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Sample records for male rat-specific nephrotoxicity

  1. d-Limonene-induced male rat-specific nephrotoxicity: Evaluation of the association between d-limonene and alpha 2u-globulin

    Lehman-McKeeman, L.D.; Rodriguez, P.A.; Takigiku, R.; Caudill, D.; Fey, M.L.

    1989-01-01

    d-Limonene is a naturally occurring monoterpene, which when dosed orally, causes a male rat-specific nephrotoxicity manifested acutely as the exacerbation of protein droplets in proximal tubule cells. Experiments were conducted to examine the retention of [ 14 C]d-limonene in male and female rat kidney, to determine whether d-limonene or one or more of its metabolites associates with the male rat-specific protein, alpha 2u-globulin, and if so, to identify the bound material. The results indicated that, 24 hr after oral administration of 3 mmol d-limonene/kg, the renal concentration of d-limonene equivalents was approximately 2.5 times higher in male rats than in female rats. Equilibrium dialysis in the presence or absence of sodium dodecyl sulfate indicated that approximately 40% of the d-limonene equivalents in male rat kidney associated with proteins in a reversible manner, whereas no significant association was observed between d-limonene equivalents and female rat kidney proteins. Association between d-limonene and male rat kidney proteins was characterized by high-performance gel filtration and reverse-phase chromatography. Gel filtration HPLC indicated that d-limonene in male rat kidney is associated with a protein fraction having a molecular weight of approximately 20,000. Separation of alpha 2u-globulin from other kidney proteins by reverse-phase HPLC indicated that d-limonene associated with a protein present only in male rat kidney which was definitively identified as alpha 2u-globulin by amino acid sequencing. The major metabolite associated with alpha 2u-globulin was d-limonene-1,2-oxide. Parent d-limonene was also identified as a minor component in the alpha 2u-globulin fraction

  2. Protective Effect of Rosemary (Rosmarinus Officinalis) Extract on Naphthalene Induced Nephrotoxicity in Adult Male Albino Rat

    Neveen M. El-Sherif; Noha Mohy Issa

    2015-01-01

    Background: Naphthalene (NA) is a common environmental contaminant and is abundant in tobacco smoke. Rosemary (Rosmarinus officinalis) is a herb commonly used as a spice and flavoring agents in food processing and is useful in the treatment of many diseases. Aim of the work: To study the nephrotoxicity of NA and to evaluate the possible protective role of rosemary extract in adult male albino rat. Materials and Methods: 25 animals were divided into three groups: Group I (Control group), G...

  3. Tribulus terrestris-induced severe nephrotoxicity in a young healthy male.

    Talasaz, Azita Hajhossein; Abbasi, Mohammad-Reza; Abkhiz, Saeed; Dashti-Khavidaki, Simin

    2010-11-01

    Herbal medications are being progressively utilized all over the world. Nevertheless, herbal remedies are not without hazards and several cases of adverse reactions have been described. Tribulus terrestris is traditionally used because of its aphrodisiac and antiurolithiatic activities with almost complete inhibition of stone formation. We report a case of T. terrestris-induced hepatotoxicity, nephrotoxicity and neurotoxicity in an Iranian male patient who used the plant's extract to prevent kidney stone formation. He presented with seizure and very high serum aminotransferases and creatinine after consuming herbal water for 2 days. Discontinuation of the herbal remedy resulted in improvement in symptoms and normalization of his liver enzymes.

  4. Effect of Taurine on Cisplatin -Induced Nephrotoxicity and Hepatoxicity in Male Rat

    Noruzi M.

    2010-06-01

    Full Text Available Background and Objectives: Cisplatin, Platinum co-ordinate complex is a widely used antineaplastic agent for treatment of metastatic tumors. Taurine is an organic acid and an endogenous antioxidant. In this study we investigated the protective effect of taurine as an endogenous antioxidant against cisplatin induced nephrotoxicity and hepatotexicity.Methods: 24 male albino rats (180-220 grams were divided into 4 groups (n=6: (1: saline-treated group (2: cisplatin-treated group (10mg/kg, ip (3: group that received taurine (400mg/kg, ip 1hr before cisplatin (10mg/kg, ip administration (4: taurine (400mg/kg, ip. The animals were killed 7days after treatment and then blood samples were collected.Results: The results of this study indicated that cisplatin significantly increased CRATININ, URE, ALT, AST levels as compared to control group. Moreover, taurine significantly decreased CRATININ, URE, ALT and AST levels compared to cisplatin group.Conclusion: According to this study taurine prevents the incease of Creatinin, BUN, ALT and AST levels assisted by cisplatin, which may be due to its antioxidant properties.Keywords: Cisplatin; Taurine; Hepatoxicity; Nephrotoxicity; Nephrons.

  5. Tiron ameliorates oxidative stress and inflammation in titanium dioxide nanoparticles induced nephrotoxicity of male rats.

    Morgan, Ashraf; Galal, Mona K; Ogaly, Hanan A; Ibrahim, Marwa A; Abd-Elsalam, Reham M; Noshy, Peter

    2017-09-01

    Although the widespread use of titanium dioxide nanoparticles (TiO 2 NPs), few studies were conducted on its hazard influence on human health. Tiron a synthetic vitamin E analog was proven to be a mitochondrial targeting antioxidant. The current investigation was performed to assess the efficacy of tiron against TiO 2 NPs induced nephrotoxicity. Eighty adult male rats divided into four different groups were used: group I was the control, group II received TiO2 NPs (100mg\\Kg BW), group III received TiO2 NPs plus tiron (470mg\\kg BW), and group IV received tiron alone. Urea, creatinine and total protein concentrations were measured in serum to assess the renal function. Antioxidant status was estimated by determining the activities of glutathione peroxidase, superoxide dismutase, malondialdehyde (MDA) level and glutathione concentration in renal tissue. As well as Renal fibrosis was evaluated though measuring of transforming growth factor-β1 (TGFβ1) and matrix metalloproteinase 9 (MMP9) expression levels and histopathological examination. TiO 2 NPs treated rats showed marked elevation of renal indices, depletion of renal antioxidant enzymes with marked increase in MDA concentration as well as significant up-regulation in fibrotic biomarkers TGFβ1 and MMP9. Oral administration of tiron to TiO 2 NPs treated rats significantly attenuate the renal dysfunction through decreasing of renal indices, increasing of antioxidant enzymes activities, down-regulate the expression of fibrotic genes and improving the histopathological picture for renal tissue. In conclusion, tiron was proved to attenuate the nephrotoxicity induced by TiO 2 NPs through its radical scavenging and metal chelating potency. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Effect of nettle (Urtica dioica extract on gentamicin induced nephrotoxicity in male rabbits

    Nadia Abdulkarim Salih

    2015-09-01

    Conclusions: Therefore, it can be assumed that the nephroprotective effect shown by nettle in gentamicin-induced nephrotoxicity can reserve intracellular levels of biological pathways and supportively enhance excretion of toxic levels of gentamicin.

  7. Protective Effect of Rosemary (Rosmarinus Officinalis Extract on Naphthalene Induced Nephrotoxicity in Adult Male Albino Rat

    Neveen M. El-Sherif

    2015-02-01

    Full Text Available Background: Naphthalene (NA is a common environmental contaminant and is abundant in tobacco smoke. Rosemary (Rosmarinus officinalis is a herb commonly used as a spice and flavoring agents in food processing and is useful in the treatment of many diseases. Aim of the work: To study the nephrotoxicity of NA and to evaluate the possible protective role of rosemary extract in adult male albino rat. Materials and Methods: 25 animals were divided into three groups: Group I (Control group, Group II (NA treated group received NA at a dose of 200 mg/kg/day dissolved in 5 ml/kg corn oil orally by gastric tube, Group III (protected group received rosemary extract (10 ml/kg/day followed after 60 min by NA at the same previous dose orally by gastric tube. The experiment lasted 30 days. The following parameters were studied: Biochemical assessment of renal function, histological, immunohistochemical, morphometric studies and statistical analysis of the results. Results: NA treatment resulted in a highly significant increase in the mean values of serum urea and creatinine. NA induced histological changes in the form of glomerular congestion. Some glomeruli demonstrated marked mesangial expansion and hence that Bowman's spaces were almost completely obliterated. Shrinkage of renal glomeruli with widening of Bowman's spaces could also be seen. Focal tubular dilatation with appearance of casts inside the tubules was observed. Congested peritubular blood vessels and interstitial hemorrhage were also seen. The medullary region demonstrated vascular congestion and fibrosis. Focal cellular infiltration was presented in the interstitium. The renal cortex of NA treated rats showed a noticeable down regulation in alkaline phosphatase positive immunoreactive cells in some proximal convoluted tubules. NA induced up regulation of positive immunoreaction for inducible nitric oxide synthase in the proximal and distal convoluted tubules as well as in the collecting tubules

  8. Effect of Nigella sativa Linn oil on tramadol-induced hepato- and nephrotoxicity in adult male albino rats

    A. Elkhateeb

    2015-01-01

    Full Text Available The present study was carried out to evaluate the role of Nigella sativa Linn (NsL oil against subacute tramadol-induced hepatotoxicity, nephrotoxicity as well as oxidative stress in adult male albino rats. Sixty adult male albino rats were divided into four groups. Group I: control group; 30 rats equally subdivided into: Ia; −ve control group, Ib; +ve control group received saline, Ic; +ve control group received corn oil. Group II: 10 rats received NsL oil; 1 mg/kg in 1 ml corn oil/day, group III: 10 rats received tramadol; 30 mg/kg/day, group IV: 10 rats received tramadol + NsL oil in the previous doses. Treatments were given by gavage for 30 days. Then rats were sacrificed and specimens from the livers and kidneys were taken for biochemical and histopathological study. Biochemical data showed elevated liver enzymes; alanine transaminase (ALT, aspartate transaminase (AST, gamma glutamyltransferase (GGT, bilirubin as well as urea and creatinine in tramadol group. A significant increase in hepatic and renal malondialdehyde (MDA and a decrease in glutathione peroxidase (GPx levels were also noticed. Histological analysis of the liver showed vacuolated hepatocyte cytoplasm indicating hydropic degeneration with binucleated cells, apoptotic nuclei, congested central veins, cellular infiltration and hemorrhage. Kidney sections revealed atrophied glomeruli with collapsed tufts and wide Bowman's space, degenerated tubules, hemorrhage and mononuclear cellular infiltration. There was also an increase in area % of collagen fibers in both organs. Concomitant use of NsL oil with tramadol induced partial improvement in the hepato- and nephrotoxic effects. In conclusion, this study suggested that concomitant use of NsL oil with tramadol proved to be capable of ameliorating tramadol-induced hepato- and nephrotoxicity which might be due to its antioxidant potential.

  9. Curcumin ameliorates diclofenac sodium-induced nephrotoxicity in male albino rats.

    Ahmed, Ahmady Y; Gad, Amany M; El-Raouf, Ola M Abd

    2017-10-01

    Exposure to drugs often results in toxicity in the kidney which represents the major control system maintaining homeostasis of the body and thus is especially susceptible to xenobiotics. Nephrotoxicity is a life-threatening side-effect of nonsteroidal anti-inflammatory drugs (NSAIDs). Diclofenac is one of the most frequently prescribed NSAIDs and have been reported to cause multiple organs damage. Curcumin (CUR) exhibits nephroprotective properties. Therefore, rats were divided into four groups; rats of groups 3 and 4 received diclofenac (100 mg/kg, i.m.), whereas rats of groups 2 and 4 received CUR (100 mg/kg, p.o.) for 3 days. Diclofenac revealed a significant increase in urea and creatinine levels and malondialdehyde concentration and marked reduction in catalase activity and reduced glutathione concentration. Histopathologically, diclofenac produced fatty changes and eosinophilic casts were detected in the renal tubules, those were attenuated by administration of CUR prior diclofenac. © 2017 Wiley Periodicals, Inc.

  10. Dosimetry considerations in the enhanced sensitivity of male Wistar rats to chronic ethylene glycol-induced nephrotoxicity

    Corley, R.A.; Wilson, D.M.; Hard, G.C.; Stebbins, K.E.; Bartels, M.J.; Soelberg, J.J.; Dryzga, M.D.; Gingell, R.; McMartin, K.E.; Snellings, W.M.

    2008-01-01

    Male Wistar rats have been shown to be the most sensitive sex, strain and species to ethylene glycol-induced nephrotoxicity in subchronic studies. A chronic toxicity and dosimetry study was therefore conducted in male Wistar rats administered ethylene glycol via the diet at 0, 50, 150, 300, or 400 mg/kg/day for up to twelve months. Subgroups of animals were included for metabolite analysis and renal clearance studies to provide a quantitative basis for extrapolating dose-response relationships from this sensitive animal model in human health risk assessments. Mortality occurred in 5 of 20 rats at 300 mg/kg/day (days 111-221) and 4 of 20 rats at 400 mg/kg/day (days 43-193), with remaining rats at this dose euthanized early (day 203) due to excessive weight loss. Increased water consumption and urine volume with decreased specific gravity occurred at 300 mg/kg/day presumably due to osmotic diuresis. Calculi (calcium oxalate crystals) occurred in the bladder or renal pelvis at ≥ 300 mg/kg/day. Rats dying early at ≥ 300 mg/kg/day had transitional cell hyperplasia with inflammation and hemorrhage of the bladder wall. Crystal nephropathy (basophilic foci, tubule or pelvic dilatation, birefringent crystals in the pelvic fornix, or transitional cell hyperplasia) affected most rats at 300 mg/kg/day, all at 400 mg/kg/day, but none at ≤ 150 mg/kg/day. No significant differences in kidney oxalate levels, the metabolite responsible for renal toxicity, were observed among control, 50 and 150 mg/kg/day groups. At 300 and 400 mg/kg/day, oxalate levels increased proportionally with the nephrotoxicity score supporting the oxalate crystal-induced nephrotoxicity mode of action. No treatment-related effects on the renal clearance of intravenously infused 3 H-inulin, a marker for glomerular filtration, and 14 C-oxalic acid were observed in rats surviving 12 months of exposure to ethylene glycol up to 300 mg/kg/day. In studies with naive male Wistar and F344 rats (a less sensitive

  11. The Role of Biotransformation and Oxidative Stress in 3,5-Dichloroaniline (3,5-DCA) Induced Nephrotoxicity in Isolated Renal Cortical Cells from Male Fischer 344 Rats

    Racine, Christopher R.; Ferguson, Travis; Preston, Debbie; Ward, Dakota; Ball, John; Anestis, Dianne; Valentovic, Monica; Rankin, Gary O.

    2016-01-01

    Among the mono- and dichloroanilines, 3,5-Dichloroaniline (3,5-DCA) is the most potent nephrotoxicant in vivo and in vitro. However, the role of renal biotransformation in 3,5-DCA induced nephrotoxicity is unknown. The current study was designed to determine the in vitro nephrotoxic potential of 3,5-DCA in isolated renal cortical cells (IRCC) obtained from male Fischer 344 rats, and the role of renal bioactivation and oxidative stress in 3,5-DCA nephrotoxicity. IRCC (~4 million cells/ml) from male rats were exposed to 3,5-DCA (0-1.0 mM) for up to 120 min. In IRCC, 3,5-DCA was cytotoxic at 1.0 mM by 60 min as evidenced by the increased release of lactate dehydrogenase (LDH), but 120 min was required for 3,5-DCA 0.5 mM to increase LDH release. In subsequent studies, IRCC were exposed to a pretreatment (antioxidant or enzyme inhibitor) prior to exposure to 3,5-DCA (1.0 mM) for 90 min. Cytotoxicity induced by 3,5-DCA was attenuated by pretreatment with inhibitors of flavin-containing monooxygenase (FMO; methimazole, N-octylamine), cytochrome P450 (CYP; piperonyl butoxide, metyrapone), or peroxidase (indomethacin, mercaptosuccinate) enzymes. Use of more selective CYP inhibitors suggested that the CYP 2C family contributed to 3,5-DCA bioactivation. Antioxidants (glutathione, N-acetyl-L-cysteine, α-tocopherol, ascorbate, pyruvate) also attenuated 3,5-DCA nephrotoxicity, but oxidized glutathione levels and the oxidized/reduced glutathione ratios were not increased. These results indicate that 3,5-DCA may be activated via several renal enzyme systems to toxic metabolites, and that free radicals, but not oxidative stress, contribute to 3,5-DCA induced nephrotoxicity in vitro. PMID:26808022

  12. Mitigating potential of Ginkgo biloba extract and melatonin against hepatic and nephrotoxicity induced by Bisphenol A in male rats

    Mayssaa M. Wahby

    2017-12-01

    Full Text Available Bisphenol A is one of the anthropogenic chemicals produced worldwide, currently released into the environment and causes endocrine-disruption. The largest environmental compartments of BPA are abiotic associated with water and suspended solids that becomes an integrated part of the food chain. The present study aimed to examine the possible protective role of Ginkgo biloba extract (GBE, melatonin and their combination against BPA-induced liver and kidney toxicity of male rats. Fifty rats were divided into five equal groups: control, BPA, BPA plus GBE, BPA plus melatonin and BPA plus GBE plus melatonin. The elevated activities of plasma ALT and AST in addition to increased levels of urea and creatinine concomitant with the decreased total plasma protein could reflect the injurious effect of BPA. Liver and kidney levels of TBARS were significantly increased, while GSH, SOD and GPX were decreased in BPA-treated rats. Also, CAT and GST activities were significantly disrupted in the liver and kidney of rats treated with BPA. Moreover, BPA significantly increased the proinflammatory cytokine TNF-α in the liver and kidney tissues. The histopathological analysis confirmed these results. All the previous alterations in the liver and kidney could be ameliorated when BPA-treated rats were co-administrated either with GBE, melatonin or their combination. These natural substances could exhibit protective effects against BPA-induced hepato- and nephrotoxicity owing to their antioxidative and anti-inflammatory potentials. Keywords: Bisphenol A, Ginkgo biloba extract, Melatonin, Lipid peroxidation, Antioxidant enzymes, Histopathological analysis

  13. Cisplatin Induced Nephrotoxicity

    Seyed Seifollah Beladi Mousavi

    2014-02-01

    The standard approach to prevent cisplatin-induced nephrotoxicity is the administration of lower doses of cisplatin in combination with the administration of full intravenous isotonic saline before and after cisplatin administration. Although a number of pharmacologic agents including sodium thiosulfate, N-acetylcysteine, theophylline and glycine have been evaluated for prevention of nephrotoxicity, none have proved to have an established role, thus, additional clinical studies will be required to confirm their probable effects.

  14. Prevention of cisplatin nephrotoxicity

    Hayati Fatemeh

    2016-01-01

    Full Text Available Cisplatin has a well-established role in the treatment of broad spectrum of malignancies; however its use is limited because of cisplatin-induced nephrotoxicity (CIN which can be progressive in more than 50% of cases. The most important risk factors for CIN include higher doses of cisplatin, previous cisplatin chemotherapy, underlying kidney damage and concurrent treatment with other potential nephrotoxin agents, such as aminoglycosides, nonsteroidal anti-inflammatory agents, or iodinated contrast media. Different strategies have been offered to diminish or prevent nephrotoxicity of cisplatin. The standard approach for prevention of CIN is the administration of lower doses of cisplatin in combination with full intravenous hydration prior and after cisplatin administration. Cisplatin-induced oxidative stress in the kidney may be prevented by natural antioxidant compounds. The results of this review show that many strategies for prevention of CIN exist, however, attention to the administration of these agent for CIN is necessary.

  15. Iodinated contrast media nephrotoxicity

    Meyrier, A.

    1994-01-01

    In the late seventies, iodinated contrast agents (ICA) were considered to be a major cause of acute iatrogenic renal failure. Over the last decade new contrast agents have been synthesized, nonionic and less hyperosmolar. The incidence of acute renal failure due to ICAs, varies from 3.7 to 70% of cases according to the series, with an average figure of 10.2%. The pathophysiology of ICA nephrotoxicity was mainly studied in laboratory animal models. Three main factors are involved in an inducing ICA-mediated decrease in glomerular filtration rate: reduction of the renal plasma flow, a direct cytotoxic effect on renal tubular cells and erythrocyte alteration leading to intra-renal sludge. Excluding dysglobulinemias with urinary excretion of immunoglobulin light chains, which represent a special case of maximum nephrotoxicity, 4 main risk factors of renal toxicity have been identified in nondiabetic subjects: previous renal failure with serum creatinine levels greater than 140 μmol per liter, extracellular dehydration, age over 60 and use of high doses of ICA and/or repeated ICA injections before serum creatinine levels return to baseline. Preventive measures for avoiding ICA nephrotoxicity are threefold: maintain or restore adequate hydration with saline infusion, stop NSAID treatment several days before ICA administration, and allow a 5 day interval before repeating contrast media injections. New, nonionic and moderately hyperosmolar contrast agents appear to be much less nephrotoxic than conventional ICAs in laboratory animals and in high-risk patients. It is advisable to select such contrast media for investigating high-risk patients. This approach was recently substantiated in well designed, randomized clinical studies which included more than 2 000 patients. (author)

  16. Hepatotoxic and Nephrotoxic Effects of Petroleum Fumes on Petrol ...

    The present study was conducted to evaluate the hepatotoxic and nephrotoxic effects of petroleum fumes on male and female petrol attendants. Investigations had been carried out on thirty (30) adult petrol attendants from different filling stations in Ibadan metropolis of Nigeria with ten (10) healthy adults as control. All the ...

  17. Nephrotoxicity of Natural Products.

    Nauffal, Mary; Gabardi, Steven

    2016-01-01

    The manufacture and sale of natural products constitute a multi-billion dollar industry. Nearly a third of the American population admit to using some form of complementary or alternative medicine, with many using them in addition to prescription medications. Most patients fail to inform their healthcare providers of their natural product use and physicians rarely inquire. Annually, thousands of natural product-induced adverse events are reported to Poison Control Centers nationwide. Natural product manufacturers are not responsible for proving safety and efficacy, as the FDA does not regulate them. However, concerns exist surrounding the safety of natural products. This review provides details on natural products that have been associated with renal dysfunction. We have focused on products that have been associated with direct renal injury, immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, hepatorenal syndrome, and common adulterants or contaminants that are associated with renal dysfunction. The potential for natural products to cause renal dysfunction is justifiable. It is imperative that natural product use be monitored closely in all patients. Healthcare practitioners must play an active role in identifying patients using natural products and provide appropriate patient education. © 2016 S. Karger AG, Basel.

  18. Nephrotoxicity and Chinese Herbal Medicine.

    Yang, Bo; Xie, Yun; Guo, Maojuan; Rosner, Mitchell H; Yang, Hongtao; Ronco, Claudio

    2018-04-03

    Chinese herbal medicine has been practiced for the prevention, treatment, and cure of diseases for thousands of years. Herbal medicine involves the use of natural compounds, which have relatively complex active ingredients with varying degrees of side effects. Some of these herbal medicines are known to cause nephrotoxicity, which can be overlooked by physicians and patients due to the belief that herbal medications are innocuous. Some of the nephrotoxic components from herbs are aristolochic acids and other plant alkaloids. In addition, anthraquinones, flavonoids, and glycosides from herbs also are known to cause kidney toxicity. The kidney manifestations of nephrotoxicity associated with herbal medicine include acute kidney injury, CKD, nephrolithiasis, rhabdomyolysis, Fanconi syndrome, and urothelial carcinoma. Several factors contribute to the nephrotoxicity of herbal medicines, including the intrinsic toxicity of herbs, incorrect processing or storage, adulteration, contamination by heavy metals, incorrect dosing, and interactions between herbal medicines and medications. The exact incidence of kidney injury due to nephrotoxic herbal medicine is not known. However, clinicians should consider herbal medicine use in patients with unexplained AKI or progressive CKD. In addition, exposure to herbal medicine containing aristolochic acid may increase risk for future uroepithelial cancers, and patients require appropriate postexposure screening. Copyright © 2018 by the American Society of Nephrology.

  19. Assessment of the Anti-Hyperglycaemic, Anti-Inflammatory and Antioxidant Activities of the Methanol Extract of Moringa Oleifera in Diabetes-Induced Nephrotoxic Male Wistar Rats.

    Omodanisi, Elizabeth I; Aboua, Yapo G; Oguntibeju, Oluwafemi O

    2017-03-23

    Diabetes mellitus is an endocrine disease of multiple aetiologies in insulin secretion. A deficiency in insulin results in hyperglycemia with metabolic disturbances of biomolecules. Moringa oleifera (MO) is endemic in the tropics with a variety of ethnomedicinal importance. The leaf of this plant has been reported to possess antioxidant and medicinal properties that may be helpful in the treatment and management of diabetes and its associated complications. Diabetes was induced intraperitoneally in rats by a single dose of streptozotocin (55 mg/kg) and treated with methanolic extract of Moringa oleifera (250 mg/kg b.wt) for six weeks. Forty-eight (48) adult male Wistar strain rats were randomly divided into four groups: normal control (NC), Moringa oleifera treated control rats (NC + MO), diabetic rats (DM) and Moringa oleifera treated diabetic rats (DM + MO). Estimation of antioxidant capacity, total polyphenols, flavonoids and flavonols content of Moringa oleifera extract was performed and serum biochemical markers were evaluated. Antioxidants such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) activities, glutathione (GSH) and inflammatory biomarkers were determined in the kidney. Results showed high antioxidant capacities of MO extract and improved serum biochemical markers, whilst lipid peroxidation (MDA) levels were reduced in non-diabetic and diabetic rats after MO treatment when compared to normal control. Subsequent administration of MO led to an increased concentration of serum albumin, globulin and total protein with a decrease in the level of MDA, and improvements in CAT, SOD, GSH, GPx, (tumour necrosis factor-alpha)TNF-α and (interleukin-6)IL-6. MO contains potent phytochemical constituents that offer protective action against diabetic-induced renal damage, reactive oxygen species (ROS) and inflammation and could therefore play a role in reducing diabetic complications, particularly in developing countries such as in

  20. Nephrotoxicities [version 1; referees: 2 approved

    Stuart L. Goldstein

    2017-01-01

    Full Text Available Nephrotoxic medication exposure is nearly ubiquitous in hospitalized patients and represents one of the most common causes of acute kidney injury (AKI in the hospitalized setting. Although provision of medications that are nephrotoxic has led to improved outcomes in terms of treatment of underlying illness, unnecessary nephrotoxic medication exposure can be viewed as a potentially modifiable adverse safety event if AKI can be prevented. The advancements in electronic health record development, standardization of AKI definitions, and the ability to identify AKI risk and development in near real time provide opportunities to reduce harm from nephrotoxicity.

  1. Concomitant gentamicin‑induced nephrotoxicity and bilateral ...

    ... injections of gentamicin. Coexisting ototoxicity and nephrotoxicity from aminoglycosides can occur, though rare. Adverse effects of aminoglycosides are better prevented by a careful exercise of discretion by prescribers. Keywords: Acute kidney injury, aminoglycosides, co‑occurrence, gentamicin, nephrotoxicity, ototoxicity ...

  2. Murine nephrotoxic nephritis as a model of chronic kidney disease

    Ougaard, M. K.E.; Kvist, P. H.; Jensen, H. E.

    2018-01-01

    Using the nonaccelerated murine nephrotoxic nephritis (NTN) as a model of chronic kidney disease (CKD) could provide an easily inducible model that enables a rapid test of treatments. Originally, the NTN model was developed as an acute model of glomerulonephritis, but in this study we evaluate...... progressive mesangial expansion and significant renal fibrosis within three weeks suggesting CKD development. CD1 and C57BL/6 females showed a similar disease progression, but female mice seemed more susceptible to NTS compared to male mice. The presence of albuminuria, GFR decline, mesangial expansion...

  3. Integrated transcriptomic and proteomic evaluation of gentamicin nephrotoxicity in rats

    Com, Emmanuelle; Boitier, Eric; Marchandeau, Jean-Pierre; Brandenburg, Arnd; Schroeder, Susanne; Hoffmann, Dana; Mally, Angela; Gautier, Jean-Charles

    2012-01-01

    Gentamicin is an aminoglycoside antibiotic, which induces renal tubular necrosis in rats. In the context of the European InnoMed PredTox project, transcriptomic and proteomic studies were performed to provide new insights into the molecular mechanisms of gentamicin-induced nephrotoxicity. Male Wistar rats were treated with 25 and 75 mg/kg/day subcutaneously for 1, 3 and 14 days. Histopathology observations showed mild tubular degeneration/necrosis and regeneration and moderate mononuclear cell infiltrate after long-term treatment. Transcriptomic data indicated a strong treatment-related gene expression modulation in kidney and blood cells at the high dose after 14 days of treatment, with the regulation of 463 and 3241 genes, respectively. Of note, the induction of NF-kappa B pathway via the p38 MAPK cascade in the kidney, together with the activation of T-cell receptor signaling in blood cells were suggestive of inflammatory processes in relation with the recruitment of mononuclear cells in the kidney. Proteomic results showed a regulation of 163 proteins in kidney at the high dose after 14 days of treatment. These protein modulations were suggestive of a mitochondrial dysfunction with impairment of cellular energy production, induction of oxidative stress, an effect on protein biosynthesis and on cellular assembly and organization. Proteomic results also provided clues for potential nephrotoxicity biomarkers such as AGAT and PRBP4 which were strongly modulated in the kidney. Transcriptomic and proteomic data turned out to be complementary and their integration gave a more comprehensive insight into the putative mode of nephrotoxicity of gentamicin which was in accordance with histopathological findings. -- Highlights: ► Gentamicin induces renal tubular necrosis in rats. ► The mechanisms of gentamicin nephrotoxicity remain still elusive. ► Transcriptomic and proteomic analyses were performed to study this toxicity in rats. ► Transcriptomic and proteomic

  4. Involvement of reversible binding to alpha 2u-globulin in 1,4-dichlorobenzene-induced nephrotoxicity.

    Charbonneau, M; Strasser, J; Lock, E A; Turner, M J; Swenberg, J A

    1989-06-01

    Similarly to unleaded gasoline, 1,4-dichlorobenzene (1,4-DCB) administered for 2 years caused a dose-related increase in the incidence of renal tumors in male but not in female rats or in either sex of mice. Unleaded gasoline and 2,2,4-trimethylpentane (TMP), a component of unleaded gasoline, increased protein droplet formation and cell proliferation in male but not in female rat kidneys. These protein droplets contained, alpha 2u-globulin, a male rat-specific low-molecular-weight protein and 2,4,4-trimethyl-2-pentanol, a metabolite of TMP that was reversibly bound to this protein. Studies were undertaken to determine if 1,4-DCB produced similar effects; 1,2-DCB was used for comparison since it did not produce renal carcinogenesis in male rats. Gel filtration chromatography of a 116,000g supernatant prepared from kidneys of 1,4-[14C]DCB-treated rats showed that radiolabel coeluted with alpha 2u-globulin as one sharp peak as opposed to a multipeak pattern observed for 1,2-[14C]DCB; the maximal quantity of radiolabel for 1,4-DCB was twice that for 1,2-DCB. Equilibrium dialysis of kidney cytosol in the presence or absence of sodium dodecyl sulfate demonstrated that the radiolabel was reversibly bound to alpha 2u-globulin; the amount for 1,4-[14C]DCB-treated rats was almost twice as much as that for 1,2-[14C]DCB-treated rats. 1,2-DCB was also shown to be covalently bound to renal alpha 2u-globulin, and covalently bound to liver and plasma high-molecular-weight proteins. 1,4-DCB and, to a minor extent, 2,5-dichlorophenol, the major metabolite of 1,4-DCB, were reversibly bound to renal alpha 2u-globulin from 1,4-DCB-treated rats. 1,4-DCB increased protein droplet formation in male but not in female rat kidneys, whereas equimolar doses of 1,2-DCB showed no effect in either sex. Renal cell proliferation, measured by [3H]thymidine incorporation into renal DNA, was increased after 1,4-DCB but not after 1,2-DCB treatment. Nephrotoxicity and biochemical alterations induced by

  5. Antibacterial-induced nephrotoxicity in the newborn.

    Fanos, V; Cataldi, L

    1999-03-01

    Antibacterials are the primary cause of drug-induced kidney disease in all age groups and these agents bring about renal damage by 2 main mechanisms, namely, direct and immunologically mediated. For some antibacterials (aminoglycosides and vancomycin) nephrotoxicity is very frequent but generally reversible upon discontinuation of the drug. However, the development of acute renal failure with these agents is possible and its incidence in the newborn seems to be increasing. Antibacterials are very often used in the neonatal period especially in very low birthweight neonates. The role of neonatal age in developing nephrotoxicity has still to be defined. Since the traditional laboratory parameters of nephrotoxicity are abnormal only in the presence of substantial renal damage, the identification of early non-invasive markers of the renal damage (urinary microglobulins, enzymes and growth factors) is of importance. Aminoglycosides and glycopeptides are still frequently used, either alone or in combination, despite their low therapeutic index. Numerous factors intervene in bringing about the kidney damage induced by these 2 classes of antibacterials, such as factors related to the antibacterial itself and others related to the associated pathology as well as pharmacological factors. Nephrotoxicity can be caused by the beta-lactams and related compounds. Their potential to cause nephrotoxicity decreases in the order: carbapenems > cephalosporins > penicillins > monobactams. Third generation cephalosporins are frequently used in neonates. However, they are well tolerated compounds at the renal level. The nephrotoxicity of other classes of antibacterials is not discussed either because they are only used in neonates in exceptional circumstances, for example, chloramphenicol and cotrimoxazole (trimethoprim-sulfamethoxazole) or are not associated with significant nephrotoxicity, for example macrolides, clindamicin, quinolones, rifampicin (rifampin) and metronidazole

  6. Protective Effect of Carvacrol on Renal Functional and Histopathological Changes in Gentamicin-Induced-Nephrotoxicity in Rats

    Hassan Ahmadvand

    2016-04-01

    Full Text Available Background Nephrotoxicity is one of the most important side effects of the use of gentamicin sulphate (GS resulted in reactive oxygen species generation. Antioxidant compounds played effective roles in reduction of renal injuries caused by using of gentamicin. Carvacrol is a strong antioxidant compound. Objectives The aim of this study is to explore the effect of carvacrol inhibition in lesions of gentamicin-induced nephrotoxicity. Materials and Methods In this experimental study, 32 male mature Sprague-Dawley rats were divided into 4 groups of 8; group1: control, group 2 sham received daily carvacrol injection (74 mg/kg for 12 days, group 3 received daily GS injection (100 mg/kg for 12 days, group 4 received daily GS (100 mg/kg and carvacrol (74 mg/kg for 12 days. After 12 days, rats were anaesthetized, blood sample were obtained and kidneys were removed then stained with hematoxylin and eosin method and then were studied histophatologically. Serum creatinine and urea were measured. Results Flow treatment of nephrotoxic animals with carvacrol could significantly inhibit leukocyte infiltration (9.42% and tubular necrosis (38.18% in comparison with the nephrotoxic untreated group. Carvacrol significantly decreased the levels of urea and creatinine in treated group compared with the nephrotoxic untreated group. Conclusions The findings showed that carvacrol alleviates loss of leukocyte infiltration (9.42% and tubular necrosis and exerts beneficial effects on kidney function test in nephrotoxic group.

  7. An integrated view of cisplatin-induced nephrotoxicity and ototoxicity

    Karasawa, Takatoshi; Steyger, Peter S.

    2015-01-01

    Cisplatin is one of the most widely-used drugs to treat cancers. However, its nephrotoxic and ototoxic side-effects remain major clinical limitations. Recent studies have improved our understanding of the molecular mechanisms of cisplatin-induced nephrotoxicity and ototoxicity. While cisplatin binding to DNA is the major cytotoxic mechanism in proliferating (cancer) cells, nephrotoxicity and ototoxicity appear to result from toxic levels of reactive oxygen species and protein dysregulation within various cellular compartments. In this review, we discuss molecular mechanisms of cisplatin-induced nephrotoxicity and ototoxicity. We also discuss potential clinical strategies to prevent nephrotoxicity and ototoxicity and their current limitations. PMID:26101797

  8. Mefenamic Acid Induced Nephrotoxicity: An Animal Model

    Muhammad Nazrul Somchit

    2014-12-01

    Full Text Available Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model. Methods: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day. Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN and creatinine activities were measured. Results: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine. Conclusion: Results from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.

  9. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies.

    Pabla, N; Dong, Z

    2008-05-01

    Cisplatin is one of the most widely used and most potent chemotherapy drugs. However, side effects in normal tissues and organs, notably nephrotoxicity in the kidneys, limit the use of cisplatin and related platinum-based therapeutics. Recent research has shed significant new lights on the mechanism of cisplatin nephrotoxicity, especially on the signaling pathways leading to tubular cell death and inflammation. Renoprotective approaches are being discovered, but the protective effects are mostly partial, suggesting the need for combinatorial strategies. Importantly, it is unclear whether these approaches would limit the anticancer effects of cisplatin in tumors. Examination of tumor-bearing animals and identification of novel renoprotective strategies that do not diminish the anticancer efficacy of cisplatin are essential to the development of clinically applicable interventions.

  10. Adefovir nephrotoxicity in a renal allograft recipient

    N George

    2015-01-01

    Full Text Available Adefovir dipivoxil, an oral prodrug of adefovir, is used in the treatment of lamivudine-resistant hepatitis B virus (HBV infection. Nephrotoxicity manifesting as proximal renal tubular dysfunction and acute tubular necrosis (ATN were commonly reported in the past, when higher doses were used for the treatment of human immunodeficiency virus infection. However, nephrotoxicity is rare at lower doses that are currently recommended for the treatment of HBV infection. A 31-year-old female was detected to be hepatitis B surface antigen positive months after a kidney transplant. The patient was initiated on lamivudine, but developed resistance after 1 year of treatment, at which time low-dose adefovir was added. The patient developed renal allograft dysfunction after 10 months of starting adefovir. Serum creatinine increased from 1.1 mg/dl to 1.9 mg/dl, along with progressively increasing sub-nephrotic proteinuria. Renal allograft biopsy revealed features of ATN. After discontinuation of adefovir, proteinuria resolved and renal dysfunction improved slowly over the next 2 years. Adefovir-induced nephrotoxicity, although uncommon at lower doses, needs to be considered in the differential diagnosis of renal dysfunction and sub-nephrotic proteinuria occurring in patients receiving adefovir for prolonged periods.

  11. Gamma-aminobutyric acid aggravates nephrotoxicity induced by cisplatin in female rats.

    Peysepar, Elham; Soltani, Nepton; Nematbakhsh, Mehdi; Eshraghi-Jazi, Fatemeh; Talebi, Ardeshir

    2016-01-01

    Cisplatin (CP) is a major antineoplastic drug for treatment of solid tumors. CP-induced nephrotoxicity may be gender-related. This is while gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the central nervous system that has renoprotective impacts on acute renal injury. This study was designed to investigate the protective role of GABA against CP-induced nephrotoxicity in male and female rats. Sixty Wistar male and female rats were used in eight experimental groups. Both genders received GABA (50 μg/kg/day; i. p.) for 14 days and CP (2.5 mg/kg/day; i. p.) was added from day 8 to the end of the study, and they were compared with the control groups. At the end of the study, all animals were sacrificed and the serum levels of blood urea nitrogen (BUN), creatinine (Cr), nitrite, malondialdehyde (MDA), and magnesium (Mg) were measured. The kidney tissue damage was also determined via staining. CP significantly increased the serum levels of Cr and BUN, kidney weight, and kidney tissue damage score in both genders (PGABA did not attenuate these markers in males; even these biomarkers were intensified in females. Serum level of Mg, and testis and uterus weights did not alter in the groups. However, the groups were significantly different in terms of nitrite and MDA levels. It seems that GABA did not improve nephrotoxicity induced by CP-treated rats, and it exacerbated renal damage in female rats.

  12. Anthocyanin – Rich Red Dye of Hibiscus Sabdariffa Calyx Modulates Cisplatin-induced Nephrotoxicity and Oxidative Stress in Rats

    Ademiluyi, Adedayo O.; Oboh, Ganiyu; Agbebi, Oluwaseun J.; Akinyemi, Ayodele J.

    2013-01-01

    This study sought to investigate the protective effect of dietary inclusion of Hibiscus sabdariffa calyx red dye on cisplatin-induced nephrotoxicity and antioxidant status in rats. Adult male rats were randomly divided into four groups of six animals each. Groups I and II were fed basal diet while groups III and IV were fed diets containing 0.5% and 1% of the dye respectively for 20 days prior to cisplatin administration. Nephrotoxicity was induced by a single dose intraperitoneal administration of cisplatin (7 mg/kg b.w) and the experiment was terminated 3 days after. The kidney and plasma were studied for nephrotoxicity and oxidative stress indices. Cisplatin administration caused a significant (Psabdariffa dye could be attributed to its anthocyanin content. PMID:24711761

  13. Gentamicin Nephrotoxicity in Subclinical Renal Disease.

    Frazier, Donita L.

    The purpose of the present study was to examine the pharmacokinetic disposition of gentamicin and to define the mechanisms which predispose to nephrotoxicity in subclinical renal disease. Subtotally nephrectomized beagle dogs were used as a model for human beings with compromised renal function secondary to a reduced number of functional nephrons. Using ultrastructural morphometry, light microscopy and clinical chemistry data, the model was defined and the nephrotoxic responses of intact dogs administered recommended doses of drug were compared to the response of subtotally nephrectomized dogs administered reduced doses based on each animal's clearance of drug. Lysosomal and mitochondrial morphometric changes suggested mechanisms for increased sensitivity. To determine if increased sensitivity in this model was dependent on altered serum concentrations, variable rate infusions based on individual pharmacokinetic disposition of drug were administered using computer-driven infusion pumps. Identical serum concentration-time profiles were achieved in normal dogs and subtotally nephrectomized dogs, however, toxicity was significantly greater in nephrectomized dogs. The difference in the nephrotoxic response was characterized by administering supratherapeutic doses of drug to dogs. Nephrectomized dogs given a recommended dose of gentamicin became oliguric during the second week of treatment and increasingly uremic after withdrawal of drug. In contrast, intact dogs administered 2 times the recommended dose of gentamicin become only slightly polyuric during week 4 of treatment. The need to individualize dosage regimens based on drug clearance and not serum creatinine nor creatinine clearance alone was substantiated by describing the pharmacokinetic disposition of gentamicin in spontaneously occurring disease states. Four individualized dosage regimens with differing predicted efficacy were then administered to nephrectomized dogs to determine their relative nephrotoxic

  14. Cumulative or delayed nephrotoxicity after cisplatin (DDP) treatment.

    Pinnarò, P; Ruggeri, E M; Carlini, P; Giovannelli, M; Cognetti, F

    1986-04-30

    The present retrospective study reports data regarding renal toxicity in 115 patients (63 males, 52 females; median age, 56 years) who received cumulative doses of cisplatin (DDP) greater than or equal to 200 mg/m2. DDP was administered alone or in combination at a dose of 50-70 mg/m2 in 91 patients, and at a dose of 100 mg/m2 in 22 patients. Two patients after progression of ovarian carcinoma treated with conventional doses of DDP received 4 and 2 courses, respectively, of high-dose DDP (40 mg/m2 for 5 days) in hypertonic saline. The median number of DDP courses was 6 (range 2-14), and the median cumulative dose was 350 mg/m2 (range, 200-1200). Serum creatinine and urea nitrogen were determined before initiating the treatment and again 13-16 days after each administration. The incidence of azotemia (creatinina levels that exceeded 1.5 mg/dl) was similar before (7.8%) and after (6.1%) DDP doses of 200 mg/m2. Azotemia appears to be related to the association of DDP with other potentially nephrotoxic antineoplastic drugs (methotrexate) more than to the dose per course of DDP. Of 59 patients followed for 2 months or more after discontinuing the DDP treatment, 3 (5.1%) presented creatinine values higher than 1.5 mg/dl. The data deny that the incidence of nephrotoxicity is higher in patients receiving higher cumulative doses of DDP and confirm that increases in serum creatinine levels may occur some time after discontinuation of the drug.

  15. Contrast-induced nephrotoxicity: possible synergistic effect of stress hyperglycemia.

    O'Donnell, David H

    2010-07-01

    Oxidative stress on the renal tubules has been implicated as a mechanism of injury in both stress hyperglycemia and contrast-induced nephrotoxicity. The purpose of this study was to determine whether the combination of these effects has a synergistic effect on accentuating renal tubular apoptosis and therefore increasing the risk of contrast-induced nephrotoxicity.

  16. The Aging Kidney: Increased Susceptibility to Nephrotoxicity

    Wang, Xinhui; Bonventre, Joseph V.; Parrish, Alan R.

    2014-01-01

    Three decades have passed since a series of studies indicated that the aging kidney was characterized by increased susceptibility to nephrotoxic injury. Data from these experimental models is strengthened by clinical data demonstrating that the aging population has an increased incidence and severity of acute kidney injury (AKI). Since then a number of studies have focused on age-dependent alterations in pathways that predispose the kidney to acute insult. This review will focus on the mechanisms that are altered by aging in the kidney that may increase susceptibility to injury, including hemodynamics, oxidative stress, apoptosis, autophagy, inflammation and decreased repair. PMID:25257519

  17. Contrast Media: Are There Differences in Nephrotoxicity among Contrast Media?

    2014-01-01

    Iodinated contrast agents are usually classified based upon their osmolality—high, low, and isosmolar. Iodinated contrast agents are also nephrotoxic in some but not all patients resulting in loss of glomerular filtration rate. Over the past 30 years, nephrotoxicity has been linked to osmolality although the precise mechanism underlying such a link has been elusive. Improvements in our understanding of the pathogenesis of nephrotoxicity and prospective randomized clinical trials have attempted to further explore the relationship between osmolality and nephrotoxicity. In this review, the basis for our current understanding that there are little if any differences in nephrotoxic potential between low and isosmolar contrast media will be detailed using data from clinical studies. PMID:24587997

  18. Nephrotoxicity of cyclosporin A and contrast media

    Thomsen, H.S.; Larsen, S.; Skaarup, P.; Hemmingsen, L.; Dieperink, H.; Golman, K.; Herlev Hospital; Herlev Hospital; Centralsygehuset, Nykoebing Falster; Odense Sygehus; Malmoe Allmaenna Sjukhus

    1989-01-01

    Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 22 h or 8 days after intravenous injection of diatrizoate, iohexol or saline in 30 adult Wistar rats in which nephrotoxicity was induced by daily peroral administration of 25 mg/kg body weight cyclosporin A over a 14-day period. Another 10 rats which had the vehicle of the cyclosporin A solution (placebo) and saline injected intravenously served as controls. The effect of iohexol and saline on the albumin excretion was similar, whereas diatrizoate increased it significantly. Both contrast media caused significantly increased excretion of all three enzymes. The contrast media had no effect on the excretion of glucose and sodium. Except for the fact that the excretion of NAG was significantly higher following iohexol than following diatrizoate 24 to 46 h after injection no significant differences between the two media were found from 24 h after injection among the rats given cyclosporin A. No contrast medium related changes were found by light microscopy of the kidneys. Neither iohexol nor diatrizoate potentiate acute cyclosporin A nephrotoxicity. (orig.)

  19. A H2S Donor GYY4137 Exacerbates Cisplatin-Induced Nephrotoxicity in Mice

    Mi Liu

    2016-01-01

    Full Text Available Accumulating evidence demonstrated that hydrogen sulfide (H2S is highly involved in inflammation, oxidative stress, and apoptosis and contributes to the pathogenesis of kidney diseases. However, the role of H2S in cisplatin nephrotoxicity is still debatable. Here we investigated the effect of GYY4137, a novel slow-releasing H2S donor, on cisplatin nephrotoxicity in mice. Male C57BL/6 mice were pretreated with GYY4137 for 72 h prior to cisplatin injection. After cisplatin treatment for 72 h, mice developed obvious renal dysfunction and kidney injury as evidenced by elevated blood urea nitrogen (BUN and histological damage. Consistently, these mice also showed increased proinflammatory cytokines such as TNF-α, IL-6, and IL-1β in circulation and/or kidney tissues. Meanwhile, circulating thiobarbituric aid-reactive substances (TBARS and renal apoptotic indices including caspase-3, Bak, and Bax were all elevated. However, application of GYY4137 further aggravated renal dysfunction and kidney structural injury in line with promoted inflammation, oxidative stress, and apoptotic response following cisplatin treatment. Taken together, our results suggested that GYY4137 exacerbated cisplatin-induced nephrotoxicity in mice possibly through promoting inflammation, oxidative stress, and apoptotic response.

  20. Renoprotective effects of antioxidants against cisplatin nephrotoxicity

    Hajian Shabnam

    2014-04-01

    Full Text Available Nephrotoxicity is the major limitation for the clinical use of cisplatin as an anti-tumoural drug. Intracellular effects of cisplatin cause tubular damage and tubular dysfunction with sodium, potassium, and magnesium wasting. Renoperotective strategies against cisplatin are classified on 8 targets: 1 Decrease of cisplatin uptake by renal cell, 2 Inhibition of cisplatin metabolism, 3 Blocking cell death pathways, 4 Cyclin-dependent kinase inhibitors, 5 Pharmacologic, molecular, and genetic blockade of p53, 6 Inhibition of specific Mitogen-activated protein kinase, 7 Antioxidants usage for renoprotection against cisplatin injury and inhibit of oxidative stress, 8 Suppress of inflammation. The oxidation reactions can produce free radicals, which start chain reactions and subsequently can cause a large number of diseases in humans. Antioxidant from natural products have attracted the physicians’ attentions, nowadays. The natural product antioxidants detoxify reactive oxygen species (ROS in kidneys, without affecting the anticancer efficacy of cisplatin. Hence, antioxidants have potential therapeutic applications.

  1. Mechanisms of herb-induced nephrotoxicity.

    Allard, T; Wenner, T; Greten, H J; Efferth, T

    2013-01-01

    Herbal therapies gained much popularity among the general public, but compared to therapies approved by official authorities, toxicological studies are frequently not available for them. Hence, there may be inherent risks and the kidneys may be especially vulnerable to toxic effects. Herbs may induce nephrotoxicity by induction of apoptosis. High oxalate contents in Star fruit (Averrhoa carambola L.) may induce acute nephropathy. Triptolide from Thunder God Vine (Triperygium wilfordii Hook) is a diterpenoid epoxide with induces reactive oxygen species and nephrotubular apoptosis. Cranberry juice is discussed as promoter of kidney stone formation (nephrolithiasis). Abuse of guaifenesin from Roughbark (Guaicum officinale L.) increases stone formation. Aristolochia acids from Aristolochia fangchi Y.C.Wu ex L.D. Chow & S.M. Hwang causes the well-known aristolochic acid nephropathy and carcinogenesis by DNA adduct formation. Carboxyatractyloside from Impila (Callilepsis laureola DC.) inhibits mitochondrial ATP synthesis. Acute allergic interstitial nephritis was diagnosed after intake of Peruvian Cat's claw (Uncaria tomentosa Willd. DC.). Whether or not Willow Bark (Salix alba L.) induces analgesic nephropathwy is a matter of discussion. Other herbal therapies are considered to affect the rennin-angiotensisn-aldosterone (RAA) system Ephedra sinica Stapf with its ingredient ephedrine. Devil's Claw (Harpagophytum procumbens DC. Ex Meisn.) and licorice (Glycyrrhiza glabra L.) may inhibit major renal transport processes needed for filtration, secretion, and absorption. Strategies to minimize nephrotoxicity include (1) quality control and standardization of herbal products, (2) research on the molecular modes of action to better understand pathophysiological mechanisms of herbal products as well as (3) clinical trials to demonstrate efficacy and safety.

  2. Hepatotoxic and Nephrotoxic Effects of Petroleum Fumes on Petrol ...

    DR SULEIMAN

    Hepatotoxic and Nephrotoxic Effects of Petroleum Fumes on Petrol Attendants in Ibadan, Nigeria. *1A.L. Ogunneye ... inhalation of petrol fumes is associated with adverse effect on the kidney and liver function. ..... neurotoxicity in mice. African ...

  3. Amelioration of Cisplatin-Induced Nephrotoxicity in Rats by Curcumin

    Keywords: Cisplatin, Oxidative stress, Curcumin, α-Tocopherol, Nephrotoxicity. Tropical ... exerts various side effects in several organs particularly in ... Previous study provides evidence which ..... chemotherapy by cisplatin but further in vivo.

  4. Biotransformation and nephrotoxicity of ochratoxin B in rats

    Mally, Angela; Keim-Heusler, Heike; Amberg, Alexander; Kurz, Michael; Zepnik, Herbert; Mantle, Peter; Voelkel, Wolfgang; Hard, Gordon C.; Dekant, Wolfgang

    2005-01-01

    Ochratoxin B (OTB), a secondary metabolite of Aspergillus ochraceus, is the nonchlorinated analogue of the mycotoxin ochratoxin A (OTA), which is one of the most potent renal carcinogens in rodents. Despite the closely related structure, OTB is considered to be of much lower toxicity. OTA is poorly metabolized and slowly eliminated, and this may play an important role in OTA toxicity, carcinogenicity, and organ specificity. Since little is known regarding biotransformation and renal toxicity of OTB, the aim of this study was to investigate biotransformation of OTB in rats and to characterize the nephrotoxicity and cytotoxicity of OTB. Male F344 rats were administered either a single dose of OTB (10 mg/kg bw) or repeated doses (2 mg/kg bw, 5 days/week for 2 weeks) and euthanized 72 h after the last dosing. In proximal tubule cells of animals treated with a single high dose of OTB, a slight increase in mitotic figures was observed, but no treatment-related changes were evident in clinical chemistry, in renal function, and histopathology after repeated administration. Excretion of OTB and metabolites in urine and feces was analyzed using both HPLC with fluorescence detection and LC-MS/MS. Ochratoxin beta, which results from cleavage of the peptide bond, was the major metabolite excreted in urine in addition to small amounts of 4-hydroxy-OTB. In total, 19% of the administered dose was recovered as OTB and ochratoxin beta in urine and feces within 72 h after a single dose. In contrast to OTA, no tissue-specific retention of OTB was evident after single and repeated administration. In LLC-PK1 cells, a renal cell culture system that retains much of the specific features of the proximal tubule, only minor differences in the extent of cytotoxicity of OTA and OTB were observed. At low concentrations (< 25 μM), treatment with OTA was slightly more toxic, whereas reduction in cell viability was similar at concentrations up to 100 μM. In summary, these data suggest that OTA

  5. Contrast media-associated nephrotoxicity - pathogenenesis and prevention

    Erley, C.M.; Duda, S.H.

    1997-01-01

    Contrast media-associated nephrotoxicity continues to be a relevant cause of acute renal failure, especially in patients with pre-existing renal insufficiency. Alterations in renal hemodynamics and direct tubular toxicity by contrast media are the primary factors believed to be responsible for contrast media-associated nephrotoxicity. We review recent insights into the pathogenesis of this complication and summarize prophylactic strategies focussing on hydration, vasoactive pharmacological agents, and prophylactic hemodialysis'. (orig.) [de

  6. Nonalbumin proteinuria predominates in biopsy-proven tenofovir nephrotoxicity.

    Sise, Meghan E; Hirsch, Jamie S; Canetta, Pietro A; Herlitz, Leal; Mohan, Sumit

    2015-05-15

    Tenofovir disoproxil fumarate (TDF) nephrotoxicity is characterized by proximal renal tubular injury and dysmorphic mitochondria resulting in proteinuria, orthoglycemic glycosuria, and other markers of proximal tubular dysfunction. The objective of this study was to determine the pattern of proteinuria in patients with biopsy-proven TDF nephrotoxicity. Retrospective chart review. Patients with biopsy-proven TDF nephrotoxicity were identified and their medical charts and biopsy reports were reviewed. Comparison was made with HIV-infected patients not on TDF who underwent kidney biopsy. We identified 43 biopsy-proven cases of TDF nephrotoxicity; mean age 54.7 ± 0.4 years, 53% men, 42% whites. Thirty-seven cases reported proteinuria by dipstick of which only 60% had at least 2+ proteinuria. Twenty-seven patients had urine protein quantified by either 24-h collection or spot urine protein-to-creatinine ratio; median proteinuria was 1742 mg/day [interquartile range (IQR) 1200-2000 mg] and 1667 mg/g creatinine (IQR 851-1967 mg/g), respectively. Ten patients had concurrent urinary albumin measured, with a median 236 mg/g creatinine (IQR 137-343 mg/g). The mean urine albumin-to-urine protein ratio (uAPR) was 0.17 (IQR 0.14-0.19), confirming that TDF nephrotoxicity is primarily associated with nonalbumin proteinuria. Control cases had a uAPR of 0.65 (IQR 0.55-0.79) P < 0.001. Histopathology showed the predominance of proximal tubular injury with characteristic mitochondrial abnormalities. In the largest published cohort of patients with biopsy-proven TDF nephrotoxicity, we show that low uAPR is a reliable feature of this disease. Because of the predominance of nonalbumin proteinuria, dipstick urinalysis may be unreliable in TDF nephrotoxicity.

  7. Effect of cyclooxygenase inhibitors on gentamicin-induced nephrotoxicity in rats

    Hosaka E.M.

    2004-01-01

    Full Text Available The frequent use of nonsteroidal anti-inflammatory drugs (NSAID in combination with gentamicin poses the additional risk of nephrotoxic renal failure. Cyclooxygenase-1 (COX-1 is the main enzyme responsible for the synthesis of renal vasodilator prostaglandins, while COX-2 participates predominantly in the inflammatory process. Both are inhibited by non-selective NSAID such as indomethacin. Selective COX-2 inhibitors such as rofecoxib seem to have fewer renal side effects than non-selective inhibitors. The objective of the present study was to determine whether the combined use of rofecoxib and gentamicin can prevent the increased renal injury caused by gentamicin and indomethacin. Male Wistar rats (250-300 g were treated with gentamicin (100 mg/kg body weight, ip, N = 7, indomethacin (5 mg/kg, orally, N = 7, rofecoxib (1.4 mg/kg, orally, N = 7, gentamicin + rofecoxib (100 and 1.4 mg/kg, respectively or gentamicin + indomethacin (100 and 5 mg/kg, respectively, N = 8 for 5 days. Creatinine clearance and alpha-glutathione-S-transferase concentrations were used as markers of renal injury. Animals were anesthetized with ether and sacrificed for blood collection. The use of gentamicin plus indomethacin led to worsened renal function (0.199 ± 0.019 ml/min, as opposed to the absence of a nephrotoxic effect of rofecoxib when gentamicin plus rofexicob was used (0.242 ± 0.011 ml/min. These results indicate that COX-2-selective inhibitors can be used as an alternative treatment to conventional NSAID, especially in situations in which risk factors for nephrotoxicity are present.

  8. Role of Free Radicals and Biotransformation in Trichloronitrobenzene-Induced Nephrotoxicity In Vitro.

    Rankin, Gary O; Tyree, Connor; Pope, Deborah; Tate, Jordan; Racine, Christopher; Anestis, Dianne K; Brown, Kathleen C; Dial, Mason; Valentovic, Monica A

    2017-05-31

    This study determined the comparative nephrotoxic potential of four trichloronitrobenzenes (TCNBs) (2,3,4-; 2,4,5-; 2,4,6-; and 3,4,5-TCNB) and explored the effects of antioxidants and biotransformation inhibitors on TCNB-induced cytotoxicity in isolated renal cortical cells (IRCC) from male Fischer 344 rats. IRCC were incubated with a TCNB up to 1.0 mM for 15-120 min. Pretreatment with an antioxidant or cytochrome P450 (CYP), flavin monooxygenase (FMO), or peroxidase inhibitor was used in some experiments. Among the four TCNBs, the order of decreasing nephrotoxic potential was approximately 3,4,5- > 2,4,6- > 2,3,4- > 2,4,5-TCNB. The four TCNBs exhibited a similar profile of attenuation of cytotoxicity in response to antioxidant pretreatments. 2,3,4- and 3,4,5-TCNB cytotoxicity was attenuated by most of the biotransformation inhibitors tested, 2,4,5-TCNB cytotoxicity was only inhibited by isoniazid (CYP 2E1 inhibitor), and 2,4,6-TCNB-induced cytotoxicity was inhibited by one CYP inhibitor, one FMO inhibitor, and one peroxidase inhibitor. All of the CYP specific inhibitors tested offered some attenuation of 3,4,5-TCNB cytotoxicity. These results indicate that 3,4,5-TCNB is the most potent nephrotoxicant, free radicals play a role in the TCNB cytotoxicity, and the role of biotransformation in TCNB nephrotoxicity in vitro is variable and dependent on the position of the chloro groups.

  9. Effect of cyclooxygenase inhibitors on gentamicin-induced nephrotoxicity in rats.

    Hosaka, E M; Santos, O F P; Seguro, A C; Vattimo, M F F

    2004-07-01

    The frequent use of nonsteroidal anti-inflammatory drugs (NSAID) in combination with gentamicin poses the additional risk of nephrotoxic renal failure. Cyclooxygenase-1 (COX-1) is the main enzyme responsible for the synthesis of renal vasodilator prostaglandins, while COX-2 participates predominantly in the inflammatory process. Both are inhibited by non-selective NSAID such as indomethacin. Selective COX-2 inhibitors such as rofecoxib seem to have fewer renal side effects than non-selective inhibitors. The objective of the present study was to determine whether the combined use of rofecoxib and gentamicin can prevent the increased renal injury caused by gentamicin and indomethacin. Male Wistar rats (250-300 g) were treated with gentamicin (100 mg/kg body weight, ip, N = 7), indomethacin (5 mg/kg, orally, N = 7), rofecoxib (1.4 mg/kg, orally, N = 7), gentamicin + rofecoxib (100 and 1.4 mg/kg, respectively) or gentamicin + indomethacin (100 and 5 mg/kg, respectively, N = 8) for 5 days. Creatinine clearance and alpha-glutathione-S-transferase concentrations were used as markers of renal injury. Animals were anesthetized with ether and sacrificed for blood collection. The use of gentamicin plus indomethacin led to worsened renal function (0.199 +/- 0.019 ml/min), as opposed to the absence of a nephrotoxic effect of rofecoxib when gentamicin plus rofexicob was used (0.242 +/- 0.011 ml/min). These results indicate that COX-2-selective inhibitors can be used as an alternative treatment to conventional NSAID, especially in situations in which risk factors for nephrotoxicity are present.

