n = 6) no other intervention happened. In I/R group (n = 10) the right renal vessels were ligated and after 60 minutes the organ was removed. The left renal vessels were clamped for 60 minutes followed by 120-minute reperfusion. In I/R+DMT group (n = 10) DMT was administered 15 minutes before the ischemia. Blood samples were taken before/after ischemia and during the reperfusion for testing hematological, metabolic parameters, erythrocyte deformability and aggregation. Lactate concentration significantly increased and accompanied with decreased blood pH. Enhanced erythrocyte aggregation and impaired deformability were observed from the 30th minute of reperfusion. In I/R+DMT group we found diminished changes compared to the I/R group (lactate, pH, electrolytes, red blood cell deformability and aggregation). Metabolic and micro-rheological parameters impair during renal I/R. DMT could reduce but not completely prevent the changes in this rat model.

Renal nerves and nNOS

DEFF Research Database (Denmark)

Kompanowska-Jezierska, Elzbieta; Wolff, Helle; Kuczeriszka, Marta

2008-01-01

). This was tested by NaLoad after chronic renal denervation with and without inhibition of nNOS by S-methyl-thiocitrulline (SMTC). In addition, the acute effects of renal denervation on MABP and sodium balance were assessed. Rats were investigated in the conscious, catheterized state, in metabolic cages...... of acutely and chronically denervated rats were less than control (15% and 9%, respectively, P reduced by renal denervation (14.5 +/- 0.2 vs. 19.3 +/- 1.3 mIU/l, P reduced...... PRC (P sodium excretion six-fold, irrespective of renal denervation and SMTC. The metabolic data demonstrated that renal denervation lowered sodium balance during the first days after denervation (P

Toxicological Significance of Renal Bcrp: Another Potential Transporter in the Elimination of Mercuric Ions from Proximal Tubular Cells

Science.gov (United States)

Bridges, Christy C.; Zalups, Rudolfs K.; Joshee, Lucy

2015-01-01

Secretion of inorganic mercury (Hg2+) from proximal tubular cells into the tubular lumen has been shown to involve the multidrug resistance-associated protein 2 (Mrp2). Considering similarities in localization and substrate specificity between Mrp2 and the breast cancer resistance protein (Bcrp), we hypothesize that Bcrp may also play a role in the proximal tubular secretion of mercuric species. In order to test this hypothesis, the uptake of Hg2+ was examined initially using inside-out membrane vesicles containing Bcrp. The results of these studies suggest that Bcrp may be capable of transporting certain conjugates of Hg2+. To further characterize the role of Bcrp in the handling of mercuric ions and in the induction of Hg2+-induced nephropathy, Sprague-Dawley and Bcrp knockout (bcrp−/−) rats were exposed intravenously to a non-nephrotoxic (0.5 μmol • kg−1), a moderately nephrotoxic (1.5 μmol • kg−1) or a significantly nephrotoxic (2.0 μmol • kg−1) dose of HgCl2. In general, the accumulation of Hg2+ was greater in organs of bcrp−/− rats than in Sprague-Dawley rats, suggesting that Bcrp may play a role in the export of Hg2+ from target cells. Within the kidney, cellular injury and necrosis was more severe in bcrp−/− rats than in controls. The pattern of necrosis, which was localized in the inner cortex and the outer stripe of the outer medulla was significantly different from that observed in Mrp2-deficient animals. These findings suggest that Bcrp may be involved in the cellular export of select mercuric species and that its role in this export may differ from that of Mrp2. PMID:25868844

Regional blood flows in the established stage of reduced renal mass (RRM) hypertension in rats

International Nuclear Information System (INIS)

Smits, G.J.; Lombard, J.H.