  10. Protective effects of the Morus alba L. leaf extracts on cisplatin-induced nephrotoxicity in rat

    Nematbakhsh, M; Hajhashemi, V; Ghannadi, A; Talebi, A; Nikahd, M

    2013-01-01

    Cisplatin (CP) as an important anti-tumor drug causes nephrotoxicity mainly by oxidative stress and renin-angiotensin system (RAS). Since flavonoids have high antioxidant activity and probable role in the inhibition of RAS, this study was designed to investigate the protective effect of hydroalcoholic extract and flavonoid fraction of Morus alba leaves on cisplatin-induced nephrotoxicity in rat. Extracts of Morus alba leaves were prepared and analyzed Phytochemically. Male rats (160-200 g) were used in this study (n=7-9). Normal group received 0.2 ml normal saline intraperitoneally (i.p.) once daily for ten days. Control animals received CP on the third day and saline in the remaining days. Other groups received either hydroalcoholic extract (200, 400 and 600 mg/kg, i.p.) or flavonoid fraction (50, 100 and 200 mg/kg, i.p.) for two days before CP administration and thereafter until tenth day. Serum concentrations of blood urea nitrogen (BUN), creatinine (Cr) and nitric oxide were measured using standard methods. Also left kidneys were prepared for pathological study. The serum levels of BUN and Cr increased in animals received CP. Hydroalcoholic extract was ineffective in reversing these alterations but flavonoid fraction (50 and 100 mg/kg) significantly inhibited CP-induced increases of BUN and Cr. None of the treatments could affect serum concentration of nitric oxide. Flavonoid fraction could also prevent CP-induced pathological damage of the kidney. It seems that concurrent use of flavonoid fraction of Morus alba with CP can protect kidneys from CP-induced nephrotoxicity. PMID:24019816

  11. [Current research situation of nephrotoxicity of Chinese herbal medicine].

    Feng, Xue; Fang, Sai-Nan; Gao, Yu-Xin; Liu, Jian-Ping; Chen, Wei

    2018-02-01

    To provide the basis for the future research on the nephrotoxicity of Chinese herbal medicine through systematic and comprehensive summary of all the Chinese herbal medicines which may lead to nephrotoxicity. Foreign resources included PubMed and Cochrane library, and domestic research resources was China Food and Drug Administration(CDFA) Adverse Drug Reaction Monitoring Center database. The databases were searched from establishment to January 1, 2017. There was no limitation on research type. 28 English studies were found, including 97 Chinese herbs or prescriptions with the risk of nephrotoxicity. The following six Chinese herbal medicines with the risk of nephrotoxicity had a large number of studies: aristolochic acid(5 studies), Tripterygium wilfordii(4 studies), Erycibe obtusifolia(2 studies), Rheum palmatum(2 studies), Ephedra sinica(2 studies), and Atractylodes lances(2 studies). The remaining 91 Chinese medicines were reported with risk of nephrotoxicity in only 1 study respectively. CDFA reported 16 Chinese herbal medicines with the risk of nephrotoxicity, including Ganmaoqing Pian(capsule), Zhenju Jiangya Pian, T. wilfordii preparation, Vc-Yinqiao Pian, Chuanhuning injection, Shuanghuanglian injection, Qingkailing injection, Lianbizhi injection, herbal decoction containing Aristolochiae Radix, Guanxin Suhe Wan, Shugan Liqi Wan, Ershiwuwei Songshi Wan, herbal decoction containing Aristolochia Fangchi, herbal granules containing root of Kaempfer Dutchmanspipe, Ganmaotong(tablets), and Longdan Xiegan Wan. Currently, in addition to aristolochic acids, the most reported Chinese herbal medicine with the risk of nephrotoxicity is T. wilfordii preparation. Copyright© by the Chinese Pharmaceutical Association.

  12. Evaluation of body weight-based vancomycin therapy and the incidence of nephrotoxicity: a retrospective study in the northwest of China.

    Dong, Mo-Han; Wang, Jing-Wen; Wu, Yin; Chen, Bei-Yu; Yu, Min; Wen, Ai-Dong

    2015-08-01

    To identify specific risk factors of vancomycin-induced nephrotoxicity in China, as the relationship between vancomycin therapy (dosing and trough concentration monitoring) and nephrotoxicity has been the subject of critical debate. The cases of 90 critically ill patients who received vancomycin therapy in Xijing Hospital in the northwest of China between March 2014 and January 2015 were reviewed retrospectively. Vancomycin dosing, blood serum trough concentration, and other independent risk factors associated with nephrotoxicity were evaluated in a multivariable model. Among the 90 critically ill patients, 59 were males; mean age was 46.3 years. The indications for vancomycin use were methicillin-resistant Staphylococcus aureus-associated pneumonia, central nervous system infection, and bacteremia. Clinical pharmacists prescribed weight-based dosing, ranging from 20 to 45mg/kg/day. Fourteen (15.6%) patients developed nephrotoxicity, with serum creatinine elevated significantly from a mean (standard deviation) of 90.0 (18.8) μmol/l to 133.8 (63.2) μmol/l (p = 0.015). It was found that those with a vancomycin dosage >38mg/kg/day (50.0% vs. 11.3%, p = 0.004) and a vancomycin serum trough concentration >20mg/l (57.1% vs. 12.0%, p = 0.01) were more likely to develop nephrotoxicity. The data from this study indicate that a vancomycin dosage >38mg/kg/day and a serum trough level >20mg/l are both independent factors associated with the development of nephrotoxicity, suggesting that renal function should be monitored closely during vancomycin treatment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Brown spider dermonecrotic toxin directly induces nephrotoxicity

    Chaim, Olga Meiri; Sade, Youssef Bacila; Bertoni da Silveira, Rafael; Toma, Leny; Kalapothakis, Evanguedes; Chavez-Olortegui, Carlos; Mangili, Oldemir Carlos; Gremski, Waldemiro; Dietrich, Carl Peter von; Nader, Helena B.; Sanches Veiga, Silvio

    2006-01-01

    culture substratum. In addition, dermonecrotic toxin treatment of MDCK cells changed their viability evaluated by XTT and Neutral-Red Uptake methodologies. The present results point to brown spider dermonecrotic toxin cytotoxicity upon renal structures in vivo and renal cells in vitro and provide experimental evidence that this brown spider toxin is directly involved in nephrotoxicity evoked during Loxosceles spider venom accidents

  14. Moringa oleifera Supplemented Diets Prevented Nickel-Induced Nephrotoxicity in Wistar Rats

    O. S. Adeyemi

    2014-01-01

    Full Text Available Background. The Moringa oleifera plant has been implicated for several therapeutic potentials. Objective. To evaluate whether addition of M. oleifera to diet has protective effect against nickel-induced nephrotoxicity in rats. Methodology. Male Wistar rats were assigned into six groups of five. The rats were given oral exposure to 20 mg/kg nickel sulphate (NiSO4 in normal saline and sustained on either normal diet or diets supplemented with Moringa oleifera at different concentrations for 21 days. 24 hours after cessation of treatments, all animals were sacrificed under slight anesthesia. The blood and kidney samples were collected for biochemical and histopathology analyses, respectively. Results. NiSO4 exposure reduced the kidney-to-body weight ratio in rats and caused significant elevation in the levels of plasma creatinine, urea, and potassium. Also, the plasma level of sodium was decreased by NiSO4 exposure. However, addition of M. oleifera to diets averted the nickel-induced alteration to the level of creatinine and urea. The histopathology revealed damaged renal tubules and glomerular walls caused by NiSO4 exposure. In contrast, the damages were ameliorated by the M. oleifera supplemented diets. Conclusion. The addition of M. oleifera to diet afforded significant protection against nickel-induced nephrotoxicity.

  15. The protective effect of curcumin against lithium-induced nephrotoxicity in rats

    Mohammad Shaterpour

    2017-08-01

    Full Text Available Lithium is an element which has been used as salts of chloride or carbonate for many years in the treatment of some psychological disorders such as mania, bipolar or schizophrenic diseases. Chronic application of lithium may induce some serious nephropathies such as natriuresis, renal tubular acidosis, tubulointerstitial nephritis progression to progressive chronic kidney disease and hypercalcemia and, most commonly, nephrogenic diabetes insipidus. Curcumin is an antioxidant derived from Curcuma longa (turmeric or curcuma which has the ability to react directly with reactive species and up-regulation of many cytoprotective and antioxidant proteins. The preventive roles of curcumin in nephropathies were reported, but there was little information on the protective effect of curcumin against lithium-induced nephrotoxicity. In this study, male Wistar rats divided into five groups of six each and were treated as follows: group1; animals were received lithium chloride as 2 mmol/kg, group 2; animals were received normal saline (0, 5%, group 3; animals were received curcumin (200 mg/kg, group 4 animals were received curcumin plus lithium and group 5; animals were received solvent intraperitoneally for three weeks. Then the animals were killed and biochemical parameters of blood were assayed and histopathological assessment was performed. The results have shown that curcumin significantly improved the biochemicals (BUN, creatinine, malondialdehyde. Curcumin prevented significantly the histological parameters that were changed by lithium administration in rats. Our results provide new insights into beneficial usages of curcumin in chronic nephrotoxicity induced by lithium salts.

  16. The Effects of Zataria Multiflora Hydroalcoholic Extract on Gentamicin Induced Nephrotoxicity in Rats

    Saeed Hajihashemi

    2015-07-01

    Full Text Available Abstract Background: Gentamicin is an aminoglycoside antibiotic that broadly is used to treat gram negative bacteria infections, although it has side effects such as nephrotoxicity. According to antioxidant, anti-inflammatory and vasodilatory properties of Zataria Multiflora, the effects of co-treatment with zataria Multiflora and hydroalcholic extract on gentamicin induced nephrotoxicitj were investigated. Materials and Methods: In this study, male rats of Vistar race were divided into 4 groups: 1.control group, 2. co-treatment with gentamicin and vehicle group, 3. co-treatment with gentamicin and zataria Multifiora extract group, 4. co-treatment with zataria Multiflora extract and normal saline solution group. Zataria Multiflora hydroalcoholic extract was added to drinking water as 800 PPm concentration. They, systolic blood pressure and renal blood flow (RBF were measured. Also, the amounts of urea, creatinine, sodium, potassium and osmolarity were measured in plasma and urine samples Results: In co-treatment group with zataria Multiflora extract, the amounts of urea, creatinine, absolute sodium excretion and relative sodium and potassium excretion and malondialdehyde (MDA that have been inceased in treatment with gentamicin, significantly were reduced. Creatinine clearance, urine osmolarity, RBF and FRAP that was decreased in gentamicin group in compare to control group, significantly increased. Conclusion: Co-treatment prevents nephrotoxicity induced by gentamicin and attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, So it can be effective to cure rats receiving gentamicin.

  17. Moringa oleifera Supplemented Diets Prevented Nickel-Induced Nephrotoxicity in Wistar Rats

    Adeyemi, O. S.; Elebiyo, T. C.

    2014-01-01

    Background. The Moringa oleifera plant has been implicated for several therapeutic potentials. Objective. To evaluate whether addition of M. oleifera to diet has protective effect against nickel-induced nephrotoxicity in rats. Methodology. Male Wistar rats were assigned into six groups of five. The rats were given oral exposure to 20 mg/kg nickel sulphate (NiSO4) in normal saline and sustained on either normal diet or diets supplemented with Moringa oleifera at different concentrations for 21 days. 24 hours after cessation of treatments, all animals were sacrificed under slight anesthesia. The blood and kidney samples were collected for biochemical and histopathology analyses, respectively. Results. NiSO4 exposure reduced the kidney-to-body weight ratio in rats and caused significant elevation in the levels of plasma creatinine, urea, and potassium. Also, the plasma level of sodium was decreased by NiSO4 exposure. However, addition of M. oleifera to diets averted the nickel-induced alteration to the level of creatinine and urea. The histopathology revealed damaged renal tubules and glomerular walls caused by NiSO4 exposure. In contrast, the damages were ameliorated by the M. oleifera supplemented diets. Conclusion. The addition of M. oleifera to diet afforded significant protection against nickel-induced nephrotoxicity. PMID:25295181

  18. Haloaniline-induced in vitro nephrotoxicity: effects of 4-haloanilines and 3,5-dihaloanilines.

    Hong, S K; Anestis, D K; Henderson, T T; Rankin, G O

    2000-04-03

    Haloanilines are widely used as chemical intermediates in the manufacture of pesticides, dyes and drugs. The purpose of this study was to examine the in vitro nephrotoxic effects of the four 4-haloaniline and four 3,5-dihaloaniline isomers using renal cortical slices obtained from the kidneys of untreated, male Fischer 344 rats. Renal cortical slices were incubated with a haloaniline hydrochloride (0.1, 0.5, 1.0 or 2.0 mM, final concentration) or vehicle for 2 h, and toxicity determined by monitoring lactate dehydrogenase (LDH) release and changes in tissue gluconeogenesis capacity. At the concentrations tested, none of the 4-haloanilines increased LDH release. 4-Bromoaniline reduced gluconeogenesis at the lowest concentration (0.1 mM), but 4-iodoaniline 2.0 mM induced the largest decrease in gluconeogenesis (92% downward arrow). Among the 3,5-dihaloanilines, 3,5-dibromoaniline proved to be the most potent nephrotoxicant and 3,5-difluoroaniline the least potent nephrotoxicant. LDH release was increased by the dibromo (1.0 and 2. 0 mM), dichloro (2.0 mM) and diiodo (2.0 mM) derivatives, but not by 3,5-difluoroaniline. These results demonstrate that 3, 5-dihaloanilines are generally more potent nephrotoxicants in vitro than the 4-haloaniline isomers, and that bromo and iodo substitutions enhanced the nephrotoxic potential of aniline to the greatest degree.

  19. Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS

    Mohamed A. Morsy

    2014-01-01

    Full Text Available Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p. for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS expression, while expression of endothelial nitric oxide synthase (eNOS was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production.

  20. The protective role of saffron petal extracts on gentamicininduced nephrotoxicity in rats

    Arash Omidi

    2016-07-01

    Full Text Available Different potentially therapeutic approaches to prevent or attenuate gentamicin sulfate (GM induced nephrotoxicity have been proposed. The present study was conducted to investigate the effect of the saffron petals extracts (Crocus sativus (SPE on male Wistar rats with kidney failure. Rats (40 were randomly assigned into five groups of 8 animals each: i the control group, that received normal saline (0.5 mL/kg; ii the GM group, that received GM (80 mg/kg by intraperitoneal (i.p. injection on a daily basis; iii the GM+SPE group that received the same dose of GM and SPE (40 mg/kg by i.p. injection on a daily basis; iv the GM+2SPE group, that received the same dose of GM and twofold of SPE (80 mg/kg by i.p. injection on a daily basis; whereas v 2SPE+GM group, that received 80 mg/kg of SPE a week before initiating the treatment with GM (prevention group. Significant differences were seen in the concentration of glucose, blood urea nitrogen (BUN, and creatinine between treatment groups and control in the male Wistar rats. GM was observed to cause nephrotoxicity, which was evidenced by an elevation of serum BUN and creatinine levels. The biochemical findings of the current study are concordant with those of histopathologic findings. The results of this study indicate that SPE especially in dose of 40 mg/kg can ameliorate harmful effects of GM on the kidney. The present results may suggest that the SPE have ameliorative effects on kidney failures induced by GM.

  1. Iodinated contrast media nephrotoxicity. Nephrotoxicite des produits de contraste iodes

    Meyrier, A. (Hopital Avicenne, 93 - Bobigny (France))

    1994-01-01

    In the late seventies, iodinated contrast agents (ICA) were considered to be a major cause of acute iatrogenic renal failure. Over the last decade new contrast agents have been synthesized, nonionic and less hyperosmolar. The incidence of acute renal failure due to ICAs, varies from 3.7 to 70% of cases according to the series, with an average figure of 10.2%. The pathophysiology of ICA nephrotoxicity was mainly studied in laboratory animal models. Three main factors are involved in an inducing ICA-mediated decrease in glomerular filtration rate: reduction of the renal plasma flow, a direct cytotoxic effect on renal tubular cells and erythrocyte alteration leading to intra-renal sludge. Excluding dysglobulinemias with urinary excretion of immunoglobulin light chains, which represent a special case of maximum nephrotoxicity, 4 main risk factors of renal toxicity have been identified in nondiabetic subjects: previous renal failure with serum creatinine levels greater than 140 [mu]mol per liter, extracellular dehydration, age over 60 and use of high doses of ICA and/or repeated ICA injections before serum creatinine levels return to baseline. Preventive measures for avoiding ICA nephrotoxicity are threefold: maintain or restore adequate hydration with saline infusion, stop NSAID treatment several days before ICA administration, and allow a 5 day interval before repeating contrast media injections. New, nonionic and moderately hyperosmolar contrast agents appear to be much less nephrotoxic than conventional ICAs in laboratory animals and in high-risk patients. It is advisable to select such contrast media for investigating high-risk patients. This approach was recently substantiated in well designed, randomized clinical studies which included more than 2 000 patients. (author).

  2. Evaluation of risk factors for vancomycin-induced nephrotoxicity.

    Park, So Jin; Lim, Na Ri; Park, Hyo Jung; Yang, Jae Wook; Kim, Min-Ji; Kim, Kyunga; In, Yong Won; Lee, Young Mee

    2018-05-09

    Background Vancomycin is a glycopeptide antibiotic of choice for the treatment of serious infections caused by multi-resistant Gram-positive bacteria. However, vancomycin-associated nephrotoxicity (VAN) often limits its use. Previous data suggested a few risk factors of VAN, including higher mean vancomycin trough level, higher daily doses, old age, long duration of vancomycin therapy, and concomitant nephrotoxins. Objective To evaluate the incidence and risk factors of VAN and determine whether higher vancomycin trough concentrations were associated with a greater risk for VAN. Settings A retrospective, observational, single-center study at the 1960-bed university-affiliated tertiary care hospital (Samsung Medical Center), Seoul, Korea. Method A retrospective analysis of adult patients who received vancomycin parenterally in a tertiary care medical center from March 1, 2013 to June 30, 2013 was performed. We excluded patients with a baseline serum creatinine level > 2 mg/dL and those who had a history of end-stage renal disease and dialysis at baseline. The clinical characteristics were compared between patients with nephrotoxicity and those without nephrotoxicity to identify the risk factors associated with VAN. Main outcome measure Incidence of VAN and VAN-associated risk factors were analyzed. Results Of the 315 vancomycin-treated patients, nephrotoxicity occurred in 15.2% of the patients. In multivariate analysis, higher vancomycin trough concentrations of > 20 mg∕L (OR 9.57, 95% CI 2.49-36.83, p < 0.01) and intensive care unit (ICU) residence (OR 2.86, 95% CI 1.41-5.82, p < 0.01) were independently associated with VAN. Conclusion Our findings suggest that higher vancomycin trough levels and ICU residence might be associated with a greater risk for VAN. More careful monitoring of vancomycin serum trough levels and patient status might facilitate the timely prevention of VAN.

  3. Physicochemical properties of radiographic contrast media, potential nephrotoxicity and prophylaxis.

    Hogstrom, Barry; Ikei, Nobuhiro

    2015-12-01

    Contrast induced nephropathy (CIN) remains a controversial topic. The clinical relevance of changes in laboratory parameters has been challenged; some authors have even suggested that CIN simply reflects natural fluctuations. Other areas of controversy include the pathophysiology of CIN, effectiveness of prophylactic approaches and differences in nephrotoxicity between individual contrast media (CM). The aim of this review is to summarize the current understanding of laboratory findings and explore its relationship to CM toxicity. © 2015 Wiley Publishing Asia Pty Ltd.

  4. Tropisetron attenuates cisplatin-induced nephrotoxicity in mice.

    Zirak, Mohammad Reza; Rahimian, Reza; Ghazi-Khansari, Mahmoud; Abbasi, Ata; Razmi, Ali; Mehr, Shahram Ejtemaei; Mousavizadeh, Kazem; Dehpour, Ahmad Reza

    2014-09-05

    Nephrotoxicity is one of the most important complications of cisplatin, a potent chemotherapeutic agent used in the treatment of various malignancies. 5-HT3 antagonists are widely used to counteract chemotherapy-induced emesis and new studies reveal that they poses notable anti-inflammatory properties. In current study, we investigated the effects of 5-HT3 antagonists on cisplatin induced nephrotoxicity in mice. To identify the underlying mechanism of renal protection by tropisetron, we investigated the probable involvement of alpha7 nicotinic acetylcholine receptor (α7nAChR). A single injection of cisplatin (20mg/kg; i.p) induced nephrotoxicity, 5-HT3 antagonists (tropisetron, granisetron and ondansetron,) were given twice daily for 3 day (3mg/kg; i.p). Finally animals were euthanized and blood sample was collected to measure urea and creatinin level. Also kidneys were removed for histopathological examination and biochemical measurements including glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) activity, inducible nitric oxide synthase (iNOS) expression and inflammatory cytokines. Tropisetron decreased the expression of inflammatory molecules including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and iNOS and improved histopathological damage and renal dysfunction. However other 5-HT3 antagonists, granisetron or ondansetron do not have any elicit effects on biochemical markers and histological damages. Since methyllycaconitine, antagonist of α7nAChR, was unable to reverse the beneficial effect of tropisetron, we concluded that this effect of tropisetron is not mediated by α7nAChR.Our results showed that tropisetron treatment markedly ameliorated the experimental cisplatin induced-nephrotoxicity and this effect might be 5-HT3 receptor and α7nAChR independent. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Novel quinolinone-phosphonic acid AMPA antagonists devoid of nephrotoxicity.

    Cordi, Alex A; Desos, Patrice; Ruano, Elisabeth; Al-Badri, Hashim; Fugier, Claude; Chapman, Astrid G; Meldrum, Brian S; Thomas, Jean-Yves; Roger, Anita; Lestage, Pierre

    2002-10-01

    We reported previously the synthesis and structure-activity relationships (SAR) in a series of 2-(1H)-oxoquinolines bearing different acidic functions in the 3-position. Exploiting these SAR, we were able to identify 6,7-dichloro-2-(1H)-oxoquinoline-3-phosphonic acid compound 3 (S 17625) as a potent, in vivo active AMPA antagonist. Unfortunately, during the course of the development, nephrotoxicity was manifest at therapeutically effective doses. Considering that some similitude exists between S 17625 and probenecid, a compound known to protect against the nephrotoxicity and/or slow the clearance of different drugs, we decided to synthesise some new analogues of S 17625 incorporating some of the salient features of probenecid. Replacement of the chlorine in position 6 by a sulfonylamine led to very potent AMPA antagonists endowed with good in vivo activity and lacking nephrotoxicity potential. Amongst the compounds evaluated, derivatives 7a and 7s appear to be the most promising and are currently evaluated in therapeutically relevant stroke models.

  6. IMRT limits nephrotoxicity after chemoradiotherapy for gastric cancer

    Trip, Anouk Kirsten; Nijkamp, Jasper; Tinteren, Harm van; Cats, Annemieke; Boot, Henk; Jansen, Edwin Petrus Marianus; Verheij, Marcel

    2014-01-01

    Objective: This observational study compares the effect of different radiotherapy techniques on late nephrotoxicity after postoperative chemoradiotherapy for gastric cancer. Patients and methods: Dosimetric parameters were compared between AP–PA, 3D-conformal and IMRT techniques. Renal function was measured by 99m Tc-MAG-3 renography, glomerular filtration rate (GFR) and the development of hypertension. Mixed effects models were used to compare renal function over time. Results: Eighty-seven patients treated between 2002 and 2010 were included, AP–PA (n = 31), 3D-conformal (n = 25) and IMRT (n = 31), all 45 Gy in 25 fractions. Concurrent chemotherapy: 5FU/leucovorin (n = 4), capecitabine (n = 37), and capecitabine/cisplatin (n = 46). Median follow-up time was 4.7 years (range 0.2–8). With IMRT, the mean dose to the left kidney was significantly lower. Left kidney function decreased progressively in the total study population, however with IMRT this occurred at a lower rate. A dose–effect relationship was present between mean dose to the left kidney and the left kidney function. GFR decreased only moderately in time, which was not different between techniques. Six patients developed hypertension, of whom none in the IMRT group. Conclusions: This study confirms progressive late nephrotoxicity in patients treated with postoperative chemoradiotherapy by different techniques for gastric cancer. Nephrotoxicity was less severe with IMRT and should be considered the preferred technique

  7. [Influence of dose regimen on gentamycin nephrotoxicity in rats].

    Oliveira, V C; Tejos, C R; Hosaka, E M; Andrade, S C; Araújo, M; Vattimo, M F

    2001-06-01

    The acute renal failure (ARF), that still presents a right mortality rate (50%) can be defined as an abrupt decline of the glomerular filtration, resultant of ischemic or toxicity event. The drugs nephrotoxicity is one of the most frequent cause (27%) of ARF and it is suggested that the interval of administration of the drug can interfere in this side effect, however the best administration regimen is not very well established. This study evaluated the renal function of rats that received gentamicin (100 mg/kg) in one dose or in two doses (2 x 50 mg/kg), by intraperitoneal infusion. The results obtained in this research, indicated that the single infusion of gentamicin determined smaller nephrotoxicity by the reduction of serum concentration of this drug in 24 hours, decreasing the intracellular accumulation of this gentamicin, which is one of the main cellular mechanisms of this renal injury. The single dose treatment regime, otherwise, shows advantages not only related to the nephrotoxicity effect, but also it is relevant to the cost and safety, which can be rationable factors in the administration of this drug.

  8. IMRT limits nephrotoxicity after chemoradiotherapy for gastric cancer.

    Trip, Anouk Kirsten; Nijkamp, Jasper; van Tinteren, Harm; Cats, Annemieke; Boot, Henk; Jansen, Edwin Petrus Marianus; Verheij, Marcel

    2014-08-01

    This observational study compares the effect of different radiotherapy techniques on late nephrotoxicity after postoperative chemoradiotherapy for gastric cancer. Dosimetric parameters were compared between AP-PA, 3D-conformal and IMRT techniques. Renal function was measured by (99m)Tc-MAG-3 renography, glomerular filtration rate (GFR) and the development of hypertension. Mixed effects models were used to compare renal function over time. Eighty-seven patients treated between 2002 and 2010 were included, AP-PA (n=31), 3D-conformal (n=25) and IMRT (n=31), all 45 Gy in 25 fractions. Concurrent chemotherapy: 5FU/leucovorin (n=4), capecitabine (n=37), and capecitabine/cisplatin (n=46). Median follow-up time was 4.7 years (range 0.2-8). With IMRT, the mean dose to the left kidney was significantly lower. Left kidney function decreased progressively in the total study population, however with IMRT this occurred at a lower rate. A dose-effect relationship was present between mean dose to the left kidney and the left kidney function. GFR decreased only moderately in time, which was not different between techniques. Six patients developed hypertension, of whom none in the IMRT group. This study confirms progressive late nephrotoxicity in patients treated with postoperative chemoradiotherapy by different techniques for gastric cancer. Nephrotoxicity was less severe with IMRT and should be considered the preferred technique. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Evaluation of novel biomarkers of nephrotoxicity in Cynomolgus monkeys treated with gentamicin

    Gautier, Jean-Charles; Zhou, Xiaobing; Yang, Yi; Gury, Thierry; Qu, Zhe; Palazzi, Xavier; Léonard, Jean-François; Slaoui, Mohamed; Veeranagouda, Yaligara; Guizon, Isabelle; Boitier, Eric; Filali-Ansary, Aziz; Berg, Bart H.J. van den; Poetz, Oliver; Joos, Thomas; Zhang, Tianyi; Wang, Jufeng; Detilleux, Philippe; Li, Bo

    2016-01-01

    Most studies to evaluate kidney safety biomarkers have been performed in rats. This study was conducted in Cynomolgus monkeys in order to evaluate the potential usefulness of novel biomarkers of nephrotoxicity in this species. Groups of 3 males were given daily intramuscular injections of gentamicin, a nephrotoxic agent known to produce lesions in proximal tubules, at dose-levels of 10, 25, or 50 mg/kg/day for 10 days. Blood and 16-h urine samples were collected on Days − 7, − 3, 2, 4, 7, and at the end of the dosing period. Several novel kidney safety biomarkers were evaluated, with single- and multiplex immunoassays and in immunoprecipitation-LC/MS assays, in parallel to histopathology and conventional clinical pathology parameters. Treatment with gentamicin induced a dose-dependent increase in kidney tubular cell degeneration/necrosis, ranging from minimal to mild severity at 10 mg/kg/day, moderate at 25 mg/kg/day, and to severe at 50 mg/kg/day. The results showed that the novel urinary biomarkers, microalbumin, α1-microglobulin, clusterin, and osteopontin, together with the more traditional clinical pathology parameters, urinary total protein and N-acetyl-β-D-glucosaminidase (NAG), were more sensitive than blood urea nitrogen (BUN) and serum creatinine (sCr) to detect kidney injury in the monkeys given 10 mg/kg/day gentamicin for 10 days, a dose leading to an exposure which is slightly higher than the desired therapeutic exposure in clinics. Therefore, these urinary biomarkers represent non-invasive biomarkers of proximal tubule injury in Cynomolgus monkeys which may be potentially useful in humans. - Highlights: • Gentamicin induced kidney tubular cell degeneration/necrosis in Cynomolgus monkey • Urinary clusterin and osteopontin were sensitive biomarkers of kidney injury. • Microalbumin and α1-microglobulin in urine were also more sensitive than serum creatinine.

  10. Evaluation of novel biomarkers of nephrotoxicity in Cynomolgus monkeys treated with gentamicin

    Gautier, Jean-Charles, E-mail: jean-charles.gautier@sanofi.com [Sanofi R& D, Vitry-sur-Seine (France); Zhou, Xiaobing [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China); Yang, Yi [Sanofi R& D, Bridgewater (United States); Gury, Thierry [Sanofi R& D, Vitry-sur-Seine (France); Qu, Zhe [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China); Palazzi, Xavier; Léonard, Jean-François; Slaoui, Mohamed; Veeranagouda, Yaligara; Guizon, Isabelle; Boitier, Eric; Filali-Ansary, Aziz [Sanofi R& D, Vitry-sur-Seine (France); Berg, Bart H.J. van den; Poetz, Oliver; Joos, Thomas [Natural and Medical Sciences Institute at the University Tübingen (Germany); Zhang, Tianyi [Frontage Laboratories, Shanghai (China); Wang, Jufeng [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China); Detilleux, Philippe [Sanofi R& D, Vitry-sur-Seine (France); Li, Bo, E-mail: libo@nifdc.org.cn [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China)

    2016-07-15

    Most studies to evaluate kidney safety biomarkers have been performed in rats. This study was conducted in Cynomolgus monkeys in order to evaluate the potential usefulness of novel biomarkers of nephrotoxicity in this species. Groups of 3 males were given daily intramuscular injections of gentamicin, a nephrotoxic agent known to produce lesions in proximal tubules, at dose-levels of 10, 25, or 50 mg/kg/day for 10 days. Blood and 16-h urine samples were collected on Days − 7, − 3, 2, 4, 7, and at the end of the dosing period. Several novel kidney safety biomarkers were evaluated, with single- and multiplex immunoassays and in immunoprecipitation-LC/MS assays, in parallel to histopathology and conventional clinical pathology parameters. Treatment with gentamicin induced a dose-dependent increase in kidney tubular cell degeneration/necrosis, ranging from minimal to mild severity at 10 mg/kg/day, moderate at 25 mg/kg/day, and to severe at 50 mg/kg/day. The results showed that the novel urinary biomarkers, microalbumin, α1-microglobulin, clusterin, and osteopontin, together with the more traditional clinical pathology parameters, urinary total protein and N-acetyl-β-D-glucosaminidase (NAG), were more sensitive than blood urea nitrogen (BUN) and serum creatinine (sCr) to detect kidney injury in the monkeys given 10 mg/kg/day gentamicin for 10 days, a dose leading to an exposure which is slightly higher than the desired therapeutic exposure in clinics. Therefore, these urinary biomarkers represent non-invasive biomarkers of proximal tubule injury in Cynomolgus monkeys which may be potentially useful in humans. - Highlights: • Gentamicin induced kidney tubular cell degeneration/necrosis in Cynomolgus monkey • Urinary clusterin and osteopontin were sensitive biomarkers of kidney injury. • Microalbumin and α1-microglobulin in urine were also more sensitive than serum creatinine.

  11. Effect of Helichrysum plicatum DC. subsp. plicatum ethanol extract on gentamicin-induced nephrotoxicity in rats.

    Apaydin Yildirim, Betul; Kordali, Saban; Terim Kapakin, Kubra Asena; Yildirim, Fatih; Aktas Senocak, Esra; Altun, Serdar

    2017-06-01

    The aim of this study was to evaluate the possible therapeutic or protective effects of Helichrysum plicatum DC. subsp. plicatum ethanol extract (HPE) against gentamicin-induced nephrotoxicity. Thirty-six Sprague Dawley male rats weighing between 200 and 250 g were used as live material. They were formed into six groups containing 6 rats each and were allowed to adapt to laboratory conditions for 7 d. Group I: control, 5% DMSO intraperitoneal (i.p.); Group II: HPE 100 mg/(kg·d) i.p.; Group III: HPE 200 mg/(kg·d) i.p.; Group IV: gentamicin as 80 mg/(kg·d) i.p.; Group V: gentamicin as 80 mg/(kg·d) i.p.+HPE 100 mg/(kg·d) i.p.; and Group VI: gentamicin as 80 mg/(kg·d) i.p.+HPE 200 mg/(kg·d) i.p. for 8 d. Following treatment, serum, liver, and kidney tissues were used to assess blood urea nitrogen (BUN), creatinine, enzymatic and non-enzymatic antioxidants, and lipid peroxidation. Gentamicin significantly increased serum BUN, creatinin, and liver and kidney levels of malondialdehyde (MDA). It also decreased the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Treatment with the HPE 100 mg/kg reversed gentamicin-induced alterations as evidenced by decreased serum BUN and creatinin, liver and kidney oxidant marker, and tubular necrosis as well as by an increase in antioxidant enzymes. It was found that HPE 200 mg/kg significantly increased liver and kidney tissue MDA levels in nephrotoxicity in rats. As a result, these findings support the proposition that HPE in 100 mg/kg dose demonstrates in the kidney and liver as free radicals and scavenger to prevent the toxic effects of gentamicin in both the biochemical and histopathology parameters.

  12. Resveratrol influences platinum pharmacokinetics: A novel mechanism in protection against cisplatin-induced nephrotoxicity.

    Darwish, Mostafa A; Abo-Youssef, Amira M; Khalaf, Marwa M; Abo-Saif, Ali A; Saleh, Ibrahim G; Abdelghany, Tamer M

    2018-06-15

    Cisplatin (CP) is a widely used drug in treatment of solid tumors. However, the use of CP was hampered by its serious side effects especially nephrotoxicity. This study aims to investigate the effect of resveratrol (RES) on CP-induced nephrotoxicity, particularly, the effect of RES on CP pharmacokinetics (PKs). Male white albino rats were divided to four group's six rats each. The first group received (1%) tween 80 in normal saline and served as control. The second group received RES (30 mg kg -1 ) per day for 14 consecutive day's i.p. The third and fourth groups were given a single i.p. injection of CP (6 mg kg -1 ) with or without pre-treatment of RES (30 mg kg -1 per day for 14 consecutive days), respectively. Following administration of CP, plasma, urine and kidney platinum concentration were monitored to study PKs of CP. Five days after the CP injection, rats were killed; blood samples were collected; kidneys were dissected; and biochemical, immunohistochemical, and histological examinations were performed. Our results revealed that CP treatment significantly deteriorated kidney functions with subsequent alteration in redox balance of the kidney. On the other hand, RES successfully ameliorated CP-induced kidney injury and recovered normal kidney tissue redox status. Importantly, while RES pre-treatment did not significantly alter the plasma CP level, it dramatically decreased the urine concentration of CP and lowered its accumulation into the kidneys. Moreover, it increased CP plasma half-life (t 1/2 ) with subsequent decrease in its elimination rate constant, indicating an important role of PKs modulation in RES protection against CP-induced renal damage. Taken together, RES may protect the kidney tissue from the deleterious effects of CP through constringe of CP renal accumulation and enhancement of CP-induced oxidative stress. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Histological Evidence of Nephroprotective Effect of Ashwagandha (Withania somnifera Root Extract against Gentamicin Induced Nephrotoxicity in Rats

    Sadia Choudhury Shimmi

    2014-01-01

    Full Text Available Background: Kidney damage can occur due to exposure to nephrotoxic drugs, chemicals, toxins and infectious agents, ultimately leading to renal failure, management of which is a great challenge. So, efforts have been focused on traditional and herbal medicines for the treatment of renal failure. Ashwagandha (Withania somnifera may have free radical scavenging activity and can be used for the prevention and treatment of kidney damage. Objective: To observe the histological evidence of nephroprotective effect of Ashwagandha root against gentamicin induced nephrotoxicity in rats. Materials and Methods: This study was done in the department of Physiology, Sir Salimullah Medical College, Dhaka. A total number of 31 male Wistar albino rats were acclimatized for 14 days. Then, these were divided into two groups, control group consisted of 18 rats (Group A and Ashwagandha pretreated and gentamicin-treated group consisted of 13 rats (Group B. Control group was again subdivided into baseline control and gentamicin-treated control groups (A1 and A2 ─ each group contained 9 rats. All the animals received basal diet for 22 consecutive days. In addition to this, animals of Group A2 received gentamicin subcutaneously (100 mg/kg body weight/day from 15th to 22nd day and animals of Group B received Ashwagandha root extract (500 mg/kg body weight/day orally for 22 consecutive days and gentamicin subcutaneously (100 mg/kg body weight/day from 15th to 22nd day. All the animals were sacrificed on 23rd day. Then kidney samples were collected and histology was done by using standard laboratory procedure. Results: Histological examination of kidney revealed abnormal histological findings in 100% of gentamicin-treated rats. But 92.31% of rats in Ashwagandha pretreated and gentamicin-treated group showed almost normal structure and 7.69% showed mild histological changes. Conclusion: Ashwagandha root may have some nephroprotective effect against gentamicin induced

  14. Severity of gentamicin's nephrotoxic effect on patients with infective endocarditis: a prospective observational cohort study of 373 patients

    Buchholtz, Kristine; Larsen, Carsten T; Hassager, Christian

    2009-01-01

    BACKGROUND: Gentamicin is often used to treat infective endocarditis (IE). Gentamicin is highly effective, but its applicability is reduced by its nephrotoxic effect. The aim of this study was to quantify the nephrotoxic effect of gentamicin and the association between the nephrotoxic effect...

  15. Polymyxin B Nephrotoxicity: From Organ to Cell Damage.

    Maria de Fátima Fernandes Vattimo

    Full Text Available Polymyxins have a long history of dose-limiting toxicity, but the underlying mechanism of polymyxin B-induced nephrotoxicity is unclear. This study investigated the link between the nephrotoxic effects of polymyxin B on renal metabolic functions and mitochondrial morphology in rats and on the structural integrity of LLC-PK1 cells. Fifteen Wistar rats were divided into two groups: Saline group, rats received 3 mL/kg of 0.9% NaCl intraperitoneally (i.p. once a day for 5 days; Polymyxin B group, rats received 4 mg/kg/day of polymyxin B i.p. once a day for 5 days. Renal function, renal hemodynamics, oxidative stress, mitochondrial injury and histological characteristics were assessed. Cell membrane damage was evaluated via lactate dehydrogenase and nitric oxide levels, cell viability, and apoptosis in cells exposed to 12.5 μM, 75 μM and 375 μM polymyxin B. Polymyxin B was immunolocated using Lissamine rhodamine-polymyxin B in LLC-PK1 cells. Polymyxin B administration in rats reduced creatinine clearance and increased renal vascular resistance and oxidative damage. Mitochondrial damage was confirmed by electron microscopy and cytosolic localization of cytochrome c. Histological analysis revealed tubular dilatation and necrosis in the renal cortex. The reduction in cell viability and the increase in apoptosis, lactate dehydrogenase levels and nitric oxide levels confirmed the cytotoxicity of polymyxin B. The incubation of LLC-PK1 cells resulted in mitochondrial localization of polymyxin B. This study demonstrates that polymyxin B nephrotoxicity is characterized by mitochondrial dysfunction and free radical generation in both LLC-PK1 cells and rat kidneys. These data also provide support for clinical studies on the side effects of polymyxin B.

  16. Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity

    Hao, Yuhui; Huang, Jiawei; Gu, Ying; Liu, Cong; Li, Hong; Liu, Jing; Ren, Jiong; Yang, Zhangyou; Peng, Shuangqing; Wang, Weidong; Li, Rong

    2015-01-01

    Depleted uranium (DU) has been widely used in both civilian and military activities, and the kidney is the main target organ of DU during acute high-dose exposures. In this study, the nephrotoxicity caused by DU in metallothionein-1/2-null mice (MT −/−) and corresponding wild-type (MT +/+) mice was investigated to determine any associations with MT. Each MT −/− or MT +/+ mouse was pretreated with a single dose of DU (10 mg/kg, intraperitoneal injection) or an equivalent volume of saline. After 4 days of DU administration, kidney changes were assessed. After DU exposure, serum creatinine and serum urea nitrogen in MT −/− mice significantly increased than in MT +/+ mice, with more severe kidney pathological damage. Moreover, catalase and superoxide dismutase (SOD) decreased, and generation of reactive oxygen species and malondialdehyde increased in MT −/− mice. The apoptosis rate in MT −/− mice significantly increased, with a significant increase in both Bax and caspase 3 and a decrease in Bcl-2. Furthermore, sodium-glucose cotransporter (SGLT) and sodium-phosphate cotransporter (NaPi-II) were significantly reduced after DU exposure, and the change of SGLT was more evident in MT −/− mice. Finally, exogenous MT was used to evaluate the correlation between kidney changes induced by DU and MT doses in MT −/− mice. The results showed that, the pathological damage and cell apoptosis decreased, and SOD and SGLT levels increased with increasing dose of MT. In conclusion, MT deficiency aggravated DU-induced nephrotoxicity, and the molecular mechanisms appeared to be related to the increased oxidative stress and apoptosis, and decreased SGLT expression. - Highlights: • MT −/− and MT +/+ mice were used to evaluate nephrotoxicity of DU. • Renal damage was more evident in the MT −/− mice after exposure to DU. • Exogenous MT also protects against DU-induced nephrotoxicity. • MT deficiency induced more ROS and apoptosis after exposure to

  17. Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity

    Hao, Yuhui; Huang, Jiawei; Gu, Ying; Liu, Cong; Li, Hong; Liu, Jing; Ren, Jiong; Yang, Zhangyou [State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing 400038 (China); Peng, Shuangqing [Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Science, 20 Dongdajie Street, Fengtai District, Beijing 100071 (China); Wang, Weidong, E-mail: wwdwyl@sina.com [Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); Li, Rong, E-mail: yuhui_hao@126.com [State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing 400038 (China)

    2015-09-15

    Depleted uranium (DU) has been widely used in both civilian and military activities, and the kidney is the main target organ of DU during acute high-dose exposures. In this study, the nephrotoxicity caused by DU in metallothionein-1/2-null mice (MT −/−) and corresponding wild-type (MT +/+) mice was investigated to determine any associations with MT. Each MT −/− or MT +/+ mouse was pretreated with a single dose of DU (10 mg/kg, intraperitoneal injection) or an equivalent volume of saline. After 4 days of DU administration, kidney changes were assessed. After DU exposure, serum creatinine and serum urea nitrogen in MT −/− mice significantly increased than in MT +/+ mice, with more severe kidney pathological damage. Moreover, catalase and superoxide dismutase (SOD) decreased, and generation of reactive oxygen species and malondialdehyde increased in MT −/− mice. The apoptosis rate in MT −/− mice significantly increased, with a significant increase in both Bax and caspase 3 and a decrease in Bcl-2. Furthermore, sodium-glucose cotransporter (SGLT) and sodium-phosphate cotransporter (NaPi-II) were significantly reduced after DU exposure, and the change of SGLT was more evident in MT −/− mice. Finally, exogenous MT was used to evaluate the correlation between kidney changes induced by DU and MT doses in MT −/− mice. The results showed that, the pathological damage and cell apoptosis decreased, and SOD and SGLT levels increased with increasing dose of MT. In conclusion, MT deficiency aggravated DU-induced nephrotoxicity, and the molecular mechanisms appeared to be related to the increased oxidative stress and apoptosis, and decreased SGLT expression. - Highlights: • MT −/− and MT +/+ mice were used to evaluate nephrotoxicity of DU. • Renal damage was more evident in the MT −/− mice after exposure to DU. • Exogenous MT also protects against DU-induced nephrotoxicity. • MT deficiency induced more ROS and apoptosis after exposure to

  18. Melamine nephrotoxicity: an emerging epidemic in an era of globalization.

    Bhalla, Vivek; Grimm, Paul C; Chertow, Glenn M; Pao, Alan C

    2009-04-01

    Recent outbreaks of nephrolithiasis and acute kidney injury among children in China have been linked to ingestion of milk-based infant formula contaminated with melamine. These cases provide evidence in humans for the nephrotoxicity of melamine, which previously had been described only in animals. The consequences of this outbreak are already severe and will likely continue to worsen. Herein we summarize the global impact of the melamine milk contamination, the reemergence of melamine-tainted animal feed, and potential mechanisms of melamine nephrotoxicity. Large-scale epidemiologic studies are necessary to further characterize this disease and to assess its potential long-term sequelae. This epidemic of environmental kidney disease highlights the morbidity associated with adulterated food products available in today's global marketplace and reminds us of the unique vulnerability of the kidney to environmental insults. Melamine is the latest in a growing list of diverse potentially toxic compounds about which nephrologists and other health-care providers responsible for the diagnosis and management of kidney disease must now be aware.

  19. Prevention of chemotherapy-induced nephrotoxicity in children with cancer

    Fatemeh Ghane Sharbaf

    2017-01-01

    Full Text Available Children with cancer treated with cytotoxic drugs are frequently at risk of developing renal dysfunction. The cytotoxic drugs that are widely used for cancer treatment in children are cisplatin (CPL, ifosfamide (IFO, carboplatin, and methotrexate (MTX. Mechanisms of anticancer drug-induced renal disorders are different and include acute kidney injury (AKI, tubulointerstitial disease, vascular damage, hemolytic uremic syndrome (HUS, and intrarenal obstruction. CPL nephrotoxicity is dose-related and is often demonstrated with hypomagnesemia, hypokalemia, and impaired renal function with rising serum creatinine and blood urea nitrogen levels. CPL, mitomycin C, and gemcitabine treatment cause vascular injury and HUS. High-dose IFO, streptozocin, and azacitidine cause renal tubular dysfunction manifested by Fanconi syndrome, rickets, and osteomalacia. AKI is a common adverse effect of MTX, interferon-alpha, and nitrosourea compound treatment. These strategies to reduce the cytotoxic drug-induced nephrotoxicity should include adequate hydration, forced diuresis, and urinary alkalization. Amifostine, sodium thiosulfate, and diethyldithiocarbamate provide protection against CPL-induced renal toxicity.

  20. Hepatotoxicity and nephrotoxicity of 3-bromopyruvate in mice.

    Pan, Qiong; Sun, Yiming; Jin, Qili; Li, Qixiang; Wang, Qing; Liu, Hao; Zhao, Surong

    2016-11-01

    To investigate the hepatotoxicity and nephrotoxicity of 3-Bromopyruvate (3BP) in mice. Fifteen nude mice were grafted subcutaneously in the left flank with MDA-MB-231 cells, then all mice were divided into control group (PBS), 3BP group (8 mg/kg), positive group (DNR: 0.8 mg/kg) when tumor volume reached approximately 100 mm3. 28 days later, tumors, livers and kidneys were stored in 4 % formalin solution and stained with hematoxylin and eosin staining. The Kunming mice experiment included control group (PBS), 3BP group (4mg/kg; 8mg/kg; 16mg/kg), positive group (DNR: 0.8 mg/kg). 24 hours later, the blood were used for the determination of hepatic damage serum biomarkers. Livers were stored in 4 % formalin solution for the later detection. 3BP at the dose of 8mg/kg had a good effect on inhibiting tumor growth in nude mice and did not damage liver and kidney tissues. Kunming mice experiment showed 3BP at the dose of 16mg/kg did damage to liver tissues. 3-Bromopyruvate at the dose of suppressing tumor growth did not exhibit hepatotoxicity and nephrotoxicity in nude mice, and the effect on liver was confirmed in Kunming mice.

  1. Variation of nephrotoxicity biomarkers by urinary storage condition in rats.

    Le, Jung-Min; Han, Young-Hwan; Choi, Su-Jeong; Park, Ju-Seong; Jang, Jeong-Jun; Bae, Re-Ji-Na; Lee, Mi Ju; Kim, Myoung Jun; Lee, Yong-Hoon; Kim, Duyeol; Lee, Hye-Young; Park, Sun-Hee; Park, Cheol-Beom; Kang, Jin Seok; Kang, Jong-Koo

    2014-12-01

    Recently, there has been an increase in the use of several nephrotoxicity biomarkers in preclinical experiments. In addition, it has been indicated that the result may have been influenced by secondary factors, such as sample storage condition or storage period. In this study, we have assessed the variation in urinary nephrotoxicity biomarkers as a result of urine storage conditions and storage period of the urine. Urine was sampled from specific pathogen-free Sprague-Dawley rats (19 weeks old), which were housed individually in hanged stainless steel wire mesh cages. Urine was stored at 20℃, at 4℃, or at -70℃ after sampling. The levels of the biomarkers such as beta-2 microglobulin (B2M), cystatin-C (Cys-C), N-acetyl-β- D-glucosaminidase (NAG), micro albumin (MA), micro protein (MP) were measured at 6, 24, 48 and 144 hr after sampling. The B2M level was significantly decreased at 6, 24, 48, and 144 hr compared to 0 hr at -70℃ (p storage conditions. Taken together, B2M and Cys-C levels were modulated by storage temperature and period. For the enhancement of test accuracy, it is suggested that strict protocols be established for samples to minimize the effects of the storage conditions on the detected levels of biomarkers.

  2. Effect of mannitol on acute amphotericin B nephrotoxicity.

    Said, R; Marin, P; Anicama, H; Quintanilla, A; Levin, M L

    1980-01-01

    This study was undertaken to examine the value of mannitol as protection against the acute nephrotoxicity of amphotericin B under controlled conditions in a reproducible model of toxicity in the dog. Eleven dogs received amphotericin B, 2.5 mg x kg-1 b. wt. by i.v. infusion over a 4-h period. Six dogs were treated with mannitol, 6.25 g, i.v. every hour and five served as controls. Urinary volume (V), inulin clearance (CIn), p-aminohippurate clearance (CPAH), and Na excretion (UNaV) were measured every hour throughout the experiment. Although a higher urinary output was maintained in mannitol-treated dogs, a progressive decline in renal function was observed in treated and in control dogs. During the 4th h, mannitol-treated dogs showed higher CIn (37.4 vs. 19.7 ml x min-1 and CPAH (95 vs. 54 ml x min-1 than controls. However, statistically the differences were barely significant. The results fail to show that mannitol offers a definite protection against amphotericin B nephrotoxicity.

  3. The protective effect of ebselen on radiocontrast-induced nephrotoxicity.

    Ozgur, Tumay; Tutanc, Murat; Zararsiz, Ismail; Motor, Sedat; Ozturk, Oktay Hasan; Yaldiz, Mehmet; Kurtgoz, Ozgur Yildirim

    2012-01-01

    Radiocontrast-induced nephropathy has become one of the most important causes of renal acute failure. The most effective management of reducing the incidence of contrast nephropathy is to understand and prevent its causes. We aimed to investigate the protective role of ebselen against radiocontrast-induced nephrotoxicity in terms of tissue oxidant/antioxidant parameters and light microscopy in rats. Albino Wistar rats were randomly separated into four groups. The Group 1 rats were treated with sodium chloride as the control group, Group 2 with radiocontrast, Group 3 with radiocontrast plus ebselen, and Group 4 with ebselen alone. After 24 h, the animals over the experimental period were euthanized and blood samples were analyzed for blood urea nitrogen (BUN) and serum creatinine (Cr) levels. Kidney sections were analyzed for malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, as well as histopathological changes. In the radiocontrast group, BUN, MDA, and GSH-Px levels increased while SOD activity decreased compared with the control group. These decays were improved by ebselen administration in the radiocontrast group. Significant histological deteriorations were observed in the radiocontrast group. We noted improvement in the histologic findings with ebselen administration. These results indicate that ebselen might produce a protective mechanism against radiocontrast-induced nephrotoxicity.

  4. Involvement of oxidative stress in the mechanism of p,p'-DDT-induced nephrotoxicity in adult rats.

    Marouani, Neila; Hallegue, Dorsaf; Sakly, Mohsen; Benkhalifa, Moncef; Ben Rhouma, Khémais; Tebourbi, Olfa

    2017-07-01

    The 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (p,p'-DDT) is an organochlorine pesticide that persists in the environment and has a risk to human health. We investigated whether p,p'-DDT-induces nephrotoxicity in rats and whether oxidative stress and apoptosis are involved in the pathogenesis of this process. Male rats received the pesticide at doses of 50 and 100 mg/kg for 10 days. Renal damage was evaluated by histopathological examination and serum markers. The oxidative stress was evaluated by lipid peroxidation (LPO), metallothioneins (MTs) and protein carbonyl levels. Antioxidant enzymes were assessed by determination of superoxide dismutase (SOD) and catalase (CAT) activities. Glutathione-dependent enzymes and reducing power in kidney were evaluated by glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) activities. Renal tubular cells apoptosis was assessed through the TUNEL assay. After 10 days of treatment, an increase of serum creatinine and urea levels occurred, LPO and protein carbonyl levels were increased, while MTs level, SOD and CAT activities were decreased. Besides, the GPx, GR, GST, and GSH activities were decreased. Histological alterations in kidney tissue and intense apoptosis in renal tubular cells were observed. These results suggest that DDT sub-acute treatment causes oxidative stress and apoptosis, which may be the chief mechanisms of DDT-induced nephrotoxicity.

  5. Evaluation of the Protective Role of Glycine max Seed Extract (Soybean Oil) in Drug-Induced Nephrotoxicity in Experimental Rats.

    Ramasamy, Anand; Jothivel, Nandhakumar; Das, Saibal; Swapna, A; Albert, Alice Padmini; Barnwal, Preeti; Babu, Dinesh

    2017-09-28

    This study was conducted to evaluate the nephroprotective effect of Glycine max seed extract (soybean oil) against gentamicin- and rifampicin-induced nephrotoxicity in Sprague-Dawley rats and to compare its effects with those of vitamin E, which has well-established antioxidant and nephroprotective effects. Sixty male Sprague-Dawley rats (body weight 150-210 g) were divided into 10 groups. The first five groups were treated for 14 consecutive days with normal saline (5 ml/kg, by mouth [p.o.]); gentamicin (80 mg/kg intraperitoneally [i.p.]); gentamicin (80 mg/kg, i.p.) + vitamin E (250 mg/kg p.o.); gentamicin (80 mg/kg i.p.) + soybean oil (2.5 ml/kg p.o.); and gentamicin (80 mg/kg, i.p.) + soybean oil (5 ml/kg p.o.), respectively. For the next five groups, the same group allocation was done, but gentamicin was replaced with rifampicin (1 g/kg i.p.). Various biomarkers for nephrotoxicity in serum and urine were evaluated along with histopathological examination of kidneys. Analysis of variance (ANOVA) was done following Tukey's multiple comparison test; p Soybean oil in both doses significantly (p Soybean oil also showed strong antioxidant effects, causing significant (p Soybean oil demonstrated good nephroprotective activity due to antioxidant effects.

  6. Assessment of 99mTc-DMSA renoscintigraphy and uptake compared with creatinine clearance in rats with drug-induced nephrotoxicity, 1

    Yamada, Masafumi

    1991-01-01

    For evaluation of technetium-99m dimercaptosuccinic acid ( 99m Tc-DMSA) renal uptake as an absolute renal function, 99m Tc-DMSA uptake was compared with endogenous creatinine clearance (Ccr) in gentamicin-induced nephrotoxicity. Gentamicin (40 mg/kg/day) was given subcutaneously to male Wistar rats for periods of 3, 6, 9 and 12 days. On the next day, the renoscintigraphy was performed 2 hours following intravenous injection of 99m Tc-DMSA and Ccr was measured. On the 7th day, 99m Tc-DMSA uptake was significantly lower in the treated rats than that in control (32.27±0.92 vs 39.84±2.24%; p 99m Tc-DMSA uptake was measured and the histological examination was done. On the 4th day, 99m Tc-DMSA uptake was significantly lower than that on the 1st day (32.32±3.00 vs 38.91±1.95%; p 99m Tc-DMSA uptake reduces earlier than Ccr in gentamicin-induced nephrotoxicity and 99m Tc-DMSA uptake is a reliable indicator in the evaluation of a renal function in drug-induced nephrotoxicity. (author)

  7. DNA damage response in nephrotoxic and ischemic kidney injury

    Yan, Mingjuan; Tang, Chengyuan [Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011 (China); Ma, Zhengwei [Department of Cellular Biology & Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, GA 30912 (United States); Huang, Shuang [Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL (United States); Dong, Zheng, E-mail: zdong@augusta.edu [Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011 (China); Department of Cellular Biology & Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, GA 30912 (United States)

    2016-12-15

    DNA damage activates specific cell signaling cascades for DNA repair, cell cycle arrest, senescence, and/or cell death. Recent studies have demonstrated DNA damage response (DDR) in experimental models of acute kidney injury (AKI). In cisplatin-induced AKI or nephrotoxicity, the DDR pathway of ATR/Chk2/p53 is activated and contributes to renal tubular cell apoptosis. In ischemic AKI, DDR seems more complex and involves at least the ataxia telangiectasia mutated (ATM), a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, and p53; however, while ATM may promote DNA repair, p53 may trigger cell death. Targeting DDR for kidney protection in AKI therefore relies on a thorough elucidation of the DDR pathways in various forms of AKI.

  8.  The potential nephrotoxicity of antiretroviral drugs

    Zofia Marchewka

    2012-09-01

    Full Text Available  The intensive studies carried out in many scientific laboratories and the efforts of numerous pharmaceutical companies have led to the development of drugs which are able to effectively inhibitHIV proliferation. At present, a number of antiretroviral agents with different mechanisms of actionare available. Unfortunately, long-term use of antiretroviral drugs, however, does not remainindifferent to the patient and can cause significant side effects.In the present work, the antiretroviral drugs with a nephrotoxicity potential most commonly usedin clinical practice are described. In the review attention has also been focused on the nephropathyresulting from the HIV infection alone and the influence of genetic factors on the occurrenceof pathological changes in the kidney.

  9. Developmental nephrotoxicity of aristolochic acid in a zebrafish model

    Ding, Yu-Ju; Chen, Yau-Hung

    2012-01-01

    Aristolochic acid (AA) is a component of Aristolochia plant extracts which is used as a treatment for different pathologies and their toxicological effects have not been sufficiently studied. The aim of this study was to evaluate AA-induced nephrotoxicity in zebrafish embryos. After soaking zebrafish embryos in AA, the embryos displayed malformed kidney phenotypes, such as curved, cystic pronephric tubes, pronephric ducts, and cases of atrophic glomeruli. The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AA increased. Furthermore, AA-treated embryos exhibited significantly reduced glomerular filtration rates (GFRs) in comparison with mock-control littermates (mock-control: 100 ± 2.24% vs. 10 ppm AA treatment for 3–5 h: 71.48 ± 18.84% ∼ 39.41 ± 15.88%), indicating that AA treatment not only caused morphological kidney changes but also induced renal failure. In addition to kidney malformations, AA-treated zebrafish embryos also exhibited deformed hearts, swollen pericardiums, impaired blood circulation and the accumulation(s) of red blood cells. Whole-mount in situ hybridization studies using cmlc2 and wt1b as riboprobes indicated that the kidney is more sensitive than the heart to AA damage. Real-time PCR showed that AA can up-regulate the expression of proinflammatory genes like TNFα, cox2 and mpo. These results support the following conclusions: (1) AA-induced renal failure is mediated by inflammation, which causes circulation dysfunction followed by serious heart malformation; and (2) the kidney is more sensitive than the heart to AA injury. -- Highlights: ► Zebrafish were used to evaluate aristolochic acid (AA)-induced nephrotoxicity. ► AA-treated zebrafish embryos exhibited deformed heart as well as malformed kidney. ► Kidney is more sensitive to AA injury than the heart.