1986-01-01

Regional blood flows were measured with 15 μm 153 Gd-labelled microspheres in 21 anesthetized (pentobarbital-50 mg/kg, i.p.) male Sprague Dawley rats 5-6 weeks after a 75% reduction in renal mass and in 6 sham operated controls (SOC). RRM rats were maintained on either a high salt (HS-RRM) diet, i.e., choice of 1% NaCl or tap water (n = 11), or on a salt-restricted (SR-RRM) diet (n = 10). Mean arterial blood pressure was significantly elevated (mean +/- SE) in the HS-RRM (168 +/- 5 mmHg) vs. either the SR-RRM (147 +/- 6 mmHg) or the SOC (138 +/- 4 mmHg). Although blood flow to the skin and femur were elevated in HS-RRM and SR-RRM relative to SOC, there were no significant differences in blood flow to skeletal muscle, spleen, liver, small intestine, stomach or testes between any of the groups. Absolute renal blood flow and renal blood flow/gm of tissue were significantly lower in HS-RRM (7.2 +/- 0.7 ml/min or 3.4 +/- 0.5 ml/min/gm) and SR-RRM (6.3 +/- 0.6 ml/min or 3.2 +/- 0.3 ml/min/gm) than in SOC (15.1 +/- 0.97 ml/min or 5.5 +/- 0.2 ml/min/gm). The present results suggest that regional blood flow is unchanged in most vascular beds during the established stage of RRM hypertension in rats

Long-term cadmium exposure induces anemia in rats through hypoinduction of erythropoietin in the kidneys

Energy Technology Data Exchange (ETDEWEB)

Horiguchi, Hyogo [Department of Public Health, Fukushima Medical College, Fukushima (Japan); Sato, Masao [Department of Biomolecular Sciences, Institute of Biomedical Sciences, Fukushima Medical College, Fukushima (Japan); Konno, Nobuhiro [Department of Public Health, Fukushima Medical College, Fukushima (Japan); Fukushima, Masaaki [Department of Public Health, Fukushima Medical College, Fukushima (Japan)

1996-11-01

Cadmium (Cd), a highly toxic heavy metal, is distributed widely in the general environment of today. The characteristic clinical manifestations of chronic Cd intoxication include renal proximal tubular dysfunction, general osteomalacia with severe pains, and anemia. We have recently reported that the serum level of erythropoietin (EPO) remained low despite the severe anemia in patients with Itai-itai disease, the most severe form of chronic Cd intoxication. In order to prove that the anemia observed in chronic Cd intoxication arises from low production of EPO in the kidneys following the renal injury, we administered Cd to rats for a long period and performed the analysis of EPO mRNA inducibility in the kidneys. The rats administered Cd for 6 and 9 months showed anemia with low levels of plasma EPO as well as biochemical and histological renal tubular damage, and also hypoinduction of EPO mRNA in the kidneys. The results indicate that chronic Cd intoxication causes anemia by disturbing the EPO-production capacity of renal cells. (orig.). With 4 figs., 4 tabs.

Amelioration of renal lesions associated with diabetes by dietary curcumin in streptozotocin diabetic rats.

Science.gov (United States)

Suresh Babu, P; Srinivasan, K

1998-04-01

Curcumin, the coloring principle of the commonly used spice turmeric (Curcuma longa) was fed at 0.5% in the diet to streptozotocin-induced diabetic Wistar rats for 8 weeks. Renal damage was assessed by the amount of proteins excreted in the urine and the extent of leaching of renal tubular enzymes: NAG, LDH, AsAT, AlAT, alkaline and acid phosphatases. The integrity of kidney was assessed by measuring the activities of several key enzymes of the renal tissue: glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, and LDH (Carbohydrate metabolism), aldose reductase and sorbitol dehydrogenase (polyol pathway), transaminases, ATPases and membrane PUFA/SFA ratio (membrane integrity). Data on enzymuria, albuminuria, activity of kidney ATPases and fatty acid composition of renal membranes in diabetic condition suggested that dietary curcumin brought about significant beneficial modulation of the progression of renal lesions in diabetes. These findings were also corroborated by histological examination of kidney sections. It is inferred that this beneficial ameliorating influence of dietary curcumin on diabetic nephropathy is possibly mediated through its ability to lower blood cholesterol levels.

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.

Erythropoietin-enhanced endothelial progenitor cell recruitment in peripheral blood and renal vessels during experimental acute kidney injury in rats.

Science.gov (United States)

Cakiroglu, Figen; Enders-Comberg, Sora Maria; Pagel, Horst; Rohwedel, Jürgen; Lehnert, Hendrik; Kramer, Jan

2016-03-01

Beneficial effects of erythropoietin (EPO) have been reported in acute kidney injury (AKI) when administered prior to induction of AKI. We studied the effects of EPO administration on renal function shortly after ischemic AKI. For this purpose, rats were subjected to renal ischemia for 30 min and EPO was administered at a concentration of 500 U/kg either i.v. as a single shot directly after ischemia or with an additional i.p. dose until 3 days after surgery. The results were compared with AKI rats without EPO application and a sham-operated group. Renal function was assessed by measurement of serum biochemical markers, histological grading, and using an isolated perfused kidney (IPK) model. Furthermore, we performed flow cytometry to analyze the concentration of endothelial progenitor cells (EPCs) in the peripheral blood and renal vessels. Following EPO application, there was only a statistically non-significant tendency of serum creatinine and urea to improve, particularly after daily EPO application. Renal vascular resistance and the renal perfusion rate were not significantly altered. In the histological analysis, acute tubular necrosis was only marginally ameliorated following EPO administration. In summary, we could not demonstrate a significant improvement in renal function when EPO was applied after AKI. Interestingly, however, EPO treatment resulted in a highly significant increase in CD133- and CD34-positive EPC both in the peripheral blood and renal vessels. © 2015 International Federation for Cell Biology.

Benazepril, an angiotensin-converting enzyme inhibitor, alleviates renal injury in spontaneously hypertensive rats by inhibiting advanced glycation end-product-mediated pathways.

Science.gov (United States)

Liu, Xue-Ping; Pang, Yue-Jiu; Zhu, Wei-Wei; Zhao, Ting-Ting; Zheng, Min; Wang, Yi-Bing; Sun, Zhi-Jian; Sun, Siao-Jing

2009-03-01

1. Advanced glycation end-products (AGE) and their receptors (RAGE) have been implicated in renal damage in diabetes. The aim of the present study was to investigate the effects of benazepril, an angiotensin-converting enzyme inhibitor (ACEI), on the formation of AGE, the expression RAGE and other associated components in the oxidative stress pathway in spontaneously hypertensive rats (SHR). 2. Groups of SHR were treated with or without 10 mg/kg per day benazepril for 12 weeks. Systolic blood pressure (SBP) and angiotensin (Ang) II levels were evaluated in SHR and control Wistar-Kyoto (WKY) rats. Renal function was investigated by determining levels of proteinuria and glomerulosclerosis. Furthermore, reactive oxygen species (ROS) in the rat renal cortex were analysed using an H(2)O(2)-based hydroxyl radical-detection assay and the renal content of AGE, RAGE, NADPH oxidase p47phox, nuclear factor (NF)-kappaB p65, phosphorylated (p-) NF-kappaB p65, vascular cell adhesion molecule (VCAM)-1 and transforming growth factor (TGF)-beta1 was determined by immunohistochemistry, quantitative real-time polymerase chain reaction and western blot analysis. 3. Treatment with benazepril inhibited the formation of AngII, reduced SBP and alleviated renal lesions in SHR compared with both untreated SHR and control WKY rats. Benazepril treatment significantly suppressed the accumulation of AGE and expression of RAGE in the kidney of SHR. In addition, benazepril treatment reduced the upregulation of NADPH oxidase p47phox, ROS generation and NF-kappaB p65, p-NF-kappaB p65, VCAM-1 and TGF-beta1 expression in the kidney of SHR compared with both untreated SHR and control WKY rats. 4. The results of the present study provide new insights into the regulation by the renin-angiotensin system of AGE-RAGE, oxidative stress and nephropathy, increasing our understanding of the role of the RAS in nephropathy.

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.

Influence of specific and non-specific endothelin receptor antagonists on renal morphology in rats with surgical renal ablation.

Science.gov (United States)