  10. Developmental nephrotoxicity of aristolochic acid in a zebrafish model

    Ding, Yu-Ju; Chen, Yau-Hung, E-mail: yauhung@mail.tku.edu.tw

    2012-05-15

    Aristolochic acid (AA) is a component of Aristolochia plant extracts which is used as a treatment for different pathologies and their toxicological effects have not been sufficiently studied. The aim of this study was to evaluate AA-induced nephrotoxicity in zebrafish embryos. After soaking zebrafish embryos in AA, the embryos displayed malformed kidney phenotypes, such as curved, cystic pronephric tubes, pronephric ducts, and cases of atrophic glomeruli. The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AA increased. Furthermore, AA-treated embryos exhibited significantly reduced glomerular filtration rates (GFRs) in comparison with mock-control littermates (mock-control: 100 ± 2.24% vs. 10 ppm AA treatment for 3–5 h: 71.48 ± 18.84% ∼ 39.41 ± 15.88%), indicating that AA treatment not only caused morphological kidney changes but also induced renal failure. In addition to kidney malformations, AA-treated zebrafish embryos also exhibited deformed hearts, swollen pericardiums, impaired blood circulation and the accumulation(s) of red blood cells. Whole-mount in situ hybridization studies using cmlc2 and wt1b as riboprobes indicated that the kidney is more sensitive than the heart to AA damage. Real-time PCR showed that AA can up-regulate the expression of proinflammatory genes like TNFα, cox2 and mpo. These results support the following conclusions: (1) AA-induced renal failure is mediated by inflammation, which causes circulation dysfunction followed by serious heart malformation; and (2) the kidney is more sensitive than the heart to AA injury. -- Highlights: ► Zebrafish were used to evaluate aristolochic acid (AA)-induced nephrotoxicity. ► AA-treated zebrafish embryos exhibited deformed heart as well as malformed kidney. ► Kidney is more sensitive to AA injury than the heart.

  11. Ameliorative potential of gemfibrozil and silymarin on experimentally induced nephrotoxicity in rats

    A.M. Kabel

    2013-12-01

    Conclusion: The combination of gemfibrozil and silymarin has protective effects against cisplatin-induced nephrotoxicity in rats better than each of these drugs alone due to anti-inflammatory and antioxidant properties of the used drugs.

  12. Protective effects of piperine on lead acetate induced-nephrotoxicity in rats

    Sri Agus Sudjarwo

    2017-11-01

    Full Text Available Objective(s: In this study, we investigated the protective effects of piperine on lead acetate-induced renal damage in rat kidney tissue. Materials and Methods: Forty male rats were divided into 5 groups: negative control (rats were given aquadest daily, positive control (rats were given lead acetate 30 mg/kg BW orally once a day for 60 days, and the treatment group (rats were given piperine 50 mg; 100 mg and 200 mg/kg BW orally once a day for 65 days, and on 5th day, were given lead acetate 30 mg/kg BW one hr after piperine administration for 60 days. On day 65 levels of blood urea nitrogen (BUN, creatinine, malondialdehyde (MDA, Superoxide Dismutase (SOD, and Glutathione Peroxidase (GPx were measured. Also, kidney samples were collected for histopathological studies. Results: The results revealed that lead acetate toxicity induced a significant increase in the levels of BUN, creatinine, and MDA; moreover, a significant decrease in SOD and GPx. Lead acetate also altered kidney histopathology (kidney damage, necrosis of tubules compared to the negative control. However, administration of piperine significantly improved the kidney histopathology, decreased the levels of BUN, creatinine, and MDA, and also significantly increased the SOD and GPx in the kidney of lead acetate-treated rats. Conclusion: From the results of this study it was concluded that piperine could be a potent natural herbal product exhibiting nephroprotective effect against lead acetate induced nephrotoxicity in rats.

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

    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.

  14. Protective effect of selenium on cisplatin induced nephrotoxicity: A double-blind controlled randomized clinical trial.

    Ghorbani, Ali; Omidvar, Bita; Parsi, Abazar

    2013-04-01

    Renal injury is common following cisplatin infusion. Some agents have been used to attenuate cisplatin nephrotoxicity. However, except hydration, none of them has been proved to be effective. In this study selenium as an antioxidant supplement was tested on cisplatin induced renal injury. 122 cancerous patients (85 male and 37 female; age range of 14 to 82 years old) were enrolled to receive chemotherapy regimens consisting cisplatin. They were allocated into two groups using a random number list . Investigators, patients and analyzers all, were blinded in allocation by using sealed opaque envelopes. Intervention group received a single 400 mcg selenium tablet and patients in control group took a placebo tablet which was similar with selenium preparation in color, weight, shape and taste. Primary end points were an increase in plasma creatinine above 1.5 mg/dl in men and 1.4mg/dl in women, or increase of plasma creatinine more than 50% from baseline or urine flow rate less than 0.5 ml/kg/h. Creatinine level was measured initially and on the 5th day after cisplatin therapy. There was no difference in cumulative dose of cisplatin between the groups (p=0.54). There were not evidences of acute renal failure (ARF) in cases. While, among placebo group, 7 patients had criteria of acute kidney injury. Conclusions :selenium could probably prevent cisplatin-induced acute kidney injury, when it is added to hydration therapy in cancerous patients.

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

    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.

  16. Risk factors for calcineurin inhibitor nephrotoxicity after renal transplantation: a systematic review and meta-analysis

    Xia T

    2018-02-01

    Full Text Available Tianyi Xia, Sang Zhu, Yan Wen, Shouhong Gao, Mingming Li, Xia Tao, Feng Zhang, Wansheng Chen Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of China Background: Nephrotoxicity of calcineurin inhibitors (CNIs is the major concern for long-term allograft survival despite its predominant role in current immunosuppressive regime after renal transplantation. CNI nephrotoxicity is multifactorial with demographic, environmental, and pharmacogenetic flexibility, whereas studies indicating risk factors for CNI nephrotoxicity obtained incomplete or conflicting results.Methods: A systematic review and meta-analysis of risk factors for CNI nephrotoxicity was performed on all retrieved studies through a comprehensive research of network database. Data were analyzed by Review Manager 5.2 with heterogeneity assessed using the Cochrane Q and I2 tests. CNI nephrotoxicity was primarily indicated with protocol biopsy or index-based clinical diagnosis, and the secondary outcome was defined as delayed graft function.Results: Twelve observational studies containing a total of 2,849 cases were identified. Donor age (odds ratio [OR], 1.01; 95% CI, 1.01–1.03; p=0.02, recipient zero-time arteriosclerosis (OR, 1.44; 95% CI, 1.04–1.99; p=0.03, and CYP3A5*3/*3 genotype (OR, 2.80; 95% CI, 2.63–2.98; p=0.00 were confirmed as risk factors for CNI nephrotoxicity. Subgroup and sensitivity analysis claimed donor age as a significant contributor in Asian and Caucasian areas.Conclusion: Older donor age, recipient zero-time arteriosclerosis, and CYP3A5*3/*3 genotype might add up the risk for CNI nephrotoxicity, which could be interpreted into a robust biomarker system. Keywords: calcineurin inhibitor, transplantation, nephrotoxicity, risk factor, systematic review, meta-analysis

  17. Determination of the effects of levofloxacin on gentamicin induced nephrotoxicity in rabbits: a comparative study

    Naeem, U.; Jamal, S.; Waheed, A.

    2015-01-01

    Objective: To determine the effects of levofloxacin on gentamicin induced nephrotoxicity in rabbits. Study Design: Comparative experimental study. Place and Duration of Study: The animal house of Army Medical College, Rawalpindi, and the pathology department of Army Medical College, Rawalpindi, from July 2009 to January 2010. Material and Methods: The effects of levofloxacin on gentamicin-induced nephrotoxicity were evaluated in rabbits. Twenty four rabbits were used in this study which were randomly divided into four groups (n= 6 in each group). Six animals were injected for 15 days with saline (NaCl; 0.9%), six with gentamicin alone at doses of 20 mg/kg of body weight/12 h (intramuscularly), six with combination of gentamicin (20 mg/kg/12 h) with low therapeutic doses of levofloxacin (30 mg/kg/24 h) and the last six were treated with gentamicin and high therapeutic doses of levofloxacin (50 mg/kg/24 h). Levofloxacin was given by intraperitoneal route. Results: Gentamicin induced nephrotoxicity was evaluated by histopathological and serum analysis. The extent of nephrotoxicity was significantly increased when gentamicin was given in combination with levofloxacin both in low and high doses. Conclusion: Levofloxacin enhances gentamicin induced nephrotoxicity and extent of this nephrotoxicity increased with increasing dose of levofloxacin. (author)

  18. Intravenous Vancomycin Associated With the Development of Nephrotoxicity in Patients With Class III Obesity.

    Choi, Yookyung Christy; Saw, Stephen; Soliman, Daniel; Bingham, Angela L; Pontiggia, Laura; Hunter, Krystal; Chuang, Linda; Siemianowski, Laura A; Ereshefsky, Benjamin; Hollands, James M

    2017-11-01

    A consensus statement recommends initial intravenous (IV) vancomycin dosing of 15-20 mg/kg every 8- 24 hours, with an optional 25- to 30-mg/kg loading dose. Although some studies have shown an association between weight and the development of vancomycin-associated nephrotoxicity, results have been inconsistent. To evaluate the correlation between incidence of nephrotoxicity associated with weight-based IV vancomycin dosing strategies in nonobese and obese patients. This retrospective cohort study evaluated hospitalized adult patients admitted who received IV vancomycin. Patients were stratified into nonobese (body mass index [BMI] obesity class I and II (BMI 30-39.9kg/m 2 ), and obesity class III (BMI≥40 kg/m 2 ) groups; patients who were overweight but not obese were excluded. Incidence of nephrotoxicity and serum vancomycin trough concentrations were evaluated. Of a total of 62 documented cases of nephrotoxicity (15.1%), 13 (8.7%), 23 (14.3%), and 26 (26.3%) cases were observed in nonobese, obesity class I and II, and obesity class III groups, respectively ( P=0.002). Longer durations of therapy ( P20 mg/L ( Pobesity were 3-times as likely to develop nephrotoxicity when compared with nonobese patients (odds ratio [OR]=2.99; CI=1.12-7.94) and obesity class I and II patients (OR=3.14; CI=1.27-7.75). Obesity and other factors are associated with a higher risk of vancomycin-associated nephrotoxicity.

  19. Identification of novel indicators of cyclosporine A nephrotoxicity in a CD-1 mouse model

    O'Connell, Sein; Slattery, Craig; Ryan, Michael P.; McMorrow, Tara

    2011-01-01

    The calcineurin inhibitor cyclosporine A (CsA) is a widely used immunosuppressive agent. However, nephrotoxicity is a serious side effect observed in patients which limits clinical use of CsA. CsA nephrotoxicity is associated with tubulointerstitial injury progressing to nephropathy. This is typically diagnosed by invasive renal biopsy and is often only detected when the disease process is well advanced. Therefore identification of novel, early indicators of CsA nephrotoxicity could be clinically advantageous. This study aimed to establish a murine model of CsA nephrotoxicity and to identify urinary proteins that may indicate the onset of CsA-induced nephropathy using 2-D gel electrophoresis. CsA nephrotoxicity was induced in CD-1 mice by daily CsA administration for 4 weeks. By week 4, elevated serum creatinine and proteinuria were observed after CsA treatment indicating significant renal dysfunction. Decreased cadherin-1, increased α-smooth muscle actin and fibroblast specific protein 1 in kidney tissue indicated disruption of normal tubular architecture. Alterations in podocin and uromodulin were also observed which may indicate damage to other segments of the nephron. Proteomic analysis of urine identified a number of differentially regulated proteins that may be involved in early CsA nephropathy including cadherin 1, superoxide dismutase and vinculin. These findings suggest novel mechanisms of CsA nephrotoxicity and identify novel potential markers of the disease.

  20. Ondansetron can enhance cisplatin-induced nephrotoxicity via inhibition of multiple toxin and extrusion proteins (MATEs)

    Li, Qing; Guo, Dong; Dong, Zhongqi; Zhang, Wei; Zhang, Lei; Huang, Shiew-Mei; Polli, James E.; Shu, Yan

    2013-01-01

    The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effect on cisplatin nephrotoxicity by altering the function of cisplatin transporters. The inhibitory potencies of ondansetron on metformin accumulation mediated by OCT2 and MATEs were determined in the stable HEK-293 cells expressing these transporters. The effects of ondansetron on drug disposition in vivo were examined by conducting the pharmacokinetics of metformin, a classical substrate for OCTs and MATEs, in wild-type and Mate1−/− mice. The nephrotoxicity was assessed in the wild-type and Mate1−/− mice received cisplatin with and without ondansetron. Both MATEs, including human MATE1, human MATE2-K, and mouse Mate1, and OCT2 (human and mouse) were subject to ondansetron inhibition, with much greater potencies by ondansetron on MATEs. Ondansetron significantly increased tissue accumulation and pharmacokinetic exposure of metformin in wild-type but not in Mate1−/− mice. Moreover, ondansetron treatment significantly enhanced renal accumulation of cisplatin and cisplatin-induced nephrotoxicity which were indicated by increased levels of biochemical and molecular biomarkers and more severe pathohistological changes in mice. Similar increases in nephrotoxicity were caused by genetic deficiency of MATE function in mice. Therefore, the potent inhibition of MATEs by ondansetron enhances the nephrotoxicity associated with cisplatin treatment in mice. Potential nephrotoxic effects of combining the chemotherapeutic cisplatin and the antiemetic 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonists, such as ondansetron, should be investigated in patients. - Highlights: • Nephrotoxicity significantly limits clinical use of the chemotherapeutic cisplatin

  1. Ondansetron can enhance cisplatin-induced nephrotoxicity via inhibition of multiple toxin and extrusion proteins (MATEs)

    Li, Qing [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Institute of Clinical Pharmacology, Central South University, Hunan 410078 (China); Guo, Dong [Institute of Clinical Pharmacology, Central South University, Hunan 410078 (China); Dong, Zhongqi [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Zhang, Wei [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Institute of Clinical Pharmacology, Central South University, Hunan 410078 (China); Zhang, Lei; Huang, Shiew-Mei [Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD (United States); Polli, James E. [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Shu, Yan, E-mail: yshu@rx.umaryland.edu [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States)

    2013-11-15

    The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effect on cisplatin nephrotoxicity by altering the function of cisplatin transporters. The inhibitory potencies of ondansetron on metformin accumulation mediated by OCT2 and MATEs were determined in the stable HEK-293 cells expressing these transporters. The effects of ondansetron on drug disposition in vivo were examined by conducting the pharmacokinetics of metformin, a classical substrate for OCTs and MATEs, in wild-type and Mate1−/− mice. The nephrotoxicity was assessed in the wild-type and Mate1−/− mice received cisplatin with and without ondansetron. Both MATEs, including human MATE1, human MATE2-K, and mouse Mate1, and OCT2 (human and mouse) were subject to ondansetron inhibition, with much greater potencies by ondansetron on MATEs. Ondansetron significantly increased tissue accumulation and pharmacokinetic exposure of metformin in wild-type but not in Mate1−/− mice. Moreover, ondansetron treatment significantly enhanced renal accumulation of cisplatin and cisplatin-induced nephrotoxicity which were indicated by increased levels of biochemical and molecular biomarkers and more severe pathohistological changes in mice. Similar increases in nephrotoxicity were caused by genetic deficiency of MATE function in mice. Therefore, the potent inhibition of MATEs by ondansetron enhances the nephrotoxicity associated with cisplatin treatment in mice. Potential nephrotoxic effects of combining the chemotherapeutic cisplatin and the antiemetic 5-hydroxytryptamine-3 (5-HT{sub 3}) receptor antagonists, such as ondansetron, should be investigated in patients. - Highlights: • Nephrotoxicity significantly limits clinical use of the chemotherapeutic

  2. Herbs with potential nephrotoxic effects according to traditional Persian medicine: Review and assessment of scientific evidence.

    Kolangi, Fatemeh; Memariani, Zahra; Bozorgi, Mahboubeh; Mozaffarpur, Seyyed Ali; Mirzapour, Mohaddeseh

    2018-04-03

    The increased use of herbal remedies particularly in patients with kidney diseases indicated the importance of studies which focused on nephrotoxic plants. The present study aimed to review and assess the kidney-damaging herbs mentioned in the Persian medicine [PM] books. The main PM books were searched for nephrotoxic herbs and their relevant reformers traditionally proposed for preventing renal damage. PubMed, Scopus and Google Scholar were investigated for evaluation of the scientific evidence relating to the nephrotoxicity of herbs. A total of 64 plants with kidney damage potential and their reformer medicaments were recorded in 7 sources included in this review. Allium schoenoprasum and Marrubium vulgare were the most repeated and emphasized nephrotoxic plants in PM books, but there was not any relevant scientific evidence. Despite the lack of clinical studies, some evidence was found for 38% of plants that were related to renal damage. The most repeated reformers for reducing the renal side effects mainly consisted of gum tragacanth, gum Arabic, mastic gum, anise, jujube and honey and some evidence was found for their nephroprotective activities. The present study reviewed and assessed the herbs with adverse renal effects in the main PM books. Some evidence was in line with the potential nephrotoxicity of plants and their ‎reformers. Despite the lack of clinical research for evaluation of their renal damage, the herbs may be focused in term of their nephrotoxicity; and there is a need for further studies on the scientific basis of their nephrotoxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Protective Effects of Cilastatin against Vancomycin-Induced Nephrotoxicity

    Blanca Humanes

    2015-01-01

    Full Text Available Vancomycin is a very effective antibiotic for treatment of severe infections. However, its use in clinical practice is limited by nephrotoxicity. Cilastatin is a dehydropeptidase I inhibitor that acts on the brush border membrane of the proximal tubule to prevent accumulation of imipenem and toxicity. The aim of this study was to investigate the potential protective effect of cilastatin on vancomycin-induced apoptosis and toxicity in cultured renal proximal tubular epithelial cells (RPTECs. Porcine RPTECs were cultured in the presence of vancomycin with and without cilastatin. Vancomycin induced dose-dependent apoptosis in cultured RPTECs, with DNA fragmentation, cell detachment, and a significant decrease in mitochondrial activity. Cilastatin prevented apoptotic events and diminished the antiproliferative effect and severe morphological changes induced by vancomycin. Cilastatin also improved the long-term recovery and survival of RPTECs exposed to vancomycin and partially attenuated vancomycin uptake by RPTECs. On the other hand, cilastatin had no effects on vancomycin-induced necrosis or the bactericidal effect of the antibiotic. This study indicates that cilastatin protects against vancomycin-induced proximal tubule apoptosis and increases cell viability, without compromising the antimicrobial effect of vancomycin. The beneficial effect could be attributed, at least in part, to decreased accumulation of vancomycin in RPTECs.

  4. Coenzyme Q10 treatment ameliorates acute cisplatin nephrotoxicity in mice

    Fouad, Amr A.; Al-Sultan, Ali Ibrahim; Refaie, Shereen M.; Yacoubi, Mohamed T.

    2010-01-01

    The nephroprotective effect of coenzyme Q10 was investigated in mice with acute renal injury induced by a single i.p. injection of cisplatin (5 mg/kg). Coenzyme Q10 treatment (10 mg/kg/day, i.p.) was applied for 6 consecutive days, starting 1 day before cisplatin administration. Coenzyme Q10 significantly reduced blood urea nitrogen and serum creatinine levels which were increased by cisplatin. Coenzyme Q10 significantly compensated deficits in the antioxidant defense mechanisms (reduced glutathione level and superoxide dismutase activity), suppressed lipid peroxidation, decreased the elevations of tumor necrosis factor-α, nitric oxide and platinum ion concentration, and attenuated the reductions of selenium and zinc ions in renal tissue resulted from cisplatin administration. Also, histopathological renal tissue damage mediated by cisplatin was ameliorated by coenzyme Q10 treatment. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the cisplatin-induced overexpression of inducible nitric oxide synthase, nuclear factor-κB, caspase-3 and p53 in renal tissue. It was concluded that coenzyme Q10 represents a potential therapeutic option to protect against acute cisplatin nephrotoxicity commonly encountered in clinical practice.

  5. Therapeutic Potential and Molecular Mechanisms of Emblica officinalis Gaertn in countering nephrotoxicity in rats induced by the chemotherapeutic agent cisplatin

    Salma Malik

    2016-10-01

    Full Text Available Emblica officinalis Gaertn. belonging to family Euphorbiaceae is commonly known as Indian gooseberry or Amla in India. It is used as a ‘rejuvenating herb’ in traditional system of Indian medicine. It has been shown to possess antioxidant, anti-inflammatory and anti-apoptotic effects. Thus, on the basis of its biological effects, the present study was undertaken to evaluate the protective effect of the dried fruit extract of the E. Officinalis (EO in cisplatin-induced nephrotoxicity in rats and also to evaluate the mechanism of its nephroprotection. The study was done on male albino Wistar rats. They were divided into 6 groups (n=6 viz. control, cisplatin-control, cisplatin and EO (150, 300 and 600 mg/kg; p.o. respectively in different groups and EO only (600 mg/kg; p.o. only. EO was administered orally to the rats for a period of 10 days and on the 7th day, a single injection of cisplatin (8 mg/kg; i.p. was administered to the cisplatin-control and EO treatment groups. The rats were sacrificed on the 10th day. Cisplatin-control rats had deranged renal function parameters and the kidney histology confirmed the presence of acute tubular necrosis. Furthermore, there were increased oxidative stress, apoptosis and inflammation along with higher expression of MAPK pathway proteins in the rat kidney from the cisplatin-control group. Contrary to this, EO (600 mg/kg significantly normalized renal function, bolstered antioxidant status and ameliorated histological alterations. The inflammation and apoptosis were markedly lower in comparison to cisplatin-control rats. Furthermore, EO (600 mg/kg inhibited MAPK phosphorylation which was instrumental in preserving renal function and morphology. In conclusion, the results of our study demonstrated that EO attenuated cisplatin-induced nephrotoxicity in rats through suppression of MAPK induced inflammation and apoptosis.

  6. Exopolysaccharide produced by Enterobacter sp. YG4 reduces uranium induced nephrotoxicity.

    K, Nagaraj; Devasya, Rekha Punchapady; Bhagwath, Arun Ananthapadmanabha

    2016-01-01

    Uranium nephrotoxicity is a health concern with very few treatment options. Bacterial exopolysaccharides (EPS) possess multiple biological activities and appear as prospective candidates for treating uranium nephrotoxicity. This study focuses on the ability of an EPS produced by a bacterial strain Enterobacter sp. YG4 to reduce uranium nephrotoxicity in vivo. This bacterium was isolated from the gut contents of a slug Laevicaulis alte (Férussac). Based on the aniline blue staining reaction and infrared spectral analysis, the EPS was identified as β-glucan and its molecular weight was 11.99×10(6)Da. The EPS showed hydroxyl radical scavenging ability and total antioxidant capacity in vitro. To assess the protection provided by the EPS against uranium nephrotoxicity, a single dose of 2mg/kg uranyl nitrate was injected intraperitoneally to albino Wistar rats. As intervention, the EPS was administered orally (100mg/kg/day) for 4 consecutive days. The rats were sacrificed on the fifth day and analyses were conducted. Increased serum creatinine and urea nitrogen levels and histopathological alterations in kidneys were observed in uranyl nitrate treated animals. All these alterations were reduced with the administration of Enterobacter sp. YG4 EPS, emphasizing a novel approach in treating uranium nephrotoxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Effect of Coenzyme-Q10 on Doxorubicin-Induced Nephrotoxicity in Rats

    Azza A. K. El-Sheikh

    2012-01-01

    Full Text Available Nephrotoxicity is one of the limiting factors for using doxorubicin (Dox as an anticancer chemotherapeutic. Here, we investigated possible protective effect of coenzyme-Q10 (CoQ10 on Dox-induced nephrotoxicity and the mechanisms involved. Two doses (10 and 100 mg/kg of CoQ10 were administered orally to rats for 8 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of Dox (15 mg/kg at day 4 of the experiment. Our results showed that the low dose of CoQ10 succeeded in reversing Dox-induced nephrotoxicity to control levels (e.g., levels of blood urea nitrogen and serum creatinine, concentrations of renal reduced glutathione (GSH and malondialdehyde, catalase activity and caspase 3 expression, and renal histopathology. Alternatively, the high dose of CoQ10 showed no superior nephroprotection over the low dose, as there were no significant improvements in renal histopathology, catalase activity, or caspase 3 expression compared to the Dox-treated group. Interestingly, the high dose of CoQ10 alone significantly decreased renal GSH level as well as catalase activity and caused a mild induction of caspase 3 expression compared to control, probably due to a prooxidant effect at this dose of CoQ10. We conclude that CoQ10 protects from Dox-induced nephrotoxicity with a precaution to dosage adjustment.

  8. Effect of nephrotoxic treatment with gentamicin on rats chronically exposed to uranium.

    Rouas, Caroline; Stefani, Johanna; Grison, Stéphane; Grandcolas, Line; Baudelin, Cédric; Dublineau, Isabelle; Pallardy, Marc; Gueguen, Yann

    2011-01-11

    Uranium is a radioactive heavy metal with a predominantly chemical toxicity, affecting especially the kidneys and more particularly the proximal tubular structure. Until now, few experimental studies have examined the effect of chronic low-dose exposure to uranium on kidney integrity: these mainly analyse standard markers such as creatinine and urea, and none has studied the effect of additional co-exposure to a nephrotoxic agent on rats chronically exposed to uranium. The aim of the present study is to examine the potential cumulative effect of treating uranium-exposed rats with a nephrotoxic drug. Neither physiological indicators (diuresis and creatinine clearance) nor standard plasma and urine markers (creatinine, urea and total protein) levels were deteriorated when uranium exposure was combined with gentamicin-induced nephrotoxicity. A histological study confirmed the preferential impact of gentamicin on the tubular structure and showed that uranium did not aggravate the histopathological renal lesions. Finally, the use of novel markers of kidney toxicity, such as KIM-1, osteopontin and kallikrein, provides new knowledge about the nephrotoxicity threshold of gentamicin, and allows us to conclude that under our experimental conditions, low dose uranium exposure did not induce signs of nephrotoxicity or enhance renal sensitivity to another nephrotoxicant. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  9. Effect of nephrotoxic treatment with gentamicin on rats chronically exposed to uranium

    Rouas, Caroline; Stefani, Johanna; Grison, Stephane; Grandcolas, Line; Baudelin, Cedric; Dublineau, Isabelle; Pallardy, Marc; Gueguen, Yann

    2011-01-01

    Uranium is a radioactive heavy metal with a predominantly chemical toxicity, affecting especially the kidneys and more particularly the proximal tubular structure. Until now, few experimental studies have examined the effect of chronic low-dose exposure to uranium on kidney integrity: these mainly analyse standard markers such as creatinine and urea, and none has studied the effect of additional co-exposure to a nephrotoxic agent on rats chronically exposed to uranium. The aim of the present study is to examine the potential cumulative effect of treating uranium-exposed rats with a nephrotoxic drug. Neither physiological indicators (diuresis and creatinine clearance) nor standard plasma and urine markers (creatinine, urea and total protein) levels were deteriorated when uranium exposure was combined with gentamicin-induced nephrotoxicity. A histological study confirmed the preferential impact of gentamicin on the tubular structure and showed that uranium did not aggravate the histopathological renal lesions. Finally, the use of novel markers of kidney toxicity, such as KIM-1, osteopontin and kallikrein, provides new knowledge about the nephrotoxicity threshold of gentamicin, and allows us to conclude that under our experimental conditions, low dose uranium exposure did not induce signs of nephrotoxicity or enhance renal sensitivity to another nephrotoxicant.

  10. Pharmacological inhibition of NADPH oxidase protects against cisplatin induced nephrotoxicity in mice by two step mechanism.

    Wang, Yimin; Luo, Xiao; Pan, Hao; Huang, Wei; Wang, Xueping; Wen, Huali; Shen, Kezhen; Jin, Baiye

    2015-09-01

    Cisplatin induced nephrotoxicity is primarily caused by ROS (Reactive Oxygen Species) induced proximal tubular cell death. NADPH oxidase is major source of ROS production by cisplatin. Here, we reported that pharmacological inhibition of NADPH oxidase by acetovanillone (obtained from medicinal herb Picrorhiza kurroa) led to reduced cisplatin nephrotoxicity in mice. In this study we used various molecular biology and biochemistry methods a clinically relevant model of nephropathy, induced by an important chemotherapeutic drug cisplatin. Cisplatin-induced nephrotoxicity was evident by histological damage from loss of the tubular structure. The damage was also marked by the increase in blood urea nitrogen, creatinine, protein nitration as well as cell death markers such as caspase 3/7 activity and DNA fragmentation. Tubular cell death by cisplatin led to pro-inflammatory response by production of TNFα and IL1β followed by leukocyte/neutrophil infiltration which resulted in new wave of ROS involving more NADPH oxidases. Cisplatin-induced markers of kidney damage such as oxidative stress, cell death, inflammatory cytokine production and nephrotoxicity were attenuated by acetovanillone. In addition to that, acetovanillone enhanced cancer cell killing efficacy of cisplatin. Thus, pharmacological inhibition of NADPH oxidase can be protective for cisplatin-induced nephrotoxicity in mice. Copyright © 2015. Published by Elsevier Ltd.

  11. Evaluation of oxidative stress in D-serine induced nephrotoxicity

    Orozco-Ibarra, Marisol; Medina-Campos, Omar Noel; Sanchez-Gonzalez, Dolores Javier; Martinez-Martinez, Claudia Maria; Floriano-Sanchez, Esau; Santamaria, Abel; Ramirez, Victoria; Bobadilla, Norma A.; Pedraza-Chaverri, Jose

    2007-01-01

    It has been suggested that oxidative stress is involved in D-serine-induced nephrotoxicity. The purpose of this study was to assess if oxidative stress is involved in this experimental model using several approaches including (a) the determination of several markers of oxidative stress and the activity of some antioxidant enzymes in kidney and (b) the use of compounds with antioxidant or prooxidant effects. Rats were sacrificed at several periods of time (from 3 to 24 h) after a single i.p. injection of D-serine (400 mg/kg). Control rats were injected with L-serine (400 mg/kg) and sacrificed 24 h after. The following markers were used to assess the temporal aspects of renal damage: (a) urea nitrogen (BUN) and creatinine in blood serum, (b) kidney injury molecule (KIM-1) mRNA levels, and (c) tubular necrotic damage. In addition, creatinine clearance, proteinuria, and urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) were measured 24 h after D-serine injection. Protein carbonyl content, malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), fluorescent products of lipid peroxidation, reactive oxygen species (ROS), glutathione (GSH) content, and heme oxygenase-1 (HO-1) expression were measured as markers of oxidative stress in the kidney. Additional experiments were performed using the following compounds with antioxidant or pro-oxidant effects before D-serine injection: (a) α-phenyl-tert-butyl-nitrone (PBN), a spin trapping agent; (b) 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron(III) (FeTPPS), a soluble complex able to metabolize peroxynitrite; (c) aminotriazole (ATZ), a catalase (CAT) inhibitor; (d) stannous chloride (SnCl 2 ), an HO-1 inductor; (e) tin mesoporphyrin (SnMP), an HO inhibitor. In the time-course study, serum creatinine and BUN increased significantly on 15-24 and 20-24 h, respectively, and KIM-1 mRNA levels increased significantly on 6-24 h. Histological analyses revealed tubular necrosis at 12 h. The activity of antioxidant enzymes

  12. Nephrotoxicity of mercapturic acids of three structurally related 2,2-difluoroethylenes in the rat. Indications for different bioactivation mechanisms.

    Commandeur, J.N.M.; Brakenhoff, J.P.G.; de Kanter, F.J.J.; Vermeulen, N.P.E.

    1988-01-01

    The biotransformation and the hepato- and nephrotoxicity of the mercapturic acids (N-acetyl-1-cysteine S-conjugates) of three structurally related 2,2-difluoroethylenes were investigated in vivo in the rat. All mercapturic acids appeared to cause nephrotoxicity, without any measureable effect on the

  13. Microsomal protein synthesis inhibition: an early manifestation of gentamicin nephrotoxicity

    Bennett, W.M.; Mela-Riker, L.M.; Houghton, D.C.; Gilbert, D.N.; Buss, W.C.

    1988-01-01

    Aminoglycoside antibiotics achieve bacterial killing by binding to bacterial ribosomes and inhibiting protein synthesis. To examine whether similar mechanisms could be present in renal tubular cells prior to the onset of overt proximal tubular necrosis due to these drugs, we isolated microsomes from Fischer rats given 20 mg/kg gentamicin every 12 h subcutaneously for 2 days and from vehicle-injected controls. Concomitant studies of renal structure, function, and mitochondrial respiration were carried out. [3H]leucine incorporation into renal microsomes of treated animals was reduced by 21.9% (P less than 0.01), whereas brain and liver microsomes from the same animals were unaffected. Gentamicin concentration in the renal microsomal preparation was 56 micrograms/ml, a value 7- to 10-fold above concentrations necessary to inhibit bacterial growth. Conventional renal function studies were normal (blood urea, serum creatinine, creatinine clearance). Treated animals showed only a mild reduction of inulin clearance, 0.71 compared with 0.93 ml.min-1.100 g-1 in controls (P less than 0.05), and an increase in urinary excretion of N-acetylglucosaminidase of 20 compared with 14.8 units/l (P less than 0.05). Renal slice transport of p-aminohippuric acid, tetraethylammonium, and the fractional excretion of sodium were well preserved. There was no evidence, as seen by light microscopy, of proximal tubular necrosis. Mitochondrial cytochrome concentrations were normal and respiratory activities only slightly reduced. Processes similar to those responsible for bacterial killing could be involved in experimental gentamicin nephrotoxicity before overt cellular necrosis

  14. The role of vitamin E in the prevention of zoledronic acid-induced nephrotoxicity in rats: a light and electron microscopy study.

    Sert, İbrahim Unal; Kilic, Ozcan; Akand, Murat; Saglik, Lutfi; Avunduk, Mustafa Cihat; Erdemli, Esra

    2018-03-01

    Bisphosphonates are widely used in metastatic cancer such as prostate and breast cancer, and their nephrotoxic effects have been established previously. In this study we aimed to evaluate both the nephrotoxic effects of zoledronic acid (ZA) and the protective effects of vitamin E (Vit-E) on this process under light and electron microscopy. A total of 30 male Sprague-Dawley rats were divided into 3 groups. The first group constituted the control group. The second group was given i.v. ZA of 3 mg/kg once every 3 weeks for 12 weeks from the tail vein. The third group received the same dosage of ZA with an additional i.m . injection of 15 mg Vit-E every week for 12 weeks. Tissues were taken 4 days after the last dose of ZA for histopathological and ultrastructural evaluation. Paller score, tubular epithelial thickness and basal membrane thickness were calculated for each group. For group 2, the p -values are all < 0.001 for Paller score, epitelial thickness, and basal membrane thickness. For group 3 (ZA + Vit. E), the p -values are < 0.001 for Paller score, 0.996 for epitelial thickness, and < 0.001 basal membrane thickness. Significant differences were also observed in ultrastructural changes for group 2. However, adding Vit-E to ZA administration reversed all the histopathological changes to some degree, with statistical significance. Administration of ZA had nephrotoxic effects on rat kidney observed under both light and electron microscopy. Concomitant administration of Vit-E significantly reduces toxic histopathological effects of ZA.

  15. Characterization of the chemical reactivity and nephrotoxicity of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide, a potential reactive metabolite of trichloroethylene.

    Irving, Roy M; Pinkerton, Marie E; Elfarra, Adnan A

    2013-02-15

    N-Acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NA-DCVC) has been detected in the urine of humans exposed to trichloroethylene and its related sulfoxide, N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (NA-DCVCS), has been detected as hemoglobin adducts in blood of rats dosed with S-(1,2-dichlorovinyl)-L-cysteine (DCVC) or S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (DCVCS). Because the in vivo nephrotoxicity of NA-DCVCS was unknown, in this study, male Sprague-Dawley rats were dosed (i.p.) with 230 μmol/kg b.w. NA-DCVCS or its potential precursors, DCVCS or NA-DCVC. At 24 h post treatment, rats given NA-DCVC or NA-DCVCS exhibited kidney lesions and effects on renal function distinct from those caused by DCVCS. NA-DCVC and NA-DCVCS primarily affected the cortico-medullary proximal tubules (S(2)-S(3) segments) while DCVCS primarily affected the outer cortical proximal tubules (S(1)-S(2) segments). When NA-DCVCS or DCVCS was incubated with GSH in phosphate buffer pH 7.4 at 37°C, the corresponding glutathione conjugates were detected, but NA-DCVC was not reactive with GSH. Because NA-DCVCS exhibited a longer half-life than DCVCS and addition of rat liver cytosol enhanced GSH conjugate formation, catalysis of GSH conjugate formation by the liver could explain the lower toxicity of NA-DCVCS in comparison with DCVCS. Collectively, these results provide clear evidence that NA-DCVCS formation could play a significant role in DCVC, NA-DCVC, and trichloroethylene nephrotoxicity. They also suggest a role for hepatic metabolism in the mechanism of NA-DCVC nephrotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Upregulation of AMWAP: a novel mechanism for HDAC inhibitors to protect against cisplatin nephrotoxicity.

    Tang, Jinhua; Zhuang, Shougang

    2016-02-01

    Histone deacetylases have been reported to protect against renal tubular damage in several animal models of acute renal injury, including cisplatin nephrotoxicity. However, the mechanism involved is not well defined. In this study, Ranganathan et al. identify activated microglia/macrophage WAP domain protein as the novel mediator of histone deacetylase inhibitor-mediated renal protection in a murine model of cisplatin nephrotoxicity. Activated microglia/macrophage WAP-mediated renal protection is associated with suppression of inflammation and renal epithelial cell apoptosis. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  17. Characterization of the chemical reactivity and nephrotoxicity of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide, a potential reactive metabolite of trichloroethylene

    Irving, Roy M.; Pinkerton, Marie E.; Elfarra, Adnan A.

    2013-01-01

    N-Acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NA-DCVC) has been detected in the urine of humans exposed to trichloroethylene and its related sulfoxide, N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (NA-DCVCS), has been detected as hemoglobin adducts in blood of rats dosed with S-(1,2-dichlorovinyl)-L-cysteine (DCVC) or S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (DCVCS). Because the in vivo nephrotoxicity of NA-DCVCS was unknown, in this study, male Sprague–Dawley rats were dosed (i.p.) with 230 μmol/kg b.w. NA-DCVCS or its potential precursors, DCVCS or NA-DCVC. At 24 h post treatment, rats given NA-DCVC or NA-DCVCS exhibited kidney lesions and effects on renal function distinct from those caused by DCVCS. NA-DCVC and NA-DCVCS primarily affected the cortico-medullary proximal tubules (S 2 –S 3 segments) while DCVCS primarily affected the outer cortical proximal tubules (S 1 –S 2 segments). When NA-DCVCS or DCVCS was incubated with GSH in phosphate buffer pH 7.4 at 37 °C, the corresponding glutathione conjugates were detected, but NA-DCVC was not reactive with GSH. Because NA-DCVCS exhibited a longer half-life than DCVCS and addition of rat liver cytosol enhanced GSH conjugate formation, catalysis of GSH conjugate formation by the liver could explain the lower toxicity of NA-DCVCS in comparison with DCVCS. Collectively, these results provide clear evidence that NA-DCVCS formation could play a significant role in DCVC, NA-DCVC, and trichloroethylene nephrotoxicity. They also suggest a role for hepatic metabolism in the mechanism of NA-DCVC nephrotoxicity. - Highlights: ► NA-DCVCS and NA-DCVC toxicity are distinct from DCVCS toxicity. ► NA-DCVCS readily reacts with GSH to form mono- and di-GSH conjugates. ► Liver glutathione S-transferases enhance NA-DCVCS GSH conjugate formation. ► Renal localization of lesions suggests a role for NA-DCVCS in TCE nephrotoxicity

  18. Characterization of the chemical reactivity and nephrotoxicity of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide, a potential reactive metabolite of trichloroethylene

    Irving, Roy M. [Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, WI 53706 (United States); Pinkerton, Marie E. [Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706 (United States); Elfarra, Adnan A., E-mail: elfarra@svm.vetmed.wisc.edu [Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, WI 53706 (United States); Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706 (United States)

    2013-02-15

    N-Acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NA-DCVC) has been detected in the urine of humans exposed to trichloroethylene and its related sulfoxide, N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (NA-DCVCS), has been detected as hemoglobin adducts in blood of rats dosed with S-(1,2-dichlorovinyl)-L-cysteine (DCVC) or S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (DCVCS). Because the in vivo nephrotoxicity of NA-DCVCS was unknown, in this study, male Sprague–Dawley rats were dosed (i.p.) with 230 μmol/kg b.w. NA-DCVCS or its potential precursors, DCVCS or NA-DCVC. At 24 h post treatment, rats given NA-DCVC or NA-DCVCS exhibited kidney lesions and effects on renal function distinct from those caused by DCVCS. NA-DCVC and NA-DCVCS primarily affected the cortico-medullary proximal tubules (S{sub 2}–S{sub 3} segments) while DCVCS primarily affected the outer cortical proximal tubules (S{sub 1}–S{sub 2} segments). When NA-DCVCS or DCVCS was incubated with GSH in phosphate buffer pH 7.4 at 37 °C, the corresponding glutathione conjugates were detected, but NA-DCVC was not reactive with GSH. Because NA-DCVCS exhibited a longer half-life than DCVCS and addition of rat liver cytosol enhanced GSH conjugate formation, catalysis of GSH conjugate formation by the liver could explain the lower toxicity of NA-DCVCS in comparison with DCVCS. Collectively, these results provide clear evidence that NA-DCVCS formation could play a significant role in DCVC, NA-DCVC, and trichloroethylene nephrotoxicity. They also suggest a role for hepatic metabolism in the mechanism of NA-DCVC nephrotoxicity. - Highlights: ► NA-DCVCS and NA-DCVC toxicity are distinct from DCVCS toxicity. ► NA-DCVCS readily reacts with GSH to form mono- and di-GSH conjugates. ► Liver glutathione S-transferases enhance NA-DCVCS GSH conjugate formation. ► Renal localization of lesions suggests a role for NA-DCVCS in TCE nephrotoxicity.

  19. Comparative acute nephrotoxicity of salicylic acid, 2,3-dihydroxybenzoic acid, and 2,5-dihydroxybenzoic acid in young and middle aged Fischer 344 rats.

    McMahon, T F; Stefanski, S A; Wilson, R E; Blair, P C; Clark, A M; Birnbaum, L S

    1991-03-11

    Experimental evidence suggests that the oxidative metabolites 2,3- and 2,5-dihydroxybenzoic acid (DIOH) may be responsible for the nephrotoxicity of salicylic acid (SAL). In the present study, enzymuria in conjunction with glucose (GLU) and protein (PRO) excretion were used as endpoints to compare the relative nephrotoxicity of SAL with 2,3- and 2,5-DIOH. In addition, the effect of age on enzymuria and GLU and PRO excretion following treatment with SAL or 2,3- and 2,5-DIOH was investigated because the elderly are at greater risk for SAL-induced nephrotoxicity. Three and 12-month male Fischer 344 rats were administered either no treatment, vehicle, SAL, 2,3-DIOH, or 2,5-DIOH at 500 mg/kg p.o. in 5 ml/kg corn oil/DMSO (5:1). Effects of these treatments on functional integrity of renal tissue was assessed from 0--72 h after dosing by measurement of urinary creatinine, GLU, and PRO, as well as excretion of proximal and distal tubular renal enzymes. Enzymes measured as indicators of proximal tubular damage were N-acetyl-beta-glucosaminidase (NAG), gamma glutamyltransferase (GGT), alanine aminotransferase (ALT), and alkaline phosphatase (AP), while urinary lactate dehydrogenase (LD) and aspartate aminotransferase (AST) were measured as indicators of distal tubular damage. In comparison to 3-month vehicle-treated rats, 2,3- and 2,5-DIOH caused a significant increase between 0-8 h in excretion of urinary GLU and activities of AST, NAG, and LD, with peak effects occurring between 4-8 h. Toxic effects of either metabolite were not evident beyond 24 h, and toxicity of 2,5-DIOH was significantly greater in comparison to 2,3-DIOH. SAL treatment resulted in similar effects on enzymuria as well as GLU and PRO excretion, but peak effects did not occur until 16-24 h, and often persisted until 72 h after dosing. Maximal enzymuria in response to SAL treatment was significantly greater in 12- vs. 3-month rats for AST, NAG, and LD. In response to 2,3-DIOH treatment, the maximal

  20. Nephrotoxicity of uranium in drinking water from private drilled wells

    Selden, Anders I.; Lundholm, Cecilia; Edlund, Bror; Hoegdahl, Camilla; Ek, Britt-Marie; Bergstroem, Bernt E.; Ohlson, Carl-Goeran

    2009-01-01

    Objectives: To investigate the association between uranium in drinking water from drilled wells and aspects of kidney function measured by sensitive urine tests. Methods: Three hundred and one of 398 eligible subjects (75.6%) aged 18-74 years with daily drinking water supplies from private drilled wells located in uranium-rich bedrock (exposed group) volunteered to participate along with 153 of 271 local controls (56.4%) who used municipal water. Participants responded to a questionnaire on their water consumption and general health, and provided a morning urine sample and drinking water for analysis. Results: The uranium content of well water samples (n=153) varied considerably (range 100 μg/l), while uranium levels in all samples of municipal water (n=14) were below the limit of quantification (0.2 μg/l). Urinary levels of uranium were more than eight times higher in exposed subjects than in controls (geometric means 38 and 4.3 ng/l, respectively; p 2 =0.66). Levels of albumin, β 2 -microglobulin, protein HC as well as kappa and lambda immunoglobulin chains in urine from exposed and controls were similar. The N-acetyl-β-D-glucosaminidase (NAG) activity was significantly lower in the exposed group vs. controls, possibly secondary to differential storage duration of samples from the two groups. Even in regression models adjusting for gender, age and smoking no association of uranium in water and the kidney function parameters was observed. Using uranium in urine in the entire study group as a marker of exposure, however, a tendency of exposure-related increases of β 2 -microglobulin, protein HC and kappa chains were noted. This tendency was enhanced after exclusion of subjects with diabetes mellitus from the analysis. Conclusions: Uranium levels in urine were strongly correlated to levels in drinking water from drilled wells. There were no clear signs of nephrotoxicity from uranium in drinking water at levels recorded in this study, but some indications of an

  1. Nefrotoxicidade por lítio Lithium nephrotoxicity

    Jobson Lopes de Oliveira

    2010-01-01

    Full Text Available O lítio é amplamente empregado na terapia do transtorno bipolar. Sua toxicidade renal inclui distúrbio na capacidade de concentração urinária e natriurese, acidose tubular renal, nefrite túbulo-intersticial evoluindo para doença renal crônica e hipercalcemia. O efeito adverso mais comum é o diabetes insipidus nefrogênico, que acomete de 20%-40% dos pacientes semanas após o início do tratamento. A nefropatia crônica correlaciona-se com a duração do uso de lítio. A detecção precoce de disfunção renal deve ser feita através de monitoração rigorosa dos pacientes e colaboração entre o psiquiatra e o nefrologista. Recentes trabalhos experimentais e clínicos começam a esclarecer os mecanismos pelos quais o lítio induz alteração da função renal. No presente trabalho, objetivamos revisar a patogênese, a apresentação clínica, os aspectos histopatológicos e o tratamento da nefrotoxicidade induzida pelo lítio.Lithium is widely used in the therapy of bipolar disorder. Its toxicity includes urinary concentration deficit and natriuresis, renal tubular acidosis, tubulointerstitial nephritis which complicates with chronic kidney disease and hypercalcemia. The most common adverse effect is diabetes insipidus, which occurs in 20-40% of patients some weeks after initiation of treatment. Such chronic nephropathy correlates with duration of lithium use. Early detection of renal dysfunction should be achieved by rigorous monitoring of patients and collaboration between the psychiatrist and nephrologist. Recent experimental and clinical studies are now clarifying the mechanisms by which lithium induces renal abnormalities. The aim of this work is to review the pathogenesis, clinical presentation, histopathologic aspects and treatment of lithium nephrotoxicity.

  2. Assessment of 99mTc-DMSA renoscintigraphy and uptake compared with creatinine clearance in rats with drug-induced nephrotoxicity, 2

    Yamada, Masafumi

    1991-01-01

    For evaluation of technetium-99m dimercaptosuccinic acid ( 99m Tc-DMSA) renal uptake as an absolute renal function, 99m Tc-DMSA uptake was compared with endogenous creatinine clearance (Ccr) in cisplatin-induced nephrotoxicity. At first, male Wistar rats were given intraperitoneally 1.8 mg/kg/day of cisplatin for periods of 3, 5, 7 and 9 days. On the next day, 99m Tc-DMSA uptake and Ccr were measured. Ccr of 5-day treated group was significantly lower than that of control (0.13±0.10 vs 0.34±0.05 ml/min/100 g; p 99m Tc-DMSA uptake did not change. 99m Tc-DMSA uptake of 7-day treated group was significantly lower than that of control (28.57±7.23 vs 39.84±2.23%; p 99m Tc-DMSA uptake was lower than that of control on the 8th, 11th and 15th day (32.40±3.86, 32.56±1.19, 35.21±2.97 vs 39.84±2.23%, respectively; p 99m Tc-DMSA uptake and Ccr was observed in the cisplatin-induced nephrotoxicity. 99m Tc-DMSA uptake was suggested to be a reliable indicator of a renal function in a different way from Ccr. (author)

  3. Honey feeding protects kidney against cisplatin nephrotoxicity through suppression of inflammation.

    Hamad, Rania; Jayakumar, Calpurnia; Ranganathan, Punithavathi; Mohamed, Riyaz; El-Hamamy, Mahmoud M I; Dessouki, Amina A; Ibrahim, Abdelazim; Ramesh, Ganesan

    2015-08-01

    Cisplatin is a highly effective chemotherapeutic drug used to treat a wide variety of solid tumors. However, its use was limited due its dose-limiting toxicity to the kidney. Currently, there are no therapies available to treat or prevent cisplatin nephrotoxicity. Honey is a naturally occurring complex liquid and widely used in traditional Ayurvedic medicine to treat many illnesses. However, its effect on cisplatin nephrotoxicity is unknown. To determine the role of honey in cisplatin nephrotoxicity, animals were pretreated orally for a week and then cisplatin was administered. Honey feeding was continued for another 3 days. Our results show that animals with cisplatin-induced kidney dysfunction, as determined by increased serum creatinine, which received honey feeding had less kidney dysfunction. Improved kidney function was associated with better preservation of kidney morphology in honey-treated group as compared to the cisplatin alone-treated group. Interestingly, honey feeding significantly reduced cisplatin-induced tubular epithelial cell death, immune infiltration into the kidney as well as cytokine and chemokine expression and excretion as compared to cisplatin treated animals. Western blot analysis shows that cisplatin-induced increase in phosphorylation of NFkB was completely suppressed with honey feeding. In conclusion, honey feeding protects the kidney against cisplatin nephrotoxicity through suppression of inflammation and NFkB activation. © 2015 Wiley Publishing Asia Pty Ltd.

  4. Histone deacetylase mediated silencing of AMWAP expression contributes to cisplatin nephrotoxicity

    Ranganathan, Punithavathi; Hamad, Rania; Mohamed, Riyaz; Jayakumar, Calpurnia; Muthusamy, Thangaraju; Ramesh, Ganesan

    2015-01-01

    Cisplatin-induced acute kidney injury is a serious problem in cancer patients during treatment of solid tumors. Currently, there are no therapies available to treat or prevent cisplatin nephrotoxicity. Since histone deacetylase (HDAC) inhibition augments cisplatin anti-tumor activity, we tested whether HDAC inhibitors can prevent cisplatin-induced nephrotoxicity and determined the underlying mechanism. Cisplatin up-regulated the expression of several HDACs in the kidney. Inhibition of HDAC with clinically used trichostatin A suppressed cisplatin-induced kidney injury, inflammation and epithelial cell apoptosis. Moreover, trichostatin A upregulated the novel anti-inflammatory protein, activated microglia/macrophage WAP domain protein (AMWAP), in epithelial cells which was enhanced with cisplatin treatment. Interestingly, HDAC1 and -2 specific inhibitors are sufficient to potently up-regulate AMWAP in epithelial cells. Administration of recombinant AMWAP or its epithelial cell-specific overexpression reduced cisplatin-induced kidney dysfunction. Moreover, AMWAP treatment suppressed epithelial cell apoptosis, and siRNA-based knockdown of AMWAP expression abolished trichostatin A-mediated suppression of epithelial cell apoptosis in vitro. Thus, HDAC-mediated silencing of AMWAP may contribute to cisplatin nephrotoxicity. Hence, HDAC1 and -2 specific inhibitors or AMWAP could be useful therapeutic agents for the prevention of cisplatin nephrotoxicity. PMID:26509586

  5. Nephroprotective, Diuretic and Antioxidant Effects of Some Medicinal Herbs in Gentamicin-Nephrotoxic Rats

    Mostafa Abbas Shalaby

    2014-02-01

    Conclusion: Aqueous extracts of Petroselinum sativum, Eruca sativa and Curcuma longa produce nephroprotective, diuretic and antioxidant effects in GM - nephrotoxic rats. These herbs may be beneficial for patients who suffer from kidney diseases and those on GM therapy. [J Intercult Ethnopharmacol 2014; 3(1.000: 1-8

  6. Aminoglycosides in septic shock: an overview, with specific consideration given to their nephrotoxic risk.

    Boyer, Alexandre; Gruson, Didier; Bouchet, Stéphane; Clouzeau, Benjamin; Hoang-Nam, Bui; Vargas, Frédéric; Gilles, Hilbert; Molimard, Mathieu; Rogues, Anne-Marie; Moore, Nicholas

    2013-04-01

    Aminoglycoside nephrotoxicity has been reported in patients with sepsis, and several risk factors have been described. Once-daily dosing and shorter treatment have reduced nephrotoxicity risk, and simplified aminoglycoside monitoring. This review focuses on nephrotoxicity associated with aminoglycosides in the subset of patients with septic shock or severe sepsis. These patients are radically different from those with less severe sepsis. They may have, for instance, renal impairment due to the shock per se, sepsis-related acute kidney injury, frequent association with pre-existing risk factors for renal failure such as diabetes, dehydration and other nephrotoxic treatments. In this category of patients, these risk factors might modify substantially the benefit-risk ratio of aminoglycosides. In addition, aminoglycoside administration in critically ill patients with sepsis is complicated by an extreme inter- and intra-individual variability in drug pharmacokinetic/pharmacodynamic characteristics: the volume of distribution (Vd) is frequently increased while the elimination constant can be either increased or decreased. Consequently, and although its effect on nephrotoxicity has not been explored, a different administration schedule, i.e. a high-dose once daily (HDOD), and several therapeutic drug monitoring (TDM) options have been proposed in these patients. This review describes the historical perspective of these different options, including those applying to subsets of patients in which aminoglycoside administration is even more complex (obese intensive care unit [ICU] patients, patients needing continuous or discontinuous renal replacement therapy [CRRT/DRRT]). A simple linear dose adjustment according to aminoglycoside serum concentration can be classified as low-intensity TDM. Nomograms have also been proposed, based on the maximum (peak) plasma concentration (Cmax) objectives, weight and creatinine clearance. The Sawchuk and Zaske method (based on the

  7. Comparative study between dimethyl sulfoxide (dmso), allopurinol and urate oxidase administration in nephrotoxic rats induced with

    Heibashy, M.I.A.; El-Nahla, A.M.; Ibrahim, A.I.; Saleh, Sh.Y.A.

    2010-01-01

    This study was conducted to show whether DMSO, allopurinol and urate oxidase could offer ameliorating effects against abnormal alterations in kidney function tests in gentamicin (GM) induced nephrotoxic rats . Two experiments were carried out, the first one showed that daily injection of 80 mg GM/kg b. wt interapertonealy (I.P) for two weeks induced acute renal failure indicated by significant elevation in serum urea, creatinine, uric acid, potassium, inorganic phosphorus, TBARS and PTH and a significant decline in serum sodium, total and ionized calcium when compared with their corresponding values in saline injected rats. In the second experiment, comparisons were made between GM induced nephrotoxic rats and other nephrotoxic groups received daily pf I.P injection of DMSO (4 ml/kg b.wt), allopurinol (1.5 mg/100 g b.wt) and urate oxidase (10 mg/100 g b.wt) for 30 days after the incidence of nephrotoxicity. At all intervals, 10,20 and 30 days; serum urea, creatinine, uric acid, potassium, inorganic phosphorus, TBARS and PTH in DMSO, allopurinol and urate oxidase treated groups exhibited significant reduction than nephrotoxic untreated rats. During the same intervals, the levels of serum total and ionized calcium showed an opposite trend. serum sodium level did not show any significant difference between all treated groups except after 20 days , it was increased significantly in urate oxidase treated group and after 30 days in both allopurinol and urate oxidase treated groups. in term time intervals, a significant correction was recorded on the level of most measured parameters. in nephritic rats, the administration of DMSO, allopurinol or urate oxidase led to a significant amelioration effects in the kidney function tests and urate oxidase was the best protective.

  8. Preventing or attenuating amphotericin B nephrotoxicity with dopamine receptor agonists: a literature review

    Iman Karimzadeh

    2016-09-01

    Full Text Available Nephrotoxicity is generally considered as the most clinically significant and dose-limiting adverse reaction of amphotericin B. Currently, only the clinical effectiveness of salt loading and administering lipid formulations of amphotericin B have been clearly demonstrated to prevent its nephrotoxicity. In this review, we collected the published data related to dopamine receptor agonists in preventing amphotericin B nephrotoxicity. A literature search was conducted by the relevant keywords like ‘‘amphotericin B”, “nephrotoxicity’’, and ‘‘dopamine’’in databases such as Scopus, Medline, Embase and ISI Web of Knowledge. Four relevant articles were considered. Results of all the 3 experimental studies demonstrated that co-administration of dopamine (0.5-10 μg/kg/min as continuous intravenous infusion, SK&F R-105058, a prodrug of fenoldopam (10 mg/kg twice daily, orally or fenoldopam, a relatively selective dopamine receptor type 1 agonist, (0.5 or 1 μg/kg/min as continuous intravenous infusion can at least significantly mitigate the decrease in creatinine clearance caused by amphotericin B. Furthermore, fenoldopam and SK&F R-105058 can also protect against or delay amphotericin B-induced tubular damage. In contrast, the only clinical trial published until now found that simultaneous continuous intravenous infusion of low dose dopamine (3 μg/kg/min had no beneficial effect on the incidence, severity and time onset of developing amphotericin B-induced nephrotoxicity in autologous bone marrow transplant and leukemia patients. Considering the lack of beneficial effects in different settings such as acute kidney injury of any cause, negative results of the only clinical trial, and risk of significant adverse reactions, continuous intravenous infusion of low dose dopamine (1-3 μg/kg/min or selective dopamine receptor type 1 agonists (e.g., fenoldopam currently appears to have no promising clinical role in preventing or attenuating

  9. Effects of royal jelly on genotoxicity and nephrotoxicity induced by valproic acid in albino mice

    Sanaa R. Galaly

    2014-03-01

    Full Text Available Epilepsy is one of the most common neurological diseases affecting at least 50 million people worldwide. Valproic acid (VPA is a widely used antiepileptic medication for both generalized and partial seizures of epilepsy. The objective of the study was to investigate the anti-mutagenic and anti-histopathologic effects of royal jelly (RJ on VPA-induced genotoxicity and nephrotoxicity in male albino mice (Mus musculus. 80 Mice were used for 21 days; they were divided into eight groups, (G1 served as normal control group, G2 received VPA (100 mg/kg and (G3–G5 received RJ at doses 50, 100 and 200 mg/kg respectively. While (G6–G8 were administrated RJ simultaneously with VPA. In RJ treated mice at doses of 50 and 100 mg/kg, the kidney sections showed normal histological structure with non significant changes in chromosomal aberrations (CA and mitotic index (MI, while RJ at dose of 200 mg/kg showed mild inflammatory cells infiltration and hyperemic glomeruli but not highly significant changes in CA and MI. The cortex of VPA treated mice revealed congested glomeruli with inflammatory cells infiltration, and marked degeneration of almost structures of the glomeruli including some vacuoles in mesangial cells with dark mesangial substances on the ultrastructure level. Some proximal tubules showed degeneration of microvilli on the apical parts of some cells. Cells of the distal tubules attained obliterated lumen and vacuolated lining epithelium. The results also revealed that valproic acid induced a high frequency of CA in bone marrow cells of mice and MI was significantly decreased indicating bone marrow cytotoxicity. The treatment of mice with RJ at doses 50, 100 and 200 mg/kg for 21 days simultaneously with VPA resulted in abating the histological alterations in renal tissues with significant reduction in chromosomal aberrations, for doses of 50 and 100 mg/kg, and elevation in mitotic index (P < 0.05. RJ at doses 50 and 100 mg/kg appeared

  10. Environmental exposure to low-doses of ionizing radiation. Effects on early nephrotoxicity in mice.

    Bellés, Montserrat; Gonzalo, Sergio; Serra, Noemí; Esplugas, Roser; Arenas, Meritxell; Domingo, José Luis; Linares, Victoria

    2017-07-01

    Nuclear accidents of tremendous magnitude, such as those of Chernobyl (1986) and Fukushima (2011), mean that individuals living in the contaminated areas are potentially exposed to ionizing radiation (IR). However, the dose-response relationship for effects of low doses of radiation is not still established. The present study was aimed at investigating in mice the early effects of low-dose internal radiation exposure on the kidney. Adult male (C57BL/6J) mice were divided into three groups. Two groups received a single subcutaneous (s.c.) doses of cesium ( 137 Cs) with activities of 4000 and 8000Bq/kg bw. A third group (control group) received a single s.c. injection of 0.9% saline. To evaluate acute and subacute effects, mice (one-half of each group) were euthanized at 72h and 10 days post-exposure to 137 Cs, respectively. Urine samples were collected for biochemical analysis, including the measurement of F2-isoprostane (F2-IsoP) and kidney injury molecule-1 (KIM-1) levels. Moreover, the concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA damage, were measured in renal tissue. Urinary excretion of total protein significantly increased at 72h in mice exposed to Cs4000. Uric acid and lactate dehydrogenase (LDH) decreased significantly at both times post-exposure in animals exposed to Cs8000. After 72h and 10d of exposure to Cs4000, a significant increase in the γ-glutamil transferase (GGT) and N-acetyl-β-D-glucosaminidase (NAG) activities was observed. In turn, F2-IsoP levels increased -mainly in the Cs4000 group- at 72h post-exposure. Following irradiation ( 137 Cs), the highest level of KIM-1 was corresponded to the Cs4000 group at 72h. Likewise, the main DNA damage was detected in mice exposed to Cs4000, mainly at 10d after irradiation. The alterations observed in several biomarkers suggest an immediate renal damage following exposure to low doses of IR (given as 137 Cs). Further investigations are required to clarify the

  11. Nigella sativa oil attenuates chronic nephrotoxicity induced by oral sodium nitrite: Effects on tissue fibrosis and apoptosis.