Nabokov, A; Amann, K; Wagner, J; Gehlen, F; Münter, K; Ritz, E

1996-03-01

Studies in experimental models of chronic renal failure suggest an important role for the endothelin system in the development of renal scarring. Endothelin receptor (ETR) anatagonists interfere with progression, but it has not been resolved (i) whether this is true for all models of renal damage, (ii) to what extent the effect is modulated by systemic blood pressure and (iii) whether the effect is similar for ETAR and ETA/ETBR antagonists. 5/6 subtotal nephrectomy (SNX) by surgical ablation in male Sprague-Dawley rats. Comparison of ACE inhibitor Trandolapril (0.1 mg/kg/day), ETAR antagonist BMS 182874 (30 mg/kg/day) and ETAR/ETBR antagonist Ro 46-2005 (30 mg/kg/day) by gavage. Duration of the experiment eight weeks. Systolic blood pressure by tail plethysmography. Perfusion fixation of kidneys and morphometric analysis ET-1 and ETA/ETBR by quantitative PCR. SNX caused a significant (P < 0.01) increase of systolic blood pressure (170 +/- 8.6 mmHg) compared to sham operated controls (131 +/- 5.3 mmHg). Blood pressure was significantly (P < 0.001) lower with Trandolapril (128 +/- 5.3 mmHg), but not with BMS 182874 (153 +/- 5.9 mmHg) or Ro 46-2005 (167 +/- 7.6 mmHg). Compared to sham operated rats (0.03 +/- 0.01) glomerulosclerosis index (GSI) was significantly (P < 0.01) higher in the untreated SNX group (0.9 +/- 0.15). Significantly lower GSI was found in Trandolapril treated (0.29 +/- 0.04), BMS 182874 treated (0.36 +/- 0.05), and Ro 46-2005 treated animals (0.45 +/- 0.11). The effect of BMS 182874 was accompanied by lower tubulointerstitial damage index. Mean glomerular volume was dramatically increased (P < 0.001) in SNX rats as compared to sham operated animals. This glomerular enlargement was partially prevented by Trandolapril (P < 0.05), but not by either ETR antagonist. ET-1 mRNA tended to be higher in SNX irrespective of treatment, while ETAR and ETBR mRNA were significantly lower. Both specific (ETAR) and non-specific (ETA/ETBR) endothelin antagonists

Depression of calcium pump activity in renal cortex of vitamin D-deficient rats with secondary hyperparathyroidism

International Nuclear Information System (INIS)

Tsukamoto, Yusuke; Saitoh, Michiyo; Takita, Yumiko; Nakano, Toshiaki; Tamura, Teiichi

1990-01-01

To examine the hormonal regulation of the ATP-dependent Ca 2+ pump in the kidneys, the ATP-dependent Ca 2+ uptake by the basolateral membrane vesicles in the renal cortex was measured using radioactive calcium ( 45 Ca 2+ ) in rats with vitamin D deficiency or rats undergoing thyroparathyroidectomy. The V max of the Ca 2+ pump activity was increased not only by administering calcitriol, but also by normalizing the serum calcium level in vitamin D-deficient rats. PTH suppressed the Ca 2+ pump activity in normocalcemic vitamin D-deficient rats. Thyroparathyroidectomy did not affect the Ca 2+ pump activity in the kidneys of normal rats. It was concluded that the ATP-dependent Ca 2+ pump activity was depressed by secondary hyperparathyroidism in vitamin D-deficient rats. (author)

Urinary C-type natriuretic peptide excretion: a potential novel biomarker for renal fibrosis during aging.

Science.gov (United States)

Sangaralingham, S Jeson; Heublein, Denise M; Grande, Joseph P; Cataliotti, Alessandro; Rule, Andrew D; McKie, Paul M; Martin, Fernando L; Burnett, John C

2011-11-01

Renal aging is characterized by structural changes in the kidney including fibrosis, which contributes to the increased risk of kidney and cardiac failure in the elderly. Studies involving healthy kidney donors demonstrated subclinical age-related nephropathy on renal biopsy that was not detected by standard diagnostic tests. Thus there is a high-priority need for novel noninvasive biomarkers to detect the presence of preclinical age-associated renal structural and functional changes. C-type natriuretic peptide (CNP) possesses renoprotective properties and is present in the kidney; however, its modulation during aging remains undefined. We assessed circulating and urinary CNP in a Fischer rat model of experimental aging and also determined renal structural and functional adaptations to the aging process. Histological and electron microscopic analysis demonstrated significant renal fibrosis, glomerular basement membrane thickening, and mesangial matrix expansion with aging. While plasma CNP levels progressively declined with aging, urinary CNP excretion increased, along with the ratio of urinary to plasma CNP, which preceded significant elevations in proteinuria and blood pressure. Also, CNP immunoreactivity was increased in the distal and proximal tubules in both the aging rat and aging human kidneys. Our findings provide evidence that urinary CNP and its ratio to plasma CNP may represent a novel biomarker for early age-mediated renal structural alterations, particularly fibrosis. Thus urinary CNP could potentially aid in identifying subjects with preclinical structural changes before the onset of symptoms and disease, allowing for the initiation of strategies designed to prevent the progression of chronic kidney disease particularly in the aging population.