    Al-Gayyar, Mohammed M H; Hassan, Hanan M; Alyoussef, Abdullah; Abbas, Ahmed; Darweish, Mohamed M; El-Hawwary, Amany A

    2016-03-01

    Sodium nitrite, a food preservative, has been reported to increase oxidative stress indicators such as lipid peroxidation, which can affect different organs including the kidney. Here, we investigated the toxic effects of oral sodium nitrite on kidney function in rats and evaluated potential protective effects of Nigella sativa oil (NSO). Seventy adult male Sprague-Dawley rats received 80 mg/kg sodium nitrite orally in the presence or absence of NSO (2.5, 5, and 10 ml/kg) for 12 weeks. Morphological changes were assessed by hematoxylin and eosin, Mallory trichome, and periodic acid-Schiff staining. Renal tissues were used for measurements of oxidative stress markers, C-reactive protein, cytochrome C oxidase, transforming growth factor (TGF)-beta1, monocyte chemotactic protein (MCP)-1, pJNK/JNK, and caspase-3. NSO significantly reduced sodium nitrite-induced elevation in serum urea and creatinine, as well as increasing normal appearance of renal tissue. NSO also prevented reductions in glycogen levels caused by sodium nitrite alone. Moreover, NSO treatment resulted in dose-dependent significant reductions in fibrosis markers after sodium nitrite-induced 3- and 2.7-fold increase in MCP-1 and TGF-beta1, respectively. Finally, NSO partially reduced the elevated caspase-3 and pJNK/JNK. NSO ameliorates sodium nitrite-induced nephrotoxicity through blocking oxidative stress, attenuation of fibrosis/inflammation, restoration of glycogen level, amelioration of cytochrome C oxidase, and inhibition of apoptosis.

  12. Gene Expression Analysis Reveals New Possible Mechanisms of Vancomycin-Induced Nephrotoxicity and Identifies Gene Markers Candidates

    Dieterich, Christine; Puey, Angela; Lyn, Sylvia; Swezey, Robert; Furimsky, Anna; Fairchild, David; Mirsalis, Jon C.; Ng, Hanna H.

    2008-01-01

    Vancomycin, one of few effective treatments against methicillin-resistant Staphylococcus aureus, is nephrotoxic. The goals of this study were to (1) gain insights into molecular mechanisms of nephrotoxicity at the genomic level, (2) evaluate gene markers of vancomycin-induced kidney injury, and (3) compare gene expression responses after iv and ip administration. Groups of six female BALB/c mice were treated with seven daily iv or ip doses of vancomycin (50, 200, and 400 mg/kg) or saline, and...

  13. Inhibition of PKCδ reduces cisplatin-induced nephrotoxicity without blocking chemotherapeutic efficacy in mouse models of cancer

    Pabla, Navjotsingh; Dong, Guie; Jiang, Man; Huang, Shuang; Kumar, M. Vijay; Messing, Robert O.; Dong, Zheng

    2011-01-01

    Cisplatin is a widely used cancer therapy drug that unfortunately has major side effects in normal tissues, notably nephrotoxicity in kidneys. Despite intensive research, the mechanism of cisplatin-induced nephrotoxicity remains unclear, and renoprotective approaches during cisplatin-based chemotherapy are lacking. Here we have identified PKCδ as a critical regulator of cisplatin nephrotoxicity, which can be effectively targeted for renoprotection during chemotherapy. We showed that early during cisplatin nephrotoxicity, Src interacted with, phosphorylated, and activated PKCδ in mouse kidney lysates. After activation, PKCδ regulated MAPKs, but not p53, to induce renal cell apoptosis. Thus, inhibition of PKCδ pharmacologically or genetically attenuated kidney cell apoptosis and tissue damage, preserving renal function during cisplatin treatment. Conversely, inhibition of PKCδ enhanced cisplatin-induced cell death in multiple cancer cell lines and, remarkably, enhanced the chemotherapeutic effects of cisplatin in several xenograft and syngeneic mouse tumor models while protecting kidneys from nephrotoxicity. Together these results demonstrate a role of PKCδ in cisplatin nephrotoxicity and support targeting PKCδ as an effective strategy for renoprotection during cisplatin-based cancer therapy. PMID:21633170

  14. Imaging MS in Toxicology: An Investigation of Juvenile Rat Nephrotoxicity Associated with Dabrafenib Administration

    Groseclose, M. Reid; Laffan, Susan B.; Frazier, Kendall S.; Hughes-Earle, Angela; Castellino, Stephen

    2015-06-01

    As part of an investigative nephrotoxicity study, kidney tissues from juvenile rats orally administered dabrafenib at different age intervals between postnatal day (PND) 7 to 35 were investigated by MALDI and LDI imaging mass spectrometry (IMS) to determine the chemical composition of tubular deposits. In the youngest age group (PND 7-13), MALDI IMS demonstrated that a dabrafenib carboxylic acid metabolite was diffusely localized to the regions of tubular deposits (medulla and corticomedullary junction); however, no dabrafenib-related material was detected directly from the deposits. Rather, the LDI IMS analysis determined that the deposits were composed primarily of calcium phosphate. Based on these data, the dabrafenib associated nephrotoxicity, including the formation of tubular deposits, was determined to be age dependent. Furthermore, immature renal function was hypothesized to be responsible for the susceptibility of the youngest pups.

  15. Contrast media-associated nephrotoxicity - pathogenenesis and prevention; Kontrastmittelnephropathie - Pathogenese und Praevention

    Erley, C.M. [Abt. Innere Medizin III, Sektion Nieren- und Hochdruckkrankheiten, Tuebingen Univ. (Germany); Duda, S.H. [Tuebingen Univ. (Germany). Abt. fuer Radiologische Diagnostik

    1997-07-01

    Contrast media-associated nephrotoxicity continues to be a relevant cause of acute renal failure, especially in patients with pre-existing renal insufficiency. Alterations in renal hemodynamics and direct tubular toxicity by contrast media are the primary factors believed to be responsible for contrast media-associated nephrotoxicity. We review recent insights into the pathogenesis of this complication and summarize prophylactic strategies focussing on hydration, vasoactive pharmacological agents, and prophylactic hemodialysis`. (orig.) [Deutsch] Die Kontrastmittelnephropathie (KMN) stellt insbesondere bei Patienten mit eingeschraenkter Nierenfunktion ein erhebliches medizinisches Problem dar. Die Genese der KMN ist nach wie vor nicht eindeutig geklaert. Neben haemodynamischen Veraenderungen durch die Kontrastmittel spielen tubulotoxische Schaeden eine grosse Rolle. Die vorliegende Uebersicht beschreibt die zur Zeit bekannten pathophysiologischen Vorgaenge bei der KMN und die zur Zeit angewendeten Praeventivmassnahmen. (orig.)

  16. Lithium and nephrotoxicity: Unravelling the complex pathophysiological threads of the lightest metal.

    Davis, J; Desmond, M; Berk, M

    2018-04-01

    While lithium remains the most efficacious treatment for bipolar disorder, it can cause significant nephrotoxicity. The molecular mechanisms behind both this process and the development of nephrogenic diabetes insipidus still remain to be fully elucidated but appear to involve alterations in glycogen synthase kinase 3 signalling, G2 cell cycle progression arrest, alterations in inositol and prostaglandin signalling pathways, and dysregulated trafficking and transcription of aquaporin 2 water channels. The end result of this is a tubulointerstitial nephropathy with microcyst formation and relative glomerular sparing, both visible on pathology specimens and increasingly noted on non-invasive imaging. This paper will elucidate on the current evidence pertaining to the pathophysiology of lithium induced nephrotoxicity. This article is protected by copyright. All rights reserved.

  17. Evaluation of nephroprotective activity of Musa paradisiaca L. in gentamicin-induced nephrotoxicity.

    Abbas, Khizar; Rizwani, Ghazala H; Zahid, Hina; Qadir, M Imran

    2017-05-01

    The objective of the study was to investigate the nephroprotective activity of methanolic extract of different morphological parts (bract, flower, trachea and tracheal fluid) of Musa paradisiaca L. (Family: Musaceae) against gentamicin-induced nephrotoxicity in mice. Gentamicin produced significant changes in biochemical (increased levels of blood urea nitrogen level, blood urea, and serum creatinine), and histological parameters in mice. Treatment with methanolic extract of bract (100 and 250mg/kg, b.w) and flowering stalk (trachea) (250 and 500mg/kg, b.w) significantly prevented biochemical and histological changes produced by gentamicin toxicity. The extracts of M. paradisiaca (bract and flowering stalk) could contribute a lead to discovery of a new drug for the treatment of drug-induced nephrotoxicity.

  18. Nephrotoxicity Of Polymyxin B: Experimental Study In Cells And Implications For Nursing Practice

    Luciana Barros de Moura Neiva

    2014-04-01

    Full Text Available The aim of the study was to characterize the cell damage mechanisms involved in the pathophysiology of cytotoxicity of polymyxin B in proximal tubular cells (LLC - PK1 and discuss about the nurses interventions to identify at risk patients and consider prevention or treatment of nephrotoxicity acute kidney injury. This is a quantitative experimental in vitro study, in which the cells were exposed to 375μM polymyxin B sulfate concentration. Cell viability was determined by exclusion of fluorescent dyes and morphological method with visualization of apoptotic bodies for fluorescence microscopy. Cells exposed to polymyxin B showed reduced viability, increased number of apoptotic cells and a higher concentration of the enzyme lactate dehydrogenase. The administration of polymyxin B in vitro showed the need for actions to minimize adverse effects such as nephrotoxicity.

  19. Protective effects of Bombyx mori, quercetin and benazepril against doxorubicin induced cardiotoxicity and nephrotoxicity

    Abdul S. Nazmi; Shibli J. Ahmad; Krishna K. Pillai; Mohammad Akhtar; Aftab Ahmad; Abul K. Najmi

    2016-01-01

    The present study was conducted with the aim of evaluating the protective effects of Bombyx mori, quercetin and benazepril on doxorubicin (DXR) induced cardiotoxicity and nephrotoxicity in rats. B. mori, quercetin and benazepril were administered for 7 days, and a single intravenous injection of 10 mg/kg body weight of DXR on day five. The animals were sacrificed 48 h after DXR administration. DXR produced a significant elevation in the malondialdehyde (MDA) level and significantly inhibited ...

  20. Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion*

    Thurlow, John S.; Little, Dustin J.; Baker, Thomas P.; Yuan, Christina M.

    2013-01-01

    We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ?5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose ...

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

    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.

  2. Plasma metabolic profiling analysis of nephrotoxicity induced by acyclovir using metabonomics coupled with multivariate data analysis.

    Zhang, Xiuxiu; Li, Yubo; Zhou, Huifang; Fan, Simiao; Zhang, Zhenzhu; Wang, Lei; Zhang, Yanjun

    2014-08-01

    Acyclovir (ACV) is an antiviral agent. However, its use is limited by adverse side effect, particularly by its nephrotoxicity. Metabonomics technology can provide essential information on the metabolic profiles of biofluids and organs upon drug administration. Therefore, in this study, mass spectrometry-based metabonomics coupled with multivariate data analysis was used to identify the plasma metabolites and metabolic pathways related to nephrotoxicity caused by intraperitoneal injection of low (50mg/kg) and high (100mg/kg) doses of acyclovir. Sixteen biomarkers were identified by metabonomics and nephrotoxicity results revealed the dose-dependent effect of acyclovir on kidney tissues. The present study showed that the top four metabolic pathways interrupted by acyclovir included the metabolisms of arachidonic acid, tryptophan, arginine and proline, and glycerophospholipid. This research proves the established metabonomic approach can provide information on changes in metabolites and metabolic pathways, which can be applied to in-depth research on the mechanism of acyclovir-induced kidney injury. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Study of protective effects of melatonin on cisplatin-induced nephrotoxicity in rabbits

    Aslam, J.; Khan, W.; Bakhtiar, S.

    2017-01-01

    To evaluate the protective effects of melatonin on cisplatin-induced nephrotoxicity in rabbits. Study Design: Laboratory based randomized control trial. Place and Duration of Study: Department of Pharmacology and Therapeutics in collaboration with Clinico Pathologic Laboratory, Army Medical College, Rawalpindi, from Apr to Jun 2015. Material and Methods: Eighteen rabbits were divided into three groups, each consisting of six rabbits. Baseline serum urea, creatinine, sodium and potassium were measured. Rabbits were weighed for dose calculation. A single dose of cisplatin 10mg/kg was given as I/P injection to the toxic group. The protective group received 5 mg/kg I/P melatonin for three days. Rabbits were sacrificed 72 hours after the cisplatin dose and both kidneys were sent for histopathology. Statistical analysis was carried out by using Microsoft Office Excel 2010 and SPSS version 21. Student's t-test and one way ANOVA, followed by 'Post Hoc Tukey' test was used for biochemical parameters, while Chi Square' test was used for histopathological comparison. Results: Moderate nephrotoxicity (grade-II) was seen in the toxic group, with substantial elevations of serum urea and creatinine (p<0.001), and serum sodium and potassium (p<0.01). Melatonin ameliorated the renal injury. Conclusion: The protective effects of melatonin on cisplatin-induced nephrotoxicity were due to its antioxidant properties. (author)

  4. Enhancement of Cisplatin Nephrotoxicity by Morphine and Its Attenuation by the Opioid Antagonist Naltrexone

    Atefeh Aminian

    2016-07-01

    Full Text Available Nephrotoxicity is a major side effect of cisplatin, a widely used chemotherapy agent. Morphine and other opioids are also used extensively in different types of cancer for the clinical management of pain associated with local or metastatic neoplastic lesions. In addition to its analgesic effects, morphine has also been reported to possess potential immunomodulatory and antioxidant properties. Herein, we investigated the effects of morphine in a rat model of cisplatin-induced nephrotoxicity. Following administration of a single dose of cisplatin (5 mg/kg, animals received intraperitoneal injections of morphine (5 mg/kg/day and/or naltrexone (20 mg/kg/day, an opioid antagonist, for 5 days. Cisplatin-induced nephrotoxicity was detected by a significant increase in plasma urea and creatinine levels in addition to alterations in kidney tissue morphology. Levels of TNF-α and IL-1β were significantly increased in the renal tissue in cisplatin group. Moreover, glutathione (GSH concentration and superoxide dismutase activity were significantly reduced in renal tissue in cisplatin group compared with control animals. Treatment with morphine aggravated the deleterious effects of cisplatin at clinical, biochemical and histopathological levels; whereas naltrexone diminished the detrimental effects of morphine in animals receiving morphine and cisplatin. Morphine or naltrexone alone had no effect on the mentioned parameters. Our findings indicate that concomitant treatment with morphine might intensify cisplatin-induced renal damage in rats. These findings suggest that morphine and other opioids should be administered cautiously in patients receiving cisplatin chemotherapy.

  5. The modulatory effect of Moringa oleifera leaf extract on endogenous antioxidant systems and inflammatory markers in an acetaminophen-induced nephrotoxic mice model

    Govindarajan Karthivashan

    2016-07-01

    Full Text Available N-Acetyl-p-Aminophenol (APAP, also known as acetaminophen, is the most commonly used over-the counter analgesic and antipyretic medication. However, its overdose leads to both liver and kidney damage. APAP-induced toxicity is considered as one of the primary causes of acute liver failure; numerous scientific reports have focused majorly on APAP hepatotoxicity. Alternatively, not many works approach APAP nephrotoxicity focusing on both its mechanisms of action and therapeutic exploration. Moringa oleifera (MO is pervasive in nature, is reported to possess a surplus amount of nutrients, and is enriched with several bioactive candidates including trace elements that act as curatives for various clinical conditions. In this study, we evaluated the nephro-protective potential of MO leaf extract against APAP nephrotoxicity in male Balb/c mice. A single-dose acute oral toxicity design was implemented in this study. Group 2, 3, 4 and 5 received a toxic dose of APAP (400 mg/kg of bw, i.p and after an hour, these groups were administered with saline (10 mL/kg, silymarin—positive control (100 mg/kg of bw, i.p, MO leaf extract (100 mg/kg of bw, i.p, and MO leaf extract (200 mg/kg bw, i.p respectively. Group 1 was administered saline (10 mL/kg during both the sessions. APAP-treated mice exhibited a significant elevation of serum creatinine, blood urea nitrogen, sodium, potassium and chloride levels. A remarkable depletion of antioxidant enzymes such as SOD, CAT and GSH-Px with elevated MDA levels has been observed in APAP treated kidney tissues. They also exhibited a significant rise in pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and decreased anti-inflammatory (IL-10 cytokine level in the kidney tissues. Disorganized glomerulus and dilated tubules with inflammatory cell infiltration were clearly observed in the histology of APAP treated mice kidneys. All these pathological changes were reversed in a dose-dependent manner after MO leaf extract

  6. Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion.

    Thurlow, John S; Little, Dustin J; Baker, Thomas P; Yuan, Christina M

    2013-06-01

    We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ∼5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose chronic exposure. This case represents possible sequelae of chronic potassium chlorate ingestion.

  7. Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion*

    Thurlow, John S.; Little, Dustin J.; Baker, Thomas P.; Yuan, Christina M.

    2013-01-01

    We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ∼5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose chronic exposure. This case represents possible sequelae of chronic potassium chlorate ingestion. PMID:26064493

  8. Neferine reduces cisplatin-induced nephrotoxicity by enhancing autophagy via the AMPK/mTOR signaling pathway.

    Li, Hui; Tang, Yuling; Wen, Long; Kong, Xianglong; Chen, Xuelian; Liu, Ping; Zhou, Zhiguo; Chen, Wenhang; Xiao, Chenggen; Xiao, Ping; Xiao, Xiangcheng

    2017-03-11

    Cisplatin is one of the most effective chemotherapeutic agents; however, its clinical use is limited by serious side effects of which nephrotoxicity is the most important. Nephrotoxicity induced by cisplatin is closely associated with autophagy reduction and caspase activation. In this study, we investigated whether neferine, an autophagy inducer, had a protective effect against cisplatin-induced nephrotoxicity. In an in vitro cisplatin-induced nephrotoxicity model, we determined that neferine was able to induce autophagy and that pretreatment with neferine not only attenuated cisplatin-induced cell apoptosis but further activated cell autophagy. This pro-survival effect was abolished by the autophagic flux inhibitor chloroquine. Furthermore, neferine pretreatment activated the AMPK/mTOR pathway; however, pharmacological inhibition of AMPK abolished neferine-mediated autophagy and nephroprotection against cisplatin-induced apoptosis. Collectively, our findings suggest for the first time the possible protective mechanism of neferine, which is crucial for its further development as a potential therapeutic agent for cisplatin-induced nephrotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Effects of Kombucha on oxidative stress induced nephrotoxicity in rats

    Gharib Ola

    2009-11-01

    Full Text Available Abstract Background Trichloroethylene (TCE may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes. Methods Twenty male albino rats were divided into four groups: (1 the control group treated with vehicle, (2 Kombucha (KT-treated group, (3 TCE-treated group and (4 KT/TCE-treated group. Kidney lipid peroxidation, glutathione content, nitric oxide (NO and total blood free radical concentrations were evaluated. Serum urea, creatinine level, gamma-glutamyl transferase (GGT and lactate dehydrogenase (LDH activities were also measured. Results TCE administration increased the malondiahyde (MDA and NO contents in kidney, urea and creatinine concentrations in serum, total free radical level in blood and GGT and LDH activities in serum, whereas it decreased the glutathione (GSH level in kidney homogenate. KT administration significantly improved lipid peroxidation and oxidative stress induced by TCE. Conclusion The present study indicates that Kombucha may repair damage caused by environmental pollutants such as TCE and may be beneficial to patient suffering from renal impairment.

  10. Effects of Kombucha on oxidative stress induced nephrotoxicity in rats.

    Gharib, Ola Ali

    2009-11-27

    Trichloroethylene (TCE) may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes. Twenty male albino rats were divided into four groups: (1) the control group treated with vehicle, (2) Kombucha (KT)-treated group, (3) TCE-treated group and (4) KT/TCE-treated group. Kidney lipid peroxidation, glutathione content, nitric oxide (NO) and total blood free radical concentrations were evaluated. Serum urea, creatinine level, gamma-glutamyl transferase (GGT) and lactate dehydrogenase (LDH) activities were also measured. TCE administration increased the malondiahyde (MDA) and NO contents in kidney, urea and creatinine concentrations in serum, total free radical level in blood and GGT and LDH activities in serum, whereas it decreased the glutathione (GSH) level in kidney homogenate. KT administration significantly improved lipid peroxidation and oxidative stress induced by TCE. The present study indicates that Kombucha may repair damage caused by environmental pollutants such as TCE and may be beneficial to patient suffering from renal impairment.

  11. The synthesis, structure-toxicity relationship of cisplatin derivatives for the mechanism research of cisplatin-induced nephrotoxicity.

    Hu, Jing; Wu, Tian-Ming; Li, Hong-Ze; Zuo, Ze-Ping; Zhao, Ying-Lan; Yang, Li

    2017-08-01

    Cisplatin is a widely used antineoplastic drug, while its nephrotoxicity limits the clinical application. Although several mechanisms contributing to nephrotoxicity have been reported, the direct protein targets are unclear. Herein we reported the synthesis of 29 cisplatin derivatives and the structure-toxicity relationship (STR) of these compounds with MTT assay in human renal proximal tubule cells (HK-2) and pig kidney epithelial cells (LLC-PK1). To the best of our knowledge, this study represented the first report regarding the structure-toxicity relationship (STR) of cisplatin derivatives. The potency of biotin-pyridine conjugated derivative 3 met the requirement for target identification, and the preliminary chemical proteomics results suggested that it is a promising tool for further target identification of cisplatin-induced nephrotoxicity. Copyright © 2017. Published by Elsevier Ltd.

  12. Evaluation of therapeutic potential of picrorhiza kurroa glycosidal extract against nimesulide nephrotoxicity: a pilot study

    Siddiqi, A.

    2015-01-01

    Picrorhiza kurroa (Pk) is a traditional Ayurvedic herb famous as a potent hepatoprotective agent, only few studies are available on the nephroprotective activity of this herb. The objective of this pilot study was to determine the therapeutic effectiveness of Pk against nimesulide induced toxicity. Methods: This laboratory based experimental study was conducted on mice at National Institute of Health, Islamabad from Dec 2012 to Jan 2013. The mice were divided in to 4 groups. One group was given only PK while the other three groups were given nimesulide in a dosage of 750 mg/kg body weight for 3 days to induce nephrotoxicity and protective effect of Pk was noted by giving 250 mg/kg and 500 mg/kg pk for 14 days to the two of the nimesulide induced nephrotoxicity groups. Biochemical assessment of kidney was done by measuring serum urea and creatinine. Also histology was done to confirm the findings of biochemical assessment. Results: In our pilot study out of 20 mice, 19 mice survived. Only 1 mouse of nimesulide group died. Mean serum urea of nimesulide group was 60 mg/dl and was decreased to 23 mg/dl and 25 mg/dl by two doses of Pk. Mean creatinine in group 2 was 0.55 mg/dl and was decreased to 0.21 and 0.19 mg/dl by two doses of Pk. Conclusion: Our study shows that nimesulide is a potential nephrotoxic drug and its toxic effects on kidney can be minimized by using glycosidal extract of Pk. (author)

  13. Virgin olive oil ameliorates deltamethrin-induced nephrotoxicity in mice: A biochemical and immunohistochemical assessment

    Ali Reza khalatbary

    Full Text Available Objective: A major class of synthetic pyrethroid insecticide, deltamethrin (DM, can elicit pathophysiological effects through oxidative stress in non-targeted organisms such as mammals. There is accumulating evidence that virgin olive oil (VOO, a rich source of polyphenolic components, have anti-oxidant, anti-inflammatory, and anti-apoptotic properties. This study aimed to determine the protective and ameliorative effects of VOO against DM-induced nephrotoxicity. Methods & materials: Mice were randomly divided into four equal groups: DM group, DM plus VOO group, VOO group, and vehicle group. Five weeks after gavaging, kidney samples were taken for biochemical assessment of malondialdehyde (MDA, glutathione (GSH and catalase (CAT, and for immunohistochemical assessment of caspase-3, cyclooxygenase-2 (cox-2 and poly (ADP-ribose polymerase (PARP. Results: The MDA level in kidney was increased in the DM group, which was significantly decreased after VOO administration in the DM plus VOO group. The GSH level and CAT activiy in kidney were decreased in the DM group, which were significantly increased after VOO administration in the DM plus VOO group. Greater expression of caspase-3, cox-2, and PARP could be detected in the DM group, which was significantly attenuated in the DM plus VOO group. Also, the histopathological changes which were detected in the DM group attenuated after VOO consumption. Conclusion: Virgin olive oil exerted protective effects against deltamethrin-induced nephrotoxicity, which might be associated with its anti-apoptotic, anti-inflammatory, and anti-oxidative properties. Keywords: Deltamethrin, Virgin olive oil, Antioxidant, Apoptosis, Inflammation, Nephrotoxicity

  14. Nephrotoxicity of uranyl acetate: effect on rat kidney brush border membrane vesicles

    Goldman, M.; Yaari, A.; Moran, A.; Doshnitzki, Z.; Cohen-Luria, R.

    2006-01-01

    Since the Gulf war exposure to depleted uranium, a known nephrotoxic agent, there is a renewed interest in the toxic effects of uranium in general and its mechanism of nephrotoxicity which is still largely unknown in particular. In order to investigate the mechanism responsible for uranium nephrotoxicity and the therapeutic effect of urine alkalization, we utilized rat renal brush border membrane vesicles (BBMV). Uranyl acetate (UA) caused a decrease in glucose transport in BBMV. The apparent K i of uranyl was 139±30 μg uranyl/mg protein of BBMV. Uranyl at 140 μg/mg protein of BBMV reduced the maximal capacity of the system to transport glucose [V max 2.2±0.2 and 0.96±0.16 nmol/mg protein for control and uranyl treated BBMV (P m (1.54±0.33 and 1.54±0.51 mM for control, and uranyl treated BBMV, respectively). This reduction in V max is at least partially due to a decrease in the number of sodium-coupled glucose transporters as apparent from the reduction in phlorizin binding to the uranyl treated membranes, V max was reduced from 247±13 pmol/mg protein in control BBMV to 119±3 pmol/mg protein in treated vesicles (P<0.001). The pH of the medium has a profound effect on the toxicity of UA on sodium-coupled glucose transport in BBMV: higher toxicity at neutral pH (around pH 7.0), and practically no toxicity at alkaline pH (7.6). This is the first report showing a direct inhibitory dose and pH dependent effect of uranyl on the glucose transport system in isolated apical membrane from kidney cortex. (orig.)

  15. Possible mechanism of PNS protection against cisplatin-induced nephrotoxicity in rat models.

    Liu, Xinwen; Huang, Zhenguang; Zou, Xiaoqin; Yang, Yufang; Qiu, Yue; Wen, Yan

    2015-01-01

    This study investigates the mechanism of the protective effect of Panax notoginsenosides (PNS) against cisplatin-induced nephrotoxicity via the hypoxia inducible factor 1 (HIF-1)/Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) pathway of autophagy. The rats underwent intraperitoneal injection with a single dose of cisplatin and a subset of rats were also intraperitoneally injected with 31.35 mg/kg PNS once a day. After 24 h exposure to cisplatin, the concentrations of urinary N-acetyl-β-D-glucosaminidase (NAG), blood urea nitrogen (BUN) and serum creatinine (Scr) were determined. The rat renal tissue was examined using H&E-staining, and the mitochondria of renal tubular epithelial cells were observed using transmission electron microscopy. The expressions of microtubule-associated protein-1 light chain (LC)3, autophagy-related gene (Atg)5, Beclin-1 and BNIP3 in rat renal tissue were detected using western blotting. The expression of HIF-1 was detected by immunohistochemistry. The results showed that PNS significantly protected against cisplatin-induced nephrotoxicity, as evidenced by decreasing the concentration of blood BUN and Scr, the attenuation of renal histopathological changes and the mitochondrial damages of renal cells, and the increase of mitochondria autophagosome in renal tubular epithelial cells. Additionally, PNS significantly increased the expression of LC3 and the ratio of LC3II/LC3I in rat renal tissue. Moreover, PNS significantly increased the expression of HIF-1α, BNIP3, Atg5 and Beclin-1 in rat renal tissue. In conclusion, the protective effect of PNS on cisplatin-induced nephrotoxicity was mainly due to its ability to enhancing the mitochondrial autophagy of renal tissue via the HIF-1α/BNIP3 pathway, and here is the first demonstration about it.

  16. Low serum zinc is associated with elevated risk of cadmium nephrotoxicity

    Lin, Yu-Sheng, E-mail: Lin.Yu-Sheng@epa.gov [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC (United States); Ho, Wen-Chao [Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan (China); Caffrey, James L. [Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX (United States); Sonawane, Babasaheb [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC (United States)

    2014-10-15

    Background: Despite animal evidence suggests that zinc modulates cadmium nephrotoxicity, limited human data are available. Objective: To test the hypothesis that low serum zinc concentrations may increase the risk of cadmium-mediated renal dysfunction in humans. Methods: Data from 1545 subjects aged 20 or older in the National Health and Nutrition Examination Survey (NHANES), 2011–2012 were analyzed. Renal function was defined as impaired when estimated glomerular filtration rate (eGFR) fell below 60 ml/min/1.73 m{sup 2} and/or the urinary albumin-to-creatinine ratio surpassed 2.5 in men and 3.5 mg/mmol in women. Results: Within the study cohort, 117 subjects had reduced eGFR and 214 had elevated urinary albumin. After adjusting for potential confounders, subjects with elevated blood cadmium (>0.53 μg/L) were more likely to have a reduced eGFR (odds ratio [OR]=2.21, 95% confidence interval [CI]: 1.09–4.50) and a higher urinary albumin (OR=2.04, 95% CI: 1.13–3.69) than their low cadmium (<0.18 μg/L) peers. In addition, for any given cadmium exposure, low serum zinc is associated with elevated risk of reduced eGFR (OR=3.38, 95% CI: 1.39–8.28). A similar increase in the odds ratio was observed between declining serum zinc and albuminuria but failed to reach statistical significance. Those with lower serum zinc/blood cadmium ratios were likewise at a greater risk of renal dysfunction (p<0.01). Conclusions: This study results suggest that low serum zinc concentrations are associated with an increased risk of cadmium nephrotoxicity. Elevated cadmium exposure is global public health issue and the assessment of zinc nutritional status may be an important covariate in determining its effective renal toxicity. - Highlights: • Blood cadmium was associated with increased risk of nephrotoxicity. • Low serum zinc may exacerbate risk of cadmium-mediated renal dysfunction. • Both zinc deficiency and elevated cadmium exposure are global public health issues.

  17. Nephrotoxicity of cyclosporin A in patients with newly diagnosed type 1 diabetes mellitus

    Feldt-Rasmussen, B; Jensen, T; Dieperink, H

    1990-01-01

    Renal function was studied in 18 patients with Type 1 diabetes mellitus. All were participating in the Canadian-European randomized placebo-controlled cyclosporin trial in newly diagnosed Type 1 diabetic patients, nine being randomized to placebo, and nine to cyclosporin A. During treatment for 12...... corrected for differences in blood glucose control it appeared that in three out of nine patients glomerular filtration rate had not completely returned to the reference range of the placebo group. We conclude that the nephrotoxic side-effects of cyclosporin A treatment for 1 year are reversible. There are...

  18. 131I-orthoiodohippurate clearance in the detection of cisplatin nephrotoxicity

    Hengst, W.; Wieler, H.; Rabs, U.; Buerger, R.A.

    1985-01-01

    In this study, 26 patients were treated with 20 mg cisplatin (CP)/m 2 body surface daily for 5 days as part of a combination therapy for testicular cancer. Simultaneously a vigorous hyperhydration (3000 ml daily) was applied to reduce the nephrotoxic effect induced by the drug. sup(131I)-orthoiodophippurate clearance values obtained by the modified method of Oberhausen did not show any significant evidence of tubular dysfunction after therapy. These results may have been due to the vigorous hydration as well as to the youth of the patients. (orig.) [de

  19. Tenofovir-related nephrotoxicity: case report and review of the literature.

    James, Christopher W; Steinhaus, Mary C; Szabo, Susan; Dressier, Robert M

    2004-03-01

    Tenofovir is a nucleotide reverse transcriptase inhibitor for treatment of human immunodeficiency virus (HIV) infection. Several cases of renal failure associated with tenofovir therapy recently have been reported. A 54-year-old man with HIV experienced decreasing renal function and Fanconi's syndrome secondary to tenofovir therapy. His condition gradually improved after discontinuation of the drug. The available medical literature for reported cases of tenofovir-related nephrotoxicity indicates that this complication is apparently rare. However, our case report and literature review underscore the importance of monitoring renal function when treating patients with any nucleotide reverse transcriptase inhibitor.

  20. Protective Effect of Bauhinia purpurea on Gentamicin-induced Nephrotoxicity in Rats

    Lakshmi, B. V. S.; Neelima, N.; Kasthuri, N.; Umarani, V.; Sudhakar, M.

    2009-01-01

    The present study was undertaken to evaluate the ethanol extract of leaves of Bauhinia purpurea and unripe pods of Bauhinia purpurea for its protective effects on gentamicin-induced nephrotoxicity in rats. Nephrotoxicity was induced in Wistar rats by intraperitoneal administration of gentamicin 100 mg/kg/d for eight days. Effect of concurrent administration of ethanol extract of leaves of Bauhinia purpurea and unripe pods of Bauhinia purpurea at a dose of 300 mg/kg/d given by oral route was determined using serum creatinine, serum uric acid, blood urea nitrogen and serum urea as indicators of kidney damage. The study groups contained six rats in each group. It was observed that the ethanol extract of leaves of Bauhinia purpurea and unripe pods of Bauhinia purpurea significantly protect rat kidneys from gentamicin-induced histopathological changes. Gentamicin-induced glomerular congestion, blood vessel congestion, epithelial desquamation, accumulation of inflammatory cells and necrosis of the kidney cells were found to be reduced in the groups receiving the leaf and unripe pods extract of Bauhinia purpurea along with gentamicin. The extracts also normalized the gentamicin-induced increase in serum creatinine, serum uric acid and blood urea nitrogen levels. This is also evidenced by the histopathological studies. PMID:20502576

  1. Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity

    Beger, Richard D.; Sun, Jinchun; Schnackenberg, Laura K.

    2010-01-01

    Hepatotoxicity and nephrotoxicity are two major reasons that drugs are withdrawn post-market, and hence it is of major concern to both the FDA and pharmaceutical companies. The number of cases of serious adverse effects (SAEs) in marketed drugs has climbed faster than the number of total drug prescriptions issued. In some cases, preclinical animal studies fail to identify the potential toxicity of a new chemical entity (NCE) under development. The current clinical chemistry biomarkers of liver and kidney injury are inadequate in terms of sensitivity and/or specificity, prompting the need to discover new translational specific biomarkers of organ injury. Metabolomics along with genomics and proteomics technologies have the capability of providing translational diagnostic and prognostic biomarkers specific for early stages of liver and kidney injury. Metabolomics has several advantages over the other omics platforms such as ease of sample preparation, data acquisition and use of biofluids collected through minimally invasive procedures in preclinical and clinical studies. The metabolomics platform is reviewed with particular emphasis on applications involving drug-induced hepatotoxicity and nephrotoxicity. Analytical platforms for metabolomics, chemometrics for mining metabolomics data and the applications of the metabolomics technologies are covered in detail with emphasis on recent work in the field.

  2. Antioxidant effect of Arabic gum against mercuric chloride-induced nephrotoxicity

    Gado AM

    2013-10-01

    Full Text Available Ali M Gado,1 Badr A Aldahmash21Forensic Medicine and Clinical Toxicology Department, College of Medicine, Tanta University, Tanta, Egypt; 2Medical Laboratory Department, College of Health Sciences, King Saud University, Riyadh, Saudi ArabiaAbstract: The effects of Arabic gum (AG against nephrotoxicity of mercury (Hg, an oxidative-stress inducing substance, in rats were investigated. A single dose of mercuric chloride (5 mg/kg intraperitoneal injection induced renal toxicity, manifested biochemically by a significant increase in serum creatinine, blood urea nitrogen, thiobarbituric acid reactive substances, and total nitrate/nitrite production in kidney tissues. In addition, reduced glutathione, glutathione peroxidase, and catalase enzymes in renal tissues were significantly decreased. Pretreatment of rats with AG (7.5 g/kg/day per oral administration, starting 5 days before mercuric chloride injection and continuing through the experimental period, resulted in a complete reversal of Hg-induced increase in creatinine, blood urea nitrogen, thiobarbituric acid reactive substances, and total nitrate/nitrite to control values. Histopathologic examination of kidney tissues confirmed the biochemical data; pretreatment of AG prevented Hg-induced degenerative changes of kidney tissues. These results indicate that AG is an efficient cytoprotective agent against Hg-induced nephrotoxicity by a mechanism related at least in part to its ability to decrease oxidative and nitrosative stress and preserve the activity of antioxidant enzymes in kidney tissues.Keywords: mercury, acacia gum, oxidative stress, lipid per oxidation, kidney toxicity

  3. Antioxidant effect of Arabic gum against mercuric chloride-induced nephrotoxicity.

    Gado, Ali M; Aldahmash, Badr A

    2013-01-01

    The effects of Arabic gum (AG) against nephrotoxicity of mercury (Hg), an oxidative-stress inducing substance, in rats were investigated. A single dose of mercuric chloride (5 mg/kg intraperitoneal injection) induced renal toxicity, manifested biochemically by a significant increase in serum creatinine, blood urea nitrogen, thiobarbituric acid reactive substances, and total nitrate/nitrite production in kidney tissues. In addition, reduced glutathione, glutathione peroxidase, and catalase enzymes in renal tissues were significantly decreased. Pretreatment of rats with AG (7.5 g/kg/day per oral administration), starting 5 days before mercuric chloride injection and continuing through the experimental period, resulted in a complete reversal of Hg-induced increase in creatinine, blood urea nitrogen, thiobarbituric acid reactive substances, and total nitrate/nitrite to control values. Histopathologic examination of kidney tissues confirmed the biochemical data; pretreatment of AG prevented Hg-induced degenerative changes of kidney tissues. These results indicate that AG is an efficient cytoprotective agent against Hg-induced nephrotoxicity by a mechanism related at least in part to its ability to decrease oxidative and nitrosative stress and preserve the activity of antioxidant enzymes in kidney tissues.

  4. Effect of Honey and Royal Jelly against Cisplatin-Induced Nephrotoxicity in Patients with Cancer.

    Osama, Hasnaa; Abdullah, Aya; Gamal, Bassma; Emad, Dina; Sayed, Doha; Hussein, Eman; Mahfouz, Eman; Tharwat, Joy; Sayed, Sally; Medhat, Shrouk; Bahaa, Treza; Abdelrahim, Mohamed E A

    2017-07-01

    Cisplatin constitutes one of the most potent antineoplastic drugs; however, nephrotoxicity limited its eligibility for optimal clinical use. This study was designed to evaluate the role of honey and royal jelly with antioxidant properties in the protection of cisplatin-induced acute kidney injury in patients with cancer. Patients with cancer assigned for cisplatin chemotherapy were randomly divided into bee honey and royal jelly groups pretreated before the initiation and during cisplatin chemotherapeutic regimen and control group on cisplatin only. Serum creatinine and urea levels were measured before and after the chemotherapeutic cycle and over 2 cycles. Patients on crude bee honey and royal jelly capsules showed lower serum levels of renal injury products (creatinine and urea) compared to those in the control group. The changes in kidney parameters were significantly (p honey group before and after cisplatin treatment. Royal jelly was found to be effective; however, the difference in creatinine and urea levels before and after chemotherapy was not statistically significant. The use of bee honey and royal jelly as natural compounds is effective in reducing cisplatin nephrotoxicity and may offer a promising chance for clinically meaningful prevention. This study has potentially important implications for the treatment of cisplatin kidney side effects and is considered to be the first to investigate this effect of honey and royal jelly in human subjects. However, due to its small sample size, we recommend further investigation using a larger sample size.

  5. Renoprotective Effects of Total Glucosides from Paeony against Nephrotoxicity Induced by Total Alkaloids from Semen Strychni

    Mingming Lv

    2017-01-01

    Full Text Available Semen Strychni have been shown to have therapeutic effect in improving blood circulation, relieving rheumatic pain, and treating cancer. However, Semen Strychni could cause severe nephrotoxicity. The present study was designed to evaluate whether treatment with total glucosides from paeony (TGP has renoprotective effect against nephrotoxicity induced by total alkaloids from Semen Strychni (TAS. The levels of blood urea nitrogen (BUN and creatinine (Cr were determined and histopathological changes were also examined to evaluate renal injury. Moreover, a HPLC-MS method was developed and validated to investigate the comparative toxicokinetics of strychnine and brucine in rats plasma after oral administration of TAS and pretreatment with TGP. Results demonstrated that the levels of BUN and Cr were significantly increased (p<0.05 in TAS group, together with tubule epithelium cloudy swelling, degeneration, and glomerular atrophy in rats’ kidneys. The TAS-induced kidney damage was alleviated after pretreatment with TGP. Besides, Tmax of strychnine and brucine were increased and T1/2 of strychnine and brucine were decreased after pretreatment with TGP. The toxicokinetics study showed that pretreatment with TGP could attenuate the absorption of strychnine and brucine, as well as accelerate their elimination. These results suggest that TGP possesses renoprotective effects.

  6. Protective effect of Heliotropium eichwaldi against cisplatin-induced nephrotoxicity in mice.

    Sharma, Surendra Kr; Goyal, Naveen

    2012-05-01

    The aim of the present study was to evaluate the nephroprotective effect of methanolic extract of Heliotropium eichwaldii (MHE) in mice with cisplatin-induced acute renal damage. Nephrotoxicity was induced by a single intraperitoneal injection of cisplatin (16mg/kg). Swiss albino mice were injected with vehicle, cisplatin, cisplatin plus MHE 200 mg/kg and cisplatin plus MHE 400mg/kg, respectively. MHE was administered for 7 d at a dose of 200 and 400 mg/kg per day orally starting 4 d before cisplatin injection. Animals were sacrificed 3d after treatment and blood as well as kidney tissue was isolated and analyzed. The various parameters such as blood urea nitrogen (BUN), serum creatinine (CRE), malondialdehyde (MDA), and catalase (CAT) and superoxide dismutase (SOD) activities were analyzed. MHE treatment significantly reduced BUN and serum CRE levels elevated by cisplatin administration (P<0.05). Also, it significantly attenuated cisplatin-induced increase in MDA level and improved the decreased CAT and SOD activities in renal cortical homogenates (P<0.05). Additionally, histopathological examination and scoring showed that MHE markedly ameliorated cisplatin-induced renal tubular necrosis. MHE can be considered a potential candidate for protection of nephrotoxicity induced by cisplatin.

  7. The renoprotective activity of hesperetin in cisplatin induced nephrotoxicity in rats: Molecular and biochemical evidence.

    Kumar, Mukesh; Dahiya, Vicky; Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Lahkar, Mangala

    2017-05-01

    Nephrotoxicity remain a major life-threatening complication in cancer patients on cisplatin chemotherapy. In this study, we investigated the protective effect and possible cellular mechanism of the hesperetin, a naturally-occurring bioflavonoid against cisplatin-induced renal injury in rats. Hesperetin was administered at a dose of 50mg/kg and 100mg/kg orally for 10days and cisplatin (7.5mg/kg, ip) was administered on the 5th day of experiment. Cisplatin induced nephrotoxicity was evidenced by alteration in the level of markers such as blood urea nitrogen, creatinine, serum albumin and severe histopathological changes in kidney. Cisplatin administration also resulted in significant increase in the tissue oxidative stress and inflammatory cytokines. The level of antioxidants enzymes were decreased significantly in the cisplatin administered rats. Hesperetin treatment (50mg/kg and 100mg/kg) normalized the renal function by attenuation of the cisplatin-induced oxidative stress, lipid peroxidation, and inflammatory cytokines and histopathological alterations. On the basis of these experimental findings our present study postulate that co-administration of hesperetin with cisplatin chemotherapy may be promising preventive approach to limit the major mortal side effect of cisplatin. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Effect of nephrotoxic drugs on the development of radiation nephropathy after bone marrow transplantation

    Lawton, C.A.; Fish, B.L.; Moulder, J.E.

    1994-01-01

    Chronic renal failure is a significant cause of late morbidity in bone marrow transplant patients whose conditioning regimen includes total body irradiation (TBI). Radiation is a major cause of this syndrome (bone marrow transplant nephropathy), but it may not be the only cause. These studies use a rat syngeneic bone marrow transplant model to determine whether nephrotoxic agents used in conjunction with bone marrow transplantation (BMT) could be enhancing or accelerating the development of radiation nephropathy. Rats received 11-17 Gy TBI in six fractions over 3 days followed by syngeneic bone marrow transplant. In conjunction with the bone marrow transplants, animals received either no drugs, cyclosporine, amphotericin, gentamicin, or busulfan. Drugs were given in schedules analogous to their use in clinical bone marrow transplantation. Drug doses were chosen so that the drug regimen alone caused detectable acute nephrotoxicity. Animals were followed for 6 months with periodic renal function tests. Gentamicin had no apparent interactions with TBI. Amphotericin increased the incidence of engraftment failure, but did not enhance radiation nephropathy. Cyclosporin with TBI caused late morbidity that appeared to be due to neurological problems, but did not enhance radiation nephropathy. Busulfan resulted in a significant enhancement of radiation nephropathy. Of the nephrotoxins used in conjunction with bone marrow transplantation only radiation and busulfan were found to be risk factors for bone marrow transplant nephropathy. 34 refs., 4 figs., 2 tabs

  9. Virgin olive oil ameliorates deltamethrin-induced nephrotoxicity in mice: A biochemical and immunohistochemical assessment.

    Khalatbary, Ali Reza; Ahmadvand, Hassan; Ghabaee, Davood Nasiry Zarrin; Malekshah, Abbasali Karimpour; Navazesh, Azam

    2016-01-01

    A major class of synthetic pyrethroid insecticide, deltamethrin (DM), can elicit pathophysiological effects through oxidative stress in non-targeted organisms such as mammals. There is accumulating evidence that virgin olive oil (VOO), a rich source of polyphenolic components, have anti-oxidant, anti-inflammatory, and anti-apoptotic properties. This study aimed to determine the protective and ameliorative effects of VOO against DM-induced nephrotoxicity. Mice were randomly divided into four equal groups: DM group, DM plus VOO group, VOO group, and vehicle group. Five weeks after gavaging, kidney samples were taken for biochemical assessment of malondialdehyde (MDA), glutathione (GSH) and catalase (CAT), and for immunohistochemical assessment of caspase-3, cyclooxygenase-2 (cox-2) and poly (ADP-ribose) polymerase (PARP). The MDA level in kidney was increased in the DM group, which was significantly decreased after VOO administration in the DM plus VOO group. The GSH level and CAT activiy in kidney were decreased in the DM group, which were significantly increased after VOO administration in the DM plus VOO group. Greater expression of caspase-3, cox-2, and PARP could be detected in the DM group, which was significantly attenuated in the DM plus VOO group. Also, the histopathological changes which were detected in the DM group attenuated after VOO consumption. Virgin olive oil exerted protective effects against deltamethrin-induced nephrotoxicity, which might be associated with its anti-apoptotic, anti-inflammatory, and anti-oxidative properties.

  10. Nephrotoxicity during tenofovir treatment: a three-year follow-up study in a Brazilian reference clinic

    Lauro Ferreira da Silva Pinto Neto

    2016-01-01

    Full Text Available In this study, 275 patients in use of tenofovir were retrospectively followed-up for three years to evaluate risk factors involved in impaired renal function. Analysis of variance (ANOVA and Tukey's test were used to verify any differences in creatinine levels and estimated clearance at 0, 6, 12, 24 and 36 months, adjusting for the co-variables sex, skin color, age >50 years, arterial hypertension, diabetes and the use of the ritonavir-boosted protease inhibitors (PI/r lopinavir/r or atazanavir/r. The software package STATISTICA 10® was used for statistical analysis. The patients’ mean age was 43.2 ± 10.7 years. Systemic arterial hypertension (SAH and diabetes were found in 20.4% and 8.7% of the patients, respectively. Overall, 96.7% were on tenofovir associated with lamivudine (TDF + 3TC, 39.3% on lopinavir/r, 29.8% on efavirenz, and 17.6% on atazanavir/r. There was a statistically significant difference in estimated creatinine clearance at 24 months, when the co-variables male (F = 3.95; p = 0.048, SAH (F = 6.964; p = 0.009, and age over 50 years (F = 45.81; p < 0.001 were taken into consideration. Analysis of the co-variable use of atazanavir/r showed a tendency toward an increased risk over time (F = 2.437; p = 0.063; however, no significant time interaction was seen. At 36-month, a statistically significant difference was found for age over 50 years, (F = 32.02; p < 0.05 and there was a significant time-by-sex interaction (F = 3.117; p = 0.0149. TDF was discontinued in 12 patients, one because of a femoral neck fracture (0.7% and 11 due to nephrotoxicity (4%. Of these latter cases, 9/11 patients were also using protease inhibitors. These data strongly alert that tenofovir use should be individualized with careful attention to renal function especially in male patients, over 50 years, with SAH, and probably those on ATV/r.

  11. Xanthohumol attenuates cisplatin-induced nephrotoxicity through inhibiting NF-κB and activating Nrf2 signaling pathways.

    Li, Fan; Yao, Yunyi; Huang, Hui; Hao, Hua; Ying, Mingzhong

    2018-06-12

    Cisplatin is a chemotherapeutic agent that widely used in the treatment of cancer. However, cisplatin has been reported to induce nephrotoxicity by directly inducing inflammatory response and oxidative stress. In this study, we aimed to investigate the protective effects and mechanism of xanthohumol on cisplatin-induced nephrotoxicity. The model of nephrotoxicity was induced by intraperitoneal injection of cisplatin and xanthohumol was given intraperitoneally for three consecutive days. The results showed that xanthohumol significantly attenuated kidney histological changes and serum creatinine and BUN production. The levels of TNF-α, IL-1ß and IL-6 in kidney tissues were suppressed by xanthohumol. The levels of malondialdehyde (MDA) and ROS were suppressed by treatment of xanthohumol. The activities of glutathione (GSH) and superoxide dismutase (SOD) decreased by cisplatin were reversed by xanthohumol. Furthermore, the expression of TLR4 and the activation of NF-κB induced by cisplatin were significantly inhibited by xanthohumol. The expression of Nrf2 and HO-1 were dose-dependently up-regulated by the treatment of xanthohumol. In conclusion, xanthohumol protects against cisplatin-induced nephrotoxicity by ameliorating inflammatory and oxidative responses. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Proteomic approaches in understanding a detected relationship between chemotherapy-induced nephrotoxicity and cell respiration in HK-2 cells.

    Perez, Juliana Dinéia; Colucci, Juliana Almada; Sakata, Maísa Mayumi; Cunha, Tatiana Sousa; Arita, Danielle Yuri; Casarini, Dulce Elena

    2011-01-01

    Nephrotoxicity is a prominent component of the profile of chemotherapeutic agents and to date proteomics has represented the main technique to identify protein profiles in response to xenobiotic exposure. We made use of two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight analysis to evaluate chemotoxicity effects of cisplatin (CPT) and carboplatin (CB) on proteins from human renal proximal tubule epithelial cells (HK-2). Tandem mass spectrometry analysis showed that ATP synthase subunit α and serine hydroxymethyltransferase were only expressed in HK-2 cells exposed to CPT. Since CPT causes damage in cellular respiration, we suggest that this might be a protective adaptation to CPT-induced nephrotoxicity. Thioredoxin-dependent peroxide reductase disappeared in the CPT group and was upregulated in the CB group, suggesting that CB exposure stimulates preventive apoptotic mechanisms. We suggest a relationship between chemotherapeutic agent-induced nephrotoxicity and cell respiration. The identification of proteins differentially expressed in HK-2 cells, when exposed to CPT and CB, not only supplies important information to understand the molecular action mechanisms, which are triggered by metal-based drugs in cell nephrotoxicity, but also can lead to the design of more effective anticancer drugs. These results provide important insights into the investigation of possible biomarker(s) of toxicity that could eventually reduce the side effects of chemotherapeutic agents. Copyright © 2011 S. Karger AG, Basel.

  13. Protective Effect of Forced Hydration with Isotonic Saline, Potassium Chloride and Magnesium Sulfate on Cisplatin Nephrotoxicity: An Initial Evaluation

    Seyed Seifollah Beladi Mousavi

    2013-12-01

    How to cite this article: Beladi Mousavi SS, Hossainzadeh M, Khanzadeh A, Hayati F, Beladi Mousavi M, Zeraati AA, et al. Protective Effect of Forced Hydration with Isotonic Saline, Potassium Chloride and Magnesium Sulfate on Cisplatin Nephrotoxicity: An Initial Evaluation. Asia Pac J Med Toxicol 2013;2:136-9.

  14. Effect of commercial (vimang and hydroalcoholic extract of Mangifera indica (Mango on gentamicin-induced nephrotoxicity in rat

    Abolfazl Khajavi Rad

    2011-09-01

    Conclusion: Mango products were able to improve kidney function in an established model of GM-induced nephrotoxicity in the rat. The beneficial effects of Mango on the rat kidney seem to be dose and time-dependent. However, more investigations are needed to elucidate Mango action on GM-induced renal toxicity.

  15. Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats: Impact on NOX-1, inflammation and apoptosis

    El-Naga, Reem N.

    2014-01-01

    Cisplatin is an effective anti-cancer drug; however, its clinical use is usually associated with nephrotoxicity as a dose-limiting side effect. Several molecular mechanisms have been found to be involved in this nephrotoxicity such as oxidative stress, inflammation and apoptosis. The aim of this study was to explore the potential nephroprotective effect of cardamonin, a flavone found in Alpinia plant, in a rat model of cisplatin-induced nephrotoxicity. The possible mechanisms underlying this nephroprotective effect were investigated. Cardamonin was given at two different doses; 10 and 30 mg/kg orally for two weeks, starting one week before giving a single nephrotoxic dose of cisplatin (7 mg/kg). Acute nephrtoxicity was evident by significantly increased blood urea nitrogen and serum creatinine levels. Also, cisplatin increased lipid peroxidation and depleted reduced glutathione level and superoxide dismutase. Additionally, cisplatin showed a marked pro-inflammatory response as evidenced by significant increase in tissue levels of IL-1β, TNF-α, NF-kB, iNOS, ICAM-1 and MCP-1. Pre-treatment with cardamonin significantly attenuated the nephrotoxic effects, oxidative stress and inflammation induced by cisplatin, in a dose-dependent manner. Also, cardamonin decreased caspase-3 expression and Bax/Bcl-2 ratio as compared to cisplatin group. Besides, cradamonin reversed cisplatin-induced decrease in EGF. Furthermore, up-regulation of NOX-1 was found to be involved in cisplatin-induced nephrotoxicity and its expression was significantly reduced by cardamonin. Histopathological examination further confirmed the nephroprotective effect of cardamonin. Moreover, pre-treatment with subtoxic concentration of cardamonin has significantly enhanced cisplatin cytotoxic activity in four different human cancer cell lines; hela, hepG2, PC3 and HCT116 cancer cell lines. In conclusion, these findings suggest that cardamonin improves therapeutic index of cisplatin and that NOX-1 is

  16. Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats: Impact on NOX-1, inflammation and apoptosis

    El-Naga, Reem N., E-mail: reemelnaga@hotmail.com

    2014-01-01

    Cisplatin is an effective anti-cancer drug; however, its clinical use is usually associated with nephrotoxicity as a dose-limiting side effect. Several molecular mechanisms have been found to be involved in this nephrotoxicity such as oxidative stress, inflammation and apoptosis. The aim of this study was to explore the potential nephroprotective effect of cardamonin, a flavone found in Alpinia plant, in a rat model of cisplatin-induced nephrotoxicity. The possible mechanisms underlying this nephroprotective effect were investigated. Cardamonin was given at two different doses; 10 and 30 mg/kg orally for two weeks, starting one week before giving a single nephrotoxic dose of cisplatin (7 mg/kg). Acute nephrtoxicity was evident by significantly increased blood urea nitrogen and serum creatinine levels. Also, cisplatin increased lipid peroxidation and depleted reduced glutathione level and superoxide dismutase. Additionally, cisplatin showed a marked pro-inflammatory response as evidenced by significant increase in tissue levels of IL-1β, TNF-α, NF-kB, iNOS, ICAM-1 and MCP-1. Pre-treatment with cardamonin significantly attenuated the nephrotoxic effects, oxidative stress and inflammation induced by cisplatin, in a dose-dependent manner. Also, cardamonin decreased caspase-3 expression and Bax/Bcl-2 ratio as compared to cisplatin group. Besides, cradamonin reversed cisplatin-induced decrease in EGF. Furthermore, up-regulation of NOX-1 was found to be involved in cisplatin-induced nephrotoxicity and its expression was significantly reduced by cardamonin. Histopathological examination further confirmed the nephroprotective effect of cardamonin. Moreover, pre-treatment with subtoxic concentration of cardamonin has significantly enhanced cisplatin cytotoxic activity in four different human cancer cell lines; hela, hepG2, PC3 and HCT116 cancer cell lines. In conclusion, these findings suggest that cardamonin improves therapeutic index of cisplatin and that NOX-1 is

  17. Are intravenous injections of contrast media really less nephrotoxic than intra-arterial injections?

    Nyman, Ulf [University of Lund, Department of Diagnostic Radiology, Trelleborg (Sweden); Almen, Torsten [Skaane University Hospital, Department of Clinical Sciences/Medical Radiology, University of Lund, Malmoe (Sweden); Jacobsson, Bo [University of Gothenburg and the Sahlgrenska Academy, Department of Diagnostic Radiology, The Queen Silvia Children' s Hospital, Goeteborg (Sweden); Aspelin, Peter [Karolinska Institute and University Hospital, Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm (Sweden)

    2012-06-15

    We oppose the opinion that the intra-arterial administration of iodine-based contrast media (CM) appears to pose a greater risk of contrast medium-induced nephropathy (CIN) than intravenous administration since (1) in intra-arterial coronary procedures and most other intra-arterial angiographic examinations, CM injections are also intravenous relative to the kidneys, (2) there is a lack of comparative trials studying the risk of CIN between intra-arterial and intravenous procedures with matched risk factors and CM doses, (3) a bias selection of patients with fewer risk factors may explain the seemingly lower rate of CIN after CT in comparison with coronary interventions, (4) the rate of CIN following intra-arterial coronary procedures may also be exaggerated owing to other causes of acute kidney failure, such as haemodynamic instability and microembolisation, (5) roughly the same gram-iodine/GFR ratio ({approx}1:1) as a limit of relatively safe CM doses has preliminarily been found for both intravenous CT and intra-arterial coronary procedures and (6) the substantially higher injected intravenous CM dose rate during CT relative to an intra-arterial coronary procedure might actually pose a higher risk of CIN following CT. Key Points circle Most intra-arterial injections of contrast media are intravenous relative to the kidneys. circle No evidence that intravenous CM injections should be less nephrotoxic than intra-arterial. circle Considerably higher dose rates of CM are used for CT relative to intra-arterial procedures. circle Higher dose rates may pose higher nephrotoxic risk for intravenous based CT studies. (orig.)

  18. The Protective Effects of Sika Deer Antler Protein on Cisplatin-Induced Nephrotoxicity

    Huihai Yang

    2017-08-01

    Full Text Available Background/Aims: This study measured the effect of Sika deer (Cervus nippon Temminck antler protein (SDAPR, glycoproteins (SDAG, and polysaccharides (SDAPO on cisplatin-induced cytotoxicity in HEK 293 cells, and investigated the effect of SDAPR against cisplatin-induced nephrotoxicity in mice. Methods: Cell viability was measured by MTT assay. ICR mice were randomly divided into five groups: control, cisplatin with vehicle, and cisplatin with SDAPR at three concentrations: 5, 10, or 20 mg/kg, p.o., 10 d. Cisplatin was injected on 7th day (25 mg/kg, i.p.. Renal function, oxidative stress, levels of inflammatory factors, and expression of apoptosis-related proteins were measured in vivo. Renal tissues were stained with TUNEL and H&E to observe renal cell apoptosis and pathological changes. Results: Pretreatment with SDAPR (125-2000 µg/mL significantly improved cell viability, with an EC50 of approximately 1000 µg/mL. SDAPR also ameliorated cisplatin-induced histopatholo- gic changes, and decreased blood urea nitrogen (BUN and creatinine (Cr (P < 0.05. Western blotting analysis showed SDAPR clearly decreased expression levels of cleaved-caspase-3 and Bax, and increased the expression level of Bcl-2 (P < 0.01. Additionally, SDAPR markedly regulated oxidative stress markers and inflammatory cytokines (P<0.05. TUNEL staining showed decreased apoptosis after SDAPR treatment (P < 0.01. Conclusions: These results indicate that SDAPR can be an effective dietary supplement, to relieve cisplatin-induced nephrotoxicity by improved antioxidase activity, suppressed inflammation, and inhibited apoptosis in vivo.

  19. Nephrotoxic contaminants in drinking water and urine, and chronic kidney disease in rural Sri Lanka.

    Rango, Tewodros; Jeuland, Marc; Manthrithilake, Herath; McCornick, Peter

    2015-06-15

    Chronic kidney disease of unknown ("u") cause (CKDu) is a growing public health concern in Sri Lanka. Prior research has hypothesized a link with drinking water quality, but rigorous studies are lacking. This study assesses the relationship between nephrotoxic elements (namely arsenic (As), cadmium (Cd), lead (Pb), and uranium (U)) in drinking water, and urine samples collected from individuals with and/or without CKDu in endemic areas, and from individuals without CKDu in nonendemic areas. All water samples - from a variety of source types (i.e. shallow and deep wells, springs, piped and surface water) - contained extremely low concentrations of nephrotoxic elements, and all were well below drinking water guideline values. Concentrations in individual urine samples were higher than, and uncorrelated with, those measured in drinking water, suggesting potential exposure from other sources. Mean urinary concentrations of these elements for individuals with clinically diagnosed CKDu were consistently lower than individuals without CKDu both in endemic and nonendemic areas. This likely stems from the inability of the kidney to excrete these toxic elements via urine in CKDu patients. Urinary concentrations of individuals were also found to be within the range of reference values measured in urine of healthy unexposed individuals from international biomonitoring studies, though these reference levels may not be safe for the Sri Lankan population. The results suggest that CKDu cannot be clearly linked with the presence of these contaminants in drinking water. There remains a need to investigate potential interactions of low doses of these elements (particularly Cd and As) with other risk factors that appear linked to CKDu, prior to developing public health strategies to address this illness. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Protective effect of hydroalcoholic extract of Pistacia vera against gentamicin-induced nephrotoxicity in rats.

    Ehsani, Vahid; Amirteimoury, Morteza; Taghipour, Zahra; Shamsizadeh, Ali; Bazmandegan, Gholamreza; Rahnama, Amir; Khajehasani, Fatemeh; Fatemi, Iman

    2017-11-01

    Pistacia vera is a plant of the family Anacardiaceae found in Central and West Asia. P. vera nut (Pistachio) possess multiple pharmacological effects such as antimicrobial, anti-hyperlipidemia, antioxidant and anti-inflammatory. This study is designed to evaluate the protective effect of the hydroalcoholic extract of pistachio on gentamicin-induced nephrotoxicity in rats. Nephrotoxicity was induced in rats by intraperitoneal injection of gentamicin (100 mg/kg/day for 7 days). Hydroalcoholic extract of pistachio (10, 50 and 100 mg/kg/p.o) was administered for 7 days. The nephroprotective activity was evaluated by determining creatinine clearance, serum creatinine, urine volume, urine glucose and blood urea nitrogen (BUN) levels. The kidneys were processed for histopathological examinations and all specimens were examined for morphologic parameters involving tubular degeneration, tubular necrosis and tubule interstitial nephritis. Results showed a significant increase in the levels of serum creatinine, urine volume, urine glucose and BUN and decrease of creatinine clearance by gentamicin (GA) administration. Co-administration with pistachio extract showed reduction in the levels of serum creatinine, urine volume, urine glucose and BUN and increase of creatinine clearance in all doses but the most significant alteration was observed in doses of 100 mg/kg. Also, the nephroprotective effect of the GA was confirmed by the histological examination of the kidneys. The study revealed the nephroprotective effect of the hydroalcoholic extract of pistachio. These findings suggest that pistachio treatment may attenuate renal dysfunction and structural damage through the reduction of oxidative stress and inflammation in the kidney.

  1. Nephrotoxic contaminants in drinking water and urine, and chronic kidney disease in rural Sri Lanka

    Rango, Tewodros; Jeuland, Marc; Manthrithilake, Herath; McCornick, Peter

    2015-01-01

    Chronic kidney disease of unknown (“u”) cause (CKDu) is a growing public health concern in Sri Lanka. Prior research has hypothesized a link with drinking water quality, but rigorous studies are lacking. This study assesses the relationship between nephrotoxic elements (namely arsenic (As), cadmium (Cd), lead (Pb), and uranium (U)) in drinking water, and urine samples collected from individuals with and/or without CKDu in endemic areas, and from individuals without CKDu in nonendemic areas. All water samples – from a variety of source types (i.e. shallow and deep wells, springs, piped and surface water) – contained extremely low concentrations of nephrotoxic elements, and all were well below drinking water guideline values. Concentrations in individual urine samples were higher than, and uncorrelated with, those measured in drinking water, suggesting potential exposure from other sources. Mean urinary concentrations of these elements for individuals with clinically diagnosed CKDu were consistently lower than individuals without CKDu both in endemic and nonendemic areas. This likely stems from the inability of the kidney to excrete these toxic elements via urine in CKDu patients. Urinary concentrations of individuals were also found to be within the range of reference values measured in urine of healthy unexposed individuals from international biomonitoring studies, though these reference levels may not be safe for the Sri Lankan population. The results suggest that CKDu cannot be clearly linked with the presence of these contaminants in drinking water. There remains a need to investigate potential interactions of low doses of these elements (particularly Cd and As) with other risk factors that appear linked to CKDu, prior to developing public health strategies to address this illness. - Highlights: • Drinking water in rural Sri Lanka contains low levels of inorganic nephrotoxicants • Urinary nephrotoxicants are consistent with reference levels from

  2. Nephrotoxic contaminants in drinking water and urine, and chronic kidney disease in rural Sri Lanka

    Rango, Tewodros, E-mail: tg67@duke.edu [Division of Earth and Ocean Sciences, Nicholas School of the Environment, Duke University, Durham, NC (United States); Jeuland, Marc [Sanford School of Public Policy and Duke Global Health Institute, Duke University, Durham, NC (United States); Institute of Water Policy, National University of Singapore (Singapore); Manthrithilake, Herath; McCornick, Peter [International Water Management Institute, Colombo (Sri Lanka)

    2015-06-15

    Chronic kidney disease of unknown (“u”) cause (CKDu) is a growing public health concern in Sri Lanka. Prior research has hypothesized a link with drinking water quality, but rigorous studies are lacking. This study assesses the relationship between nephrotoxic elements (namely arsenic (As), cadmium (Cd), lead (Pb), and uranium (U)) in drinking water, and urine samples collected from individuals with and/or without CKDu in endemic areas, and from individuals without CKDu in nonendemic areas. All water samples – from a variety of source types (i.e. shallow and deep wells, springs, piped and surface water) – contained extremely low concentrations of nephrotoxic elements, and all were well below drinking water guideline values. Concentrations in individual urine samples were higher than, and uncorrelated with, those measured in drinking water, suggesting potential exposure from other sources. Mean urinary concentrations of these elements for individuals with clinically diagnosed CKDu were consistently lower than individuals without CKDu both in endemic and nonendemic areas. This likely stems from the inability of the kidney to excrete these toxic elements via urine in CKDu patients. Urinary concentrations of individuals were also found to be within the range of reference values measured in urine of healthy unexposed individuals from international biomonitoring studies, though these reference levels may not be safe for the Sri Lankan population. The results suggest that CKDu cannot be clearly linked with the presence of these contaminants in drinking water. There remains a need to investigate potential interactions of low doses of these elements (particularly Cd and As) with other risk factors that appear linked to CKDu, prior to developing public health strategies to address this illness. - Highlights: • Drinking water in rural Sri Lanka contains low levels of inorganic nephrotoxicants • Urinary nephrotoxicants are consistent with reference levels from

  3. Effect of normobaric hyperoxia on gentamicin-induced nephrotoxicity in rats

    Majid Tavafi

    2014-04-01

    Full Text Available Objective(s:Gentamicin sulphate (GS nephrotoxicity seems to be related to the generation of reactive oxygen species. There is evidence that oxygen preconditioning increases the activity of antioxidant enzymes. Materials and Methods: Forty eight female rats were divided into 6 groups (n=8 as follows: group 1 was the control, group 2 received daily GS, groups 3,4 and 5 received oxygen 2 hr/day for 2 days, 4 hr/day for 2 days, 4 hr/day for 4 days, recpectively and then received daily GS, group 6 received oxygen 2 hr/day for 2 days and then received 2 hr oxygen before daily GS injection. Oxygen (with 90% purity used at the flow rate of 4 l/min. GS administred for 8 days (100 mg/kg, IP. Tissue sections prepared from the left kidney, stained with PAS method and then studied hisopathologically and stereologically. The right kidneys were homogenized and the supernatants were prepared. Serum MDA, creatinine and urea, renal  MDA, gluthatione and catalase activity were measured. The data were analyzed by Mann-Whitney U test at the significant level of PResults: Oxygen therapy significantly improves serum creatinine and urea, preserve tubular volume density, reduce tubular necrosis in groups 4 and 6 compared to group 2. Oxygen therapy significantly increases renal catalase in groups 4 and 6 compared to group 2.   Conclusion: Pretreatment with normobaric hyperoxia and daily oxygen therapy improved gentamicin nephrotoxicity possibly via inhibition of lipid peroxidation and increasing the renal catalase activity but could not restore any parameter at the same levels as control group.

  4. Chitosan Prevents Gentamicin-Induced Nephrotoxicity via a Carbonyl Stress-Dependent Pathway

    Chu-Kung Chou

    2015-01-01

    Full Text Available Aminoglycosides are widely used to treat infections; however, their applications are limited by nephrotoxicity. With the increase of antibiotic resistance, the use of aminoglycosides is inevitable. Low-molecular-weight chitosan (LMWC has shown renal protective effects in dialysis patients. However, no study has evaluated LMWC for preventing aminoglycoside-induced nephrotoxicity or determined the mechanisms underlying the renal protective effects. In this study, LMWC (165 or 825 mg/kg/day or metformin (100 mg/kg/day was orally administered for 13 days to rats with nephropathy induced by gentamicin (GM, a kind of aminoglycoside (150 mg/kg/day i.p. for 6 days. Both LMCW doses improved renal function. Serum creatinine levels improved in rats treated with 165 and 825 mg/kg/day LMWC (from 2.14 ± 0.74 mg/dL to 1.26 ± 0.46 mg/dL and 0.69 ± 0.12 mg/dL, resp., P < 0.05. Blood urea nitrogen levels were also improved in these rats (from 73.73 ± 21.13 mg/dL to 58.70 ± 22.71 mg/dL and 28.82 ± 3.84 mg/dL, resp., P < 0.05. Additionally, renal tissue morphology improved after LMWC treatment, and accumulation of renal methylglyoxal, a damage factor associated with carbonyl stress, was reversed. These results show that LMWC prevents GM-induced renal toxicity via a carbonyl stress-dependent pathway.

  5. Proteomic candidate biomarkers of drug-induced nephrotoxicity in the rat.

    Rodney Rouse

    Full Text Available Improved biomarkers of acute nephrotoxicity are coveted by the drug development industry, regulatory agencies, and clinicians. In an effort to identify such biomarkers, urinary peptide profiles of rats treated with two different nephrotoxins were investigated. 493 marker candidates were defined that showed a significant response to cis-platin comparing a cis-platin treated cohort to controls. Next, urine samples from rats that received three consecutive daily doses of 150 or 300 mg/kg gentamicin were examined. 557 potential biomarkers were initially identified; 108 of these gentamicin-response markers showed a clear temporal response to treatment. 39 of the cisplatin-response markers also displayed a clear response to gentamicin. Of the combined 147 peptides, 101 were similarly regulated by gentamicin or cis-platin and 54 could be identified by tandem mass spectrometry. Most were collagen type I and type III fragments up-regulated in response to gentamicin treatment. Based on these peptides, classification models were generated and validated in a longitudinal study. In agreement with histopathology, the observed changes in classification scores were transient, initiated after the first dose, and generally persistent over a period of 10-20 days before returning to control levels. The data support the hypothesis that gentamicin-induced renal toxicity up-regulates protease activity, resulting in an increase in several specific urinary collagen fragments. Urinary proteomic biomarkers identified here, especially those common to both nephrotoxins, may serve as a valuable tool to investigate potential new drug candidates for the risk of nephrotoxicity.

  6. Activation of the polyol pathway may contribute to increased risk of radiocontrast agent nephrotoxicity in diabetes

    Kaplan, D.L.; Mann, P.L.; Zager, P.G.; Smith, M.A.

    1991-01-01

    The incidence of radiocontrast (RC) agent nephrotoxicity is higher in diabetic than non-diabetic patients. RC nephropathy involves both glomerular and tubular cells. The authors postulate that activation of the polyol pathway contributes to the increased susceptibility of diabetics to RC nephrotoxicity. Mesangial cells modulate GFR by altering the capillary surface area available for filtration. Toxic insult to mesangial cells can impair glomerular function. The present study was performed to determine if mesangial cells isolated from galactose fed rats, the classic model for studying the effects of polyol accumulation, demonstrate increased susceptibility to RC toxicity. A cellular model was developed to study the effects of RC agents on mesangial cells isolated from rats maintained on diets of 50% galactose (MCG) and 50% dextrin (MCD). MCG's and MCD's were plated in 96 well trays at a density of 6.25 x 10 4 cells/ml. Cells were exposed to Hypaque 90 at concentrations of 10 mM to 1 uM for 1, 2, 4 and 24 hrs. Cell viability was determined by fluorescein diacetate/propidium iodide staining. 3H-thymidine incorporation was used to determine cell proliferation rates. Hypaque 90 produced no direct cytotoxicity at any time points or concentrations tested. An increase in cell proliferation was observed 1 hr after exposure to 1 uM to 1mM Hypaque. Higher concentrations blunted cell proliferation rates. Hypaque 90 produced no direct cytotoxicity at any time points or concentrations tested. An increase in cell proliferation was observed 1 hr after exposure to 1 uM to 1mM Hypaque. Higher concentrations blunted cell proliferation. No significant effects on 3H-thymidine incorporation were observed at later time points. The effects on 3H-thymidine incorporation were more pronounced in MCG's than MCD's. Activation of the polyol pathway amplifies the proliferative response of MC to RC agents. This activation may contribute to the risk of RC nephropathy in diabetics

  7. The efficacy and nephrotoxicity associated with colistin use in an intensive care unit in Vietnam: Use of colistin in a population of lower body weight

    Nguyen Gia Binh

    2015-06-01

    Conclusion: A personalized dosing protocol of colistin was effective, with low nephrotoxicity, among critically ill Vietnamese patients with low body weight. Further studies are warranted for assessing the efficacy and toxicity in a larger cohort.

  8. Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with {sup 177}Lu-octreotate

    Sabet, Amir; Ezziddin, Khaled; Reichman, Karl; Haslerud, Torjan; Ahmadzadehfar, Hojjat; Biersack, Hans-Juergen; Ezziddin, Samer [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Pape, Ulrich-Frank [Charite, University Medicine Berlin, Campus Virchow Clinic, Department of Hepatology and Gastroenterology, Berlin (Germany); Nagarajah, James [University Hospital, Department of Nuclear Medicine, Essen (Germany)

    2014-03-15

    Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine - allowing only approximate estimates of GFR - the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement. Nephrotoxicity was analysed using {sup 99m}Tc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with {sup 177}Lu-octreotate. The mean follow-up period was 21 months (range 12-50) with a median of five GFR measurements per patient. The change of GFR was analysed by linear curve fit. Potential risk factors including diabetes mellitus, arterial hypertension, previous chemotherapy, renal impairment at baseline and cumulative administered activity were analysed regarding potential impact on renal function loss. In addition, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were used to compare nephrotoxicity determined by {sup 99m}Tc-DTPA clearance versus serum creatinine. The alteration in GFR differed widely among the patients (mean -2.1 ± 13.1 ml/min/m{sup 2} per year, relative yearly reduction -1.8 ± 18.9 %). Fifteen patients (21 %) experienced a mild (2-10 ml/min/m{sup 2} per year) and 16 patients (22 %) a significant (>10 ml/min/m{sup 2} per year) decline of GFR following PRRT. However, 11 patients (15 %) showed an increase of >10 ml/min/m{sup 2} per year. Relevant nephrotoxicity according to CTCAE (grade ≥3) was observed in one patient (1.3 %) with arterial hypertension and history of chemotherapy. Nephrotoxicity according to serum creatinine was discordant to that defined by GFR in 15 % of the assessments and led to underestimation in 12 % of

  9. Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with 177Lu-octreotate

    Sabet, Amir; Ezziddin, Khaled; Reichman, Karl; Haslerud, Torjan; Ahmadzadehfar, Hojjat; Biersack, Hans-Juergen; Ezziddin, Samer; Pape, Ulrich-Frank; Nagarajah, James

    2014-01-01

    Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine - allowing only approximate estimates of GFR - the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement. Nephrotoxicity was analysed using 99m Tc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with 177 Lu-octreotate. The mean follow-up period was 21 months (range 12-50) with a median of five GFR measurements per patient. The change of GFR was analysed by linear curve fit. Potential risk factors including diabetes mellitus, arterial hypertension, previous chemotherapy, renal impairment at baseline and cumulative administered activity were analysed regarding potential impact on renal function loss. In addition, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were used to compare nephrotoxicity determined by 99m Tc-DTPA clearance versus serum creatinine. The alteration in GFR differed widely among the patients (mean -2.1 ± 13.1 ml/min/m 2 per year, relative yearly reduction -1.8 ± 18.9 %). Fifteen patients (21 %) experienced a mild (2-10 ml/min/m 2 per year) and 16 patients (22 %) a significant (>10 ml/min/m 2 per year) decline of GFR following PRRT. However, 11 patients (15 %) showed an increase of >10 ml/min/m 2 per year. Relevant nephrotoxicity according to CTCAE (grade ≥3) was observed in one patient (1.3 %) with arterial hypertension and history of chemotherapy. Nephrotoxicity according to serum creatinine was discordant to that defined by GFR in 15 % of the assessments and led to underestimation in 12 % of patients. None of the investigated

  10. Caffeic Acid Phenethyl Ester as a Protective Agent against Nephrotoxicity and/or Oxidative Kidney Damage: A Detailed Systematic Review

    Sumeyya Akyol

    2014-01-01

    Full Text Available Caffeic acid phenethyl ester (CAPE, an active component of propolis, has been attracting the attention of different medical and pharmaceutical disciplines in recent years because of its antioxidant, anti-inflammatory, antiproliferative, cytotoxic, antiviral, antifungal, and antineoplastic properties. One of the most studied organs for the effects of CAPE is the kidney, particularly in the capacity of this ester to decrease the nephrotoxicity induced by several drugs and the oxidative injury after ischemia/reperfusion (I/R. In this review, we summarized and critically evaluated the current knowledge regarding the protective effect of CAPE in nephrotoxicity induced by several special medicines such as cisplatin, doxorubicin, cyclosporine, gentamycin, methotrexate, and other causes leading to oxidative renal injury, namely, I/R models and senility.

  11. Tempol, a Superoxide Dismutase Mimetic Agent, Ameliorates Cisplatin-Induced Nephrotoxicity through Alleviation of Mitochondrial Dysfunction in Mice

    Ahmed, Lamiaa A.; Shehata, Nagwa I.; Abdelkader, Noha F.; Khattab, Mahmoud M.

    2014-01-01

    Background Mitochondrial dysfunction is a crucial mechanism by which cisplatin, a potent chemotherapeutic agent, causes nephrotoxicity where mitochondrial electron transport complexes are shifted mostly toward imbalanced reactive oxygen species versus energy production. In the present study, the protective role of tempol, a membrane-permeable superoxide dismutase mimetic agent, was evaluated on mitochondrial dysfunction and the subsequent damage induced by cisplatin nephrotoxicity in mice. Methods and Findings Nephrotoxicity was assessed 72 h after a single i.p. injection of cisplatin (25 mg/kg) with or without oral administration of tempol (100 mg/kg/day). Serum creatinine and urea as well as glucosuria and proteinuria were evaluated. Both kidneys were isolated for estimation of oxidative stress markers, adenosine triphosphate (ATP) content and caspase-3 activity. Moreover, mitochondrial oxidative phosphorylation capacity, complexes I–IV activities and mitochondrial nitric oxide synthase (mNOS) protein expression were measured along with histological examinations of renal tubular damage and mitochondrial ultrastructural changes. Tempol was effective against cisplatin-induced elevation of serum creatinine and urea as well as glucosuria and proteinuria. Moreover, pretreatment with tempol notably inhibited cisplatin-induced oxidative stress and disruption of mitochondrial function by restoring mitochondrial oxidative phosphorylation, complexes I and III activities, mNOS protein expression and ATP content. Tempol also provided significant protection against apoptosis, tubular damage and mitochondrial ultrastructural changes. Interestingly, tempol did not interfere with the cytotoxic effect of cisplatin against the growth of solid Ehrlich carcinoma. Conclusion This study highlights the potential role of tempol in inhibiting cisplatin-induced nephrotoxicity without affecting its antitumor activity via amelioration of oxidative stress and mitochondrial dysfunction

  12. Tempol, a superoxide dismutase mimetic agent, ameliorates cisplatin-induced nephrotoxicity through alleviation of mitochondrial dysfunction in mice.

    Lamiaa A Ahmed

    Full Text Available Mitochondrial dysfunction is a crucial mechanism by which cisplatin, a potent chemotherapeutic agent, causes nephrotoxicity where mitochondrial electron transport complexes are shifted mostly toward imbalanced reactive oxygen species versus energy production. In the present study, the protective role of tempol, a membrane-permeable superoxide dismutase mimetic agent, was evaluated on mitochondrial dysfunction and the subsequent damage induced by cisplatin nephrotoxicity in mice.Nephrotoxicity was assessed 72 h after a single i.p. injection of cisplatin (25 mg/kg with or without oral administration of tempol (100 mg/kg/day. Serum creatinine and urea as well as glucosuria and proteinuria were evaluated. Both kidneys were isolated for estimation of oxidative stress markers, adenosine triphosphate (ATP content and caspase-3 activity. Moreover, mitochondrial oxidative phosphorylation capacity, complexes I-IV activities and mitochondrial nitric oxide synthase (mNOS protein expression were measured along with histological examinations of renal tubular damage and mitochondrial ultrastructural changes. Tempol was effective against cisplatin-induced elevation of serum creatinine and urea as well as glucosuria and proteinuria. Moreover, pretreatment with tempol notably inhibited cisplatin-induced oxidative stress and disruption of mitochondrial function by restoring mitochondrial oxidative phosphorylation, complexes I and III activities, mNOS protein expression and ATP content. Tempol also provided significant protection against apoptosis, tubular damage and mitochondrial ultrastructural changes. Interestingly, tempol did not interfere with the cytotoxic effect of cisplatin against the growth of solid Ehrlich carcinoma.This study highlights the potential role of tempol in inhibiting cisplatin-induced nephrotoxicity without affecting its antitumor activity via amelioration of oxidative stress and mitochondrial dysfunction.

  13. Male Infertility

    ... hypothalamus, pituitary, thyroid and adrenal glands. Low testosterone (male hypogonadism) and other hormonal problems have a number of possible underlying causes. Defects of tubules that transport sperm. Many ... syndrome — in which a male is born with two X chromosomes and one ...

  14. Nephrotoxicity of Bence-Jones proteins: interference in renal epithelial cell acidification

    Nicastri A.L.

    2002-01-01

    Full Text Available The aim of the present study was to evaluate the acidification of the endosome-lysosome system of renal epithelial cells after endocytosis of two human immunoglobulin lambda light chains (Bence-Jones proteins, BJP obtained from patients with multiple myeloma. Renal epithelial cell handling of two BJP (neutral and acidic BJP was evaluated by rhodamine fluorescence. Renal cells (MDCK were maintained in culture and, when confluent, were incubated with rhodamine-labeled BJP for different periods of time. Photos were obtained with a fluorescence microscope (Axiolab-Zeiss. Labeling density was determined on slides with a densitometer (Shimadzu Dual-Wavelength Flying-Spot Scanner CS9000. Endocytosis of neutral and acidic BJP was correlated with acidic intracellular compartment distribution using acridine orange labeling. We compared the pattern of distribution after incubation of native neutral and acidic BJP and after complete deglycosylation of BJP by periodate oxidation. The subsequent alteration of pI converted neutral BJP to acidic BJP. There was a significant accumulation of neutral BJP in endocytic structures, reduced lysosomal acidification, and a diffuse pattern of acidification. This pattern was reversed after total deglycosylation and subsequent alteration of the pI to an acidic BJP. We conclude that the physicochemical characteristics of BJP interfere with intracellular acidification, possibly explaining the strong nephrotoxicity of neutral BJP. Lysosomal acidification is fundamental for adequate protein processing and catabolism.

  15. Proximal Tubular Injury in Medullary Rays Is an Early Sign of Acute Tacrolimus Nephrotoxicity

    Diane Cosner

    2015-01-01

    Full Text Available Tacrolimus (FK506 is one of the principal immunosuppressive agents used after solid organ transplantations to prevent allograft rejection. Chronic renal injury induced by tacrolimus is characterized by linear fibrosis in the medullary rays; however, the early morphologic findings of acute tacrolimus nephrotoxicity are not well characterized. Kidney injury molecule-1 (KIM-1 is a specific injury biomarker that has been proven to be useful in the diagnosis of mild to severe acute tubular injury on renal biopsies. This study was motivated by a patient with acute kidney injury associated with elevated serum tacrolimus levels in whom KIM-1 staining was present only in proximal tubules located in the medullary rays in the setting of otherwise normal light, immunofluorescent, and electron microscopy. We subsequently evaluated KIM-1 expression in 45 protocol and 39 indicated renal transplant biopsies to determine whether higher serum levels of tacrolimus were associated with acute segment specific injury to the proximal tubule, as reflected by KIM-1 staining in the proximal tubules of the cortical medullary rays. The data suggest that tacrolimus toxicity preferentially affects proximal tubules in medullary rays and that this targeted injury is a precursor lesion for the linear fibrosis seen in chronic tacrolimus toxicity.

  16. Protective Effects of Intralipid and Caffeic Acid Phenethyl Ester on Nephrotoxicity Caused by Dichlorvos in Rats

    Muhammet Murat Celik

    2015-01-01

    Full Text Available The protective effects of Caffeic Acid Phenethyl Ester (CAPE and intralipid (IL on nephrotoxicity caused by acute Dichlorvos (D toxicity were investigated in this study. Forty-eight Wistar Albino rats were divided into 7 groups as follows: Control, D, CAPE, intralipid, D + CAPE, D + IL, and D + CAPE + IL. When compared to D group, the oxidative stress index (OSI values were significantly lower in Control, CAPE, and D + IL + CAPE groups. When compared to D + IL + CAPE group, the TOS and OSI values were significantly higher in D group (P<0.05. When mitotic cell counts were assessed in the renal tissues, it was found that mitotic cell count was significantly higher in the D group while it was lower in the D + CAPE, D + IL, and D + IL + CAPE groups when compared to the control group (P<0.05. Also, immune reactivity showed increased apoptosis in D group and low profile of apoptosis in the D + CAPE group when compared to the Control group. The apoptosis level was significantly lower in D + IL + CAPE compared to D group (P<0.05 in the kidneys. As a result, we concluded that Dichlorvos can be used either alone or in combination with CAPE and IL as supportive therapy or as facilitator for the therapeutic effect of the routine treatment in the patients presenting with pesticide poisoning.

  17. Effect of acclimation to caging on nephrotoxic response of rats to uranium.

    Damon, E G; Eidson, A F; Hobbs, C H; Hahn, F F

    1986-02-01

    Animal studies of the toxicity and metabolism of radionuclides and chemicals often require housing of rats in metabolism cages for excreta collection. Response of rats to toxic substances may be affected by environmental factors such as the type of cage used. Dose-response studies were conducted to assess the effects of two types of cages on the nephrotoxic response of rats to uranium from implanted refined uranium ore (yellowcake). The LD50/21 days was 6 mg of uranium ore per kilogram body weight (6 mg U/kg). The 95% confidence limit (C.L.) was 3-8 mg U/kg for rats housed in metabolism cages beginning on the day of implantation (naive rats). However, for rats housed in metabolism cages for 21 days before implantation (acclimated rats) the LD50/21 days was 360 mg U/kg (95% C.L. = 220-650 mg U/kg), which was the same value obtained for rats housed continuously in polycarbonate cages. This significant difference (P less than 0.01) in response of naive rats compared to response of acclimated rats appeared related to a significantly lower water consumption by the naive rats.

  18. Benfotiamine enhances antioxidant defenses and protects against cisplatin-induced DNA damage in nephrotoxic rats.

    Harisa, Gamaleldin I

    2013-08-01

    The objective of the present study was to assess superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), paraoxonase (PON1), glutathione reductase (GR), and catalase (CAT) activities ratio and their relationship with DNA oxidative damage in rats treated with cisplatin (3 mg/kg bwt/day) in the presence and absence of benfotiamine (100 mg/kg/day) for 25 days. Cisplatin-induced renal damage was evidenced by renal dysfunction and elevated oxidative stress markers. SOD activity and levels of nitric oxide, protein carbonyl, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine were significantly increased by cisplatin treatment. Moreover, the ratios of GPx/GR, SOD/GPx, SOD/CAT, and SOD/PON1 were significantly increased compared to control. In contrast, glutathione levels were significantly decreased by cisplatin treatment. Simultaneous treatment of rats with cisplatin and benfotiamine ameliorate these variables to values near to those of control rats. This study suggests that benfotiamine can prevent cisplatin-induced nephrotoxicity by inhibiting formation reactive species of oxygen and nitrogen. © 2013 Wiley Periodicals, Inc.

  19. Phellinus rimosus improves mitochondrial energy status and attenuates nephrotoxicity in diabetic rats.

    Rony, K A; Ajith, T A; Kuttikadan, Tony A; Blaze, R; Janardhanan, K K

    2017-09-26

    Mitochondrial dysfunction and increase in reactive oxygen species during diabetes can lead to pathological consequences in kidneys. The present study was aimed to investigate the effect of Phellinus rimosus in the streptozotocin (STZ)-induced diabetic rat renal mitochondria and the possible mechanism of protection. Phellinus rimosus (50 and 250 mg/kg, p.o) was treated after inducing diabetes by STZ (45 mg/kg, i.p) in rats. The serum samples were subjected to creatinine and urea estimation. Mitochondrial antioxidant status such as mitochondrial superoxide dismutase, glutathione peroxidase, and reduced glutathione; adenosine triphosphate level; and lipid peroxidation were measured. The activities of Krebs cycle enzymes such as isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase as well as mitochondrial complexes I, III, and IV in kidney mitochondria were also determined. Administration of P. rimosus (250 mg/kg b.wt) once daily for 30 days, significantly (p<0.05) enhanced the activities of Krebs cycle dehydrogenases, mitochondrial electron transport chain complexes, and ATP level. Further, P. rimosus had significantly protected the renal mitochondrial antioxidant status and lipid peroxidation. The results of the study concluded that by limiting the extent of renal mitochondrial damage in the hyperglycemic state, P. rimosus alleviated nephrotoxicity.

  20. Protective effects of Bombyx mori, quercetin and benazepril against doxorubicin induced cardiotoxicity and nephrotoxicity

    Abdul S. Nazmi

    2016-09-01

    Full Text Available The present study was conducted with the aim of evaluating the protective effects of Bombyx mori, quercetin and benazepril on doxorubicin (DXR induced cardiotoxicity and nephrotoxicity in rats. B. mori, quercetin and benazepril were administered for 7 days, and a single intravenous injection of 10 mg/kg body weight of DXR on day five. The animals were sacrificed 48 h after DXR administration. DXR produced a significant elevation in the malondialdehyde (MDA level and significantly inhibited the activity of glutathione (GSH in the heart and the kidney followed by the activity of catalase (CAT in the heart tissue with a significant rise in the serum levels of aspartate transaminase (AST, lactate dehydrogenase (LDH, blood urea nitrogen (BUN, creatinine and a reduction in serum GSH levels indicating acute cardiac toxicity. B. mori, quercetin and benazepril pretreatment significantly reduced the MDA concentration and ameliorated the inhibition of cardiac GSH and CAT activity. B. mori, quercetin and benazepril also significantly improved the serum levels of AST, LDH, BUN, creatinine and GSH in DXR-treated rats. Furthermore, histological examination of the heart sections confirmed the myocardial injury with DXR administration, and the near normal pattern with B. mori, quercetin and benazepril pretreatment. The results provide clear evidence that the B. mori, quercetin and benazepril pretreatments offer significant protection against DXR-induced enzymatic changes in serum, cardiac and renal tissue damage.

  1. Male Hypogonadism

    ... the hormone that plays a key role in masculine growth and development during puberty — or has an ... Adulthood In adult males, hypogonadism may alter certain masculine physical characteristics and impair normal reproductive function. Signs ...

  2. Male Infertility

    ... to have a baby? If treatment doesn’t work, what are our other options? Resources National Institute of Child Health and Human Development, What Causes Male Infertility? Last Updated: May 30, 2017 This ...

  3. Male contraception.

    Amory, John K

    2016-11-01

    Although female contraceptives are very effective at preventing unintended pregnancy, some women can not use them because of health conditions or side-effects, leaving some couples without effective contraceptive options. In addition, many men wish to take active responsibility for family planning. Thus, there is a great need for male contraceptives to prevent unintended pregnancies, of which 80-90 million occur annually. At present, effective male contraceptive options are condoms and vasectomy, which are not ideal for all men. Therefore, efforts are under way to develop novel male contraceptives. This paper briefly reviews the advantages and disadvantages of condoms and vasectomies and then discusses the research directed toward development of novel methods of male contraception. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  4. Condoms - male

    Prophylactics; Rubbers; Male condoms; Contraceptive - condom; Contraception - condom; Barrier method - condom ... your health care provider or pharmacy about emergency contraception ("morning-after pills"). PROBLEMS WITH CONDOM USE Some ...

  5. Male contraception

    Mathew, Vivek; Bantwal, Ganapathi

    2012-01-01

    Contraception is an accepted route for the control of population explosion in the world. Traditionally hormonal contraceptive methods have focused on women. Male contraception by means of hormonal and non hormonal methods is an attractive alternative. Hormonal methods of contraception using testosterone have shown good results. Non hormonal reversible methods of male contraception like reversible inhibition of sperm under guidanceare very promising. In this article we have reviewed the curren...

  6. Male sexuality.

    Ginsberg, Terrie B

    2010-05-01

    It should be recognized that sexuality in the aging male is of such import that a complete sexual history must be performed. By taking a complete sexual history, facts can be obtained that will allow for appropriate focus relating to a holistic evaluation and will enable us to dispel antiquated sexual myths pertaining to the aging male. If initiated by the history taker, questions concerning sexuality may be discussed more comfortably by the patient. Erectile dysfunction, male sexual response cycle, testosterone, sexually transmitted diseases, human immunodeficiency virus, long-term illness, along with religion and culture are explored in this article with the aim of improving one's knowledge base, self reflection, and awareness of the importance of male sexuality. A complete understanding and appreciation of the aging male's medical history, surgical history, social history, and emotional history as well as his sexual, cultural, and religious concepts will allow the health care provider to better analyze information, and to recommend and provide appropriate advice and treatment to the aging male patient. Copyright 2010 Elsevier Inc. All rights reserved.

  7. Stevia and stevioside protect against cisplatin nephrotoxicity through inhibition of ERK1/2, STAT3, and NF-κB activation.

    Potočnjak, Iva; Broznić, Dalibor; Kindl, Marija; Kropek, Matija; Vladimir-Knežević, Sanda; Domitrović, Robert

    2017-09-01

    We investigated the effect of natural sweetener Stevia rebaudiana and its constituent stevioside in cisplatin (CP)-induced kidney injury. Male BALB/cN mice were orally administered 10, 20, and 50 mg/kg body weight of Stevia rebaudiana ethanol extract (SE) or stevioside 50 mg/kg, 48 h after intraperitoneal administration of CP (13 mg/kg). Two days later, CP treatment resulted in histopathological changes showing kidney injury. Increased expression of 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT), and heme oxygenase-1 (HO-1) in mice kidneys suggested oxidative stress. CP treatment also increased renal expression of nuclear factor-kappaB (NF-κB) p65 subunit and phosphorylated inhibitor of NF-κB (IκBα), as well as expression of pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α). Induction of apoptosis and inhibition of the cell cycle in kidneys was evidenced by increased expression of p53, Bax, caspase-9, and p21, proteolytic cleavage of poly (ADP-ribose) polymerase (PARP), with concomitant suppression of Bcl-2 and cyclin D1 expression. The number of apoptotic cells in kidneys was also assessed. CP administration resulted in activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3). Both SE and stevioside attenuated CP nephrotoxicity by suppressing oxidative stress, inflammation, and apoptosis through mechanism involving ERK1/2, STAT3, and NF-κB suppression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Ameliorated effects of Lactobacillus delbrueckii subsp. lactis DSM 20076 and Pediococcus acidilactici NNRL B-5627 on Fumonisin B1-induced Hepatotoxicity and Nephrotoxicity in rats

    Amira A. Abdellatef

    2016-04-01

    Full Text Available Oxidative stress has been implicated in a number of human regeneration and disease processes including atherosclerosis, pulmonary fibrosis, cancer, and different neurodegenerative diseases. The aim of this study was to evaluate the protective effects of Lactobacillus delbrueckii subsp. lactis DSM 20076 (LL-DSM and Pediococcus acidilactici NNRL B-5627 (PA-NNRL against the hepatic- and nephro-toxicity of fumonisin B1 (FB1 in FB1-treated rats for an experimental period of 4-weeks. Eighty mature male Sprague-Dawley rats were divided to 12 groups: 1 untreated group; 3 groups fed by a FB1-contaminated diet (50, 100 and 200 mg FB1/kg diet, respectively; 1 group fed orally by LL-DSM (1 ml/d; 1 group fed orally by PA-NNRL (1 ml/d; 3 groups co-administered by FB1-contaminated diet and LL-DSM (1 ml/d, and 3 groups co-administered by FB1-contaminated diet and PA-NNRL (1 ml/d. Malonaldehyde (MDA nitric oxide, glutathione content, SOD activity, total antioxidant capacity (TAC, total oxidant status (TOS and oxidative stress index (OSI were determined. DPA assay was used to assess apoptosis in liver and kidney tissues. The animals fed with FB1-contaminated diet showed a significant increase in oxidative stress markers and DNA fragmentation accompanied with significant decrease in GSH content, SOD activity, and TAC in liver and kidney tissues, especially at high-dosage of FB1 (T200. Probiotics antioxidant strains (LL-DSM and PA-NNRL relatively succeeded to restore almost all parameters investigated as well as to reduce DNA fragmentation in liver and kidney tissues. As a conclusion, probiotics may induce its protective role via increasing the antioxidant capacity, inhibition of lipid peroxidation, scavenging of free radicals and decreasing DNA lesions in liver and kidney of experimental animals tested.

  9. Comparison of Protective Effect of Green Tea and Vitamin C Against Cypermethrin Induce Nephrotoxicity in Mice

    Manzoor, S.; Mehboob, K.; Naveed, A. K.

    2016-01-01

    Background: Insecticide toxicity is the problem of every person in under developed countries. It is necessary to counteract its effect by natural and cheap remedies like green tea and vitamin C. In this manner common man can also enjoy blessings of life. The current research was performed to compare the protective function of green tea and vitamin C on experimental cypermethrin provoked nephrotoxicity Method: Forty healthy Balb/C mice purchased from National Institute of Health, Islamabad, Pakistan and divided in to four groups (10 each). Group a was control which received only normal diet. Group B, group C and group D were experimental groups which were given Cypermethrin, Cypermethrin with green tea and Cypermethrin with vitamin C respectively. These groups were also given normal diet. After 1 month blood was drawn by intra-cardiac method to assess renal parameters. Results: One month research showed increase in serum urea to 6.8±.48 m.mol/l (n=3.9±.44) while green tea and vitamin C normalize them to 4.0±.83 m.mol/l and 3.4±.33 m.mol/l respectively. Serum creatinine increased to 42.90±3.28 m.mol/l (n=29.50±3.95) while green tea and vitamin C normalize them to 28.80±4.58 m.mol/l and 22.60±2.06 m.mol/l correspondingly. Conclusion The results showed that green tea and vitamin C neutralized toxicity induced by Cypermethrin in mice and their effect is comparable. (author)

  10. Exposure to nerve growth factor worsens nephrotoxic effect induced by Cyclosporine A in HK-2 cells.

    Donatella Vizza

    Full Text Available Nerve growth factor is a neurotrophin that promotes cell growth, differentiation, survival and death through two different receptors: TrkA(NTR and p75(NTR. Nerve growth factor serum concentrations increase during many inflammatory and autoimmune diseases, glomerulonephritis, chronic kidney disease, end-stage renal disease and, particularly, in renal transplant. Considering that nerve growth factor exerts beneficial effects in the treatment of major central and peripheral neurodegenerative diseases, skin and corneal ulcers, we asked whether nerve growth factor could also exert a role in Cyclosporine A-induced graft nephrotoxicity. Our hypothesis was raised from basic evidence indicating that Cyclosporine A-inhibition of calcineurin-NFAT pathway increases nerve growth factor expression levels. Therefore, we investigated the involvement of nerve growth factor and its receptors in the damage exerted by Cyclosporine A in tubular renal cells, HK-2. Our results showed that in HK-2 cells combined treatment with Cyclosporine A + nerve growth factor induced a significant reduction in cell vitality concomitant with a down-regulation of Cyclin D1 and up-regulation of p21 levels respect to cells treated with Cyclosporine A alone. Moreover functional experiments showed that the co-treatment significantly up-regulated human p21promoter activity by involvement of the Sp1 transcription factor, whose nuclear content was negatively regulated by activated NFATc1. In addition we observed that the combined exposure to Cyclosporine A + nerve growth factor promoted an up-regulation of p75 (NTR and its target genes, p53 and BAD leading to the activation of intrinsic apoptosis. Finally, the chemical inhibition of p75(NTR down-regulated the intrinsic apoptotic signal. We describe two new mechanisms by which nerve growth factor promotes growth arrest and apoptosis in tubular renal cells exposed to Cyclosporine A.

  11. Amelioration of cisplatin-induced nephrotoxicity by ethanolic extract of Bauhinia purpurea: An in vivo study in rats.

    Rana, Md Azmat; Khan, Rahat Ali; Nasiruddin, Mohammad; Khan, Aijaz Ahmed

    2016-01-01

    Our objective is to study the nephroprotective activity and antioxidant potential of Bauhinia purpurea unripe pods and bark against cisplatin-induced nephrotoxicity. Healthy adult albino rats of either sex (150-200 g) were randomly divided into six groups of six animals each Group I (vehicle control) and Group II (negative control). Group III (BBE200) and Group IV (BBE400) were administered the ethanolic extract of Bauhinia purpurea bark in doses of 200 and 400 mg/kg/day p.o., respectively, and Group V (BPE200) and Group VI (BPE400) were administered the ethanolic extract of Bauhinia purpurea unripe pods at doses of 200 and 400 mg/kg/day p.o., respectively. All the treatments were given for nine days. Cisplatin in a single dose of 6 mg/kg i.p. was given on the 4 th day to all groups, except the vehicle control group. On the 10 th day, blood and urine were collected for biochemical tests and the rats were sacrificed. The kidney was removed for histology and lipid peroxidation-antioxidant test. Cisplatin caused nephrotoxicity as evidenced by elevated blood urea, serum creatinine and urine glucose, and there was decreased creatinine clearance in Group II as compared with Group I. Administration of BBE and BPE at doses of 200 and 400 mg/kg in Group III and Group VI caused a dose-dependant reduction in the rise of blood urea, serum creatinine and urine glucose, and there was a dose-dependant increase in creatinine clearance compared with Group II. There was increased catalase and glutathione and decreased malondialdehyde levels in Group II, while BBE 400 (Group IV) and BPE 400 (Group VI) treatments significantly reversed the changes toward normal values. Histological examination of the kidney revealed protection in Group IV and Group VI compared with Group II. The ethanolic extract of Bauhinia purpurea unripe pods and bark has a nephroprotective activity against cisplatin-induced nephrotoxicity in rats.

  12. Role of biomarkers of nephrotoxic acute kidney injury in deliberate poisoning and envenomation in less developed countries.

    Mohamed, Fahim; Endre, Zoltan H; Buckley, Nicholas A

    2015-07-01

    Acute kidney injury (AKI) has diverse causes and is associated with increased mortality and morbidity. In less developed countries (LDC), nephrotoxic AKI (ToxAKI) is common and mainly due to deliberate ingestion of nephrotoxic pesticides, toxic plants or to snake envenomation. ToxAKI shares some pathophysiological pathways with the much more intensively studied ischaemic AKI, but in contrast to ischaemic AKI, most victims are young, previously healthy adults. Diagnosis of AKI is currently based on a rise in serum creatinine. However this may delay diagnosis because of the kinetics of creatinine. Baseline creatinine values are also rarely available in LDC. Novel renal injury biomarkers offer a way forward because they usually increase more rapidly in AKI and are normally regarded as absent or very low in concentration, thereby reducing the need for a baseline estimate. This should increase sensitivity and speed of diagnosis. Specificity should also be increased for urine biomarkers since many originate from the renal tubular epithelium. Earlier diagnosis of ToxAKI should allow earlier initiation of appropriate therapy. However, translation of novel biomarkers of ToxAKI into clinical practice requires better understanding of non-renal factors in poisoning that alter biomarkers and the influence of dose of nephrotoxin on biomarker performance. Further issues are establishing LDC population-based normal ranges and assessing sampling and analytical parameters for low resource settings. The potential role of renal biomarkers in exploring ToxAKI aetiologies for chronic kidney disease of unknown origin (CKDu) is a high research priority in LDC. Therefore, developing more sensitive biomarkers for early diagnosis of nephrotoxicity is a critical step to making progress against AKI and CKDu in the developing world. © 2015 The British Pharmacological Society.

  13. The effect of sulforaphane on the levels of serum cystatin-c in acetaminophen- induced nephrotoxicity in rats

    Eda Dokumacioglu

    2016-09-01

    Full Text Available Objective: The exposure of living creatures to drugs and chemicals often results in toxicity of liver and kidney. Drugs constitute an important and big part of the commu­nity and hospital-acquired kidney diseases. In this study, we investigated the effect of sulforaphane (SFN on the levels of cystatin-C and lipid peroxidation on acetamino­phen (APAP- induced nephrotoxicity in rats. Methods: Thirty-six Sprague-Dawley rats were separat­ed equally into four experimental groups: control group, SFN group, APAP group, and APAP + SFN group. In the experimental treatment groups APAP was administered oral gavage at 1 g/kg 3 h after SFN treatment in last day and, in the APAP + SFN group, SFN was administered oral gavage at a dose of 500 μg/kg exactly for three days. Rats were euthanized and sacrificed 24 h after APAP ad­ministration. Results: APAP administration showed to significant in­crease in serum BUN, creatinine, urea and LDH concen­trations as compared to the control datas indicating the induction of severe nephrotoxicity (p<0.001. SFN treat­ment significantly decreased the cystatin-C levels and lipid peroxidation compared to APAP group (p<0.05. Conclusion: The present study demonstrate that the at­tachment of SFN to the nephrotoxicity treatment protocol will be beneficial and further studies should be conducted for cystatin C which plays an important role in kidney tox­icity and disease to be routinized as a biomarker.

  14. Parp1 protects against Aag-dependent alkylation-induced nephrotoxicity in a sex-dependent manner.

    Calvo, Jennifer A; Allocca, Mariacarmela; Fake, Kimberly R; Muthupalani, Sureshkumar; Corrigan, Joshua J; Bronson, Roderick T; Samson, Leona D

    2016-07-19

    Nephrotoxicity is a common toxic side-effect of chemotherapeutic alkylating agents. Although the base excision repair (BER) pathway is essential in repairing DNA alkylation damage, under certain conditions the initiation of BER produces toxic repair intermediates that damage healthy tissues. We have shown that the alkyladenine DNA glycosylase, Aag (a.k.a. Mpg), an enzyme that initiates BER, mediates alkylation-induced whole-animal lethality and cytotoxicity in the pancreas, spleen, retina, and cerebellum, but not in the kidney. Cytotoxicity in both wild-type and Aag-transgenic mice (AagTg) was abrogated in the absence of Poly(ADP-ribose) polymerase-1 (Parp1). Here we report that Parp1-deficient mice expressing increased Aag (AagTg/Parp1-/-) develop sex-dependent kidney failure upon exposure to the alkylating agent, methyl methanesulfonate (MMS), and suffer increased whole-animal lethality compared to AagTg and wild-type mice. Macroscopic, histological, electron microscopic and immunohistochemical analyses revealed morphological kidney damage including dilated tubules, proteinaceous casts, vacuolation, collapse of the glomerular tuft, and deterioration of podocyte structure. Moreover, mice exhibited clinical signs of kidney disease indicating functional damage, including elevated blood nitrogen urea and creatinine, hypoproteinemia and proteinuria. Pharmacological Parp inhibition in AagTg mice also resulted in sensitivity to MMS-induced nephrotoxicity. These findings provide in vivo evidence that Parp1 modulates Aag-dependent MMS-induced nephrotoxicity in a sex-dependent manner and highlight the critical roles that Aag-initiated BER and Parp1 may play in determining the side-effects of chemotherapeutic alkylating agents.

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

    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.

  16. Male baldness.

    Clarke, Philip

    2016-04-01

    Male baldness is very common. Its effect on individuals is extremely variable, and in some people it will have a significant adverse effect on their quality of life. The objectives of this article are to help general practitioners (GPs) be aware of potential health problems related to male baldness, to have an approach to assessing hair loss and to be aware of treatment options. Male baldness is, most often, a normal occurrence, but it may have significant effects on a man's health. It may also be a pointer to other potential health issues. The GP is in the ideal position to conduct an initial evaluation, consider other health issues and advise on treatment options.

  17. Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection

    Sahu, Bidya Dhar [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Tatireddy, Srujana [National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037 (India); Koneru, Meghana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Borkar, Roshan M. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Kumar, Jerald Mahesh [CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad 500 007 (India); Kuncha, Madhusudana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Srinivas, R. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Shyam Sunder, R. [Faculty of Pharmacy, Osmania University, Hyderabad 500 007 (India); Sistla, Ramakrishna, E-mail: sistla@iict.res.in [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India)

    2014-05-15

    Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in

  18. P2X7 receptor blockade protects against cisplatin-induced nephrotoxicity in mice by decreasing the activities of inflammasome components, oxidative stress and caspase-3

    Zhang, Yuanyuan; Yuan, Fahuan; Cao, Xuejiao [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China); Zhai, Zhifang [Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Gang Huang [Department of Medical Genetics, Third Military Medical University, Chongqing 430038 (China); Du, Xiang; Wang, Yiqin; Zhang, Jingbo; Huang, Yunjian; Zhao, Jinghong [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China); Hou, Weiping, E-mail: hwp0518@aliyun.com [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China)

    2014-11-15

    Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. The purinergic 2X7 receptor (P2X7R) plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the expression of P2X7R in cisplatin-induced nephrotoxicity in C57BL/6 mice, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after P2X7R blockade in vivo using an antagonist A-438079. Moreover, we measured the changes of nod-like receptor family, pyrin domain containing proteins (NLRP3) inflammasome components, oxidative stress, and proapoptotic genes in renal tissues in cisplatin-induced nephrotoxicity after treatment with A-438079. We found that the expression of P2X7R was significantly upregulated in the renal tubular epithelial cells in cisplatin-induced nephrotoxicity compared with that of the normal control group. Furthermore, pretreatment with A-438079 markedly attenuated the cisplatin-induced renal injury while lightening the histological damage, inflammatory response and apoptosis in renal tissue, and improved the renal function. These effects were associated with the significantly reduced levels of NLRP3 inflammasome components, oxidative stress, p53 and caspase-3 in renal tissues in cisplatin-induced nephrotoxicity. In conclusions, our studies suggest that the upregulated activity of P2X7R might play important roles in the development of cisplatin-induced nephrotoxicity, and P2X7R blockade might become an effective therapeutic strategy for this disease. - Highlights: • The P2X7R expression was markedly upregulated in cisplatin-induced nephrotoxicity. • P2X7R blockade significantly attenuated the cisplatin-induced renal injury. • P2X7R blockade reduced activities of NLRP3 inflammasome components in renal tissue. • P2X7R blockade

  19. Gene expression analysis reveals new possible mechanisms of vancomycin-induced nephrotoxicity and identifies gene markers candidates.

    Dieterich, Christine; Puey, Angela; Lin, Sylvia; Lyn, Sylvia; Swezey, Robert; Furimsky, Anna; Fairchild, David; Mirsalis, Jon C; Ng, Hanna H

    2009-01-01

    Vancomycin, one of few effective treatments against methicillin-resistant Staphylococcus aureus, is nephrotoxic. The goals of this study were to (1) gain insights into molecular mechanisms of nephrotoxicity at the genomic level, (2) evaluate gene markers of vancomycin-induced kidney injury, and (3) compare gene expression responses after iv and ip administration. Groups of six female BALB/c mice were treated with seven daily iv or ip doses of vancomycin (50, 200, and 400 mg/kg) or saline, and sacrificed on day 8. Clinical chemistry and histopathology demonstrated kidney injury at 400 mg/kg only. Hierarchical clustering analysis revealed that kidney gene expression profiles of all mice treated at 400 mg/kg clustered with those of mice administered 200 mg/kg iv. Transcriptional profiling might thus be more sensitive than current clinical markers for detecting kidney damage, though the profiles can differ with the route of administration. Analysis of transcripts whose expression was changed by at least twofold compared with vehicle saline after high iv and ip doses of vancomycin suggested the possibility of oxidative stress and mitochondrial damage in vancomycin-induced toxicity. In addition, our data showed changes in expression of several transcripts from the complement and inflammatory pathways. Such expression changes were confirmed by relative real-time reverse transcription-polymerase chain reaction. Finally, our results further substantiate the use of gene markers of kidney toxicity such as KIM-1/Havcr1, as indicators of renal injury.

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

    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.

  1. Kidney-on-a-Chip: a New Technology for Predicting Drug Efficacy, Interactions, and Drug-induced Nephrotoxicity.

    Lee, Jeonghwan; Kim, Sejoong

    2018-03-08

    The kidneys play a pivotal role in most drug-removal processes and are important when evaluating drug safety. Kidney dysfunction resulting from various drugs is an important issue in clinical practice and during the drug development process. Traditional in vivo animal experiments are limited with respect to evaluating drug efficacy and nephrotoxicity due to discrepancies in drug pharmacokinetics and pharmacodynamics between humans and animals, and static cell culture experiments cannot fully reflect the actual microphysiological environment in humans. A kidney-on-a-chip is a microfluidic device that allows the culture of living renal cells in 3-dimensional channels and mimics the human microphysiological environment, thus simulating the actual drug filtering, absorption, and secretion process.. In this review, we discuss recent developments in microfluidic culturing technique and describe current and future kidney-on-a-chip applications. We focus on pharmacological interactions and drug-induced nephrotoxicity, and additionally discuss the development of multi-organ chips and their possible applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. A novel approach to contrast-induced nephrotoxicity: the melatonergic agent agomelatine

    Karaman, Adem; Diyarbakir, Busra; Kose, Duygu; Özbek-Bilgin, Asli; Topcu, Atilla; Gundogdu, Cemal; Durur-Karakaya, Afak; Bayraktutan, Zafer; Alper, Fatih

    2016-01-01

    Objective: To study the potential nephroprotective role of agomelatine in rat renal tissue in cases of contrast-induced nephrotoxicity (CIN). The drug's action on the antioxidant system and proinflammatory cytokines, superoxide dismutase (SOD) activity, levels of glutathione (GSH) and malondialdehyde (MDA) and the gene expression of interleukin-6 (IL-6), tumour necrosis factor (TNF)-α and nuclear factor kappa B (NF-κB) was measured. Tubular necrosis and hyaline and haemorrhagic casts were also histopathologically evaluated. Methods: The institutional ethics and local animal care committees approved the study. Eight groups of six rats were put on the following drug regimens: Group 1: healthy controls, Group 2: GLY (glycerol), Group 3: CM (contrast media—iohexol 10 ml kg−1), Group 4: GLY+CM, Group 5: CM+AGO20 (agomelatine 20 mg kg−1), Group 6: GLY+CM+AGO20, Group 7: CM+AGO40 (agomelatine 40 mg kg−1) and Group 8: GLY+CM+AGO40. The groups were evaluated by one-way analysis of variance and Duncan's multiple comparison test. Results: Agomelatine administration significantly improved the serum levels of blood urea nitrogen (BUN) and creatinine, SOD activity, GSH and MDA. The use of agomelatine had substantial downregulatory consequences on TNF-α, NF-κB and IL-6 messenger RNA levels. Mild-to-severe hyaline and haemorrhagic casts and tubular necrosis were observed in all groups, except in the healthy group. The histopathological scores were better in the agomelatine treatment groups. Conclusion: Agomelatine has nephroprotective effects against CIN in rats. This effect can be attributed to its properties of reducing oxidative stress and inhibiting the secretion of proinflammatory cytokines (NF-κB, TNF-α and IL-6). Advances in knowledge: CIN is one of the most important adverse effects of radiological procedures. Renal failure, diabetes, malignancy, old age and non-steroidal anti-inflammatory drug use pose the risk of CIN in patients. Several

  3. Oleic acid loading does not add to the nephrotoxic effect of albumin in an amphibian and chronic rat model of kidney injury

    van Timmeren, Mirjan M.; Gross, Marie-Luise; Hanke, Wilfried; Klok, Pieter A.; van Goor, Harry; Stegeman, Coen A.; Bakker, Stephan J. L.

    2008-01-01

    Background. Under proteinuric conditions, ultrafiltrated albumin can induce an inflammatory and fibrotic response in proximal tubular cells. It is unclear whether albumin per se or compounds bound to albumin are nephrotoxic. Some studies have supported the toxicity of albumin-bound fatty acids;

  4. Antioxidantes da dieta como inibidores da nefrotoxicidade induzida pelo antitumoral cisplatina Dietary antioxidants as inhibitors of cisplatin-induced nephrotoxicity

    Lusânia Maria Greggi Antunes

    2004-03-01

    Full Text Available A cisplatina é uma droga antineoplásica altamente efetiva contra vários tipos de cânceres humanos, tais como tumores do testículo e ovário, câncer da cabeça e pescoço e câncer do pulmão. Entretanto, a nefrotoxicidade é um dos principais efeitos colaterais da terapia com a cisplatina. A gravidade da nefrotoxicidade induzida pela cisplatina está relacionada com a concentração de platina nos rins. As evidências mostram que a nefrotoxicidade induzida pela cisplatina é atribuída ao dano oxidativo resultante da geração de radicais livres, e que a administração de antioxidantes é eficiente na inibição destes efeitos colaterais. Uma abordagem alternativa para proteger os roedores dos efeitos colaterais da cisplatina é o uso de conhecidos antioxidantes da dieta. Alguns estudos têm sido realizados para diminuir a peroxidação lipídica e os efeitos citotóxicos induzidos pela cisplatina, com o emprego de antioxidantes da dieta, tais como, selenito de sódio, vitaminas C e E, curcumina e o carotenóide bixina. Nós sugerimos que aqueles antioxidantes da dieta têm efeito nefroprotetor, e que os mecanismos antioxidantes destes compostos deveriam ser explorados durante a quimioterapia com a cisplatina.Cisplatin is a highly effective antineoplastic drug used against several types of human cancers, such as testicular and ovarian tumors; head and neck; and lung cancer. However, nephrotoxicity is one of the most important side-effects of cisplatin therapy. The severity of cisplatin nephrotoxicity is related to platinum concentration in the kidneys. There is a growing amount of evidence that cisplatin-induced nephrotoxicity is ascribed to oxidative damage resulting from free radical generation and that the administration of antioxidants is efficient in inhibiting these side effects. An alternative approach aiming to protect rodents against cisplatin side-effects is the introduction of known dietary antioxidants. Some studies have been

  5. Investigations on the nephrotoxicity and hepatotoxicity of trivalent and hexavalent chromium compounds.

    Dartsch, P C; Hildenbrand, S; Kimmel, R; Schmahl, F W

    1998-09-01

    In contrast to trivalent chromium (Cr(III)) compounds, hexavalent chromium ((Cr(VI)) compounds are oxidizing agents capable of directly inducing tissue damage and possessing carcinogenic, mutagenic and teratogenic potency. After oral or dermal absorption of Cr(VI), the kidney is the main target organ for chromium accumulation, which might result in acute tubular necrosis in humans. In contrast, an acute toxic effect of Cr(VI) on the liver has not yet been described. Therefore, we used two established epithelial cell lines from the kidney (Opossum kidney cells) and the liver (Hep G2 cells) to design an in vitro-assay which is able to examine acute toxic effects of chromium compounds. Cells of both cell lines were treated with various concentrations of Cr(III) and Cr(VI) ranging from 0.01 micromol/l to 1 mmol/l for 24 h. Thereafter, cell morphology, organization of the intracellular cytoskeleton, number of viable cells and mean cell volume were examined. The results show that Cr(VI), but not Cr(III), has an acute cytotoxic effect and causes a dose-dependent loss in cell viability. The effective dose that caused 50% of cell death was 5 micromol/l for kidney epithelial cells and 50 micromol/l for liver epithelial cells. This means that kidney epithelial cells are 10 times more sensitive towards Cr(VI) treatment than liver epithelial cells and this might explain the known nephrotoxicity in vivo. The loss in cell viability was accompanied by a rounding and detachment of the cells and a marked reduction of intracellular F-actin-containing stress fibers. Microtubules and intermediate-sized filaments were observed to be unaffected. Only in the case of kidney epithelial cells, a dose-dependent cell volume increase was observed after Cr(VI) treatment at concentrations up to 50 micromol/l. At higher concentrations, the cell volume decreased due to the high number of cells undergoing lysis and the appearance of cellular fragments. Various chloride channel blockers with

  6. A Study of the Nephrotoxicity and Metabolism of Tetralin and Indan in Fischer 344 Rats.

    1988-02-08

    that 19,700 Americans, approximately two-thirds of them male, would develop renal cancer and 8,900 would die from the disease . The relevance of...pathologic evaluations. "Old-rat nephropathy" is a common degenerative kidney disease predominantly seen in the male rat. By careful examination of tissues...been performed with n-hexane and n-heptane to characterize their metabolism and role in neurotoxicity (Perbellini et al., 1982; Bahima et al., 1984

  7. Attenuation of gentamycin-induced nephrotoxicity in rats by dietary inclusion of ginger (Zingiber officinale) and turmeric (Curcuma longa) rhizomes.