Renal content and output of epidermal growth factor in long-term adrenergic agonist-treated rats

DEFF Research Database (Denmark)

Thulesen, J; Nexø, Ebba; Poulsen, Steen Seier

2000-01-01

This study investigates the renal and urinary levels of epidermal growth factor (EGF) in rats under long-term treatment with alpha- or beta-adrenergic agonists. Urine samples were obtained on days 7, 14 and 21, and renal tissue samples on day 21. EGF was quantified by ELISA and tissue sections were...... material in the distal tubules. Concomitantly, reduced levels of EGF and EGF mRNA were observed, and also the urinary levels of EGF were reduced. Together, these observations indicate alpha-adrenergic treatment to affect the distal tubules. Treatment with the beta-adrenergic agonist did not change...... fractional kidney weight, but initially the urinary excretion of EGF was reduced. The data add further evidence to the suggestion that activity of the sympathetic nervous system influences renal homeostasis of EGF, either directly or indirectly through renal histopathological changes....

Renal ischemia-reperfusion injury in the rat is prevented by a novel immune modulation therapy

Czech Academy of Sciences Publication Activity Database

Tremblay, J.; Chen, H.; Peng, J.; Kuneš, Jaroslav; Vu, M. D.; Der Sarkissian, S.; deBlois, D.; Bolton, A. E.; Gaboury, L.; Marshansky, V.; Gouadon, E.; Hamet, P.

2002-01-01

Roč. 74, č. 10 (2002), s. 1425-1433 ISSN 0041-1337 Grant - others:Vasogen Inc.(CA) - Institutional research plan: CEZ:AV0Z5011922 Keywords : renal ischemia * immune therapy * rat Subject RIV: ED - Physiology Impact factor: 3.265, year: 2002

TELMISARATAN PROVIDES BETTER RENAL PROTECTION THAN VALSARTAN IN A RAT MODEL OF METABOLIC SYNDROME

Science.gov (United States)

Khan, Abdul Hye; Imig, John D.

2013-01-01

BACKGROUND Angiotension receptor blockers (ARB), telmisartan and valsartan were compared for renal protection in spontaneously hypertensive rats (SHR) fed high fat diet. We hypothesized that in cardiometabolic syndrome, telmisartan an ARB with PPAR-γ activity will offer better renal protection. METHODS SHR were fed either normal (SHR-NF, 7% fat) or high fat (SHR-HF, 36% fat) diet and treated with an ARB for 10 weeks. RESULTS Blood pressure was similar between SHR-NF (190±3 mmHg) and SHR-HF (192±4 mmHg) at the end of the 10 week period. Telmisartan and valsartan decreased blood pressure to similar extents in SHR-NF and SHR-HF groups. Body weight was significantly higher in SHR-HF (368±5g) compared to SHR-NF (328±7g). Telmisartan but not valsartan significantly reduced the body weight gain in SHR-HF. Telmisartan was also more effective than valsartan in improving glycemic and lipid status in SHR-HF. Monocyte chemoattractant protein-1 (MCP-1), an inflammatory marker, was higher in SHR-HF (24±2 ng/d) compared to SHR-NF (14±5 ng/d). Telmisartan reduced MCP-1 excretion in both SHR-HF and SHR-NF to a greater extent than valsartan. An indicator of renal injury, urinary albumin excretion increased to 85±8 mg/d in SHR-HF compared to 54±9 mg/d in SHR-NF. Telmisartan (23±5 mg/d) was more effective than valsartan (45±3 mg/d) in lowering urinary albumin excretion in SHR-HF. Moreover, telmisartan reduced glomerular damage to a greater extent than valsartan in the SHR-HF. CONCLUSIONS Collectively, our data demonstrate that telmisartan was more effective than valsartan in reducing body weight gain, renal inflammation, and renal injury in a rat model of cardiometabolic syndrome. PMID:21415842

Effect of soy protein on obesity-linked renal and pancreatic disorders in female rats

International Nuclear Information System (INIS)

Osman, H.F.; El-Sherbiny, E.M.