    Ademiluyi, Adedayo O; Oboh, Ganiyu; Ogunsuyi, Opeyemi B; Akinyemi, Ayodele J

    2012-10-01

    This study sought to investigate the modulatory effects of dietary inclusion of ginger (Zingiber officinale) and turmeric (Curcuma longa) rhizomes on antioxidant status and renal damage induced by gentamycin in rats. Renal damage was induced in albino rats pretreated with dietary inclusion of ginger and turmeric (2% and 4%) by intraperitoneal (i.p.) administration of gentamycin (100 mg/kg body weight) for three days. Assays for renal damage biomarkers (plasma creatinine, plasma urea, blood urea nitrogen and plasma uric acid), malondialdehyde (MDA) content and reduced glutathione (GSH) content as well as renal antioxidant enzymes (catalase, glutathione-S-transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD)) were carried out. The study revealed significant (p turmeric rhizome (2% and 4%) prior to gentamycin administration significantly (p turmeric rhizomes may protect against gentamycin-induced nephrotoxicity and oxidative stress.

  8. Assessment of hepatotoxic and nephrotoxic effects of occupational exposure to unleaded gasoline: A study in shiraz petrol stations

    M. Neghab

    2014-09-01

    Full Text Available Introduction: Gasoline is a complex mixture of more than 500 various hydrocarbons. The elimination of lead from petrol has been associated with the production of significant amounts of hepatotoxic and nephrotoxic monocyclic aromatic hydrocarbons such as benzene, toluene and xylene (BTX. The main purpose of this study was to ascertain whether or not exposure to unleaded petrol, under normal working conditions, is associated with any hepatotoxic or nephrotoxic response. .Materials and Methods: This was a retrospective cohort study in which 200 subjects with current exposure to unleaded petrol working in Shiraz petrol stations as well as 200 unexposed employees were investigated. Using standard methods, atmospheric concentrations of BTX were measured. Additionally, blood and urine samples were taken from subjects for routine biochemical tests of kidney and liver function. .Results: The geometric means of airborne concentrations of BTX were found to be 0.24, 0.37 and 0.64 ppm, respectively. The result of blood chemistry tests showed that means of direct bilirubin, ALT, AST, urea and plasma creatinine were significantly higher in exposed subjects than in unexposed employees, although all of these parameters were in the normal range. Conversely, serum albumin, total protein and serum concentration of calcium and sodium were significantly lower in petrol station workers than in their unexposed counterparts. .Conclusions: The average exposure of petrol station workers to BTX is lower than the current TLVs for these chemicals. However, clinical significance and long-term results of observed changes in liner and kidney of exposed workers needs more evident in comparison with unexposed group.

  9. Intragastric exposure to titanium dioxide nanoparticles induced nephrotoxicity in mice, assessed by physiological and gene expression modifications

    2013-01-01

    Background Numerous studies have demonstrated that titanium dioxide nanoparticles (TiO2 NPs) induced nephrotoxicity in animals. However, the nephrotoxic multiple molecular mechanisms are not clearly understood. Methods Mice were exposed to 2.5, 5 and 10 mg/kg TiO2 NPs by intragastric administration for 90 consecutive days, and their growth, element distribution, and oxidative stress in kidney as well as kidney gene expression profile were investigated using whole-genome microarray analysis technique. Results Our findings suggest that TiO2 NPs resulted in significant reduction of renal glomerulus number, apoptosis, infiltration of inflammatory cells, tissue necrosis or disorganization of renal tubules, coupled with decreased body weight, increased kidney indices, unbalance of element distribution, production of reactive oxygen species and peroxidation of lipid, protein and DNA in mouse kidney tissue. Furthermore, microarray analysis showed significant alterations in the expression of 1, 246 genes in the 10 mg/kg TiO2 NPs-exposed kidney. Of the genes altered, 1006 genes were associated with immune/inflammatory responses, apoptosis, biological processes, oxidative stress, ion transport, metabolic processes, the cell cycle, signal transduction, cell component, transcription, translation and cell differentiation, respectively. Specifically, the vital up-regulation of Bcl6, Cfi and Cfd caused immune/ inflammatory responses, the significant alterations of Axud1, Cyp4a12a, Cyp4a12b, Cyp4a14, and Cyp2d9 expression resulted in severe oxidative stress, and great suppression of Birc5, Crap2, and Tfrc expression led to renal cell apoptosis. Conclusions Axud1, Bcl6, Cf1, Cfd, Cyp4a12a, Cyp4a12b, Cyp2d9, Birc5, Crap2, and Tfrc may be potential biomarkers of kidney toxicity caused by TiO2 NPs exposure. PMID:23406204

  10. The ameliorative effects of virgin olive oil and olive leaf extract on amikacin-induced nephrotoxicity in the rat.

    Abdel-Gayoum, Abdelgayoum A; Al-Hassan, Abdelrahman A; Ginawi, Ibrahim A; Alshankyty, Ibraheem M

    2015-01-01

    Amikacin is an important antibiotic, and its use is limited because of the induced nephrotoxicity. Thus, search for natural and synthetic agents that can moderate amikacin toxicity never stopped. The present study aims to investigate the possible ameliorative effects of virgin olive oil and olive leaf extract against the amikacin-induced nephrotoxicity in rat. 48 rats were distributed into 6 groups: 1-Animals of control (C) group were injected intraperitoneally (ip) with saline, 2-(AK); injected ip with amikacin {300 mg/kg/day for 12days}, 3-(OO) group: given olive oil {7 ml/kg/day for 16days}, 4-(OOAK) group: given olive oil as in OO and amikacin for 12days, 5-(OL) group: given olive leaf extract {50 mg/kg/day for 16days}, 6-(OLAK) group: given leaf extract as in OL and amikacin for 12days. Animals were fasted and sacrificed. Serum was used for biochemical analysis and kidneys for histopathology. Serum urea and creatinine were significantly ( P  groups. Serum uric acid was reduced in AK by 45.29%. Kidneys from AK showed necrosis, whereas, those from OOAK and OLAK showed mild histology. The serum triglyceride was decreased by 17.8% in OL, by 37.02% in OOAK and by 31.48% in OLAK. The calculated amikacin effect showed a significant positive correlation with urea ( r  = 0.521, P  = 0.0004), and a negative correlation with uric acid ( r  = ⿿ 0.58, P  virgin olive oil and by olive leaf extract. Amikacin did not cause dyslipidemia but reduced serum uric acid.

  11. Nephrotoxicity of Bence-Jones proteins: correlation with endocytosis by BHK cells and intracellular movement

    Ana Lucia Nicastri

    2001-06-01

    Full Text Available The aim of this investigation was to evaluate the endocytosis of two Bence-Jones proteins by renal cells in order to elucidate the interference of their physical and chemical characteristics on nephrotoxicity. Bence-Jones proteins (AK and GL were purified and isolated from the urine of two patients with multiple myeloma. The isotype of both proteins was characterised as being human monoclonal lambda light chain. The AK protein presented mainly an Ip>7.0, a high content of galactose and a low amount of sialic acid molecules. On the other hand, the GL protein presented a single band with an Ip of 4.3, a higher level of sialic acid and a reduced amount of galactose, in comparison with the AK protein. Baby Hamster Kidney (BHK cells were maintained in culture in bottles at 37ºC, using DMEM culture media supplemented with 10% of calf serum with a pH of 7.4. Once the monolayer was observed to be confluent, the BHK cells were incubated with the two proteins, dissolved in a serum-free medium for 1, 5, 15, 30, 60 minutes and 24 hours. Control cells were established omitting the incubation with Bence-Jones proteins, but maintaining all of the other conditions. After, this the cells were washed, trypsinised, centrifuged and fixed in a solution of 4% paraformaldehyde and 0.5% glutaraldehyde on a 0.1 M, pH 7.4 phosphate buffer. Cells were processed for immunocytochemical reactions by using protein A coupled with colloidal gold and further silver enhancement. Semi-thin sections of the pellets were obtained and submitted to the cytochemical reactions. Detection of labelling was made by using light microscopy. It was observed that GL protein tended to be directed towards a perinuclear position, whereas the AK protein tended to suffer lysosomal deviation, suggesting that there is a direct contribution of physical and chemical characteristics on intracellular direction taken by Bence-Jones proteins.O objetivo deste trabalho foi avaliar a endocitose de duas prote

  12. Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin–cadmium induced diabetic nephrotoxic rats

    Kandasamy, Neelamegam; Ashokkumar, Natarajan

    2014-01-01

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)–cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ–Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ–Cd induced diabetic nephrotoxic rats. - Highlights: • Diabetic rats are more susceptible to cadmium nephrotoxicity. • Cadmium plays as a cumulative

  13. Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin–cadmium induced diabetic nephrotoxic rats

    Kandasamy, Neelamegam; Ashokkumar, Natarajan, E-mail: npashokkumar1@gmail.com

    2014-09-01

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)–cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ–Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ–Cd induced diabetic nephrotoxic rats. - Highlights: • Diabetic rats are more susceptible to cadmium nephrotoxicity. • Cadmium plays as a cumulative

  14. Antioxidant and anti-inflammatory effects of virgin coconut oil supplementation abrogate acute chemotherapy oxidative nephrotoxicity induced by anticancer drug methotrexate in rats.

    Famurewa, Ademola C; Aja, Patrick M; Maduagwuna, Ekenechukwu K; Ekeleme-Egedigwe, Chima A; Ufebe, Odomero G; Azubuike-Osu, Sharon O

    2017-12-01

    Methotrexate (MTX) is an efficacious anticancer agent constrained in clinical use due to its toxicity on non-targeted tissue, a considerable source of worry to clinicians. Because the toxicity is associated with oxidative stress and inflammation, the study explored antioxidant and anti-inflammatory effect of virgin coconut oil (VCO) supplementation in nephrotoxicity induced by MTX in rats. Rats were randomized into 4 groups (n=6) as follows: Control group; MTX group injected with single dose of MTX (20mg/kg, ip) on day 14; VCO (5%)+MTX and VCO (15%)+MTX groups were pre-treated with VCO diet and injected with single dose of MTX (20mg/kg, ip) on day 14. After 3 days of MTX injection, serum kidney markers, renal activities of antioxidant enzymes and glutathione (GSH) content were determined. Lipid peroxidation level and inflammatory markers- interleukin-6 (IL-6), nitric oxide (NO) and C-reactive protein (CRP) were estimated in kidney. Histopathological alterations were examined for kidney damage. MTX nephrotoxicity was evidenced by markedly elevated serum renal markers along with significant decreases in renal GSH and activities of antioxidant enzymes confirmed by histopathology. Lipid peroxidation level, IL-6, NO and CRP markedly increased compared to control. VCO supplementation prior to MTX injection attenuated MTX-induced oxidative nephrotoxicity via prominent increases in GSH and antioxidant enzyme activities in a dose-dependent manner. The renal inflammatory markers and MDA depleted considerably compared to MTX control group. Histopathological alterations were mitigated to confirm the biochemical indices. VCO supplementation demonstrates nephroprotective activity by attenuating MTX oxidative nephrotoxicity via antioxidant and anti-inflammatory activities in kidney. Our results suggested that VCO may benefit cancer patients on MTX chemotherapy against kidney injury. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Alteration in cellular viability, pro-inflammatory cytokines and nitric oxide production in nephrotoxicity generation by Amphotericin B: involvement of PKA pathway signaling.

    França, F D; Ferreira, A F; Lara, R C; Rossoni, J V; Costa, D C; Moraes, K C M; Tagliati, C A; Chaves, M M

    2014-12-01

    Amphotericin B is one of the most effective antifungal agents; however, its use is often limited owing to adverse effects, especially nephrotoxicity. The purpose of this study was to evaluate the effect of inhibiting the PKA signaling pathway in nephrotoxicity using Amphotericin B from the assessment of cell viability, pro-inflammatory cytokines and nitric oxide (NO) production in LLC-PK1 and MDCK cell lines. Amphotericin B proved to be cytotoxic for both cell lines, as assessed by the mitochondrial enzyme activity (MTT) assay; caused DNA fragmentation, determined by flow cytometry using the propidium iodide (PI) dye; and activated the PKA pathway (western blot assay). In MDCK cells, the inhibition of the PKA signaling pathway (using the H89 inhibitor) caused a significant reduction in DNA fragmentation. In both cells lines the production of interleukin-6 (IL)-6 proved to be a dependent PKA pathway, whereas tumor necrosis factor-alpha (TNF-α) was not influenced by the inhibition of the PKA pathway. The NO production was increased when cells were pre-incubated with H89 followed by Amphotericin B, and this production produced a dependent PKA pathway in LLC-PK1 and MDCK cells lines. Therefore, considering the present study's results as a whole, it can be concluded that the inhibition of the PKA signaling pathway can aid in reducing the degree of nephrotoxicity caused by Amphotericin B. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Evaluation of the protective effect of agmatine against cisplatin nephrotoxicity with 99mTc-DMSA renal scintigraphy and cystatin-C.

    Salihoglu, Yavuz Sami; Elri, Tarik; Gulle, Kanat; Can, Murat; Aras, Mustafa; Ozacmak, Hale Sayan; Cabuk, Mehmet

    2016-10-01

    The aim of the current study was to investigate whether agmatine (AGM) has a protective effect against cisplatin-induced nephrotoxicity. Thirty-two rats were randomly divided into four groups: (1) Saline (control); (2) Cisplatin (CDDP; 7.5 mg/kg intraperitoneally); (3) Agmatine (AGM; 10 mg/kg intraperitoneally); (4) Cisplatin plus agmatine (CDDP + AGM). Agmatine was given before and two consecutive days after cisplatin injection. All the animals underwent renal scintigraphy with 99mTc-DMSA. The levels of serum creatinine, cystatin C, and blood urea nitrogen (BUN) were measured in addition to examination of the tissue samples with light microscopy. Acute renal injury was assessed with biochemical analyses, scintigraphic imaging, and histopathological evaluation. In the cisplatin group, the levels of BUN, creatinine, and cystatin C were significantly higher than that of the controls. Histopathological examination showed remarkable damage of tubular and glomerular structures. Additionally, cisplatin caused markedly decreased renal 99mTc-DMSA uptake. AGM administration improved renal functions. Serum creatinine, BUN, and cystatin C levels had a tendency to normalize and, scintigraphic and histopathological findings showed significantly less evidence of renal toxicity than those observed in animals receiving cisplatin alone. Our data indicate that AGM has a protective effect against cisplatin-induced nephrotoxicity. Therefore, it may improve the therapeutic index of cisplatin. In addition, the early renal damage induced by cisplatin and protective effects of AGM against cisplatin nephrotoxicity was accurately demonstrated with 99mTc-DMSA renal scintigraphy.

  17. S-Allylmercaptocysteine Attenuates  Cisplatin-Induced Nephrotoxicity through  Suppression of Apoptosis, Oxidative Stress, and  Inflammation.

    Zhu, Xiaosong; Jiang, Xiaoyan; Li, Ang; Zhao, Zhongxi; Li, Siying

    2017-02-20

    Cisplatin is a potent chemotherapeutic agent, but its clinical usage is limited by nephrotoxicity. S-allylmercaptocysteine (SAMC), one of the water-soluble organosulfur garlic derivatives, has antioxidant and anti-inflammatory properties and plays an important role in protecting cells from apoptosis. This study aims to examine the protective effects of SAMC on cisplatin nephrotoxicity and to explore the mechanism of its renoprotection. Rats were treated with cisplatin with or without pre-treatment with SAMC. Renal function, histological change, oxidative stress markers and antioxidant enzyme activities were investigated. Apoptotic marker, nuclearfactor (NF)-κB activity, expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase 1 (NQO1) and inflammatory cytokines were also examined. The effect of SAMC on cell viability and apoptosis was examined in cultured human kidney (HK-2) cells. SAMC was confirmed to significantly attenuate cisplatin-induced renal damage by using histological pathology and molecular biological method. Pre-treatment with SAMC reduced NF-κB activity, up-regulated Nrf2 and NQO1 expression and down-regulated inflammatory cytokine levels after cisplatin administration. Cisplatin-induced apoptosis in HK-2 cells was significantly attenuated by SAMC. Thus our results suggest that SAMC could be a potential therapeutic agent in the treatment of the cisplatin-induced nephrotoxicity through its anti-apoptotic, anti-oxidant and anti-inflammatory effects.

  18. Comparison of Rates of Nephrotoxicity Associated with Vancomycin in Combination with Piperacillin-Tazobactam Administered as an Extended versus Standard Infusion.

    Mousavi, Mariam; Zapolskaya, Tanya; Scipione, Marco R; Louie, Eddie; Papadopoulos, John; Dubrovskaya, Yanina

    2017-03-01

    Despite recent reports of relatively high rates (16-37%) of acute kidney injury (AKI) in patients receiving the combination of intravenous piperacillin-tazobactam (PTZ) and vancomycin, data are limited evaluating the impact of PTZ infusion strategy on the occurrence of nephrotoxicity. The objective of this study was to compare the rates of nephrotoxicity in patients receiving vancomycin in combination with PTZ administered as an extended infusion (EI) versus a standard infusion (SI). Single-center, retrospective, matched-cohort study. Large academic tertiary care hospital. Two hundred eighty adults with a creatinine clearance (CrCl) of 40 ml/minute or higher who received at least 96 hours of vancomycin plus PTZ EI (140 patients) or vancomycin plus PTZ SI (140 patients) between January 1, 2009, and December 31, 2011, and between January 1, 2013, and December 31, 2014 (year 2012 was skipped due the closure of inpatient units following Superstorm Sandy); 48 patients in each group were admitted to the intensive care unit. The median age of all patients was 67 (interquartile range [IQR] 54-77) years, and CrCl was 75 (IQR 55-107) ml/minute. Nephrotoxicity was assessed by the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN) criteria. Rates of AKI, according to these criteria, were similar between groups: 17.9% versus 17.1% (p=1) and 32.9% versus 29.3% (p=0.596) for the PTZ EI and PTZ SI groups, respectively. When controlling for residual differences between groups in a conditional logistic regression analysis, no association was observed between receipt of PTZ EI and RIFLE-defined AKI (odds ratio 0.522, 95% confidence interval 0.043-6.295, p=0.609). Time to onset of nephrotoxicity was 4 (IQR 3-6) days, with no significant difference noted between groups (p=0.887). Our findings suggest a similar rate of nephrotoxicity between patients who received vancomycin in combination with PTZ EI versus PTZ SI. These results need

  19. The role of magnesium supplementation in cisplatin-induced nephrotoxicity in a rat model: No nephroprotectant effect

    Farzaneh Ashrafi

    2012-01-01

    Results: All CP-treated animals lost weight, and the percentage of weight loss in Group 1 (low dose Mg sulfate treated was significantly higher compared with the positive control group (Group 4, P < 0.05. The increase in blood urea nitrogen (BUN and creatinine (Cr levels in serum in Group 1 were more than those in other groups ( P < 0.05. No statistical differences were observed in serum magnesium, nitrite, and total protein levels among the groups. The kidney tissue damage in Groups 1-3 was not significantly different when compared with Group 4. Moreover, the kidney and testis weights in Group 1 were significantly greater than those in the positive control group (P < 0.05. Conclusion: Regarding the BUN and Cr levels in the serum, kidneys weight, and the histopathological study, the low dose of Mg supplementation intensifies kidney toxicity and renal dysfunction in CP-induced nephrotoxicity in the rat model. However, the protective role of Mg with moderate and high doses is not certain.

  20. Luteolin ameliorates cisplatin-induced nephrotoxicity in mice through inhibition of platinum accumulation, inflammation and apoptosis in the kidney

    Domitrović, Robert; Cvijanović, Olga; Pugel, Ester Pernjak; Zagorac, Gordana Blagojević; Mahmutefendić, Hana; Škoda, Marko

    2013-01-01

    The aim of this study was to investigate the effects of flavone luteolin against cisplatin (CP)-induced kidney injury in mice. Luteolin at doses of 10 mg/kg was administered intraperitoneally (ip) once daily for 3 days following single CP (10 or 20 mg/kg) ip injection. Mice were sacrificed 24 h after the last dose of luteolin. The CP treatment significantly increased serum creatinine and blood urea nitrogen and induced pathohistological changes in the kidneys. Renal oxidative/nitrosative stress was evidenced by decreased glutathione (GSH) levels and increased 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) formation as well as cytochrome P450 2E1 (CYP2E1) expression. The CP administration triggered inflammatory response in mice kidneys through activation of nuclear factor-kappaB (NF-κB) and overexpression of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2). Simultaneously, the increase in renal p53 and caspase-3 expression indicated apoptosis of tubular cells. The administration of luteolin significantly reduced histological and biochemical changes induced by CP, decreased platinum (Pt) levels and suppressed oxidative/nitrosative stress, inflammation and apoptosis in the kidneys. These results suggest that luteolin is an effective nephroprotective agent, with potential to reduce Pt accumulation in the kidneys and ameliorate CP-induced nephrotoxicity

  1. Protective effect and mechanism of action of lupane triterpenes from Cornus walteri in cisplatin-induced nephrotoxicity.

    Lee, Seulah; Jung, Kiwon; Lee, Dahae; Lee, Seoung Rak; Lee, Kang Ro; Kang, Ki Sung; Kim, Ki Hyun

    2015-12-01

    The present study reports a renoprotective effect and the mechanism of action of lupane triterpenes isolated from Cornus walteri in cisplatin-induced renal toxicity. A phytochemical investigation of the MeOH extract of the stems and stem bark of C. walteri resulted in the isolation and identification of twelve lupane triterpenes. Among these, betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol ameliorated cisplatin-induced nephrotoxicity to 80% of the control value at 125 μM. Upregulated phosphorylation of JNK, ERK, and p38 following cisplatin treatment were markedly decreased after co-treatment with betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol. In addition, the protein expression level of cleaved caspase-3 and the percentage of apoptotic cells were also significantly reduced after co-treatment with betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol. These results show that blocking the MAPK signaling cascade plays a critical role in mediating the renoprotective effect of betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol isolated from C. walteri extract. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Male pattern baldness

    Alopecia in men; Baldness - male; Hair loss in men; Androgenetic alopecia ... Male pattern baldness is related to your genes and male sex hormones. It usually follows a pattern of receding hairline and ...

  3. Genital sores - male

    Sores - male genitals; Ulcers - male genitals ... A common cause of male genital sores are infections that are spread through sexual contact, such as: Genital herpes (small, painful blisters filled with clear ...

  4. Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats.

    Caires, A; Fernandes, G S; Leme, A M; Castino, B; Pessoa, E A; Fernandes, S M; Fonseca, C D; Vattimo, M F; Schor, N; Borges, F T

    2017-12-11

    Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

  5. Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats

    A. Caires

    2017-12-01

    Full Text Available Cyclosporin-A (CsA is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1 receptor blockade with bosentan (BOS and macitentan (MAC antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg or MAC (25 mg/kg by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP, RBF and renal vascular resistance (RVR, and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

  6. Effect of quercetin on metallothionein, nitric oxide synthases and cyclooxygenase-2 expression on experimental chronic cadmium nephrotoxicity in rats

    Morales, Ana I.; Vicente-Sanchez, Cesar; Jerkic, Mirjana; Santiago, Jose M.; Sanchez-Gonzalez, Penelope D.; Perez-Barriocanal, Fernando; Lopez-Novoa, Jose M.

    2006-01-01

    Inflammation can play a key role in Cd-induced dysfunctions. Quercetin is a potent oxygen free radical scavenger and a metal chelator. Our aim was to study the effect of quercetin on Cd-induced kidney damage and metallothionein expression. The study was performed in Wistar rats that were administered during 9 weeks with either cadmium (1.2 mg Cd/kg/day, s.c.), quercetin (50 mg/kg/day, i.p.) or cadmium + quercetin. Renal toxicity was evaluated by measuring blood urea nitrogen concentration and urinary excretion of enzymes marker of tubular damage. Endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) renal expression were assessed by Western blot. Renal expression of metallothionein 1 and 2 (MT-1, MT-2) and eNOS mRNA was assessed by Northern blot. Our data demonstrated that Cd-induced renal toxicity was markedly reduced in rats that also received quercetin. MT-1 and MT-2 mRNA levels in kidney were substantially increased during treatment with Cd, being even higher when the animals received Cd and quercetin. Renal eNOS expression was significantly higher in rats receiving Cd and quercetin than in animals receiving Cd alone or in control rats. In the group that received Cd, COX-2 and iNOS expression was markedly higher than in control rats. In the group Cd + quercetin, no changes in COX-2 and iNOS expression were observed compared with the control group. Our results demonstrate that quercetin treatment prevents Cd-induced overexpression of iNOS and COX-2, and increases MT expression. These effects can explain the protection by quercetin of Cd-induced nephrotoxicity

  7. Possible role of mtDNA depletion and respiratory chain defects in aristolochic acid I-induced acute nephrotoxicity

    Jiang, Zhenzhou, E-mail: jiangcpu@yahoo.com.cn; Bao, Qingli, E-mail: bao_ql@126.com; Sun, Lixin, E-mail: slxcpu@126.com; Huang, Xin, E-mail: huangxinhx66@sohu.com; Wang, Tao, E-mail: wangtao1331@126.com; Zhang, Shuang, E-mail: cat921@sina.com; Li, Han, E-mail: hapo1101@163.com; Zhang, Luyong, E-mail: lyzhang@cpu.edu.cn

    2013-01-15

    This report describes an investigation of the pathological mechanism of acute renal failure caused by toxic tubular necrosis after treatment with aristolochic acid I (AAI) in Sprague–Dawley (SD) rats. The rats were gavaged with AAI at 0, 5, 20, or 80 mg/kg/day for 7 days. The pathologic examination of the kidneys showed severe acute tubular degenerative changes primarily affecting the proximal tubules. Supporting these results, we detected significantly increased concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in the rats treated with AAI, indicating damage to the kidneys. Ultrastructural examination showed that proximal tubular mitochondria were extremely enlarged and dysmorphic with loss and disorientation of their cristae. Mitochondrial function analysis revealed that the two indicators for mitochondrial energy metabolism, the respiratory control ratio (RCR) and ATP content, were reduced in a dose-dependent manner after AAI treatment. The RCR in the presence of substrates for complex I was reduced more significantly than in the presence of substrates for complex II. In additional experiments, the activity of respiratory complex I, which is partly encoded by mitochondrial DNA (mtDNA), was more significantly impaired than that of respiratory complex II, which is completely encoded by nuclear DNA (nDNA). A real-time PCR assay revealed a marked reduction of mtDNA in the kidneys treated with AAI. Taken together, these results suggested that mtDNA depletion and respiratory chain defects play critical roles in the pathogenesis of kidney injury induced by AAI, and that the same processes might contribute to aristolochic acid-induced nephrotoxicity in humans. -- Highlights: ► AAI-induced acute renal failure in rats and the proximal tubule was the target. ► Tubular mitochondria were morphologically aberrant in ultrastructural examination. ► AAI impair mitochondrial bioenergetic function and mtDNA replication.

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

    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

  9. Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin-cadmium induced diabetic nephrotoxic rats.

    Kandasamy, Neelamegam; Ashokkumar, Natarajan

    2014-09-01

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)-cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ-Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ-Cd induced diabetic nephrotoxic rats. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Administration of colistin sulfate in endotoxic model at slow and sustained fashion may reverse shock without causing nephrotoxicity in its optimal concentration.

    Haque, Anwarul; Ishii, Yoshikazu; Akasaka, Yoshikiyo; Matsumoto, Tetsuya; Tateda, Kazuhiro

    2017-12-01

    Despite of proven LPS neutralizing activity, intravenous polymyxin use was waned due to experience of associated nephrotoxicity. But, increasing resistance to all available antibiotics has necessitated their resurgence and the prodrug of colistin sulfate (CS), known as colistin-methanesulfonate (CMS), is increasingly used as the only therapeutic option in many infections. Currently available CMS employ very different dose definitions and thus because of complex pharmacokinetics/pharmacodynamics information and short half-life, this drug use remains confusing. We aimed to expose CS in endotoxic shock models by micro-osmotic pump and evaluated its effectiveness. We used micro-osmotic pumps to deliver either sterile saline or CS at different dosages ranging from 0.25mg/day to 7mg/day for consecutive 3days in LPS (8mg/kg body weight) induced endotoxic mice and observed their outcome twice daily for a week to determine the survival rate. Serum pro-inflammatory cytokine levels and apoptosis in renal tissues in these models were evaluated. We showed endotoxic shock was reversed and all mice survived with a CS administration at a dosage of 2mg/day for 3 days, in comparison to survival rate with saline administration (p≤0.0001) in endotoxic models. CS infusion in shock models using micro-osmotic pump ameliorated rising of serum TNF-α, IL-12p70 and IL-6 levels. Nephrotoxicity was evident only with a higher dosage, but not with a lower dosage which was optimum to control endotoxic shock in models. These results highlighted that an optimal dosage of CS effectively improved outcome in endotoxic shock models without causing nephrotoxicity when administered at a slow and sustained manner. And a higher CS dosage administration was nephrotoxic and fatal. Thus this study bought an opportunity to consider future investigations with CS administration in murine Gram-negative bacterial infections in a novel way. Copyright © 2017 International Society for Chemotherapy of Infection

  11. Efeito renoprotetor dos flavonoides do vinho na nefrotoxicidade do imunossupressor Tacrolimus Efecto renoprotector de los flavonoides del vino en la nefrotoxicidad del inmunosupresor Tacrolimus Renoprotective effects of wine flavonoids in nephrotoxicity of the immunosuppressant Tacrolimus

    Wanessa Teixeira Silva

    2011-01-01

    confirmaron la lesión nefrotóxica inducida por el Tacrolimus y demostraron el efecto renoprotector del Vitis Vinifera L.OBJECTIVE: To investigate the renoprotective effects of the extract of Vitis vinifera L in the Tacrolimus-induced nephrotoxicity in experimental studies with rats. METHODS: Quantitative survey with an experimental model in which adult male, Wistar rats, weighing between 250g - 300g, were used. The rats were treated once a day for cincodias by gavage as follows: Saline (control, sodium chloride, 0.1 ml; Vitis (Vitis vinifera L 3mg/kg, FK (0.5 mg / kg; and, FK + Vitis (0.5 mg / kg + 3 mg / kg, respectively. Renal function was assessed by creatinine clearance (CrCL / 100g, Jaffe method and lipid peroxidation by measurement of urinary peroxides (PU, FOX-2. RESULTS: The administration of FK increased the excretion of peroxides and reduced creatinine clearance, and simultaneous administration with Vitis vinifera L protected the renal function in these parameters. CONCLUSION: These data confirm the injury induced by nephrotoxic Tacrolimus and demonstrated the renoprotective effect of Vitis vinifera L.

  12. Nephrotoxic effects of lead nitrate exposure in diabetic and nondiabetic rats: Involvement of oxidative stress and the protective role of sodium selenite.

    Baş, Hatice; Kalender, Yusuf

    2016-10-01

    Heavy metals are known to be toxic to organisms. The present study was undertaken to evaluate the protective effect of sodium selenite against lead nitrate (LN)-induced nephrotoxicity in diabetic and nondiabetic rats. Animals were divided into eight groups where the first was served as a control, whereas the remaining groups were treated with sodium selenite (1 mg/kg b.w.), LN (22.5 mg/kg b.w.) and a combination of LN and sodium selenite and diabetic forms of these groups. Changes in antioxidant enzyme activities, malondialdehide levels, serum urea, uric acid, creatinine levels, body, and kidney weights and histopathological changes were determined after 28 days. LN caused severe histopathological changes, increment in urea, uric acid, creatinine, and MDA levels, also decreasing in antioxidant enzyme activities, body, and kidney weights. In sodium selenite + LN group, we observed the protective effect of sodium selenite on examining parameters. Also diabetes caused alterations on these parameters compared with nondiabetic animals. We found that sodium selenite did not show protective effect on diabetes caused damages. As a result, LN caused nephrotoxicity and sodium selenite alleviated this toxicity but sodium selenite did not protect kidneys against diabetes mediated toxicity. Also, LN caused more harmfull effects in diabetic groups compared with nondiabetic groups. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1229-1240, 2016. © 2015 Wiley Periodicals, Inc.

  13. Vitamin E, Vitamin C, or Losartan Is Not Nephroprotectant against Cisplatin-Induced Nephrotoxicity in Presence of Estrogen in Ovariectomized Rat Model

    Mehdi Nematbakhsh

    2012-01-01

    Full Text Available Background. The nephroprotective effect of vitamins E and C or losartan against cisplatin (CP- induced nephrotoxicity when they are accompanied by estrogen was investigated. Methods. The ovariectomized rats received estradiol valerate for two weeks. At the end of the first week, a single dose of CP (7 mg/kg, IP was also administered, and they received placebo (group 1, vitamin E (group 2, vitamin C (group 3, or losartan (group 4 every day during the second week, and they were compared with another three control groups. Results. CP alone increased the serum levels of blood urea nitrogen (BUN, creatinine (Cr, and kidney tissue damage score (KTDS, significantly (P<0.05, however at the presence of estradiol and CP, vitamin C, vitamin E, or losartan not only did not decrease these parameters, but also increased them significantly (P<0.05. The serum level of superoxidase dismutase (SOD was reduced by CP (P<0.05, but it was increased when estradiol or estradiol plus vitamin C or losartan were added (P<0.05. Conclusion. The particular pharmacological dose of estrogen used in this study abolish the nephroprotective effects vitamins C and E or losartan against CP-induced nephrotoxicity.

  14. Metabolomic Analysis of Complex Chinese Remedies: Examples of Induced Nephrotoxicity in the Mouse from a Series of Remedies Containing Aristolochic Acid

    Dong-Ming Tsai

    2013-01-01

    Full Text Available Aristolochic acid nephropathy is caused by aristolochic acid (AA and AA-containing herbs. In traditional Chinese medicine, a principle called “Jun-Chen-Zou-Shi” may be utilized to construct a remedial herbal formula that attempts to mitigate the toxicity of the main ingredient. This study used Bu-Fei-A-Jiao-Tang (BFAJT to test if the compound remedy based on a principle of “Jun-Chen-Zou-Shi” can decrease the toxicity of AA-containing herbs. We compared the three toxicities of AA standard, Madouling (an Aristolochia herb, and a herbal formula BFAJT. AA standard was given for BALB/c mice at a dose of 5 mg/kg bw/day or 7.5 mg/kg bw/day for 10 days. Madouling and BFAJT were given at an equivalence of AA 0.5 mg/kg bw/day for 21 days. Nephrotoxicity was evaluated by metabolomics and histopathology. The urinary metabolomics profiles were characterized by 1H NMR spectroscopy. The spectral data was analyzed with partial least squares discriminant analysis, and the significant differential metabolites between groups were identified. The result showed different degrees of acute renal tubular injuries, and metabolomics analysis found that the kidney injuries were focused in proximal renal tubules. Both metabolomics and pathological studies revealed that AA standard, Madouling, and BFAJT were all nephrotoxicants. The compositions of the compound remedy did not diminish the nephrotoxicity caused by AA.

  15. Male pattern baldness (image)

    Male pattern baldness is a sex-linked characteristic that is passed from mother to child. A man can more accurately predict his chances of developing male pattern baldness by observing his mother's father than by looking ...

  16. [Male urinary incontinence

    Boer, T.A. de; Heesakkers, J.P.F.A.

    2008-01-01

    *Urinary incontinence in males is gaining increasingly more attention. *Male urinary incontinence can be classified as storage incontinence due to overactive bladder syndrome or stress incontinence due to urethral sphincter dysfunction. *Most patients benefit from the currently available treatment

  17. Self catheterization - male

    ... male; CIC - male Images Catheterization References Davis JE, Silverman MA. Urologic procedures. In: Roberts JR, ed. Roberts ... provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial ...

  18. Prostatitis and male infertility.

    Alshahrani, Saad; McGill, John; Agarwal, Ashok

    2013-11-01

    The prostate gland plays an important role in male reproduction. Inflammation of the prostate gland (prostatitis) is a common health problem affecting many young and middle aged men. Prostatitis is considered a correctable cause of male infertility, but the pathophysiology and appropriate treatment options of prostatitis in male infertility remain unclear. This literature review will focus on current data regarding prostatitis and its impact on male infertility. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Varicocele and male infertility

    Jensen, Christian Fuglesang S.; Østergren, Peter; Dupree, James M.

    2017-01-01

    The link between varicoceles and male infertility has been a matter of debate for more than half a century. Varicocele is considered the most common correctable cause of male infertility, but some men with varicoceles are able to father children, even without intervention. In addition, improvements...... if the male partner has a clinically palpable varicocele and affected semen parameters....

  20. Tumorigenicity of sodium ascorbate in male rats.

    Cohen, S M; Anderson, T A; de Oliveira, L M; Arnold, L L

    1998-06-15

    urinary tract in this study are similar to those seen with sodium saccharin when administered in a two-generation bioassay. Mechanistic information suggests that this is a high-dose, rat-specific phenomenon.

  1. Metabolism of L-cysteine S-conjugates and N-(trideuteroacetyl)-L-cysteine S-conjugates of four fluoroethylenes in the rat. Role of balance of deacetylation and acetylation in relation to the nephrotoxicity of mercapturic acids.

    Commandeur, J.N.M.; Stijntjes, G.J.; Wijngaard, J.; Vermeulen, N.P.E.

    1991-01-01

    The relationship between the relative nephrotoxicity of the mercapturic acids (NAc) of the fluorinated ethylanes tetrafluoroethylene (TFE), chlorotrifluoroethylene (CTFE), 1,1-dichloro-2,2-difluoroethylene (DCDFE) and 1,1-dibromo-2,2-difluoroethylene (DBDFE), and the biotransformation by activating

  2. Cooking methods employing natural anti-oxidant food additives effectively reduced concentration of nephrotoxic and carcinogenic aristolochic acids in contaminated food grains.

    Li, Weiwei; Chan, Chi-Kong; Wong, Yee-Lam; Chan, K K Jason; Chan, Ho Wai; Chan, Wan

    2018-10-30

    Emerging evidence suggests that aristolochic acids (AA) produced naturally by a common weed Aristolochia clematitis in the cultivation fields is contaminating the food products in Balkan Peninsula and acting as the etiological agent in the development of Balkan endemic nephropathy. In this study, we investigated the combined use of natural anti-oxidative "food additives" and different cooking methods to find a solution for the widespread contamination of AA in food products. The results indicated that the addition of healthy dietary supplements (such as cysteine, glutathione, ascorbic acid, citric acid and magnesium) during cooking, is a highly efficient method in lowering the concentration of AA in the final food products. Because previous observation indicated one of the toxicological mechanisms by which AA exert its toxicity is to induce oxidative stress in internal organs, it is anticipated that these added anti-oxidants will also help to attenuate the nephrotoxicity of AA. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Biodegradable in situ gelling system for subcutaneous administration of ellagic acid and ellagic acid loaded nanoparticles: evaluation of their antioxidant potential against cyclosporine induced nephrotoxicity in rats.

    Sharma, G; Italia, J L; Sonaje, K; Tikoo, K; Ravi Kumar, M N V

    2007-03-12

    Ellagic acid (EA) is a potent antioxidant marketed as a nutritional supplement. Its pharmacological activity has been reported in wide variety of disease models; however its use has been limited owing to its poor biopharmaceutical properties, thereby poor bioavailability. The objective of the current study was to develop chitosan-glycerol phosphate (C-GP) in situ gelling system for sustained delivery of ellagic acid (EA) via subcutaneous route. EA was incorporated in the system employing propylene glycol (PG) and triethanolamine (TEA) as co-solvents; on the other hand EA loaded PLGA nanoparticles (np) were dispersed in the gelling system using water. These in situ gelling systems were thoroughly characterized for mechanical, rheological and swelling properties. These systems are liquid at room temperature and gels at 37 degrees C. The EA C-GP system showed an initial burst release in vitro with about 85% drug released in 12 h followed by a steady release till 160 h, on the other hand EA nanoparticles entrapped in the C-GP system displayed sustained release till 360 h. The histopathological analysis indicates the absence of inflammation on administration, suggesting that these formulations are safe during the studied period. Furthermore, the antioxidant potential of EA C-GP and EA np C-GP gels has been evaluated against cyclosporine induced nephrotoxicity in rats. The data indicates that formulations were effective against cyclosporine induced nephrotoxicity, where the EA C-GP gels showed activity at 10 times lower dose and the EA np C-GP gels at 150 times lower dose when compared to orally given EA. Formulating nanoparticles of EA and incorporating them in C-GP system results in 15 times lowering of dose in comparison EA C-GP gels which is quite significant. Together, these results indicate that the bioavailability of ellagic acid can be improved by subcutaneous formulations administered as simple EA or EA nps.

  4. Ameliorative effect of fisetin on cisplatin-induced nephrotoxicity in rats via modulation of NF-κB activation and antioxidant defence.

    Bidya Dhar Sahu

    Full Text Available Nephrotoxicity is a dose-dependent side effect of cisplatin limiting its clinical usage in the field of cancer chemotherapy. Fisetin is a bioactive flavonoid with recognized antioxidant and anti-inflammatory properties. In the present study, we investigated the potential renoprotective effect and underlying mechanism of fisetin using rat model of cisplatin-induced nephrotoxicity. The elevation in serum biomarkers of renal damage (blood urea nitrogen and creatinine; degree of histopathological alterations and oxidative stress were significantly restored towards normal in fisetin treated, cisplatin challenged animals. Fisetin treatment also significantly attenuated the cisplatin-induced IκBα degradation and phosphorylation and blocked the NF-κB (p65 nuclear translocation, with subsequent elevation of pro-inflammatory cytokine, TNF-α, protein expression of iNOS and myeloperoxidase activities. Furthermore, fisetin markedly attenuated the translocation of cytochrome c protein from the mitochondria to the cytosol; decreased the expression of pro-apoptotic proteins including Bax, cleaved caspase-3, cleaved caspase-9 and p53; and prevented the decline of anti-apoptotic protein, Bcl-2. The cisplatin-induced mRNA expression of NOX2/gp91phox and NOX4/RENOX and the NADPH oxidase enzyme activity were also significantly lowered by fisetin treatment. Moreover, the evaluated mitochondrial respiratory enzyme activities and mitochondrial antioxidants were restored by fisetin treatment. Estimation of platinum concentration in kidney tissues revealed that fisetin treatment along with cisplatin did not alter the cisplatin uptake in kidney tissues. In conclusion, these findings suggest that fisetin may be used as a promising adjunct candidate for cisplatin use.

  5. Ameliorative Effect of Fisetin on Cisplatin-Induced Nephrotoxicity in Rats via Modulation of NF-κB Activation and Antioxidant Defence

    Sahu, Bidya Dhar; Kalvala, Anil Kumar; Koneru, Meghana; Mahesh Kumar, Jerald; Kuncha, Madhusudana; Rachamalla, Shyam Sunder; Sistla, Ramakrishna

    2014-01-01

    Nephrotoxicity is a dose-dependent side effect of cisplatin limiting its clinical usage in the field of cancer chemotherapy. Fisetin is a bioactive flavonoid with recognized antioxidant and anti-inflammatory properties. In the present study, we investigated the potential renoprotective effect and underlying mechanism of fisetin using rat model of cisplatin-induced nephrotoxicity. The elevation in serum biomarkers of renal damage (blood urea nitrogen and creatinine); degree of histopathological alterations and oxidative stress were significantly restored towards normal in fisetin treated, cisplatin challenged animals. Fisetin treatment also significantly attenuated the cisplatin-induced IκBα degradation and phosphorylation and blocked the NF-κB (p65) nuclear translocation, with subsequent elevation of pro-inflammatory cytokine, TNF-α, protein expression of iNOS and myeloperoxidase activities. Furthermore, fisetin markedly attenuated the translocation of cytochrome c protein from the mitochondria to the cytosol; decreased the expression of pro-apoptotic proteins including Bax, cleaved caspase-3, cleaved caspase-9 and p53; and prevented the decline of anti-apoptotic protein, Bcl-2. The cisplatin-induced mRNA expression of NOX2/gp91phox and NOX4/RENOX and the NADPH oxidase enzyme activity were also significantly lowered by fisetin treatment. Moreover, the evaluated mitochondrial respiratory enzyme activities and mitochondrial antioxidants were restored by fisetin treatment. Estimation of platinum concentration in kidney tissues revealed that fisetin treatment along with cisplatin did not alter the cisplatin uptake in kidney tissues. In conclusion, these findings suggest that fisetin may be used as a promising adjunct candidate for cisplatin use. PMID:25184746

  6. 5-Aminolevulinic acid protects against cisplatin-induced nephrotoxicity without compromising the anticancer efficiency of cisplatin in rats in vitro and in vivo.

    Yoshio Terada

    Full Text Available Nephrotoxicity is a frequent and major limitation in cisplatin (CDDP-based chemotherapy. 5-Aminolevulinic acid (ALA is widely distributed in animal cells, and it is a precursor of tetrapyrole compounds such as heme that is fundamentally important in aerobic energy metabolism. The aim of this study is to evaluate the protective role of ALA in CDDP-induced acute kidney injury (AKI.We used CDDP-induced AKI rat model and cultured renal tubular cells (NRK-52E. We divided four groups of rats: control, CDDP only, CDDP + ALA(post;(ALA 10 mg/kg + Fe in drinking water after CDDP, CDDP + ALA(pre & post.CDDP increased Cr up to 6.5 mg/dl, BUN up to 230 mg/dl, and ALA significantly reduced these changes. ALA ameliorates CDDP-induced morphological renal damages, and reduced tubular apoptosis evaluated by TUNEL staining and cleaved caspase 3. Protein and mRNA levels of ATP5α, complex(COX IV, UCP2, PGC-1α in renal tissue were significantly decreased by CDDP, and ALA ameliorates reduction of these enzymes. In contrast, Heme Oxigenase (HO-1 level is induced by CDDP treatment, and ALA treatment further up-regulates HO-1 levels. In NRK-52E cells, the CDDP-induced reduction of protein and mRNA levels of mitochondrial enzymes was significantly recovered by ALA + Fe. CDDP-induced apoptosis were ameliorated by ALA + Fe treatment. Furthermore, we evaluated the size of transplantated bladder carcinoma to the rat skin, and ALA did not change the anti cancer effects of CDDP.These data suggested that the protective role of ALA in cisplatin-induced AKI is via protection of mitochondrial viability and prevents tubular apoptosis. Also there are no significant effects of ALA on anticancer efficiency of CDDP in rats. Thus, ALA has the potential to prevent CDDP nephrotoxicity without compromising its anticancer efficacy.

  7. Insuficiência renal aguda nefrotóxica: prevalência, evolução clínica e desfecho Nephrotoxic acute renal failure: prevalence, clinical course and outcome

    Patrícia S. Pinto

    2009-09-01

    Full Text Available INTRODUÇÃO: A insuficiência renal aguda (IRA nefrotóxica é frequente e importante causa de morbimortalidade. OBJETIVO: Avaliar a prevalência, o curso clínico e o desfecho da IRA nefrotóxica. PACIENTES e MÉTODOS: Coorte histórica realizada em um hospital de ensino terciário, no período de fevereiro a novembro de 1997. Foram incluídos pacientes acima de 12 anos, com diagnóstico de IRA, acompanhados pela equipe de Interconsulta de Nefrologia. Foram excluídos transplantados renais, portadores de insuficiência renal crônica, dialisados por intoxicação exógena e aqueles transferidos de hospital durante o tratamento. RESULTADOS: Dos 234 pacientes acompanhados, 12% apresentaram IRA nefrotóxica e 24%, IRA multifatorial associada ao uso de drogas nefrotóxica. Entre as comorbidades mais prevalentes, estão hipertensão arterial, hepatopatias, neoplasias, insuficiência cardíaca congestiva e diabetes mellitus. Quinze por cento necessitaram de diálise, e o tipo mais frequentemente usado foi hemodiálise venovenosa contínua; 42% eram oligúricos, 44,7% evoluíram para óbito e 33% recuperaram a função renal. Antibióticos, AINH e contraste radiológico foram as drogas nefrotóxicas mais prevalentes.Os medicamentos nefrotóxicos implicados foram, em ordem de frequência, vancomicina, aminoglicosídeos, aciclovir, quimioterápicos e contraste radiológico. Hepatopatia foi a única variável com significância estatística (p = 0,03, IC = 1,08 a 6,49 em análise multivariada. Na comparação entre IRA nefrotóxica e não nefrotóxica, houve aumento da mortalidade proporcionalmente aos dias de internação. CONCLUSÃO: IRA nefrotóxica é frequente, grave e deve ser continuamente monitorada, tanto ambulatorialmente quanto no ambiente intra-hospitalar.INTRODUCTION: Nephrotoxic acute renal failure (ARF is a frequent and important cause of morbidity and mortality. OBJECTIVE: To assess the prevalence, clinical course, and outcome of

  8. Male Adolescent Contraceptive Utilization.

    Finkel, Madelon Lubin; Finkel, David J.

    1978-01-01

    The contraceptive utilization of a sample of sexually active, urban, high school males (Black, Hispanic, and White) was examined by anonymous questionnaire. Contraceptive use was haphazard, but White males tended to be more effective contraceptors than the other two groups. Reasons for nonuse were also studied. (Author/SJL)

  9. Male mating biology

    Howell, Paul I.; Knols, Bart G. J.

    2009-01-01

    Before sterile mass-reared mosquitoes are released in an attempt to control local populations, many facets of male mating biology need to be elucidated. Large knowledge gaps exist in how both sexes meet in space and time, the correlation of male size and mating success and in which arenas matings

  10. Male breast cancer

    Lautrup, Marianne D; Thorup, Signe S; Jensen, Vibeke

    2018-01-01

    OBJECTIVE: Describe prognostic parameters of Danish male breast cancer patients (MBCP) diagnosed from 1980-2009. Determine all-cause mortality compared to the general male population and analyze survival/mortality compared with Danish female breast cancer patients (FBCP) in the same period...

  11. Male depression in females?

    Möller-Leimkühler, Anne Maria; Yücel, Mete

    2010-02-01

    Scientific evidence for a male-typed depression ("male depression") is still limited, but mainly supports this concept with respect to single externalizing symptoms or symptom clusters. In particular, studies on non-clinical populations including males and females are lacking. The present study aims at assessing general well-being, the risk and the symptoms of male depression dependent on biological sex and gender-role orientation on instrumental (masculine) and expressive (feminine) personality traits in an unselected community sample of males and females. Students (518 males, 500 females) of the Ludwig-Maximilians-University of Munich, Germany, were asked to participate in a "stress study" and complete the following self-report questionnaires: the WHO-5 Well-being Index [Bech, P., 1998. Quality of Life in the Psychiatric Patient. Mosby-Wolfe, London], the Gotland Scale for Male Depression [Walinder, J., Rutz, W., 2001. Male depression and suicide. International Clinical Psychopharmacology 16 (suppl 2), 21-24] and the German Extended Personal Attribute Questionnaire [Runge, T.E., Frey, D., Gollwitzer, P.M., et al., 1981. Masculine (instrumental) and feminine (expressive) traits. A comparison between students in the United States and West Germany. Journal of Cross-Cultural Psychology 12, 142-162]. General well-being of the students was significantly lower compared to population norms. Contrary to expectations, female students had a greater risk of male depression than male students (28.9% vs. 22.4%; p<0.05). Overall, prototypic depressive symptoms as well as externalizing symptoms were more pronounced in females. In the subgroup of those at risk for male depression, biological sex and kind of symptoms were unrelated. Principal component analyses revealed a similar symptom structure for males and females. Low scores on masculinity/instrumentality significantly predicted higher risk of male depression, independent of biological sex. The study sample is not

  12. Demand for male contraception.

    Dorman, Emily; Bishai, David

    2012-10-01

    The biological basis for male contraception was established decades ago, but despite promising breakthroughs and the financial burden men increasingly bear due to better enforcement of child support policies, no viable alternative to the condom has been brought to market. Men who wish to control their fertility must rely on female compliance with contraceptives, barrier methods, vasectomy or abstinence. Over the last 10 years, the pharmaceutical industry has abandoned most of its investment in the field, leaving only nonprofit organisations and public entities pursuing male contraception. Leading explanations are uncertain forecasts of market demand pitted against the need for critical investments to demonstrate the safety of existing candidate products. This paper explores the developments and challenges in male contraception research. We produce preliminary estimates of potential market size for a safe and effective male contraceptive based on available data to estimate the potential market for a novel male method.

  13. Male depression and suicide.

    Wålinder, J; Rutzt, W

    2001-03-01

    Based on the experiences of the Gotland Study that education of general practitioners about depressive illness resulted in a statistically significant reduction in the number of female suicides, leaving the rate of male suicides almost unaffected, we propose the concept of a male depressive syndrome. This syndrome comprises a low stress tolerance, an acting-out behavior, a low impulse control, substance abuse and a hereditary loading of depressive illness, alcoholism and suicide. This notion is supported by data from The Amish study as well as the concept of van Praag of a stress-precipitated, cortisol-induced, serotonin-related and anxiety-driven depressive illness most often seen in males. In order to identify depressed males, the Gotland Male Depression Scale has been developed. Some preliminary data using the scale in a group of alcohol-dependant patients are presented.

  14. Male Body Practices.

    Lefkowich, Maya; Oliffe, John L; Hurd Clarke, Laura; Hannan-Leith, Madeline

    2017-03-01

    The pressure on boys and men to engage in extensive body practices (e.g., closely monitored eating and exercise habits) and achieve ideal male bodies has grown significantly over the past 20 years. Central to the depiction of ideal male bodies and body practices are both the pursuit and achievement of lean and well-defined muscles. The labels "pitches," "purchases," and "performativities" were inductively derived from the literature, and used to describe the multifaceted connections between masculinities, muscularity, and idealized male body practices. "Pitches" distil how popular culture posture norms of masculinity, and manly bodies and behaviors attainable and necessary. "Purchases" refer to men's diverse buy-in to dominant discourses about acceptable male bodies and practices. "Performativities" chronicle how men embody and navigate gender norms as they evaluate their own bodies, behaviors, and eating habits and those of their peers. Based on findings from the current scoping review, future research could benefit from fully linking masculinities with the drive for muscularity to address health and social risks associated with the pursuit of the idealized male body. In highlighting the plurality of masculinities and the complexity of men's diverse identities, health care providers can better reach and support men. Focusing on, and celebrating, a wider range of male bodies could help recenter dominant discourses about how and whose bodies and experiences are idealized. The current scoping review article offers an overview of how masculinities and muscularity have been linked to male body practices, and recommendations to advance this emergent field.

  15. Cytogenetic of Male Infertility

    Lutfiye Ozpak

    2011-08-01

    Full Text Available Infertility by definition, is not to get pregnant within one year of regular sexual relationship without protection, affects 15-20% of reproductive age couples. Approximately 30% of infertility cases are male originated. Male infertility is caused by endocrine-related genetic defects affecting urogenital system function. These defects adversely affect subsequent spermatogenesis, sexual function, fertility, early embryonic stage of sexual maturation. Autosomal and gonosomal, numerical and structural chromosome abnormalities and related syndromes rank at the top causes of male infertility. Similar chromosome abnormalities are detected in male infertility and as the rate of these abnormalities increase, it was found to reduce sperm count especially in azospermic and oligozoospermic men. [Archives Medical Review Journal 2011; 20(4.000: 230-245

  16. Males and Eating Disorders

    ... Bar Home Current Issue Past Issues Males and Eating Disorders Past Issues / Spring 2008 Table of Contents For ... this page please turn Javascript on. Photo: PhotoDisc Eating disorders primarily affect girls and women, but boys and ...

  17. Male hypogonadism (Part 1)

    Ye.V. Luchytskyy; V.Yе. Luchytskyy; M.D. Tronko

    2017-01-01

    The first part of the review presents the current data on the prevalence of male hypogonadism, methods of diagnosing different forms of hypogonadism, describes the clinical manifestations of the most common forms of this disease.

  18. Male hypogonadism (Part 1

    Ye.V. Luchytskyy

    2017-05-01

    Full Text Available The first part of the review presents the current data on the prevalence of male hypogonadism, methods of diagnosing different forms of hypogonadism, describes the clinical manifestations of the most common forms of this disease.

  19. Male breast lesions

    Matushita, J.P.K.; Andrade, L.G. de; Carregal, E.; Marimatsu, R.I.; Matushita, J.S.

    1989-01-01

    Roentgenographic examination of the male breast is an important aspect of the continued, intensive investigation of the radiologic morphology of the normal and diseased breast conducted in 17 cases examined at the Instituto Nacional do Cancer - RJ. It is purpose of this report to present the Roentgen appearance of various lesions of the male breast as they have been found in our practice and also to stress some of the difficulties in the differential diagnosis of these lesions. (author) [pt

  20. Thyroid and male reproduction

    Anand Kumar

    2014-01-01

    Full Text Available Male reproduction is governed by the classical hypothalamo-hypophyseal testicular axis: Hypothalamic gonadotropin releasing hormone (GnRH, pituitary luteinizing hormone (LH and follicle stimulating hormone (FSH and the gonadal steroid, principally, testosterone. Thyroid hormones have been shown to exert a modulatory influence on this axis and consequently the sexual and spermatogenic function of man. This review will examine the modulatory influence of thyroid hormones on male reproduction.

  1. Role of garlic extract and silymarin compared to dimercaptosuccinic acid (DMSA in treatment of lead induced nephropathy in adult male albino rats

    Iman A. El-Khishin

    2015-01-01

    Full Text Available Lead poisoning has been known as an important disorder that affects individuals through acute, sub-acute and chronic exposure in environmental and occupational settings. This study was conducted to compare the curative role of garlic combined with silymarin versus dimercaptosuccinic acid (DMSA in decreasing lead induced nephrotoxicity in adult male albino rats. The period of lead intoxication extended for 3 months followed by either 1 month treatment with garlic and silymarin or 5 days treatment with DMSA. Lead poisoning caused non-significant difference in kidney function tests (BUN and serum creatinine while, it caused significant elevation in kidney lead level, significant decrease in renal antioxidant enzyme glutathione peroxidase and significant elevation in kidney malondialdehyde. Histologically, lead induced disorganization and shrinkage of glomeruli with sloughing and vaculation of epithelium, widening of Bowman's space and inflammatory infiltration in renal medulla. Treatment by garlic extract combined with silymarin as well as treatment with DMSA resulted in significant improvement in the affected parameters. Also, both methods of treatment resulted in improvement of the histopathological changes. It can be concluded that garlic extract combined to silymarin is comparable to DMSA in amelioration of lead induced nephrotoxicity.

  2. Genetically conditioned male sterility

    Gottschalk, W.

    1976-01-01

    A survey is given of two different types of genetically controlled male sterility in higher plants. 'Functional' male sterility is due to the action of mutated genes causing a misdifferentiation of the growing points in different specific ways. Under the influence of the genes of this group either the stamens or the archespore tissues are not differentiated. In other mutants functionable male germ cells are produced but cannot be used for fertilizing the egg cells because the anthers remain closed or anthers and stigma become spatially separated from each other. Other genes of the group are responsible for the transformation of stamens into carpels, i.e. for a change of the hermaphrodite flower into a unisexually female one. A second type of male sterility is due to the action of ms genes influencing the course of micro-sporogenesis directly. They cause the breakdown of this process in a specific meiotic stage characteristic for each gene of the group. This breakdown is introduced by the degeneration of PMCs, microspores, or pollen grains preventing the production of male germ cells. The female sex organs remain uninfluenced. (author)

  3. Male sterility in chestnuts

    Omura, Mitsuo; Akihama, Tomoya

    1982-01-01

    A tentative plan was proposed for chestnuts based on their pollination system, male sterility and restoration. The studies on the male sterility of 1,063 cultivars and clones suggested that there were three types of male sterility. The first type (S-1) was characterized by antherless florets. In the second type (S-2), the catkins fell before anthesis, and the third type (S-3) appeared to develop normally in gross floral morphology, but the pollen grains were abnormal in shape and did not have germinating power. In an interspecific hybrid clone CS which belonged to S-1, fertility was restored in an open pollinated progeny. The use of CS and CSO-3 with its restored fertility, permitted the planning of breeding the chestnut hybrid cultivars propagated by seeds. The inbred clones with either male sterility or restorer genes are first bred mainly by back crossing with parents with favorable pollen. The clones are selected individually for early bearing, wasp and disease resistance, and restoration. Then, the hybrid seedling lines between male sterile and restorer inbreds are evaluated for homogenity in nut characters and tree habits. Next, the hybrid seedling lines selected will be examined for crop yield, vigor and cross compatibility. The superior seedling lines are finally selected, and the parental inbreds are grafted to be propagated for seed production orchards. (Kaihara, S.)

  4. Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: a rapid in vivo screening method for nanotoxicity.

    Lei, Ronghui; Wu, Chunqi; Yang, Baohua; Ma, Huazhai; Shi, Chang; Wang, Quanjun; Wang, Qingxiu; Yuan, Ye; Liao, Mingyang

    2008-10-15

    Despite an increasing application of copper nanoparticles, there is a serious lack of information concerning their impact on human health and the environment. In this study, the biochemical compositions of urine, serum, and extracts of liver and kidney tissues of rats treated with nano-copper at the different doses (50, 100, and 200 mg/kg/d for 5 d) were investigated using (1)H NMR techniques with the pattern recognition methods. Serum biochemical analysis and histopathological examinations of the liver and kidney of all the rats were simultaneously performed. All the results indicated that the effects produced by nano-copper at a dose of 100 or 50 mg/kg/d were less than those induced at a higher dose of 200 mg/kg/d. Nano-copper induced overt hepatotoxicity and nephrotoxicity at 200 mg/kg/d for 5 d, which mainly involved scattered dot hepatocytic necrosis and widespread renal proximal tubule necrosis. Increased citrate, succinate, trimethylamine-N-oxide, glucose, and amino acids, accompanied by decreased creatinine levels were observed in the urine; furthermore, elevated levels of lactate, 3-hydroxybutyrate, acetate, creatine, triglycerides, and phosphatide and reduced glucose levels were observed in the serum. The predominant changes identified in the liver tissue aqueous extracts included increased lactate and creatine levels together with reduced glutamine and taurine levels, and the metabolic profile of the kidney tissue aqueous extracts showed an increase in lactate and a drop in glucose. In the chloroform/methanol extracts of the liver and kidney tissues, elevated triglyceride species were identified. These changes suggested that mitochondrial failure, enhanced ketogenesis, fatty acid beta-oxidation, and glycolysis contributed to the hepatotoxicity and nephrotoxicity induced by nano-copper at 200 mg/kg/d for 5 d. An increase in triglycerides in the serum, liver and kidney tissues could serve as a potential sensitive biomarker reflecting the lipidosis induced

  5. Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: A rapid invivo screening method for nanotoxicity

    Lei Ronghui; Wu Chunqi; Yang Baohua; Ma Huazhai; Shi Chang; Wang Quanjun; Wang Qingxiu; Yuan Ye; Liao Mingyang

    2008-01-01

    Despite an increasing application of copper nanoparticles, there is a serious lack of information concerning their impact on human health and the environment. In this study, the biochemical compositions of urine, serum, and extracts of liver and kidney tissues of rats treated with nano-copper at the different doses (50, 100, and 200 mg/kg/d for 5 d) were investigated using 1 H NMR techniques with the pattern recognition methods. Serum biochemical analysis and histopathological examinations of the liver and kidney of all the rats were simultaneously performed. All the results indicated that the effects produced by nano-copper at a dose of 100 or 50 mg/kg/d were less than those induced at a higher dose of 200 mg/kg/d. Nano-copper induced overt hepatotoxicity and nephrotoxicity at 200 mg/kg/d for 5 d, which mainly involved scattered dot hepatocytic necrosis and widespread renal proximal tubule necrosis. Increased citrate, succinate, trimethylamine-N-oxide, glucose, and amino acids, accompanied by decreased creatinine levels were observed in the urine; furthermore, elevated levels of lactate, 3-hydroxybutyrate, acetate, creatine, triglycerides, and phosphatide and reduced glucose levels were observed in the serum. The predominant changes identified in the liver tissue aqueous extracts included increased lactate and creatine levels together with reduced glutamine and taurine levels, and the metabolic profile of the kidney tissue aqueous extracts showed an increase in lactate and a drop in glucose. In the chloroform/methanol extracts of the liver and kidney tissues, elevated triglyceride species were identified. These changes suggested that mitochondrial failure, enhanced ketogenesis, fatty acid β-oxidation, and glycolysis contributed to the hepatotoxicity and nephrotoxicity induced by nano-copper at 200 mg/kg/d for 5 d. An increase in triglycerides in the serum, liver and kidney tissues could serve as a potential sensitive biomarker reflecting the lipidosis induced by

  6. Male gametogenesis without centrioles.

    Riparbelli, Maria Giovanna; Callaini, Giuliano

    2011-01-15

    The orientation of the mitotic spindle plays a central role in specifying stem cell-renewal by enabling interaction of the daughter cells with external cues: the daughter cell closest to the hub region is instructed to self-renew, whereas the distal one starts to differentiate. Here, we have analyzed male gametogenesis in DSas-4 Drosophila mutants and we have reported that spindle alignment and asymmetric divisions are properly executed in male germline stem cells that lack centrioles. Spermatogonial divisions also correctly proceed in the absence of centrioles, giving rise to cysts of 16 primary spermatocytes. By contrast, abnormal meiotic spindles assemble in primary spermatocytes. These results point to different requirements for centrioles during male gametogenesis of Drosophila. Spindle formation during germ cell mitosis may be successfully supported by an acentrosomal pathway that is inadequate to warrant the proper execution of meiosis. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. A tortoiseshell male cat

    Pedersen, A. S.; Berg, Lise Charlotte; Almstrup, Kristian

    2014-01-01

    Tortoiseshell coat color is normally restricted to female cats due to X-linkage of the gene that encodes the orange coat color. Tortoiseshell male cats do, however, occur at a low frequency among tortoiseshell cats because of chromosome aberrations similar to the Klinefelter syndrome in man...... tissue from a tortoiseshell male cat referred to us. Chromosome analysis using RBA-banding consistently revealed a 39,XXY karyotype. Histological examinations of testis biopsies from this cat showed degeneration of the tubules, hyperplasia of the interstitial tissue, and complete loss of germ cells....... Immunostaining using anti-vimentin and anti-VASA (DDX4) showed that only Sertoli cells and no germ cells were observed in the testicular tubules. As no sign of spermatogenesis was detected, we conclude that this is a classic case of a sterile, male tortoiseshell cat with a 39,XXY chromosome complement. © 2013 S...

  8. How Effective Is Male Contraception?

    ... Twitter Pinterest Email Print How effective is male contraception? Not all contraceptive methods are appropriate for all ... is best for them. For men, methods of contraception include male condoms and sterilization (vasectomy). Male condoms. ...

  9. Stages of Male Breast Cancer

    ... Breast & Gynecologic Cancers Breast Cancer Screening Research Male Breast Cancer Treatment (PDQ®)–Patient Version General Information about Male Breast Cancer Go to Health Professional Version Key Points Male ...

  10. Male Reproductive System

    ... With the Male Reproductive System Print en español Sistema reproductor masculino Reproduction All living things reproduce. Reproduction — ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for ...

  11. TRICHOMONAS URETHRITIS IN MALES

    Le Duc, Ector

    1955-01-01

    Trichomonas urethritis in the male should be suspected in all chronic cases of urethritis. The diagnosis is easily established by the hanging-drop method of examining the urethral discharge, or the first-glass urine specimen. Curative treatment is readily accomplished by the use of urethral instillations of Carbarsone suspension using 1 capsule of Carbarsone per ounce of distilled water. PMID:13270111

  12. Lycopene and male infertility

    Durairajanayagam, Damayanthi; Agarwal, Ashok; Ong, Chloe; Prashast, Pallavi

    2014-01-01

    Excessive amounts of reactive oxygen species (ROS) cause a state of oxidative stress, which result in sperm membrane lipid peroxidation, DNA damage and apoptosis, leading to decreased sperm viability and motility. Elevated levels of ROS are a major cause of idiopathic male factor infertility, which is an increasingly common problem today. Lycopene, the most potent singlet oxygen quencher of all carotenoids, is a possible treatment option for male infertility because of its antioxidant properties. By reacting with and neutralizing free radicals, lycopene could reduce the incidence of oxidative stress and thus, lessen the damage that would otherwise be inflicted on spermatozoa. It is postulated that lycopene may have other beneficial effects via nonoxidative mechanisms in the testis, such as gap junction communication, modulation of gene expression, regulation of the cell cycle and immunoenhancement. Various lycopene supplementation studies conducted on both humans and animals have shown promising results in alleviating male infertility—lipid peroxidation and DNA damage were decreased, while sperm count and viability, and general immunity were increased. Improvement of these parameters indicates a reduction in oxidative stress, and thus the spermatozoa is less vulnerable to oxidative damage, which increases the chances of a normal sperm fertilizing the egg. Human trials have reported improvement in sperm parameters and pregnancy rates with supplementation of 4–8 mg of lycopene daily for 3–12 months. However, further detailed and extensive research is still required to determine the dosage and the usefulness of lycopene as a treatment for male infertility. PMID:24675655

  13. Glyphosate, Hard Water and Nephrotoxic Metals: Are They the Culprits Behind the Epidemic of Chronic Kidney Disease of Unknown Etiology in Sri Lanka?

    Jayasumana, Channa; Gunatilake, Sarath; Senanayake, Priyantha

    2014-01-01

    The current chronic kidney disease epidemic, the major health issue in the rice paddy farming areas in Sri Lanka has been the subject of many scientific and political debates over the last decade. Although there is no agreement among scientists about the etiology of the disease, a majority of them has concluded that this is a toxic nephropathy. None of the hypotheses put forward so far could explain coherently the totality of clinical, biochemical, histopathological findings, and the unique geographical distribution of the disease and its appearance in the mid-1990s. A strong association between the consumption of hard water and the occurrence of this special kidney disease has been observed, but the relationship has not been explained consistently. Here, we have hypothesized the association of using glyphosate, the most widely used herbicide in the disease endemic area and its unique metal chelating properties. The possible role played by glyphosate-metal complexes in this epidemic has not been given any serious consideration by investigators for the last two decades. Furthermore, it may explain similar kidney disease epidemics observed in Andra Pradesh (India) and Central America. Although glyphosate alone does not cause an epidemic of chronic kidney disease, it seems to have acquired the ability to destroy the renal tissues of thousands of farmers when it forms complexes with a localized geo environmental factor (hardness) and nephrotoxic metals. PMID:24562182

  14. Influence of fluoride on streptozotocin induced diabetic nephrotoxicity in mice: Protective role of Asian ginseng (Panax ginseng & banaba (Lagerstroemia speciosa on mitochondrial oxidative stress

    Mahaboob P Basha

    2013-01-01

    Full Text Available Background & objectives: Chronic fluoride intoxication through drinking water is a serious health problem. Patients with diabetes are known to have impaired renal function and elimination of fluoride from the body is mainly done through kidney. Fluoride toxicity in diabetes patients may aggravate complications. In this study, the influence of fluoride was assessed on streptozotocin (STZ induced diabetes in mice as also the efficacy/protective effective of oral supplementation of ginseng (GE and banaba leaf extracts (BLE. Methods: The efficacy of plant extracts, GE and BLE at doses of 50, 150, 250 mg/kg b.w./day alone and in combination, was tested for a period of 15 days on fluoride treated STZ induced diabetic animals. Results: Fluoride exposure to mice with STZ-induced diabetes produced significant changes in OSI (organo-somatic index, fluoride content, blood glucose, urea, serum creatinine and oxidative stress indices in kidney tissues with evident histological alterations. Among the antioxidant treatments, combination therapy of GE and BLE at 150 mg/kg b.w. significantly normalized the impaired biochemical variables in kidney tissues of fluoride toxicated diabetic mice. Interpretations & conclusions: High fluoride uptake was found to be diabetogenic and further aggravated the renal oxidative damage and thereby the toxicity in mice with STZ induced diabetes mice. GE and BLE exposure individually or in combination at a dose of 150 mg/kg b.w./day for 15 days exhibited protective effects on fluoride toxicated STZ induced nephrotoxicity in mice.

  15. Biochemical indicators of nephrotoxicity in blood serum of rats treated with novel 4-thiazolidinone derivatives or their complexes with polyethylene glycol-containing nanoscale polymeric carrier

    L. I. Kоbylinska

    2016-02-01

    Full Text Available The aim of this study was to compare the effect of new synthetic 4-thiazolidinone derivatives (potential anticancer compounds denoted as 3882, 3288 and 3833 and doxorubicin (positive control in free form and in their complexes with synthetic polyethylene glycol-containing nanoscale polymeric carrier on the biochemical indicators of nephrotoxicity in blood serum of rats. The concentration of total protein, urea, creatinine, glucose, ions of sodium, potassium, calcium, iron and chloride was measured. It was found that after injection of the investigated compounds, the concentration of sodium cations and chloride anions in blood serum was increased compared with control (untreated animals. Doxorubicin’s injection was accompanied by a decrease in the concentration of iron cations. The concentration of total protein, urea and creatinine decreased under the influence of the studied compounds. Complexation of these аntineoplastic substances with a synthetic polymeric nanocarrier lowered the concentration of the investigated metabolites substantially compared to the effect of these compounds in free form. The normalization of concentration of total protein, urea and creatinine in blood serum of rats treated with complexes of the studied compounds with the polymeric carrier comparing with increased concentration of these indicators at the introduction of such compounds in free form was found.

  16. Hyper-alkalinization without hyper-hydration for the prevention of high-dose methotrexate acute nephrotoxicity in patients with osteosarcoma.

    Mir, Olivier; Ropert, Stanislas; Babinet, Antoine; Alexandre, Jérôme; Larousserie, Frédérique; Durand, Jean-Philippe; Enkaoua, Eric; Anract, Philippe; Goldwasser, François

    2010-11-01

    To evaluate the reliability and renal safety of an original schedule of high-dose methotrexate (HDMTX) administration with hyper-alkalinization, and without hyper-hydration. Patients with osteosarcoma received HDMTX (8-12 g/m(2)) as a 4-h infusion. Hypertonic 8.4% sodium bicarbonate was infused prior to HDMTX, then once daily for 3 days. Methotrexate serum concentrations were measured at hour 4 (Cmax), hour 24, hour 48, and hour 72. Urinary pH was measured on each miction. Serum creatinine was assessed on days 1, 3, and 8. Twenty-six patients (median age: 18 years, range: 15-25) received a total of 344 cycles of HDMTX, including 16 patients treated in an outpatient basis. Urinary pH remained constantly higher than 7.5 in all patients. Grade 1 creatininemia toxicity was observed in 31 cycles (9%), and grade 2 creatinine toxicity was observed in one patient. No episode of acute severe nephrotoxicity was observed. No significant worsening was observed in serum creatinine and calculated creatinine clearance from baseline to the end of therapy (P = 0.74). The main extra-renal toxicity was alkalinization-related hypokalemia from H48. No re-hospitalization was required. Hyper-alkalinization appears an efficient and reliable method to prevent the acute renal toxicity of HDMTX and allows its safe administration in the outpatient setting.

  17. Male breast pathology

    Puebla, C.; Sainz, J.M.; Pujala, M.; Villavieja, J.L.

    1998-01-01

    To review the specific radiological signs of male breast pathology observed in our center over the past five years, as well as the pertinent medical literature. A retrospective study was carried out of the 47 mammographic studies performed in 41 men. Oblique mediolateral and craniocaudal views were employed. The distribution of different types of male breast pathology among our patients was as follows: gynecomastia was detected in 30 cases (73.1%), pseudogynectomastia in 4 (9.7%), carcinoma in 3(7.3%), abscess in 2 (4.9%), lipoma in 1 (2.5%) and epidermoid cyst in the remaining patient (2.5%). The results obtained agree with those reported in the literature reviewed. The most significant findings were the low incidence of carcinoma and the high rate of gynecomastia. (Author) 26 refs

  18. Advances in Male Contraception

    Page, Stephanie T.; Amory, John K.; Bremner, William J.

    2008-01-01

    Despite significant advances in contraceptive options for women over the last 50 yr, world population continues to grow rapidly. Scientists and activists alike point to the devastating environmental impacts that population pressures have caused, including global warming from the developed world and hunger and disease in less developed areas. Moreover, almost half of all pregnancies are still unwanted or unplanned. Clearly, there is a need for expanded, reversible, contraceptive options. Multicultural surveys demonstrate the willingness of men to participate in contraception and their female partners to trust them to do so. Notwithstanding their paucity of options, male methods including vasectomy and condoms account for almost one third of contraceptive use in the United States and other countries. Recent international clinical research efforts have demonstrated high efficacy rates (90–95%) for hormonally based male contraceptives. Current barriers to expanded use include limited delivery methods and perceived regulatory obstacles, which stymie introduction to the marketplace. However, advances in oral and injectable androgen delivery are cause for optimism that these hurdles may be overcome. Nonhormonal methods, such as compounds that target sperm motility, are attractive in their theoretical promise of specificity for the reproductive tract. Gene and protein array technologies continue to identify potential targets for this approach. Such nonhormonal agents will likely reach clinical trials in the near future. Great strides have been made in understanding male reproductive physiology; the combined efforts of scientists, clinicians, industry and governmental funding agencies could make an effective, reversible, male contraceptive an option for family planning over the next decade. PMID:18436704

  19. Endometriosis in the male.

    Martin, J D; Hauck, A E

    1985-07-01

    An 83-year-old man with an endometrioma of the lower abdominal wall has been reported. This occurred following the administration of 25 mg of TACE for a period of about 10 years for what was thought to be carcinoma of the prostate. A second transurethral resection done by Dr. R. C. Thompson proved to be adenocarcinoma. Subsequent to this he was continued on TACE. A review of the more commonly accepted theories of the development of endometriosis in the female has been presented. It is pointed out that the separation between the male and female urogenital systems occurs in the embryo between the eighth week and the fourth month. There is always a possibility for remnants of the opposite sex to remain in individuals. No such was seen in the case which is herein reported. Normal phenotype male was demonstrated in the chromosomal evaluation. A review of the literature on endometriosis in the male reveals several cases which have occurred; the origin of which is though to be from the prostatic utricle which is a remnant of the uterus existing in the male. After a prolonged course the patient reported was followed until he died in 1979. There was no recurrence of the abdominal wall mass but persistent low grade carcinoma of the prostate remained. The terminal process was related to cardiovascular disease and not carcinoma of the prostate. There was delay in publication of this unusual case. The original plan was to await final confirmation of the exact pathologic nature of this condition; unfortunately this was never done since a postmortem examination was not performed.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Male Body Contouring.

    Singh, Babu; Keaney, Terrence; Rossi, Anthony M

    2015-09-01

    Men are increasingly turning to dermatologists and plastic surgeons to request procedures that correct or enhance physical features. With the advent of this emerging new patient population, alterations in preexisting aesthetic techniques, gender-specific uses of existing devices and overall approaches need to be revisited and adapted to obtain results that are suitable for the male patient. Recently, body contouring has become one of the most sought out procedures by men. Although the majority of clinical studies involving body contouring esthetics are performed with female patients, gains from such studies can be extrapolated to men. Body contouring can be broadly classified as non-invasive or invasive, depending on the modality used. Non-invasive contouring is most frequently performed with devices that target subcutaneous adipose with focused electrical or thermal energy, including low-level laser, cryolipolysis, ultrasonography, and radiofrequency. Invasive body contouring modalities useful for male body contouring include liposuction, pectoral and abdominal wall etching, jawline fillers, synthetic deoxycholic acid injections, and solid silicone implants. The purpose of this review is to bring attention to the unique aspects, strategies, and modalities used in aesthetic body contouring for the male patient.

  1. Gender-disturbed males.

    Levine, S B

    1993-01-01

    Adolescent and adult cross-dressing or "transvestism" is the most common antecedent behavioral pattern among those who request sex reassignment surgery. Transvestites are actually a diverse group of men who differ in their gender identities, orientation, and intention. They do, however, have in common a soothing image of themselves as women. Because of this, whether cross-dressing occurs among masculine or feminine males or heterosexuals, homosexuals, bisexuals, or asexuals, or among those with paraphilia, the behavior should be considered the expression of their consciously felt femininity. The confusing differences among cross-dressing males may be explained by their diversity along three dimensions: 1) the ambition for heterosexual intercourse; 2) the natural history of their sexual arousal to female clothing; 3) their current capacity to integrate their masculine and feminine strivings into separate compartments. When cross-dressers give up all vestiges of male gender role behaviors and successfully live and work full time as women, the appropriate descriptive term for them becomes "transsexual."

  2. Cross-study and cross-omics comparisons of three nephrotoxic compounds reveal mechanistic insights and new candidate biomarkers

    Matheis, Katja A.; Com, Emmanuelle; Gautier, Jean-Charles; Guerreiro, Nelson; Brandenburg, Arnd; Gmuender, Hans; Sposny, Alexandra; Hewitt, Philip; Amberg, Alexander; Boernsen, Olaf; Riefke, Bjoern; Hoffmann, Dana; Mally, Angela; Kalkuhl, Arno; Suter, Laura; Dieterle, Frank; Staedtler, Frank

    2011-01-01

    The European InnoMed-PredTox project was a collaborative effort between 15 pharmaceutical companies, 2 small and mid-sized enterprises, and 3 universities with the goal of delivering deeper insights into the molecular mechanisms of kidney and liver toxicity and to identify mechanism-linked diagnostic or prognostic safety biomarker candidates by combining conventional toxicological parameters with 'omics' data. Mechanistic toxicity studies with 16 different compounds, 2 dose levels, and 3 time points were performed in male Crl: WI(Han) rats. Three of the 16 investigated compounds, BI-3 (FP007SE), Gentamicin (FP009SF), and IMM125 (FP013NO), induced kidney proximal tubule damage (PTD). In addition to histopathology and clinical chemistry, transcriptomics microarray and proteomics 2D-DIGE analysis were performed. Data from the three PTD studies were combined for a cross-study and cross-omics meta-analysis of the target organ. The mechanistic interpretation of kidney PTD-associated deregulated transcripts revealed, in addition to previously described kidney damage transcript biomarkers such as KIM-1, CLU and TIMP-1, a number of additional deregulated pathways congruent with histopathology observations on a single animal basis, including a specific effect on the complement system. The identification of new, more specific biomarker candidates for PTD was most successful when transcriptomics data were used. Combining transcriptomics data with proteomics data added extra value.

  3. Gynecomastia in Adolescent Males

    Lemaine, Valerie; Cayci, Cenk; Simmons, Patricia S.; Petty, Paul

    2013-01-01

    Gynecomastia is defined as an enlargement of the male breast. It is often benign, and can be the source of significant embarrassment and psychological distress. A general medical history and careful physical examination are essential to distinguish normal developmental variants from pathological causes. Treatment is geared toward the specific etiology when identified. In the majority of cases of pubertal gynecomastia, observation and reassurance are the mainstays of therapy as the condition usually resolves naturally. Pharmacological treatment and surgery are recommended only in selected cases. PMID:24872741

  4. Characteristics of genomic signatures derived using univariate methods and mechanistically anchored functional descriptors for predicting drug- and xenobiotic-induced nephrotoxicity.

    Shi, Weiwei; Bugrim, Andrej; Nikolsky, Yuri; Nikolskya, Tatiana; Brennan, Richard J

    2008-01-01

    ABSTRACT The ideal toxicity biomarker is composed of the properties of prediction (is detected prior to traditional pathological signs of injury), accuracy (high sensitivity and specificity), and mechanistic relationships to the endpoint measured (biological relevance). Gene expression-based toxicity biomarkers ("signatures") have shown good predictive power and accuracy, but are difficult to interpret biologically. We have compared different statistical methods of feature selection with knowledge-based approaches, using GeneGo's database of canonical pathway maps, to generate gene sets for the classification of renal tubule toxicity. The gene set selection algorithms include four univariate analyses: t-statistics, fold-change, B-statistics, and RankProd, and their combination and overlap for the identification of differentially expressed probes. Enrichment analysis following the results of the four univariate analyses, Hotelling T-square test, and, finally out-of-bag selection, a variant of cross-validation, were used to identify canonical pathway maps-sets of genes coordinately involved in key biological processes-with classification power. Differentially expressed genes identified by the different statistical univariate analyses all generated reasonably performing classifiers of tubule toxicity. Maps identified by enrichment analysis or Hotelling T-square had lower classification power, but highlighted perturbed lipid homeostasis as a common discriminator of nephrotoxic treatments. The out-of-bag method yielded the best functionally integrated classifier. The map "ephrins signaling" performed comparably to a classifier derived using sparse linear programming, a machine learning algorithm, and represents a signaling network specifically involved in renal tubule development and integrity. Such functional descriptors of toxicity promise to better integrate predictive toxicogenomics with mechanistic analysis, facilitating the interpretation and risk assessment of

  5. Diabetic mice are protected from normally lethal nephrotoxicity of S-1,2-dichlorovinyl-L-cysteine (DCVC): role of nephrogenic tissue repair

    Dnyanmote, Ankur V.; Sawant, Sharmilee P.; Lock, Edward A.; Latendresse, John R.; Warbritton, Alan A.; Mehendale, Harihara M.

    2006-01-01

    Streptozotocin (STZ)-induced diabetic (DB) rats are protected from nephrotoxicity of gentamicin, cisplatin and mercuric chloride, although the mechanisms remain unclear. Ninety percent of DB mice receiving a LD90 dose (75 mg/kg, ip) of S-1,2-dichlorovinyl-L-cysteine (DCVC) survived in contrast to only 10% of the nondiabetic (NDB) mice surviving the same dose. We tested the hypothesis that the mechanism of protection is upregulated tissue repair. In the NDB mice, DCVC produced steep temporal increases in blood urea nitrogen (BUN) and plasma creatinine, which were associated with proximal tubular cell (PTC) necrosis, acute renal failure (ARF), and death within 48 h. In contrast, in the DB mice, BUN and creatinine increased less steeply, declining after 36 h to completely resolve by 96 h. HPLC analysis of plasma and urine revealed that DB did not alter the toxicokinetics of DCVC. Furthermore, activity of renal cysteine conjugate β-lyase, the enzyme that bioactivates DCVC, was unaltered in DB mice, undermining the possibility of lower bioactivation of DCVC leading to lower injury. [3H]-thymidine pulse labeling and PCNA analysis indicated an early onset and sustained nephrogenic tissue repair in DCVC-treated DB mice. BRDU immunohistochemistry revealed a fourfold increase in the number of cells in S-phase in the DB kidneys even without exposure to DCVC. Blocking the entry of cells into S-phase by antimitotic intervention using colchicine abolished stimulated nephrogenic tissue repair and nephroprotection. These findings suggest that preplacement of S-phase cells in the kidney due to diabetes is critical in mitigating the progression of DCVC-initiated renal injury by upregulation of tissue repair, leading to survival of the DB mice by avoiding acute renal failure

  6. The Effect of Boric Acid and Borax on Oxidative Stress, Inflammation, ER Stress and Apoptosis in Cisplatin Toxication and Nephrotoxicity Developing as a Result of Toxication.

    Hazman, Ömer; Bozkurt, Mehmet Fatih; Fidan, Abdurrahman Fatih; Uysal, Fadime Erkan; Çelik, Sefa

    2018-03-02

    The development of treatment protocols that can reduce side effects in chemotherapy applications is extremely important in terms of cancer treatment. In this context, it was aimed to investigate the effects of boric acid and borax on cisplatin toxicity (nephrotoxicity) in rats. In the experimental phase, eight groups were formed from rats. Boric acid and borax were given to the treatment groups with three different doses using gavage. On the fifth day of the study, cisplatin (10 mg/kg) was administered to all rats except the control group. At the end of the study, oxidative stress-related (GSH, MDA, PCO, GPx, 8-OHdG), inflammation-related (TNF-α, IL-1β, IL-18, MCP-1, ICAM, TGF-β), apoptosis-related (p53, caspase 1, 3, 8, 12, bcl-2, bcl-xL, NFkB), and ER stress-related (GRP78, ATF-6, PERK) basic parameters were analyzed in serum, erythrocyte, and kidney tissues. Kidney tissues were also examined by histopathological and immunohistochemical methods. Borax and boric acid at different doses decreased inflammation and oxidative stress caused by cisplatin toxicity and increased ER stress. As a result of the treatments applied to experimental animals, it was determined that boric acid and borax reduced apoptotic damage in kidney tissue, but the decrease was statistically significant only in 200 mg/kg boric acid-administered group. In the study, low anti-apoptotic effects of borate doses with the anti-inflammatory and antioxidant effect may be due to increased ER stress at the relevant doses. Further studies on the effects of boron compounds on ER stress and apoptotic mechanisms may clarify this issue. Thus, possible side effects or if there are new usage areas of borone compounds which have many usage areas in clinics can be detected.

  7. Experiencing Male Infertility

    Esmée Hanna

    2015-10-01

    Full Text Available This article examines the qualitative research literature that exists in relation to men’s experiences of male infertility. Since men have often been marginalized in the realm of reproduction, including academic research on infertility, it is important to focus on any qualitative research that gives voices to male perspectives and concerns. Given the distress documented by studies of infertile women, we focus in particular on the emotive responses and lived experiences of men in relation to infertility. In this article then, we present an analysis of the core themes across 19 qualitative articles, which include “infertility as crisis”; “emoting infertility- men as “being strong”’ “infertility as a source of stigma”; and the “desire for fatherhood.” In light of these insights, we identify key areas for future research and development including men’s emotional responses to infertility, how men seek support for infertility, the intersection between masculinity and infertility, the relationship between the desire to father and infertility, and the outcomes of infertility for men in terms of other aspects of their lives. We suggest that such research would facilitate making the experiences of men more central within our understandings of infertility within a field that has primarily been female focused.

  8. Imaging of male urethra

    Pavlica, Pietro; Barozzi, Libero; Menchi, Ilario

    2003-01-01

    The male urethral imaging and pathology is not widespread in the radiology literature because this part of the urinary tract is easily studied by urologists with clinical or endoscopic examinations. Ultrasonography and MR imaging are increasingly being used in association with voiding cystourethrography and retrograde urethrography. The posterior urethra is being studied with voiding cystourethrography or voiding sonography which allows the detection of bladder neck pathology, post-surgical stenosis, and neoplasms. The functional aspects of the bladder neck and posterior urethra can be monitored continuously in patients with neuromuscular dysfunction of the bladder. The anterior urethral anatomy and pathology is commonly explored by retrograde urethrography, but recently sonourethrography and MR imaging have been proposed, distending the lumen with simple saline solution instead of iodinated contrast media. They are being used to study the urethral mucosa and the periurethral spongy tissue which can be involved in the urethral pathologies such as strictures, diverticula, trauma, and tumors. Imaging has an important role to play in the study of the diseases of the male urethra since it can detect pathology not visible on urethroscopy. The new imaging techniques in this area, such as sonography and MR, can provide adjunct information that cannot be obtained with other modalities. (orig.)

  9. Male breast cancer

    Ferrando, F.; Vidal, M.A.; Caballero, A.J.; Martinez, A.; Lluch, A.

    1997-01-01

    To analyze the radiological and ultrasonographic signs that contribute to the diagnosis of male breast cancer to establish its differential diagnosis with regard to the most common pathologies involving the male breast. We studied 14 patients diagnosed as heaving breast cancer over the past 23 years. We reviewed their medical records, personal and familial history disease, use of pharmacological agents and the mammographic and ultrasonographic findings. The literature on this subject was also reviewed. Given the fact that his lesion is rare and unexpected in men, a large percentage of the cases, especially those studied in the early years of the study period, involved very advanced stages of the disease at diagnosis. The most common clinical finding was retroarelar mass. Mammography usually reveals a well.defined mass and ultrasound shows a well-defined, hypoechoic, heterogeneous mass. The most frequent histological type is, an in women, the infiltrating ductal carcinoma. A palpable breast mass in a man should suggest possible malignant disease. Thus, mammographic and ultrasonographic studies should be performed early, accompanied, if necessary, by aspiration biopsy; with these measures the prognosis may approximate that of women. (Author) 21 refs

  10. Imaging of male urethra

    Pavlica, Pietro [Department of Diagnostic Radiology, Hospital M. Malpighi, Via Palagi 9, 40138 Bologna (Italy); Barozzi, Libero [Department of Emergency Radiology, Hospital S. Orsola-Malpighi, 40138 Bologna (Italy); Menchi, Ilario [Department of Diagnostic Radiology, Hospital S. Maria Nuova, 55100 Florence (Italy)

    2003-07-01

    The male urethral imaging and pathology is not widespread in the radiology literature because this part of the urinary tract is easily studied by urologists with clinical or endoscopic examinations. Ultrasonography and MR imaging are increasingly being used in association with voiding cystourethrography and retrograde urethrography. The posterior urethra is being studied with voiding cystourethrography or voiding sonography which allows the detection of bladder neck pathology, post-surgical stenosis, and neoplasms. The functional aspects of the bladder neck and posterior urethra can be monitored continuously in patients with neuromuscular dysfunction of the bladder. The anterior urethral anatomy and pathology is commonly explored by retrograde urethrography, but recently sonourethrography and MR imaging have been proposed, distending the lumen with simple saline solution instead of iodinated contrast media. They are being used to study the urethral mucosa and the periurethral spongy tissue which can be involved in the urethral pathologies such as strictures, diverticula, trauma, and tumors. Imaging has an important role to play in the study of the diseases of the male urethra since it can detect pathology not visible on urethroscopy. The new imaging techniques in this area, such as sonography and MR, can provide adjunct information that cannot be obtained with other modalities. (orig.)

  11. Protective effect of Moringa oleifera oil against HgCl2-induced hepato- and nephro-toxicity in rats.

    Abarikwu, Sunny O; Benjamin, Sussan; Ebah, Sunday Godspower; Obilor, Godbless; Agbam, Goodluck

    2017-07-26

    Various parts of the Moringa oleifera (M. oleifera) tree are widely accepted to have ameliorative effects against metal toxicity. In the present study, M. oleifeira oil (MO) was tested against HgCl2-induced tissue pathologies and oxidative stress. Male Wistar rats were administered MO (1.798 mg/kg p.o.) or HgCl2 (5 mg/kg body wt) alone or in combination (5 mg/kg HgCl2+1.798 mg/kg MO p.o.) three times per week for 21 days. After exposure and treatment periods, rats were sacrificed; blood collected and the oxidative status of the liver and kidney homogenates were evaluated. In the liver, malondialdehyde (MDA) level, glutathione (GSH), and superoxide dismutase (SOD) activities were higher whereas catalase (CAT) activity was lower in the HgCl2 group than in the control group. In the kidney, MDA level, SOD, and CAT activities were higher whereas GSH activity was unchanged in the HgCl2 group compared to the control group. In the liver, MDA level, SOD, and CAT activities were lower in the HgCl2+MO group than in the HgCl2 group. In the kidney, MDA level, SOD and CAT activities were lower in the HgCl2+MO than in the HgCl2 group. Furthermore, Hg-induced increases in creatinine and bilirubin levels as well as the increase in γ-glutamyl transferase, lactate dehydrogenase, and alkaline phosphatase activities were attenuated in the combine exposure group and the animals showed improvement in the histology of the liver and kidney. MO decreased the negative effects of Hg-induced oxidative stress in rats.

  12. Hepatotoxicity, Nephrotoxicity and Oxidative Stress in Rat Testis Following Exposure to Haloxyfop-p-methyl Ester, an Aryloxyphenoxypropionate Herbicide

    Ebenezer Tunde Olayinka

    2015-10-01

    Full Text Available Haloxyfop-p-methyl ester (HPME ((R-2-{4-[3-chloro-5-(trifluoromethyl-2-pyridyloxy]phenoxy}propionic acid, is a selective aryloxyphenoxypropionate (AOPP herbicide. It exerts phytotoxicity through inhibition of lipid metabolism and induction of oxidative stress in susceptible plants. This study investigated the toxicological potentials of HPME in rats. Twenty-four male Wistar rats (170–210 g were randomized into four groups (I–IV. Group I (control received 1 mL of distilled water, while animals in Groups II, III and IV received 6.75, 13.5 and 27 mg/kg body weight HPME, respectively, for 21 days. There was a significant (p < 0.05 increase in renal and hepatic function biomarkers (urea, creatinine, total bilirubin, ALP, ALT, AST in the plasma of treated animals compared to control. Levels of testicular antioxidants, ascorbic acid and glutathione, and activities of glutathione-S-transferase, superoxide dismutase and catalase were reduced significantly after 21 days of HPME administration in a dose-dependent manner. The testicular malondialdehyde level increased significantly in the HPME-treated rats relative to the control. A significant decrease in testicular lactate dehydrogenase, acid phosphatase and γ-glutamyl transferase was also observed in HPME-treated animals. Testicular histology revealed severe interstitial edema and sections of seminiferous tubules with necrotic and eroded germinal epithelium in the HPME-treated rats. Overall, data from this study suggest that HPME altered hepatic and renal function and induced oxidative stress and morphological changes in the testis of rats.

  13. Peptide receptor radionuclide therapy with 177Lu-DOTA-octreotate: dosimetry, nephrotoxicity, and the effect of hematological toxicity on survival.

    Löser, Anastassia; Schwarzenböck, Sarah M; Heuschkel, Martin; Willenberg, Holger S; Krause, Bernd J; Kurth, Jens

    2018-03-01

    Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (Lu)-DOTATATE is regarded as a safe treatment option with promising results for patients with neuroendocrine neoplasia (NEN). We aimed to study the absorbed organ and tumor doses, the renal and hematological toxicity as well as their mutual interaction. Another aim was the identification of adverse effects as possible predictors which may affect survival. A total of 30 (14 female and 16 male) patients with inoperable/metastatic NEN were treated with 7.4 GBq of Lu-DOTATATE. Occurrence of renal and hematological toxicity wasretrospectively studied. Morever, we examined the effects of hematological toxicity on survival after Lu-DOTATATE-PRRT. In 49 treatment cycles, the mean absorbed dose to the kidneys was 5.13±2.12, 4.49±2.49 Gy to the liver, and 14.44±8.97 Gy to the spleen, whereas tumor lesions absorbed a mean dose of 31.43±36.86 Gy. Comparing different localizations of metastases, no significant differences in absorbed dose were observed. Clinical response status revealed regressive disease in 47.6%, stable disease in 38.1%, and progressive disease in 14.3% of cases (n=21). Biochemically, 81.3% of patients showed reduced serotonin values (n=16; P<0.05) following Lu-DOTATATE-PRRT. No severe subacute renal or hematological toxicity occurred (one Common Terminology Criteria for Adverse Events-grade 3 for thrombocytopenia and another one for leukocytopenia). No statistically significant relation between baseline kidney function and post-therapeutic hematological changes was identified. The findings indicate that Lu-DOTATATE-PRRT is a safe and effective treatment method for patients with NEN. Moreover, these data strongly suggest that hematological parameters may affect survival so a further re-evaluation in prospective studies is warranted.

  14. Sexual Selection on male cuticular hydrocarbons via male-male competition and female choice.

    Lane, S M; Dickinson, A W; Tregenza, T; House, C M

    2016-07-01

    Traditional views of sexual selection assumed that male-male competition and female mate choice work in harmony, selecting upon the same traits in the same direction. However, we now know that this is not always the case and that these two mechanisms often impose conflicting selection on male sexual traits. Cuticular hydrocarbons (CHCs) have been shown to be linked to both social dominance and male attractiveness in several insect species. However, although several studies have estimated the strength and form of sexual selection imposed on male CHCs by female mate choice, none have established whether these chemical traits are also subject to sexual selection via male-male competition. Using a multivariate selection analysis, we estimate and compare sexual selection exerted by male-male competition and female mate choice on male CHC composition in the broad-horned flour beetle Gnatocerus cornutus. We show that male-male competition exerts strong linear selection on both overall CHC abundance and body size in males, while female mate choice exerts a mixture of linear and nonlinear selection, targeting not just the overall amount of CHCs expressed but the relative abundance of specific hydrocarbons as well. We discuss the potential implications of this antagonistic selection with regard to male reproductive success. © 2016 The Authors. Journal of Evolutionary Biology published by John Wiley & Sons Ltd on behalf of European Society for Evolutionary Biology.

  15. Hepatic injury induces contrasting response in liver and kidney to chemicals that are metabolically activated: Role of male sex hormone

    Kim, Young C.; Yim, Hye K.; Jung, Young S.; Park, Jae H.; Kim, Sung Y.

    2007-01-01

    Injury to liver, resulting in loss of its normal physiological/biochemical functions, may adversely affect a secondary organ. We examined the response of the liver and kidney to chemical substances that require metabolic activation for their toxicities in mice with a preceding liver injury. Carbon tetrachloride treatment 24 h prior to a challenging dose of carbon tetrachloride or acetaminophen decreased the resulting hepatotoxicity both in male and female mice as determined by histopathological examination and increases in serum enzyme activities. In contrast, the renal toxicity of the challenging toxicants was elevated markedly in male, but not in female mice. Partial hepatectomy also induced similar changes in the hepatotoxicity and nephrotoxicity of a challenging toxicant, suggesting that the contrasting response of male liver and kidney was associated with the reduction of the hepatic metabolizing capacity. Carbon tetrachloride pretreatment or partial hepatectomy decreased the hepatic xenobiotic-metabolizing enzyme activities in both sexes but elevated the renal p-nitrophenol hydroxylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase activities significantly only in male mice. Increases in Cyp2e1 and Cyp2b expression were also evident in male kidney. Castration of males or testosterone administration to females diminished the sex-related differences in the renal response to an acute liver injury. The results indicate that reduction of the hepatic metabolizing capacity induced by liver injury may render secondary target organs susceptible to chemical substances activated in these organs. This effect may be sex-specific. It is also suggested that an integrated approach should be taken for proper assessment of chemical hazards

  16. Investigations of nephrotoxicity caused by ionic and non-ionic contrast media in rats with previously damaged and not previously damaged kidneys and special view to urinary enzyme determinations

    Hofmeister, R.

    1988-01-01

    In this study ionic (meglumine amidotrizoate) and non-ionic contrast media (SHH 340 AB, Iohexol, Iopromide, Iosimide and Iopamidol) were tested for their nephrotoxicity in rats. During the experiment detections of urea nitrogen, serum creatinine and urinary enzymes as well as histological examinations of the kidneys were carried out for the diagnosis of acute renal damage. The results obtained in this study demonstrate that rats are not very sensitive to non-ionic contrast media with regard to kidney damage and determinations of urinary enzymes are valuable for the diagnosis of contrast media induced acute kidney damage in living animals. (orig./MG) [de

  17. Gene expression changes induced by ochratoxin A in renal and hepatic tissues of male F344 rat after oral repeated administration

    Arbillaga, Leire; Vettorazzi, Ariane; Gil, Ana G; Delft, Joost van; Garcia-Jalon, Jose Antonio; Lopez de Cerain, Adela

    2008-01-01

    Ochratoxin A (OTA), a naturally occurring mycotoxin, is nephrotoxic in all animal species tested and is considered a potent renal carcinogen, particularly in male rats. Its mechanism of toxicity is still unknown, although oxidative stress appears to be a plausible mechanism. Therefore, the objective of this study was to identify the biological pathways that are modulated in vivo by OTA in male F344 rats in order to gain further insight into its mechanism of renal toxicity. Rats were gavaged daily with OTA (500 μg/kg bw) and gene expression profiles in target and non-target organs were analyzed after 7 and 21 days administration. As was expected, a time-dependent increase of OTA concentrations was found in plasma, kidney and liver, with the concentrations found in both tissues being quite similar. However, histopathological examinations only revealed changes in kidney; signs of nephrotoxicity involving single cell necrosis and karyomegalic nuclei were observed in the treated rats. The number of differentially expressed genes in kidney was much higher than in liver (541 versus 11 at both time points). Several similarities were observed with other in vivo gene expression data. However, great differences were found with previous in vitro gene expression data, with the exception of DNA damage response which was not observed at mRNA level in any of our study conditions. Down-regulation was the predominant effect. Oxidative stress response pathway and genes involved in metabolism and transport were inhibited at both time points. RGN (regucalcin) - a gene implicated in calcium homeostasis - was strongly inhibited at both time points and genes implicated in cell survival and proliferation were up-regulated at day 21. Moreover, translation factors and annexin genes were up-regulated at both time points. Apart from oxidative stress, alterations of the calcium homeostasis and cytoskeleton structure may be present at the first events of OTA toxicity

  18. Occupational causes of male infertility

    Bonde, Jens P E

    2013-01-01

    To highlight and discuss the new evidence on occupational and environmental risk to male reproductive function.......To highlight and discuss the new evidence on occupational and environmental risk to male reproductive function....

  19. Sport and male sexuality.

    Sgrò, P; Di Luigi, L

    2017-09-01

    The relationships between sport and sexuality in males are of great social and clinical interest, because of sports and motor activities that highly promote social and sexual relationships. Even if few literature exist, two main questions should be taken into account: whether and how physical exercise and sport positively or negatively influence sexual health and behavior and/or whether and how sexual behavior may affect a sub-sequent sport performance. Physical exercise and sport per se can influence, positively or negatively, the hypothalamic-pituitary-testicular axis function and, consequently, the individual's reproductive and/or sexual health. This depends on individual factors such as genetic and epigenetic ones and on different variables involved in the practice of sport activities (type of sport, intensity and duration of training, doping and drug use and abuse, nutrition, supplements, psychological stress, allostatic load, etc.). If well conducted, motor and sport activities could have beneficial effects on sexual health in males. Among different lifestyle changes, influencing sexual health, regular physical activity is fundamental to antagonize the onset of erectile dysfunction (ED). However, competitive sport can lead both reproductive and/or sexual tract damages and dysfunctions, transient (genital pain, hypoesthesia of the genitalia, hypogonadism, DE, altered sexual drive, etc.) or permanent (hypogonadism, DE, etc.), by acting directly (traumas of the external genitalia, saddle-related disorders in cyclists, etc.) or indirectly (exercise-related hypogonadism, drug abuse, doping, stress, etc.). Sexual activities shortly performed before a sport competition could differently influence sport performance. Due to the few existing data, it is advisable to avoid an absolute pre-competition sexual abstinence.

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

    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.

  1. Coaching the alpha male.

    Ludeman, Kate; Erlandson, Eddie

    2004-05-01

    Highly intelligent, confident, and successful, alpha males represent about 70% of all senior executives. Natural leaders, they willingly take on levels of responsibility most rational people would find overwhelming. But many of their quintessential strengths can also make alphas difficult to work with. Their self-confidence can appear domineering. Their high expectations can make them excessively critical. Their unemotional style can keep them from inspiring their teams. That's why alphas need coaching to broaden their interpersonal tool kits while preserving their strengths. Drawing from their experience coaching more than 1,000 senior executives, the authors outline an approach tailored specifically for the alpha. Coaches get the alpha's attention by inundating him with data from 360-degree feedback presented in ways he will find compelling--both hard-boiled metrics and vivid verbatim comments from colleagues about his strengths and weaknesses. A 360-degree assessment is a wake-up call for most alphas, providing undeniable proof that their behavior doesn't work nearly as well as they think it does. That paves the way for a genuine commitment to change. In order to change, the alpha must venture into unfamiliar--and often uncomfortable--psychological territory. He must admit vulnerability, accept accountability not just for his own work for others', connect with his underlying emotions, learn to motivate through a balance of criticism and validation, and become aware of unproductive behavior patterns. The goal of executive coaching is not simply to treat the alpha as an individual problem but to improve the entire team dynamic. Initial success creates an incentive to persevere, and the virtuous cycle reverberates throughout the entire organization.

  2. The aging male project

    Farid Saad

    2001-06-01

    alpha estradiol have been synthesized some of which show selectivity for the central nervous system. CNS effects have been demonstrated in female and male animals. Cardiovascular protection by estrogens has been shown in animal and human studies. Atherosclerotic plaque size was reduced after estrogen injections in cholesterol-fed rabbits. Phytoestrogen-fed monkeys had lower total cholesterol and LDL cholesterol and higher HDL cholesterol. Apart from atherosclerotic lesions, coronary artery vascular reactivity was improved. Some of these experimental findings were confirmed in human studies in postmenopausal women with and without estrogen treatment. Whether all of the described estrogenic effects can be seen in men remains to be investigated. (Med J Indones 2001; 10: 127-33Keywords : aging, andropause, testosterone, estrogens

  3. Interferência do intervalo de administração da droga sobre a nefrotoxicidade da gentamicina em ratos Influence of the dose regimen on the gentamicin nephrotoxicity in rats

    Verônica Cunha Rodrigues Oliveira

    2001-06-01

    Full Text Available A insuficiência renal aguda (IRA que apresenta índice de mortalidade em torno de 50%, pode ser definida como um abrupto declínio da filtração glomerular, resultante de isquemia ou toxicidade. A nefrotoxicidade por drogas é uma das etiologias mais freqüentes (27% e sugere-se que o intervalo de administração da droga pode interferir neste efeito colateral, entretanto o melhor regime de administração ainda não está bem estabelecido. Este conhecimento proporcionaria uma atuação mais direcionada de enfermagem na prevenção desta IRA hospitalar. Os resultados obtidos nesta pesquisa, indicam que a infusão única de gentamicina determina menor nefrotoxicidade, provavelmente devido à redução da sua concentração plasmática nas 24hs, diminuindo o acúmulo intracelular deste fármaco, um dos principais mecanismos celulares deste tipo de lesão. Este regime de tratamento mostra portanto vantagens quanto ao custo, efeito nefrotóxico e segurança quanto à eficácia terapêutica.The acute renal failure (ARF, that still presents a righ mortality rate (50% can be defined as an abrupt decline of the glomerular filtration, resultant of isquemic or toxicity event. The drugs nephrotoxicity is one of the most frequent cause (27% of ARF and it is suggested that the interval of administration of the drug can interfere in this side effect, however the best administration regimen is not very well established. This study evaluated the renal function of rats that received gentamicin (100mg/kg in one dose or in two doses (2x 50mg/kg,by intraperitoneal infusion. The results obtained in this research, indicated that the single infusion of gentamicin determined smaller nephrotoxicity by the reduction of serum concentration of this drug in 24 hours, decreasing the intracelular accumulation of this gentamicin, which is one of the main cellular mechanisms of this renal injury. The single dose treatment regime, otherwise, showes advantages not only related

  4. EAMJ Nephrotoxicity Sep 09.indd

    2009-09-01

    Sep 1, 2009 ... Secondary objective was to determine all-cause mortality in the same group. Design: Prospective ... and hypomagnesaemia were high in this studied population. ... used tests include serum urea and serum creatinine.

  5. Male Depression: Understanding the Issues

    ... a healthy lifestyle, including healthy eating and regular physical activity, to help promote better mental health. Many effective treatments are available for depression. So don't try to tough out male ...

  6. Triadic male-infant-male interaction serves in bond maintenance in male Assamese macaques.

    Josefine Kalbitz

    Full Text Available While the ultimate consequences of social bonds start to be better understood, the proximate behavioural mechanisms underlying the formation and maintenance of these close affiliative relationships have received less attention. We investigated the possible function of male-infant-male interactions (MIMIs in male-male social bonding processes by analysing about 9000h of focal animal observations collected on two groups of wild Assamese macaques. In support of an agonistic buffering function of MIMIs, after engaging in a MIMI upon approach, subordinates stayed longer in close proximity of a dominant male. Overall, the frequency of MIMIs increased the stronger the affiliative relationship between two males, suggesting that MIMIs like grooming function in relationship maintenance. We did not find support for a role of MIMIs in bond formation as the frequency of MIMIs did not affect the time a male dyad spent in proximity in the consecutive year. Our results contribute to the general debate on behaviours influencing social dynamics in group living mammals.

  7. Ureaplasma Urealyticum in Male Infertility

    L P Deodbar

    1986-01-01

    Full Text Available Semen examination with special reference to semen analysis and culture for Ureaplasma urealyticum was carried out in 50 male infertile patients in the age group of 25 to 40 years, attending a private infertility clinic. Isolation of Ureaplasma urealyticum in 14 (28% patients and the abnormalities in count and motility of spermatozoa suggest that ureaplasmas may play a role in human male infertility.

  8. Hormonal Approaches to Male contraception

    Wang, Christina; Swerdloff, Ronald S.

    2010-01-01

    Purpose of review Condoms and vasectomy are male controlled family planning methods but suffer from limitations in compliance (condoms) and limited reversibility (vasectomy); thus many couples desire other options. Hormonal male contraceptive methods have undergone extensive clinical trials in healthy men and shown to be efficacious, reversible and appear to be safe. Recent Findings The success rate of male hormonal contraception using injectable testosterone alone is high and comparable to methods for women. Addition of progestins to androgens improved the rate of suppression of spermatogenesis. Supported by government or non-government organizations, current studies aim to find the best combination of testosterone and progestins for effective spermatogenesis suppression and to explore other delivery methods for these hormones. Translation of these advances to widespread use in the developed world will need the manufacturing and marketing skills of the pharmaceutical industry. Availability of male contraceptives to the developing world may require commitments of governmental and non-governmental agencies. In a time when imbalance of basic resources and population needs are obvious, this may prove to be a very wise investment. Summary Male hormonal contraception is efficacious, reversible and safe for the target population of younger men in stable relationships. Suppression of spermatogenesis is achieved with a combination of an androgen and a progestin. Partnership with industry will accelerate the marketing of a male hormonal contraceptive. Research is ongoing on selective androgen and progesterone receptor modulators that suppress spermatogenesis, minimize potential adverse events while retaining the androgenic actions. PMID:20808223

  9. Adolescent Male Human Papillomavirus Vaccination

    Vivian C. Nanagas MD, MSc

    2016-04-01

    Full Text Available Objective. To determine male vaccination rates with quadrivalent human papillomavirus vaccine (HPV4 before and after the October 2011 national recommendation to routinely immunize adolescent males. Methods. We reviewed HPV4 dose 1 (HPV4-1 uptake in 292 adolescent males in our urban clinic prior to national recommendations and followed-up for HPV4 series completion rates. After national recommendation, 248 urban clinic and 247 suburban clinic males were reviewed for HPV4-1 uptake. Factors associated with HPV4-1 refusal were determined with multiple logistic regression. Results. Of the initial 292 males, 78% received HPV4-1 and 38% received the 3-dose series. After recommendation, HPV4-1 uptake was 59% and 7% in urban and suburban clinics, respectively. Variables associated with HPV4-1 uptake/refusal included time period, race, type of insurance, and receipt of concurrent vaccines. Conclusions. HPV4-1 vaccination rates in our urban clinic were high before and after routine HPV vaccine recommendations for adolescent males. Our vaccination rates were much higher than in a suburban practice.

  10. Bilateral male breast cancer with male potential hypogonadism

    Kurokawa Yasushi

    2007-06-01

    Full Text Available Abstract Background Male breast cancer is a comparatively rare disease, and simultaneous bilateral male breast cancer is considered to be an extremely rare event. Risk factors are said to be genetic factors and hormonal abnormalities due to obesity or testicular diseases. Case presentation The patient was a 47-year-old Japanese male. His family had no history of female breast cancer. This patient also had hypospadias and hormonal examination indicated the presence of primary testicular potential hypogonadism, and these hormonal abnormalities seemed to be present since childhood or the fetal period. The bilateral breast cancer developed in this man at a comparatively young age, and histopathological studies of multiple sections showed that there was almost no normal epithelial cell in the ducts, while the ducts were almost completely filled with breast cancer cells. Conclusion It is thought that male breast cancer is caused by an imbalance between estrogen and testosterone. We cannot rule out the possibility that the breast cancer developed due to the effect of the slight elevation of estrogen over a long period of time, but the actual causative factors in this patient were unable to be definitively identified. In the future, we hope to further elucidate the causes of male breast cancer.

  11. Effect of Tea (Camellia sinensis and Olive (Olea europaea L. Leaves Extracts on Male Mice Exposed to Diazinon

    Atef M. Al-Attar

    2013-01-01

    Full Text Available The present study was aimed to evaluate the effects of tea and olive leaves extracts and their combination in male mice intoxicated with a sublethal concentration of diazinon. Exposure of mice to 6.5 mg/kg body weight of diazinon for seven weeks resulted in statistical increases of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase, creatine kinase, creatinine, glucose, triglycerides, and cholesterol, while the value of serum total protein was declined. Treating diazinon-intoxicated mice with tea and olive leaves extracts or their combination significantly attenuated the severe alterations in these hematobiochemical parameters. Moreover, the results indicated that the supplementation with combination of tea and olive leaves extracts led to more attenuation effect against diazinon toxicity. Additionally, these new findings suggest that the effect of tea and olive leaves extracts and their combination against toxicity of diazinon may be due to antioxidant properties of their chemical constituents. Finally, the present study indicated that the extracts of tea and olive leaves and their combination can be considered as promising therapeutic agents against hepatotoxicity, cardiotoxicity, nephrotoxicity, and metabolic disorders induced by diazinon and maybe by other toxicants and pathogenic factors.

  12. Protective Role of Carnitine against the Harmful Biological Effects of Paracetamol and Radiation Exposure in Male Albino Rats

    Abd El Rahman, N.A.

    2012-01-01

    L-carnitine, a natural component of mammalian tissue, is a necessary factor in the utilization of long-chain fatty acids to produce energy. Furthermore it has been shown to protect cells from per oxidative stress. The objective of the present study was to evaluate the efficacy of L-carnitine on hepatotoxicity and nephrotoxicity induced by paracetamol, γ-radiation, and paracetamol + γ-radiation. Male albino rats were divided into 8 groups. 1-Control group: rats not subject to any treatment, 2-Carnitine group: rats received L-carnitine (0.5 ml/Kg body weight) via intraperitoneal injection during 21 days, 3-Paracetamol group: rats received paracetamol (50 mg/kg body) via intraperi-toneal injection during 21 days, 4- Carnitine + Paracetamol group: rats received L-carnitine in parallel to paracetamol treatment, 5- Radiation groups: rats were whole body gamma irradiated with 7 Gy, 6- Carnitine + Radiation group: rats received L-carnitine for 21 days before whole body gamma irradiation with 7Gy, 7- Paracetamol + Radiation group: rats received paracetamol during 21 days before whole body gamma irradiation, 8- Carnitine + Paracetamol + Radiation group: rats received L-carnitine parallel to paracetamol during 21 days before whole body gamma irradiation.The results demonstrated that rats receiving paracetamol, as well as whole body gamma irradiated rats and rats receiving paracetamol and irradiated showed a significant increase of alanine amino transferase (ALT), aspartate amino transferase (AST), and alkaline phosphatase (ALP) activities, and a significant decrease of gamma-glutamyl transpeptidase (GGT) activity indicating liver injury. A significant increase of urea, creatinine and uric acid levels was recorded also indicating kidney damage. Alteration in liver and kidney functions was accompanied by a significant increase in the content of thiobarbituric acid reactive substances (TBARS) associated with a significant decrease in glutathione (GSH) content and superoxide

  13. [Male sexual and reproductive rights].

    Diaz, A M

    1998-06-01

    In late 1997, PROFAMILIA began a study of the role of male sexual and reproductive rights as part of the construction of new masculine identities. The work was approached from the disciplines of law and sociology. Patriarchy, as a system of domination, permeated most cultures, giving men a position of power in relation to women and leading to a series of violent and self-destructive male behaviors. The patriarchal system imposed aggressive, promiscuous, risky, and irresponsible behaviors on men, which created a climate for sexual abuse, unwanted pregnancy, propagation of sexually transmitted diseases, and violence against women. Changes in female roles have created the need for changes in male roles. The most visible sexual and reproductive needs of men were studied through literature reviews and semistructured questionnaires with PROFAMILIA clients. Among the needs identified were a new type of male participation in family and domestic life, a new content for male sexual freedom, greater participation of men in reproductive decisions and in raising their children, and new ways of relating to others and sharing feelings and emotions. The need to avoid behaviors that put health at risk was also identified. A review of the evolution of existing sexual and reproductive rights and of the documents that constitute their ethical and juridical framework led to the conclusion that the construction of new rights specifically for men is not necessary, or juridically possible, in the current historical context.

  14. Male density affects large-male advantage in the golden silk spider, Nephila clavipes

    Clare C. Rittschof

    2010-01-01

    Across a variety of animal taxa, the outcome of male--male contests depends on male body size; winners are usually the larger males or the males with bigger weapons. However, high male density can either increase or reverse large-male advantage because density changes the frequency and intensity of male--male interactions. In the golden orb-web spider Nephila clavipes, large males have a competitive advantage in male--male contests. However, this species shows more than 2-fold variation in ma...

  15. Management of male breast cancer

    Nikolay V. Dimitro v

    2011-12-01

    Full Text Available The management of male breast cancer is still under discussion due to lack of information from prospective, randomized clinical trials and low incidence of this disease. Current management is based largely on extrapolation from data related to treatment of female breast cancer. Over the last two decades, several review articles have discussed mainly retrospective and anecdotal data related to hormonal and chemotherapy treatment modalities. In this review, we present the most recent information and future considerations related to the management of male breast cancer. In addition to the conventional treatment options we will discuss the possible role of targeted therapy. Establishing a national or global registry for male breast cancer will provide more precise information about the natural history of the disease and will facilitate the design and execution of prospective, randomized multicenter clinical trials.

  16. Lifestyle causes of male infertility

    Damayanthi Durairajanayagam

    2018-03-01

    Full Text Available Objective: To examine the potential effects of lifestyle factors on male reproductive health. Evidence of a global decline in human sperm quality over recent decades has been accumulating. Environmental, occupational, and modifiable lifestyle factors may contribute to this decline. This review focuses on key lifestyle factors that are associated with male infertility such as smoking cigarettes, alcohol intake, use of illicit drugs, obesity, psychological stress, advanced paternal age, dietary practices, and coffee consumption. Other factors such as testicular heat stress, intense cycling training, lack of sleep and exposure to electromagnetic radiation from mobile phone use are briefly discussed. Materials and method: A comprehensive literature search was performed to identify and synthesise all relevant information, mainly from within the last decade, on the major lifestyle factors associated with male infertility and semen quality. Database searches were limited to reports published in English only. A manual search of bibliographies of the reports retrieved was conducted to identify additional relevant articles. Results: In all, 1012 articles were identified from the database search and after reviewing the titles and abstract of the reports, 104 articles met the inclusion criteria. Of these, 30 reports were excluded as the full-text could not be retrieved and the abstract did not have relevant data. The remaining 74 reports were reviewed for data on association between a particular lifestyle factor and male infertility and were included in the present review. Conclusion: The major lifestyle factors discussed in the present review are amongst the multiple potential risk factors that could impair male fertility. However, their negative impact may well be mostly overcome by behaviour modification and better lifestyle choices. Greater awareness and recognition of the possible impact of these lifestyle factors are important amongst couples seeking

  17. Nigella sativa oil Ameliorates ionizing Radiation induced cellular injury in Male Albino Rats

    Mohamed, E.T.; El-Kady, A.A.