2006-01-01

The purpose of this study was to identify the effect of soy protein based diet on renal and pancreatic disorders in female obese rats. Animals assigned into group I in which 30 rats fed on a balanced diet. Group II contained 30 rats fed on a diet containing 30% fats for 4 weeks. At the end of the 4 th week, one-half of each group was treated as group III which contain 15 rats (half of group I) fed on diet containing 25% soy protein for 3 weeks and represents soy protein group, and the other half served as control. Group IV contained 15 rats (half of group II) fed on a diet containing 25% soy protein for 3 weeks and served as obese + soy protein group, and the other half fed on a normal balanced diet for 3 weeks and represents the obese group. Body weights of rats were recorded every week during the experimental period. Renal and pancreatic functions were measured as urea, creatinine, glomerular filtration rate (creatinine clearance), ammonia, sodium and potassium ions, total protein, albumin, globulin, glucose, insulin and alpha-amylase activity. Feeding with soy protein led to a very high significant increase in urea while creatinine was significantly decreased and creatinine clearance was significantly increased in the groups fed on soy protein. Ammonia concentration was increased in all groups and there was non-significant alteration in sodium and potassium ion concentrations. In soy protein groups (groups III and IV), total protein, albumin and globulin levels were increased. Glucose level was increased in obese rats and significantly decreased in groups III and IV. In group IV, insulin level was decreased which implicated to insulin excess in obesity. Soy protein decreased alpha-amylase activity in groups III and IV as compared to control rats. From these results, soy protein have a direct and protective effect on glomerular disorders and pancreatic secretions. This may be due to isoflavone contents in soy which can modulate the disturbance in metabolism

Differential patterns of injury to the proximal tubule of renal cortical slices following in vitro exposure to mercuric chloride, potassium dichromate, or hypoxic conditions.

Science.gov (United States)

Ruegg, C E; Gandolfi, A J; Nagle, R B; Brendel, K

1987-09-15

The innate susceptibility of renal cell types to these agents was investigated using precision-cut rabbit renal cortical slices made perpendicular to the cortical-papillary axis. Slices were incubated in DME/F12 medium containing 10 microM, 100 microM, or 1 mM concentrations of either metal for 12 hr or in Krebs-Hepes buffer gassed with nitrogen (100%) for 0.75 to 5 hr of hypoxic exposure. To simulate postischemic reperfusion, some slices were transferred to vessels gassed with oxygen after an initial hypoxic period. Mercuric chloride (100 microM) exposure resulted in damage to the straight regions of proximal tubules by 12 hr leaving convoluted regions unaffected. Hypoxia (2.25 hr) and potassium dichromate (100 microM for 12 hr) both caused injury to the convoluted proximal tubules without affecting straight proximal tubular regions. Mercury concentrations of 10 microM and 1 mM had no effect or injured all cell types within the slice, respectively. Similar results were observed for hypoxic periods less than 1.5 hr or greater than 3 hr of exposure. Potassium dichromate had no measurable affect at 10 microM, but at 1 mM focal lesions were observed after 4 hr of exposure, and by 12 hr all cell types within the slice were affected. Intracellular potassium content normalized to DNA correlated well, but always preceded the pathological lesions observed. These results demonstrate that injury to specific regions of the proximal tubule by these agents relates to an innate susceptibility of the intoxicated cell type independent of physiologic feedback or blood delivery patterns proposed as mechanisms of selective injury from in vivo studies.

The rebirth of interest in renal tubular function.

Science.gov (United States)

Lowenstein, Jerome; Grantham, Jared J

2016-06-01

The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mass and in patients with reduced renal function have identified small gut-derived, protein-bound uremic retention solutes ("uremic toxins") that are poorly filtered but are secreted into the lumen by organic anion transporters (OATs) in the proximal renal tubule. These are not effectively removed by conventional hemodialysis or peritoneal dialysis. Residual renal function, urine produced in patients with advanced renal failure or undergoing dialysis treatment, may represent, at least in part, secretion of fluid and uremic toxins, such as indoxyl sulfate, mediated by proximal tubule OATs and might serve as a useful survival function. In light of this new evidence of the physiological role of proximal tubule OATs, we suggest that measurement of renal tubular function and renal plasma flow may be of considerable value in understanding and managing chronic kidney disease. Data obtained in normal subjects indicate that renal plasma flow and renal tubular function might be measured by the clearance of the endogenous aryl amine, hippurate. Copyright © 2016 the American Physiological Society.