    2013-01-01

    Nigella sativa (NS), commonly known as black seed, is a plant spices in which thymoquinone is the main active ingredient isolated from the black seeds. The seeds of Nigella sativa are used in herbal medicine all over the world for the treatment and prevention of a number of diseases. The aim of this study was focused on investigating the possible protective effect of NS against gamma radiation induced nephrotoxicity and inflammatory changes in male albino rats. Twenty four albino rats were divided into four equal groups as follows: control group, irradiated group (animals subjected to whole body gamma irradiation at a dose of 6 Gy), treated group (rats treated with 0.2 ml/kg, i.p., NS oil for 4 weeks), and treated irradiated group (animals treated with 0.2 mL/kg, i.p., NS oil for 4 weeks then exposed to whole body gamma irradiation at a dose of 6 Gy). The obtained results revealed that the administration of Nigella sativa oil to irradiated rats significantly ameliorated the changes induced in kidney antioxidant system; catalase and glutathione peroxidase activities as well as reduced glutathione concentration. Also, NS oil restored the kidney function indices (urea and creatinine) near normal level when compared with their equivalent values in irradiated rats. In addition, the changes in serum tumor necrosis factor alpha (TNF-α), Interleukin-1β (IL-1β) and Interleukin-6 (IL-6) activities were markedly improved compared to the corresponding values of irradiated group. The histopathological results showed distinctive pattern of ischemic renal injury in irradiated group, while in treated- irradiated group the renal tissues showed relatively well-preserved architecture with or without focal degeneration. In conclusion, NS acts in the kidney as a potent scavenger of free radicals to prevent or ameliorates the toxic effects of gamma irradiation as shown in the biochemical and histopathological study and also NS oil might provide substantial protection against

  18. Do pheromones reveal male immunocompetence?

    Rantala, Markus J; Jokinen, Ilmari; Kortet, Raine; Vainikka, Anssi; Suhonen, Jukka

    2002-01-01

    Pheromones function not only as mate attractors, but they may also relay important information to prospective mates. It has been shown that vertebrates can distinguish, via olfactory mechanisms, major histocompatibility complex types in their prospective mates. However, whether pheromones can transmit information about immunocompetence is unknown. Here, we show that female mealworm beetles (Tenebrio molitor) prefer pheromones from males with better immunocompetence, indicated by a faster encapsulation rate against a novel antigen, and higher levels of phenoloxidase in haemolymph. Thus, the present study indicates that pheromones could transmit information about males' parasite resistance ability and may work as a reliable sexual ornament for female choice. PMID:12204128

  19. [Male sexuality in the elderly].

    Rinnab, L; Schrader, A J; Schrader, M; Zengerling, F

    2012-10-01

    Male sexuality in the elderly is an important issue with a growing relevance. In contrast to the assumption of an asexual state when becoming older, recent representative surveys show that the majority of men maintain sexual desires and fantasies into old age. Sexual activity primarily depends on the availability of a partner and on maintaining intimacy and sexuality in the face of changes in the sexual response cycle and increasing comorbidity. This review aims to clarify the normal aging process, the sexual behavior of aging males and the prevalence of sexual dysfunction.

  20. Male contraception: history and development.

    Kogan, Paul; Wald, Moshe

    2014-02-01

    Although the twentieth century has seen great strides in the development of female contraception, not a single new agent has been introduced as an approved method for common use for male contraception. Condoms (considered uncomfortable by some) and vasectomy (a permanent invasive procedure) are the only options provided to men, leaving an undue burden on women to bear contraceptive responsibility. Significant developments have, however, been made with regard to hormonal and nonhormonal contraception, and minor, reversible, procedural contraception. This article reviews the currently available, soon to be available, and theoretically possible methods of male contraception. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Vocal competition in male Xenopus laevis frogs

    Tobias, Martha L.; Corke, Anna; Korsh, Jeremy; Yin, David; Kelley, Darcy B.

    2010-01-01

    Male Xenopus laevis frogs produce underwater advertisement calls that attract gravid females and suppress calling by male competitors. Here we explore whether groups of males establish vocal ranks and whether auditory cues alone suffice for vocal suppression. Tests of male–male pairs within assigned groups reveal linear vocal dominance relations, in which each male has a defined rank. Both the duration over which males interact, as well as the number of competitive opportunities, affect linea...

  2. Upper respiratory tract nociceptor stimulation and stress response following acute and repeated Cyfluthrin inhalation in normal and pregnant rats: Physiological rat-specific adaptions can easily be misunderstood as adversities.

    Pauluhn, Juergen

    2018-01-05

    This paper reviews the results from past regulatory and mechanistic inhalation studies in rats with the type II pyrethroid Cyfluthrin. Apart from many chemical irritants, Cyfluthrin was shown to be a neuroexcitatory agent without any inherent tissue-destructive or irritant property. Thus, any Cyfluthrin-induced neuroexcitatory afferent sensory stimulus from peripheral nociceptors in the upper respiratory tract is likely to be perceived as a transient stimulus triggering annoyance and/or avoidance by both rats and humans. However, while thermolabile rats respond to such stresses reflexively, homeothermic humans appear to respond psychologically. With this focus in mind, past inhalation studies in rats and human volunteers were reevaluated and assessed to identify common denominators to such neuroexcitatory stimuli upon inhalation exposure. This analysis supports the conclusion that the adaptive physiological response occurring in rats secondary to such chemosensory stimuli requires inhalation exposures above the chemosensory threshold. Rats, a species known to undergo adaptively a hibernation-like physiological state upon environmental stresses, experienced reflexively-induced bradypnea, bradycardia, hypothermia, and changes in acid-base status during inhalation exposure. After cessation of the sensory stimulus, rapid recovery occurred. Physiological data of male and female rats from a 4-week repeated inhalation study (exposure 6-h/day, 5-times/week) were used to select concentration for a 10-day developmental inhalation toxicity study in pregnant rats. Maternal hypothermia and hypoventilation were identified as likely cause of fetal and placental growth retardations because of a maternal adaptation-driven reduced feto-placental transfer of oxygen. In summary, maternal reflex-hypothermia, reduced cardiac output and placental perfusion, and disruption of the gestation-related hyperventilation are believed to be the maternally mediated causes for developmental

  3. Male fertility in cystic fibrosis.

    Chotirmall, S H

    2011-04-05

    Infertility rates among males with cystic fibrosis (CF) approximate 97%. No information is currently available within Ireland determining an understanding of fertility issues and the best methods of information provision to this specialized group. This study aimed to determine understanding and preferred approaches to information provision on fertility issues to Irish CF males. A Descriptive Study utilizing prospective coded questionnaires was mailed to a male CF cohort (n=50). Sections included demographics, fertility knowledge & investigation. Response rate was 16\\/50 (32%). All were aware that CF affected their fertility. More than two-thirds (n=11) were able to provide explanations whilst only one-third (n=5) provided the correct explanation. Significant numbers stated thoughts of marriage and a future family. Half have discussed fertility with a healthcare professional (HCP). Mean age of discussion was 21.9 years. One third preferred an earlier discussion. The commonest first source for information was written material which was also the preferred source. Three-quarters requested further information preferring again, written material. Significant gaps in sex education of Irish CF males exist. Discussion should be initiated by HCPs and centre-directed written material devised to address deficiencies.

  4. Male Reproductive System (For Teens)

    ... Affecting the Male Reproductive System Print en español Sistema reproductor masculino All living things reproduce. Reproduction — the ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on TeensHealth® is for ...

  5. Ferocious fighting between male grasshoppers.

    Kate D L Umbers

    Full Text Available Contests among individuals over mating opportunities are common across diverse taxa, yet physical conflict is relatively rare. Due to the potentially fatal consequences of physical fighting, most animals employ mechanisms of conflict resolution involving signalling and ritualistic assessment. Here we provide the first evidence of ubiquitous escalated fighting in grasshoppers. The chameleon grasshopper (Kosciuscola tristis is an Australian alpine specialist, in which males engage in highly aggressive combat over ovipositing females. We describe discrete agonistic behaviours including mandible flaring, mounting, grappling, kicking and biting, and their use depending on the individual's role as challenger or defender. We show that male role predicts damage, with challengers being more heavily damaged than males defending females (defenders. Challengers also possess wider mandibles than defenders, but are similar in other metrics of body size. Our data suggest that fights escalate between males matched in body size and that mandibles are used as weapons in this species. This system represents an exciting opportunity for future research into the evolution of costly fighting behaviour in an otherwise placid group.

  6. Male parentage in army ants

    Kronauer, Daniel J C; Schöning, Caspar; Boomsma, Jacobus J

    2006-01-01

    of active research in insect sociobiology. Here we present microsatellite data for 176 males from eight colonies of the African army ant Dorylus (Anomma) molestus. Comparison with worker genotypes and inferred queen genotypes from the same colonies show that workers do not or at best very rarely reproduce...

  7. Ferocious Fighting between Male Grasshoppers

    Umbers, Kate D. L.; Tatarnic, Nikolai J.; Holwell, Gregory I.; Herberstein, Marie E.

    2012-01-01

    Contests among individuals over mating opportunities are common across diverse taxa, yet physical conflict is relatively rare. Due to the potentially fatal consequences of physical fighting, most animals employ mechanisms of conflict resolution involving signalling and ritualistic assessment. Here we provide the first evidence of ubiquitous escalated fighting in grasshoppers. The chameleon grasshopper (Kosciuscola tristis) is an Australian alpine specialist, in which males engage in highly aggressive combat over ovipositing females. We describe discrete agonistic behaviours including mandible flaring, mounting, grappling, kicking and biting, and their use depending on the individual’s role as challenger or defender. We show that male role predicts damage, with challengers being more heavily damaged than males defending females (defenders). Challengers also possess wider mandibles than defenders, but are similar in other metrics of body size. Our data suggest that fights escalate between males matched in body size and that mandibles are used as weapons in this species. This system represents an exciting opportunity for future research into the evolution of costly fighting behaviour in an otherwise placid group. PMID:23166725

  8. Testosterone replacement in male hypogonadism

    Kalra, Sanjay; Agrawal, Navneet; Kumar, Satish; Sharma, Amit

    2010-01-01

    Sanjay Kalra1, Navneet Agrawal2, Satish Kumar3, Amit Sharma11Department of Endocrinology, Bharti Hospital, Karnal, India; 2Dept of Medicine, GR Medical College, Gwalior, India; 3Clinical Research, EXCEL Life Sciences, NOIDA, IndiaAbstract: This article contains a review of the clinical aspects of testosterone replacement in androgen deficiency of the aging male.Keywords: testosterone, supplementation, hypogonadism, ADAM

  9. Lifestyle causes of male infertility.

    Durairajanayagam, Damayanthi

    2018-03-01

    To examine the potential effects of lifestyle factors on male reproductive health. Evidence of a global decline in human sperm quality over recent decades has been accumulating. Environmental, occupational, and modifiable lifestyle factors may contribute to this decline. This review focuses on key lifestyle factors that are associated with male infertility such as smoking cigarettes, alcohol intake, use of illicit drugs, obesity, psychological stress, advanced paternal age, dietary practices, and coffee consumption. Other factors such as testicular heat stress, intense cycling training, lack of sleep and exposure to electromagnetic radiation from mobile phone use are briefly discussed. A comprehensive literature search was performed to identify and synthesise all relevant information, mainly from within the last decade, on the major lifestyle factors associated with male infertility and semen quality. Database searches were limited to reports published in English only. A manual search of bibliographies of the reports retrieved was conducted to identify additional relevant articles. In all, 1012 articles were identified from the database search and after reviewing the titles and abstract of the reports, 104 articles met the inclusion criteria. Of these, 30 reports were excluded as the full-text could not be retrieved and the abstract did not have relevant data. The remaining 74 reports were reviewed for data on association between a particular lifestyle factor and male infertility and were included in the present review. The major lifestyle factors discussed in the present review are amongst the multiple potential risk factors that could impair male fertility. However, their negative impact may well be mostly overcome by behaviour modification and better lifestyle choices. Greater awareness and recognition of the possible impact of these lifestyle factors are important amongst couples seeking conception.

  10. Promotores' perspectives on a male-to-male peer network.

    Macia, Laura; Ruiz, Hector Camilo; Boyzo, Roberto; Documet, Patricia Isabel

    2016-06-01

    Little documentation exists about male community health workers (promotores) networks. The experiences of promotores can provide input on how to attract, train, supervise and maintain male promotores in CHW programs. We present the experience and perspectives of promotores who participated in a male promotores network assisting Latino immigrant men in an emerging Latino community. All promotores in this community-based participatory study received payment for work 10 hours a week. We conducted qualitative interviews with all promotores starting the program, after 5 and 13 months. Three main themes emerged: 1) Men decided to become promotores to help others, yet appreciated being paid. 2) Promotores' learning experience was ongoing and was facilitated by a cooperative dynamic among them. Learning how to listen was crucial for promotores 3) Promotores experienced difficulty separating their personal lives form their role as a promotor We conclude that paying promotores facilitates the fulfillment of their drive to serve the community. Enhancing listening abilities needs to be part of promotores' training curricula. Finally, it is advisable to build a project with many opportunities for promotores and project staff to share professional and non-professional time and discuss their challenges. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  11. The physiology and timing of male puberty

    Tinggaard, Jeanette; Mieritz, Mikkel Grunnet; Sørensen, Kaspar

    2012-01-01

    To describe available markers of male puberty, discuss associations between adiposity and pubertal timing and to review recent evidence of a possible secular trend in male pubertal timing.......To describe available markers of male puberty, discuss associations between adiposity and pubertal timing and to review recent evidence of a possible secular trend in male pubertal timing....

  12. Androgens and the ageing male

    Juul, Anders; Skakkebaek, Niels E

    2002-01-01

    Hypogonadal men share a variety of signs and symptoms such as decreased muscle mass, osteopoenia, increased fat mass, fatigue, decreased libido and cognitive dysfunctions. Controlled trials have demonstrated favourable effects of androgen substitution therapy on these signs and symptoms in men...... 'andropause' has been suggested. However, testosterone levels show no or only modest variation with age in men; with large prospective studies suggesting a maximal decline of total testosterone of 1.6% per year. Thus, in contrast to the sudden arrest of gonadal activity in females around menopause, men do...... not have an andropause. As large placebo-controlled studies of androgen treatment in elderly males are lacking, proper risk assessment of adverse effects such as prostate cancer following testosterone treatment in elderly males is completely lacking. In the future, testosterone therapy may prove beneficial...

  13. Some dynamics of male chauvinism.

    Woods, S M

    1976-01-01

    Male chauvinism was studied in the psychoanalytic therapy of 11 men. It refers to the maintenance of fixed beliefs and attitudes of male superiority, associated with overt or covert depreciation of women. Challenging chauvinist attitudes often results in anxiety or other symptoms. It is frequently not investigated in psychotherapy because it is ego-syntonic, parallels cultural attitudes, and because therapists often share similar bias or neurotic conflict. Chauvinism was found to represent an attempt to ward off anxiety and shame arising from one or more of four prime sources: unresolved infantile strivings and regressive wishes, hostile envy of women, oedipal anxiety, and power and dependency conflicts related to masculine self-esteem. Mothers were more important than fathers in the development of chauvinism, and resolution was sometimes associated with decompensation in wives.

  14. Semiprotective Effects of Hempseed Oil on Carbon Tetrachloride-induced Hepatotoxicity in Male Rats: An Ultra-short Toxicological Intervention

    Mona Hashemzadeh

    2017-12-01

    Full Text Available This study was designed to investigate the protective activity of hempseed oil on carbon tetrachloride (CCl4 hepatotoxicity in male rats at Islamic Azad University, Saveh Branch, Saveh, Iran in 2015. Normal control (NC group was injected intraperitoneally (i.p. with distilled water (0.5 ml/kg; CCl4-intoxicated group (TCC injected CCl4; hempseed oil treated group (HSO gavaged hempseed oil; TCC-HSO group was injected CCl4 prior to intake of hempseed oil and HSO-TCC group was gavaged hempseed oil prior to being injected with CCl4. In all treated groups, toxicity was induced by i.p. injection of CCl4 (0.5 ml/kg for two consecutive days and hemp seed, oil was gavaged at 8 ml/kg in respective group once daily for one week. Plasma alanine aminotransferase (ALT and aspartate transaminase (AST levels increased in TCC. Protection against toxicity in HSO-TCC and TCC-HSO reduced AST and ALT activities compared to TCC. Plasma alkaline phosphatase activity in TCC-HSO and HSO-TCC increased as compared with other groups. CCl4 decreased plasma high-density lipoprotein cholesterol (HDL-C in TCC. Hempseed oil decreased total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C, very low-density lipoprotein cholesterol, and triacylglycerols in HSO compared to NC. Hempseed oil in TCC-HSO and HSO-TCC restored TC, HDL-C, and LDL-C levels to those of NC. Atherogenic index was lower in HSO in comparison to TCC. Based on histopathology, hempseed oil improved CCl4-induced-cardio- and hepatotoxicity in TCC-HSO and HSO-TCC; however, hempseed oil did not prevent CCl4-induced nephrotoxicity. To sum up, hempseed oil has mild protective effects against CCl4 toxicity in male rats.

  15. Male hypogonadism: Symptoms and treatment

    Peeyush Kumar; Nitish Kumar; Devendra Singh Thakur; Ajay Patidar

    2010-01-01

    Male hypogonadism is a condition in which the body does not produce enough of the testosterone hormone; the hormone that plays a key role in masculine growth and development during puberty. There is a clear need to increase the awareness of hypogonadism throughout the medical profession, especially in primary care physicians who are usually the first port of call for the patient. Hypogonadism can significantly reduce the quality of life and has resulted in the loss of livelihood and separatio...

  16. Leptin levels in infertile males

    Jahan, S.; Bibi, R.; Ahmed, S.

    2011-01-01

    Objective: To determine the leptin levels in the serum of normal, sub fertile and infertile men. Study Design: Analytical study. Place and Duration of Study: Department of Animal Sciences Quaid-e-Azam University, Islamabad, National Institute of Health (NIH), Islamabad and Dr. Salma and Kafeel Medical Centre, Islamabad, from April to December 2009. Methodology: Serum leptin levels hormonal concentrations (LH, FSH and testosterone) were determined by EIA in 154 males including 24 (15.58%) fertile, 19 (12.34%) polyzoospermic (PZs), 26 (16.88%) teratozoospermic (TZs), 27 (17.53%) astheno-teratozoospermic (ATZs), 18 (11.69%) oligozoospermic (OZs), 18 (11.69%) oligo-astheno-teratozoospermic (OATZs), 11 (7.14%) obstructive azoospermic (OBST-AZOOs) and 11 (7.14%) non-obstructive azoospermic (NON-OBST-AZOOs). BMI was also determined, divided into groups of greater than 24. Hormonal concentrations were compared by ANOVA and correlation was performed by using Graph pad prism version 5. Results: Significantly high levels of leptin concentrations were found in fertile (p 24 compared to fertile and infertile male patients with BMI 24. Leptin showed a significant positive correlation with LH (p < 0.01) and FSH (p < 0.002) and a significant negative correlation with testosterone (p < 0.001). Conclusion: Abnormal leptin level was significantly associated with fertility problems in males. Providing a link between leptin and reproduction factors contributing in control of testosterone and gonadotropins secretion in many aspects depending on fertility status in male subjects. BMI appears to have significant association with serum leptin levels. (author)

  17. Male contraception: another Holy Grail.

    Murdoch, Fern E; Goldberg, Erwin

    2014-01-15

    The idea that men should participate in family planning by playing an active role in contraception has become more acceptable in recent years. Up to the present the condom and vasectomy have been the main methods of male contraception. There have been and continue to be efforts to develop an acceptable hormonal contraceptive involving testosterone (T) suppression. However the off target affects, delivery of the analogs and the need for T replacement have proven difficult obstacles to this technology. Research into the development of non-hormonal contraception for men is progressing in several laboratories and this will be the subject of the present review. A number of promising targets for the male pill are being investigated. These involve disruption of spermatogenesis by compromising the integrity of the germinal epithelium, interfering with sperm production at the level of meiosis, attacking specific sperm proteins to disrupt fertilizing ability, or interfering with the assembly of seminal fluid components required by ejaculated sperm for acquisition of motility. Blocking contractility of the vas deferens smooth muscle vasculature to prevent ejaculation is a unique approach that prevents sperm from reaching the egg. We shall note the lack of interest by big pharma with most of the support for male contraception provided by the NIH. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Chromosomal disorders and male infertility

    Gary L Harton; Helen G Tempest

    2012-01-01

    infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family.Despite this,the molecular and genetic factors underlying the cause of infertility remain largely undiscovered.Nevertheless,more and more genetic factors associated with infertility are being identified.This review will focus on our current understanding of the chromosomal basis of male infertility specifically:chromosomal aneuploidy,structural and numerical karyotype abnormalities and Y chromosomal microdeletions.Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans.Aneuploidy is predominantly maternal in origin,but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts.Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm.Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed,as well as the application of preimplantation genetic diagnosis (PGD) in such cases.Clinical recommendations where possible will be made,as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.

  19. Male-mediated developmental toxicity

    Diana Anderson

    2014-02-01

    Full Text Available Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental toxicity in the early 1990s when it was reported that men working at Sellafield might be causing leukemia in their children. Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the increasing understanding that there is histone retention and modification, protamine incorporation into the chromatin and DNA methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm, heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies, it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to the offspring is now recognized as a complex issue with genetic as well as epigenetic components.

  20. [Male contraception and its perspectives].

    Belaisch, J

    1982-11-01

    Doctors specializing in male contraception are aware of the very real difficulties hindering the development of an effective method in this field. Others believe that the reason this type of contraception is lagging behind is male chauvinism or a certain fear that men have of losing their virility along with their fertilizing capacity. Since available methods of contraception (condom, vasectomy) have low levels of acceptability and reversibility, research has proceeded along other avenues. 1) Gossypol reduces the number and motility of spermatozoa but its general side effects are not exceptional. 2) Restraining hormonal action (progrestogens, LH-RH agonists) also reduce testicular function and for this reason, require simultaneous administration of androgens. Thus far this has not been resolved; azoospermia is not obtained in every case and when it is, it does not necessarily last. 3) A method involving the epididymis, with a view to preventing spermatozoa from acquiring their normal motility and fertilizing capacity by affecting protein and enzyme synthesis, is also being studied. Perhaps, as has been suggested by the Bicetre Hospital research team, we should be content with methods applicable to certain categories of men. Male contraception would then develop step by step rather than by huge bounds as female contraception. full text

  1. Effect of Soybean on Male Reproductive Physiology in Male Mice

    M Modaresi

    2011-01-01

    Full Text Available Introduction & Objective: Soybean (Soja hispida Moench is a member of Fabaceae family. It is a species of legume native to East Asia. Soy contains significant amount of all the essential amino acids for humans therefore, is a good source of protein .Soy has an important role in the improvement and treatment of some cancers such as colon, prostate, and breast. The aim of this study was to investigate the effect of soybeans on reproductive system in male mice. Materials & Methods: This experimental study was conducted at Isfahan Payam e Noor University in 2009. In this research, 32 male mice were randomly grouped into four experimental groups. The control group was fed with soy-free basic diet. The experimental groups 1, 2, and 3 were fed with a diet containing 20%, 30% and 50% soy diet respectively.At the end of 9 weeks of treatment, blood samples were collected and serum levels of testosterone, LH and FSH were measured. The collected data was analyzed with SPSS software using one way ANOVA with Dunnett's post test and Duncan test. Results : In the experimental group which received 20% soy diet, the level of testosterone had a meaningful decrease in comparison with the control group (P<0.05, but in the experimental group which received a 50% soy diet, the level of testosterone had a meaningful increase (P<0.05 .The LH level in 30% and 50% groups had a meaningful increase but no significant differences were observed in FSH level & weight of testicles (P<0.05.The number of sperms in all of the treatment regimes had a meaningful decrease (P0.05 Conclusion: Results of this research indicated that the 20, 30, and 50 percent soy diet had a negative effect on the male reproductive system in mice.

  2. Dose–response assessment of nephrotoxicity from a twenty-eight-day combined-exposure to melamine and cyanuric acid in F344 rats

    Gamboa da Costa, Gonçalo; Jacob, Cristina C.; Von Tungeln, Linda S.; Hasbrouck, Nicholas R.; Olson, Greg R.; Hattan, David G.; Reimschuessel, Renate; Beland, Frederick A.

    2012-01-01

    The adulteration of pet food with melamine and derivatives, including cyanuric acid, has been implicated in the kidney failure and death of cats and dogs in the USA and other countries. In a previous 7-day dietary study in F344 rats, we established a no-observed-adverse-effect level (NOAEL) for a co-exposure to melamine and cyanuric acid of 8.6 mg/kg bw/day of each compound, and a benchmark dose lower confidence limit (BMDL) of 8.4–10.9 mg/kg bw/day of each compound. To ascertain the role played by the duration of exposure, we treated F344 rats for 28 days. Groups of male and female rats were fed diet containing 0 (control), 30, 60, 120, 180, 240, or 360 ppm of both melamine and cyanuric acid. The lowest dose that produced histopathological alterations in the kidney was 120 ppm, versus 229 ppm in the 7-day study. Wet-mount analysis of kidney sections demonstrated the formation of melamine cyanurate spherulites in one male and two female rats at the 60 ppm dose and in one female rat at the 30 ppm dose, establishing a NOAEL of 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females, and BMDL values as low as 1.6 mg/kg bw/day for both sexes. These data demonstrate that the length of exposure is an important component in the threshold of toxicity from a co-exposure to these compounds and suggest that the current risk assessments based on exposures to melamine alone may not reflect sufficiently the risk of a co-exposure to melamine and cyanuric acid. -- Highlights: ► A 28-day dietary co-exposure to melamine and cyanuric acid was conducted in F344 rats. ► The NOAELs were 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females. ► BMDL values as low as 1.6 mg/kg bw/day for both sexes were determined. ► The length of exposure plays an important role in the threshold of toxicity. ► Current assessments may underestimate the risk of melamine and cyanuric acid.

  3. Dose–response assessment of nephrotoxicity from a twenty-eight-day combined-exposure to melamine and cyanuric acid in F344 rats

    Gamboa da Costa, Gonçalo, E-mail: goncalo.gamboa@fda.hhs.gov [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Jacob, Cristina C.; Von Tungeln, Linda S. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Hasbrouck, Nicholas R. [Center for Veterinary Medicine, Laurel, MD 20708 (United States); Olson, Greg R. [Toxicologic Pathology Associates, Jefferson, AR 72079 (United States); Hattan, David G. [Center for Food Safety and Applied Nutrition, College Park, MD 20740 (United States); Reimschuessel, Renate [Center for Veterinary Medicine, Laurel, MD 20708 (United States); Beland, Frederick A. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States)

    2012-07-15

    The adulteration of pet food with melamine and derivatives, including cyanuric acid, has been implicated in the kidney failure and death of cats and dogs in the USA and other countries. In a previous 7-day dietary study in F344 rats, we established a no-observed-adverse-effect level (NOAEL) for a co-exposure to melamine and cyanuric acid of 8.6 mg/kg bw/day of each compound, and a benchmark dose lower confidence limit (BMDL) of 8.4–10.9 mg/kg bw/day of each compound. To ascertain the role played by the duration of exposure, we treated F344 rats for 28 days. Groups of male and female rats were fed diet containing 0 (control), 30, 60, 120, 180, 240, or 360 ppm of both melamine and cyanuric acid. The lowest dose that produced histopathological alterations in the kidney was 120 ppm, versus 229 ppm in the 7-day study. Wet-mount analysis of kidney sections demonstrated the formation of melamine cyanurate spherulites in one male and two female rats at the 60 ppm dose and in one female rat at the 30 ppm dose, establishing a NOAEL of 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females, and BMDL values as low as 1.6 mg/kg bw/day for both sexes. These data demonstrate that the length of exposure is an important component in the threshold of toxicity from a co-exposure to these compounds and suggest that the current risk assessments based on exposures to melamine alone may not reflect sufficiently the risk of a co-exposure to melamine and cyanuric acid. -- Highlights: ► A 28-day dietary co-exposure to melamine and cyanuric acid was conducted in F344 rats. ► The NOAELs were 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females. ► BMDL values as low as 1.6 mg/kg bw/day for both sexes were determined. ► The length of exposure plays an important role in the threshold of toxicity. ► Current assessments may underestimate the risk of melamine and cyanuric acid.

  4. The dynamics of male-male competition in Cardiocondyla obscurior ants

    Cremer Sylvia

    2012-06-01

    Full Text Available Abstract Background The outcome of male-male competition can be predicted from the relative fighting qualities of the opponents, which often depend on their age. In insects, freshly emerged and still sexually inactive males are morphologically indistinct from older, sexually active males. These young inactive males may thus be easy targets for older males if they cannot conceal themselves from their attacks. The ant Cardiocondyla obscurior is characterised by lethal fighting between wingless (“ergatoid” males. Here, we analyse for how long young males are defenceless after eclosion, and how early adult males can detect the presence of rival males. Results We found that old ergatoid males consistently won fights against ergatoid males younger than two days. Old males did not differentiate between different types of unpigmented pupae several days before emergence, but had more frequent contact to ready-to-eclose pupae of female sexuals and winged males than of workers and ergatoid males. In rare cases, old ergatoid males displayed alleviated biting of pigmented ergatoid male pupae shortly before adult eclosion, as well as copulation attempts to dark pupae of female sexuals and winged males. Ergatoid male behaviour may be promoted by a closer similarity of the chemical profile of ready-to-eclose pupae to the profile of adults than that of young pupae several days prior to emergence. Conclusion Young ergatoid males of C. obscurior would benefit greatly by hiding their identity from older, resident males, as they are highly vulnerable during the first two days of their adult lives. In contrast to the winged males of the same species, which are able to prevent ergatoid male attacks by chemical female mimicry, young ergatoids do not seem to be able to produce a protective chemical profile. Conflicts in male-male competition between ergatoid males of different age thus seem to be resolved in favour of the older males. This might represent selection

  5. Semen proteomics and male infertility.

    Jodar, Meritxell; Soler-Ventura, Ada; Oliva, Rafael

    2017-06-06

    Semen is a complex body fluid containing an admixture of spermatozoa suspended in secretions from the testes and epididymis which are mixed at the time of ejaculation with secretions from other accessory sex glands such as the prostate and seminal vesicles. High-throughput technologies have revealed that, contrary to the idea that sperm cells are simply a silent delivery vehicle of the male genome to the oocyte, the sperm cells in fact provide both a specific epigenetically marked DNA together with a complex population of proteins and RNAs crucial for embryogenesis. Similarly, -omic technologies have also enlightened that seminal fluid seems to play a much greater role than simply being a medium to carry the spermatozoa through the female reproductive tract. In the present review, we briefly overview the sperm cell biology, consider the key issues in sperm and seminal fluid sample preparation for high-throughput proteomic studies, describe the current state of the sperm and seminal fluid proteomes generated by high-throughput proteomic technologies and provide new insights into the potential communication between sperm and seminal fluid. In addition, comparative proteomic studies open a window to explore the potential pathogenic mechanisms of infertility and the discovery of potential biomarkers with clinical significance. The review updates the numerous proteomics studies performed on semen, including spermatozoa and seminal fluid. In addition, an integrative analysis of the testes, sperm and seminal fluid proteomes is also included providing insights into the molecular mechanisms that regulate the generation, maturation and transit of spermatozoa. Furthermore, the compilation of several differential proteomic studies focused on male infertility reveals potential pathways disturbed in specific subtypes of male infertility and points out towards future research directions in the field. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Male homosexuality: nature or culture?

    Jannini, Emmanuele A; Blanchard, Ray; Camperio-Ciani, Andrea; Bancroft, John

    2010-10-01

    Debate continues on whether or not male homosexuality (MH) is a result of biological or cultural factors. The debate persists despite the fact that these two sides have different abilities to create a scientific environment to support their cause. Biological theorists produced evidence, however, that these are not always robust. On the other hand, social theorists, without direct evidence confirming their positions, criticize, with good argument, methods and results of the other side. The aim of this Controversy is to understand the reasons of both perspectives. Two scientists (R.B. and A.C.C.) with expertise in the area of biology of MH were asked to contribute their opinions. The nurture position is discussed by a third expert in sexology (J.B.). Expert opinion supported by the critical review of the currently available literature. The role of the Controversy's editor (E.A.J.) is to highlight the strengths and weaknesses of both sides. The two experts of the biological issue answer with their data to the questions: “Is male homosexuality partly explainable by immunology?” and “How is male homosexuality a Darwinian paradox?”, respectively. Genetic and immunological factors, birth order, and fertility of relatives are largely discussed. Finally, the expert sustaining the idea that culture and experiences are important determining factors in sexual orientation used a psychosocial and holistic perspective to explain his position. The JSM's readers should recognize that there are several biological factors in MH. However, these findings do not seem to be able to explain all cases of homosexuality. Some others may be due to particular environmental factors. The issue is complicated and multifactorial, suggesting that further research should be undertaken to produce the final answer to the question raised in this Controversy section.

  7. The male breast: radiological abnormalities

    Maranhao, Norma; Costa, Isis; Nascimento, Raquel Cristine Gomes do

    1998-01-01

    Mammography of male breast account for less than 1% of mammographic examinations in most breast services. Due to the low incidence of breast cancer in men the significant majority of mammographic diagnosis reveals benign diseases, mostly gynecomastia. Therefore it is most important to identify features of benign conditions, such as gynecomastia, in order to reduce the number of unnecessary surgical biopsies performed in these patients, for the same reason suspicious lesions must be recognized as well. Indications for mammography in men include evaluation of palpable mass, recent onset of breast nipple-areolar skin changes or papillary discharge, and previous history of cancer. (author)

  8. Androgens and the ageing male

    Juul, Anders; Skakkebaek, Niels E

    2002-01-01

    with severe primary or secondary hypogonadism. Thus, androgen substitution therapy is warranted in men with true hypogonadism at all ages. Symptoms experienced by otherwise healthy ageing males are non-specific and vague, although some may be similar to symptoms of hypogonadism. Therefore, the term...... 'andropause' has been suggested. However, testosterone levels show no or only modest variation with age in men; with large prospective studies suggesting a maximal decline of total testosterone of 1.6% per year. Thus, in contrast to the sudden arrest of gonadal activity in females around menopause, men do...

  9. Male-mediated developmental toxicity

    Anderson, Diana

    2005-01-01

    In recent years, the public has become more aware that exposure of males to certain agents can adversely affect their offspring and cause infertility and cancer. The hazards associated with exposure to ionising radiation have been recognised for nearly a century, but interest was aroused when a cluster of leukaemia cases was identified in young children living in Seascale, close to the nuclear processing plant at Sellafield in West Cumbria. There was a civil court case on behalf of two of the alleged victims of paternal irradiation at Seascale against British Nuclear Fuels. The case foundered on 'the balance of probabilities'. Nevertheless, there was support for paternal exposure from Japanese experimental X-ray studies in mice. The tumours were clearly heritable as shown by F2 transmission. Also, effects of a relatively non-toxic dose of radiation (1Gy) on cell proliferation transmitted to the embryo were manifested in the germ line of adult male mice even after two generations. In addition in humans, smoking fathers appear to give rise to tumours in the F 1 generation. Using rodent models, developmental abnormalities/congenital malformations and tumours can be studied after exposure of males in an extended dominant lethal assay and congenital malformations can be determined which have similar manifestations in humans. The foetuses can also be investigated for skeletal malformations and litters can be allowed to develop to adulthood when tumours, if present, can be observed. Karyotype analysis can be performed on foetuses and adult offspring to determine if induced genetic damage can be transmitted. Using this study design, cyclophosphamide, 1,3-butadiene and urethane have been examined and each compound produced positive responses: cyclophosphamide in all endpoints examined, 1,3-butadiene in some and urethane only produced liver tumours in F 1 male offspring. This suggests the endpoints are determined by independent genetic events. The results from heritable

  10. Job strain and male fertility.

    Hjollund, Niels Henrik I; Bonde, Jens Peter E; Henriksen, Tine Brink; Giwercman, Aleksander; Olsen, Jørn

    2004-01-01

    Job strain, defined as high job demands and low job control, has not previously been explored as a possible determinant of male fertility. We collected prospective data on job strain among men, and describe the associations with semen quality and probability of conceiving a clinical pregnancy during a menstrual cycle. Danish couples (N = 399) who were trying to become pregnant for the first time were followed for up to 6 menstrual periods. All men collected semen samples, and a blood sample was drawn from both partners. Job demand and job control were measured by a self-administered questionnaire at entry, and in each cycle the participants recorded changes in job control or job demand during the previous 30 days. In adjusted analyses, no associations were found between any semen characteristic or sexual hormones and any job strain variable. The odds for pregnancy were not associated with job strain. Psychologic job strain encountered in normal jobs in Denmark does not seem to affect male reproductive function.

  11. KIDNEY TOXICOGENOMICS OF ACUTE SODIUM AND POTASSIUM BROMATE EXPOSURE IN F344 MALE RAT

    Bromate, used in both the food and cosmetics industry, is a drinking water disinfection by-product that is nephrotoxic and carcinogenic to rodents. To gain insight into the carcinogenic mechanism of action, identify possible biomarkers of exposure, and determine if the cation, po...

  12. KIDNEY TOXICOGENOMICS OF CHRONIC POTASSIUM BROMATE EXPOSURE IN F344 MALE RAT

    Potassium bromate (KBrO3), used in both the food and cosmetics industry, and a drinking water disinfection by-product, is a nephrotoxic compound and rodent carcinogen. To gain insight into the carcinogenic mechanism of action and provide possible biomarkers of KBrO3 exposure, the...

  13. Aging changes in the male reproductive system

    ... ency/article/004017.htm Aging changes in the male reproductive system To use the sharing features on this page, please enable JavaScript. Aging changes in the male reproductive system may include changes in testicular tissue, sperm production, ...

  14. Males collectively defend their one-male units against bachelor males in a multi-level primate society.

    Xiang, Zuo-Fu; Yang, Bang-He; Yu, Yang; Yao, Hui; Grueter, Cyril C; Garber, Paul A; Li, Ming

    2014-07-01

    Group-level male-male co-operation, which has been documented in several primate and non-primate societies, may be mutualistically advantageous to the participants when confronted with threats such as takeovers and cuckoldry by external males. Co-operation among members of distinct social units-while universal among humans-is extremely rare in non-human primates. We present the first observations of collective action or co-operation among males of different one-male units (OMU) in a multi-level society of Rhinopithecus roxellana. A total of 59 instances of male co-operation were recorded. Male co-operation included coordinated chasing, joint vigilance, and patrolling behavior directed at lone adult males trying to enter an OMU. Male co-operation was significantly more frequent during the mating season when the risk of incursions and extra-group paternity was higher. Paternity of infants born in the subsequent birth season and kin relationships among resident males were identified using microsatellite genotype. All infants were sired by OMU males, which we interpret as possible evidence for their success at thwarting mating attempts by satellite males. OMU males were principally unrelated suggesting that male co-operation is best understood in terms of the mutual direct benefits individuals obtain through collective action. Our findings lend support to the bachelor threat hypothesis in which the cooperative behavior of several individuals is more effective than the lone action of a single individual in providing mate defense. Our research has implications for understanding male bonding, higher-level collective action, and the evolution of social co-operation in human societies. © 2013 Wiley Periodicals, Inc.

  15. Psychobiology of Male Homosexuality: Recent Findings

    Annicchiarico Iseda, Ivan Darío; Universidad Nacional de Colombia

    2009-01-01

    In this paper, empirical and theoretical reports which question the causes of male homosexuality are examined. According to these reports, male homosexuality differs from female homosexuality in some respects. Additionally, evidence favouring the consideration of male homosexuality as a biological condition is shown: there are brain differences between gay men and heterosexual men, there are genetic and perinatal factors associated to male homosexuality, there are cognitive and behavioral dif...

  16. African American Males Navigate Racial Microaggressions

    Hotchkins, Bryan K.

    2016-01-01

    Background/Context: High school educational environments find Black males experience systemic racial microaggressions in the form of discipline policies, academic tracking and hegemonic curriculum (Allen, Scott, & Lewis, 2013). Black males in high school are more likely than their White male peers to have high school truancies and be viewed as…

  17. Song and Male Quality in Prairie Warblers

    Bruce E. Byers; Michael E. Akresh; David I. King; W. Koenig

    2016-01-01

    To determine if the songs of male prairie warblers could potentially reveal to female listeners information about the quality of singers, we compared various aspects of prairie warbler song structure and performance to attributes that might reflect a male singer's potential to enhance the fitness of his mate. We found that all the tested male attributes—arrival...

  18. Male reproductive health and yoga

    Pallav Sengupta

    2013-01-01

    Full Text Available Now-a-days reproductive health problems along with infertility in male is very often observed. Various Assisted Reproductive Technologies have been introduced to solve the problem, but common people cannot afford the cost of such procedures. Various ayurvedic and other alternative medicines, along with regular yoga practice are proven to be not only effective to enhance the reproductive health in men to produce a successful pregnancy, but also to regulate sexual desire in men who practice celibacy. Yoga is reported to reduce stress and anxiety, improve autonomic functions by triggering neurohormonal mechanisms by the suppression of sympathetic activity, and even, today, several reports suggested regular yoga practice from childhood is beneficial for reproductive health. In this regard the present review is aimed to provide all the necessary information regarding the effectiveness of yoga practice to have a better reproductive health and to prevent infertility.

  19. Reproductive health of male radiographers

    Shakhatreh, Farouk M.

    2001-01-01

    To compare certain reproductive health problems reported in 2 groups of males, one of which was exposed to x-ray radiation (radiographers) and the other group that was not exposed to x-ray radiation. The reproductive health problems were miscarriage, congenital anomalies, still births and infertility. Two groups of men were selected (90 in each group). The first group consisted of radiographers and the other groups consisted of men not exposed to x-ray radiation. The 2 groups were matched for age and source. Relative risk, attributable risk percentage and level of significance were calculated. Incidence rate of reproductive health problems was increasing with the increase in duration of exposure to x-ray radiation ranging between 17% (for those exposed for 1-5 years) to 91% (for those exposed for more than 15 years). There were significant associations between exposure to radiation and miscarriage (relative risk = 1.67, attributable risk percentage = 40%), congenital anomalies (relative risk = 10, attributable risk percentage 90%), still birth (relative risk = 7, attributable risk percentage = 86%), and infertility (relative risk = 4.5, attributable risk = 78%). The incidence rates of reproductive health problems reported by male radiographers were significantly higher than that reported by the non exposed group and higher than the incidence rates reported in community-based studies in Jordan. The incidence rates of fetal death (miscarriage and stillbirth together) and infertility reported by our radiographers were higher than had been reported by the British radiographers. An immediate plan of action is needed to protect our radiographers. Further studies are needed in this field taking into account all extraneous variables that may affect the reproductive health of radiographers. (author)

  20. Caribbean male: macho and insensitive?

    1991-01-01

    185, 50, and 104 men aged 15-44 years were interviewed, respectively, in Barbados, St. Lucia, and Grenada in three attitudinal studies designed to get an objective look at male attitudes in the region on family planning and human sexuality. Qualitative information was obtained on fertility and contraceptive use, attitudes toward premarital sex, fidelity and relationships, and influences upon male behavior. Men wanted an average of 2.5 children in Barbados, 4 in St. Lucia, and 3.5 in Grenada. Monogamy was not paramount, with 56% of Grenadian men reporting having overlapping sexual relations. There was also a substantial tolerance for illegitimacy, especially among married men and men with post-secondary education. In St. Lucia, relationships are conducted on the man's terms. For example, men may have sexual relationships with multiple women, but it is unacceptable for women to have other men. Most men, however, agreed that fathers should have a say in the upbringing of their children and should visit and support them financially even if the parents do not live together. Many respondents had unstable relationships with their fathers, and a large proportion had not lived with them. 63% of respondents knew their fathers had outside women. Men were aware and supportive of family planning, and generally try to use contraception. 78% of men interviewed in Grenada and 75% of men interviewed in St. Lucia endorse birth control, while 52% of the respondents in St. Lucia practice family planning. Younger, relatively inexperienced men were most typically in need of more knowledge and greater practice of family planning. Family planning programs should be targeted accordingly.

  1. The ameliorative effect of grape seed extract(GSE) on sodium borate-inducing kidney injury of male albino rats

    Ayad, S.K.Y.

    2013-01-01

    Borax (sod-borate) is a toxic compound that is implicated daily to environmental pollutant, so occupational exposure leading to adverse effects on functions of some organs causing their damage as nephrotoxicity, neurotoxicity, hepatotoxicity and testicular atrophy . In particularly, kidney is the most organ that is affected by borax exposure due to continuous exposure with slow rate of excretion leading to accumulation in the renal tissue. Supplementation with high potent antioxidant grape seed extract may alleviate the worse damage effects induced in the kidney as a result of continual exposure of borax in our daily life. The current study aimed to evaluate the ameliorative effect of grape seed extract on renal injury of male albino rats intoxicated with sod-borate. Twenty eight male albino rats were classified to 4 groups(GI and II and III and IV).GI served as a control, group GII was a group intoxicated with sod-borate for 45 days, where as rats in GIII supplemented with GSE beside sod-borate for 45 days , GIV was a group supplemented with GSE only. Serum and kidney samples were collected for biochemical, histopathological and DNA examinations. Significant elevation in the levels of blood urea and creatinine in GII were observed when compared to control group(GI). Significant decline were prominent in biochemical kidney functions when intoxicated group supplemented with GSE(GIII) , where as non significant changes were observed between control group and group supplemented with GSE only (GIV). Significant increase in both cytokines TNF-α and IL-6 was observed in group intoxicated with sod-borate(GII) when compared to control rats(GI). Oral supplementation with high potent antioxidant GSE (GIII) caused alleviation in the kidney injury leading to the reduction of both pro-inflammatory mediator cytokines TNF-α and IL-6. DNA% fragment migration showed that worse significant migration of DNA fragements were observed in toxicated group(GII) followed by increase in

  2. The Effects of Pretreatment with Various Doses of L-Arginine on Cisplatin-Induced Nephropathy of Male Rats

    B Rasoulian

    2016-09-01

    Full Text Available Introduction: Cisplatin is a widely used anti-cancer drug, which its application is limited by nephrotoxicity. In this study, the effect of pretreatment with different l-arginine doses on Cisplatin-induced renal functional injury was investigated. Methods: 63 male rats were divided into 7 groups: In groups 3, 4, 5 and 6, 60 min before the Cisplatin injection (5mg/kg; L-Arginine with doses of 50,100,200 or 400mg/kg was injected, respectively. In group7, normal saline was injected before Cisplatin administration. In groups 1 and 2, normal saline was injected instead of Cisplatin. In group 2, 60min before normal saline injection, 400mg/kg L-Arginine was administered and in group1, instead of L-arginine, normal saline was injected too. Injections were intraperitoneal. 72h after Cisplatin injection, blood sampling and plasma separation were done. Urine sample was collected 24 hours before blood sampling by metabolic cage. The mean of plasma urea and creatinine levels and creatinine clearance (ml/day.kg and fractional excretion of Na (FENa, % were compared among different groups as renal functional parameters. Results: In comparison to group 7, L-arginine injection in a dose of 400mg/kg led to significant amelioration of all parameters. 200 mg/kg L-arginine administration led to significant decrease in plasma urea level and FENa. 100mg/kg L-arginine caused significant improvement in fractional excretion of sodium. L-arginine injection with 50mg/kg dose, significantly ameliorate all renal function tests instead of creatinine clearance. Conclusion: Pretreatment with L-arginine administration with 400 or 50 mg/kg doses, respectively, had the highest effect on reducing Cisplatin-induced nephropathy. L-arginine injection with intermediate doses i.e. 200 or 100 mg/kg had less effect in reducing Cisplatin-induced nephropathy and it needs more investigations.

  3. Sexual Violence Among Male Inmates.

    Hilinski-Rosick, Carly M; Freiburger, Tina L

    2018-04-01

    Inmate misconduct has been a widely studied topic for many decades. General studies of misconduct have found that there are certain factors that contribute to misconduct, including age, gender, sentence length, and facility type. Few studies, however, have examined the factors predicting sexual offenses in a prison conduct. Although many studies of victims of sexual offenses in prison have been conducted, there is a lack of studies examining the perpetrators of prison sexual violence. The current study attempted to expand this body of literature by examining the correlates of sexual misconduct among a sample of male inmates incarcerated in the state of North Carolina during 2010. Deprivation and importation theories of inmate behavior were used to guide the analysis, and measures of deprivation and importation factors were both included in the analytical models. Findings indicate that Black, nonmarried, younger inmates, who had more previous incarcerations and had been incarcerated longer, had greater odds of having a sexual infraction. Additional findings, as well as policy implications, are discussed.

  4. [Hormone regulation of male fertility].

    Anselmo, J G

    1975-01-01

    An innocuous, sure, reversible means of male fertility control which does not disturb the libido is being sought. 20 healthy volunteers from ages 20 to 36 participated, using a 2nd form of protection when necessary. 10 received implants of 60 mg testosterone equally divided into 3 tubes, and began oral ingestion of 100 mg weekly, divided into daily doses, of R2323 (13-ethyl-17-hydroxy-gonen 4,9,11, trien-3-one) until the sperm became ineffective. Then oral doses were given according to personal requirements from 50 to 25 mg. The 2nd series of 10 received no testosterone implants, but followed the same scheme for oral ingestion. All patients but 1 reduced their sperm count and 80% were low enough to consider the sperm inactive. For those who used the hormone treatment as the only protection against pregnancy, no pregnancy occurred. Of the 1st group, 2 had excessive weight gain, 3 felt their libido reduced, and 1 had pain in the nipples and 1 had pain in the hepatic region. Recuperation of normal sperm characteristics was slow, especially motility and vitality. The spermogram is so altered during treatment that any accidental pregnancy could result in a defective egg and serious complications. It should definitely be avoided.

  5. The Puzzle of Male Chronophilias.

    Seto, Michael C

    2017-01-01

    In this article, I return to the idea that pedophilia, a sexual interest in prepubescent children, can be considered a sexual orientation for age, in conjunction with the much more widely acknowledged and discussed sexual orientation for gender. Here, I broaden the scope to consider other chronophilias, referring to paraphilias for age/maturity categories other than young sexually mature adults. The puzzle of chronophilias includes questions about etiology and course, how chronophilias are related to each other, and what they can tell us about how human (male) sexuality is organized. In this article, I briefly review research on nepiophilia (infant/toddlers), pedophilia (prepubescent children), hebephilia (pubescent children), ephebophilia (postpubescent, sexually maturing adolescents), teleiophilia (young sexually mature adults, typically 20s and 30s), mesophilia (middle-aged adults, typically 40s and 50s), and gerontophilia (elderly adults, typically 60s and older) in the context of a multidimensional sexual orientations framework. Relevant research, limitations, and testable hypotheses for future work are identified.

  6. Microwave heating for male contraception

    Jiang, H.B.

    1985-01-01

    A study at Sichuan University investigated microwave irradiation as a reversible male contraception. In the first phase of the study, the testes of rabbits were exposed to 2450 MHz microwaves with intensity of 15-35 mW/cm/sup 2/ for 15-20 minutes. The animals' sperm count was reduced from 5.86 x 10/sup 8/ +- 1.67 x 10/sup 8//ml (S.D.), to 0.273 x 10/sup 8/ +- 0.385 x 10/sup -8//ml 35 days after exposure. The impregnation ability was lost for about two months, even though the animals retained a normal sexual desire and physical condition. In the second phase, a group of 200 human volunteers received 2450 MHz microwave exposure with an intensity of 80-100 mW/cm/sup 2/ at the surface of the scrotum for 40-60 minutes. The volunteers' sperm counts were reduced from 7511 x 10/sup 4/ +- 2758 x 10/sup 4//ml to 366 x 10/sup 4/ +- 352 x 10/sup 4//ml at 39 +- 5.4 days after exposure; reduction amounting to approximately 95 percent. The viability and motility of the sperm were also reduced. Two months after the last exposure, the sperm counts of the volunteers recovered to 4625 x 10/sup 4/ +- 1897 x 10/sup 4//ml. No obvious changes were found either in medical examinations or in the daily lifestyles of the volunteers

  7. Male hypogonadism: Symptoms and treatment

    Peeyush Kumar

    2010-01-01

    Full Text Available Male hypogonadism is a condition in which the body does not produce enough of the testosterone hormone; the hormone that plays a key role in masculine growth and development during puberty. There is a clear need to increase the awareness of hypogonadism throughout the medical profession, especially in primary care physicians who are usually the first port of call for the patient. Hypogonadism can significantly reduce the quality of life and has resulted in the loss of livelihood and separation of couples, leading to divorce. It is also important for doctors to recognize that testosterone is not just a sex hormone. There is an important research being published to demonstrate that testosterone may have key actions on metabolism, on the vasculature, and on brain function, in addition to its well-known effects on bone and body composition. This article has been used as an introduction for the need to develop sensitive and reliable assays for sex hormones and for symptoms and treatment of hypogonadism.

  8. Male Hypogonadism. A Case Report

    Lisandro Hernández Madrazo

    2012-07-01

    Full Text Available The case of a 26 years old male patient who attended the Internal Medicine consultation at the La Fortaleza Integral Diagnostic Center in Maracaibo, Zulia State, Venezuela because of decreased external genitalia size, with poor development from childhood and swelling of the breasts is presented. Physical examination showed a trunk of feminoid configuration caused by adipose tissue accumulated in the lower abdomen, breast and pubic; wide pelvis; lower limb dominance over higher limbs; enucoid proportions; volume diffusely  increased in both breasts (gynecomastia; deposit of fatty tissue at the pelvic girdle, and absent or sparse facial, axillary and pubic hair. We observed decreased size, poor pigmentation, and soft consistency in penis and testicles. Exam was performed on plasma testosterone, luteinizing hormone and follicle stimulating hormone, thus concluding, by the Endocrinology Service at the Maracaibo University Hospital, to be the case of hypogonadotropic hypogonadism of improvable cause. The clinical diagnosis of hypogonadism in adults is unusual in medical practice, a fact that provides with relevance the case we present.

  9. Comparison of male and female foot shape.

    Luo, Gangming; Houston, Vern L; Mussman, Martin; Garbarini, Maryanne; Beattie, Aaron C; Thongpop, Chaiya

    2009-01-01

    Morphological and geometric differences between male and female feet can be the decisive factor of whether well-fitting, functional, and comfortable footwear is available for both men and women. Optical scans, plaster wrap casts, and a set of manual measurements from the right feet of 51 female participants, aged 20 to 59 years (32 +/- 10.2 years), and 39 male participants, aged 22 to 71 years (47.1 +/- 12.1 years), were taken to determine which parameters were the most significant in characterizing pedal geometry and which had the largest difference between male and female feet. Analysis showed that the heel-to-ball length (ball length) of the male participants' feet (181.5 mm) was significantly longer, on average, than that of the female participants' feet (165.0 mm). The width of the male paticipants' feet at the ball, instep, and heel regions, as well as the ball circumference, normalized by the ball length, were all significantly larger on average, than the female test participants' feet. However, toe region, instep, and medial and lateral malleoli heights were larger, on average, for the female participants than for the male. The results show that female feet differ in size and shape from male feet and are not algebraically scaled, smaller versions of male feet, as is often assumed. The study shows that the average male participants' feet are longer than that of the female participants' feet, while the female feet are relatively narrower but higher than those of the male participants.

  10. The evolution of postpairing male mate choice.

    Lyu, Nan; Servedio, Maria R; Lloyd, Huw; Sun, Yue-Hua

    2017-06-01

    An increasing number of empirical studies in animals have demonstrated male mate choice. However, little is known about the evolution of postpairing male choice, specifically which occurs by differential allocation of male parental care in response to female signals. We use a population genetic model to examine whether such postpairing male mate choice can evolve when males face a trade-off between parental care and extra-pair copulations (EPCs). Specifically, we assume that males allocate more effort to providing parental care when mated to preferred (signaling) females, but they are then unable to allocate additional effort to seek EPCs. We find that both male preference and female signaling can evolve in this situation, under certain conditions. First, this evolution requires a relatively large difference in parental investment between males mated to preferred versus nonpreferred females. Second, whether male choice and female signaling alleles become fixed in a population versus cycle in their frequencies depends on the additional fecundity benefits from EPCs that are gained by choosy males. Third, less costly female signals enable both signaling and choice alleles to evolve under more relaxed conditions. Our results also provide a new insight into the evolution of sexual conflict over parental care. © 2017 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

  11. Grooming reciprocity in male Tibetan macaques.

    Xia, Dong-Po; Li, Jin-Hua; Garber, Paul A; Matheson, Megan D; Sun, Bing-Hua; Zhu, Yong

    2013-10-01

    In several primate species, adult males are reported to compete for access to reproductive partners as well as forming affiliative and cohesive social bonds based on the exchange of goods or services. We hypothesized that among a broad set of fitness-maximizing strategies, grooming can be used by individual adult males to enhance social relationships through reciprocity and/or through the interchange of grooming for a different but equivalent good or service. We used focal animal sampling and continuously recorded dyadic grooming and agonistic interactions to test a series of predictions regarding male social interactions in a free-ranging group of Tibetan macaques (Macaca thibetana) at Huangshan, China. During the non-mating season or between males of similar rank throughout the year, grooming effort given was matched by grooming effort received. However, lower ranking males groomed higher ranking males at a greater rate and/or for a longer duration during both the mating and non-mating periods. We found that higher ranking males directed less aggression towards males with whom they formed a frequent grooming partnership, indicating that grooming received was interchanged for increased social tolerance. These data suggest that individual male Tibetan macaques employ alternative social strategies associated with grooming reciprocity or interchange depending on dominance rank and rates of aggression, and highlight the importance of both biological markets and grooming reciprocity as behavioral mechanisms used by resident adult males to form and maintain affiliative social bonds. © 2013 Wiley Periodicals, Inc.

  12. Mutation of Drosophila dopamine receptor DopR leads to male-male courtship behavior.

    Chen, Bin; Liu, He; Ren, Jing; Guo, Aike

    2012-07-06

    In Drosophila, dopamine plays important roles in many biological processes as a neuromodulator. Previous studies showed that dopamine level could affect fly courtship behaviors. Disturbed dopamine level leads to abnormal courtship behavior in two different ways. Dopamine up-regulation induces male-male courtship behavior, while down-regulation of dopamine level results in increased sexual attractiveness of males towards other male flies. Until now, the identity of the dopamine receptor involved in this abnormal male-male courtship behavior remains unknown. Here we used genetic approaches to investigate the role of dopamine receptors in fly courtship behavior. We found that a dopamine D1-like receptor, DopR, was involved in fly courtship behavior. DopR mutant male flies display male-male courtship behavior. This behavior is mainly due to the male's increased propensity to court other males. Expression of functional DopR successfully rescued this mutant phenotype. Knock-down of D2-like receptor D2R and another D1-like receptor, DAMB, did not induce male-male courtship behavior, indicating the receptor-type specificity of this phenomenon. Our findings provide insight into a possible link between dopamine level disturbance and the induced male-male courtship behavior. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. No detectable nephrotoxic side effect using a dimer, non-ionic contrast media in cerebral perfusion computed tomography in case of suspected brain ischemia

    Petrik, M.; Weigel, C.; Kirsch, M.; Hosten, N.

    2005-01-01

    Purpose: In suspected brain ischemia, the perfusion cerebral computed tomography (cCT) should be performed with the lowest amount of contrast media to avoid a contrast media induced nephropathy (CIN) even if the patient already is in renal failure. We were interested to find the best parameters for this examination. Material and methods: From February 2000 to March 2003, 138 patients (58 females, 80 males, mean age 66.8 years) underwent cCT-perfusion immediately after the admission to our stroke unit. Of these patients, 62% (n=86) had normal renal function and 38% (n=52) renal failure (up to 381 μmol/l basic serum creatinine). We varied volume (20-80 ml), flow (5 vs. 7.2. ml/s) and concentration (270 vs. 320 ml/mg iodine) of a dimer, non-ionic contrast media (Visipaque registered ) to establish 5 groups. So we got patients receiving 6 g, 12 g, 16 g, 19 g and 25 g of iodine. After generating the perfusion maps, two radiologists reviewed the quality of the maps and scored it (1-5). We measured the serum creatinine before contrast application and at follow up cCt (days 3 and 7). Results: The quality of the maps increases with increasing amount of iodine. However, the diagnostic result was not significantly better using more than about 16 g of iodine (e.g., 60 ml-7.2 ml/s - 270 mg/ml) in cCT-perfusion studies. Only one patient had a pathologic increase in serum creatinine (day 1: 93; day 4: 146 μmol/l) but died at day 5 because of massive co-morbidity and septic pneumonia. No CIN occurred even in the patient group with pre-existent renal failure. Conclusions: About 60 ml contrast media and a moderate flow rate of about 7 ml/s ensure good results in perfusion-cCT, even if the patients have poor blood circulation or arteriosclerosis. The use of a dimer, non-ionic contrast media (range of 6-25 g iodine) seems to minimize the risk of CIN in the daily routine. (orig.)

  14. Youth masculinities: compelling male heterosexuality.

    Richardson, Diane

    2010-12-01

    This article seeks to extend understandings of heterosexual masculine identities through an examination of young men's constructions of what motivates young men to engage in heterosexual practices and relationships, and what not having sex might mean for them. Using the masculinity literature and work on heterosexuality to frame the discussion and to contextualize the findings, it explores the complex dynamics that frame the relationship between masculinity and heterosexuality. Specifically, how dominant or 'hegemonic' discourses of heterosexuality shape young men's identities, beliefs and behaviour. It considers these questions using empirical data from a qualitative study of young people living in close-knit working-class communities in the North East of England, with a specific focus on cultural and social attitudes towards sexuality and sexual practices. Peer group networks are a key site for the construction and (re)production of masculinity and, therefore, an important arena within which gendered social approval and acceptance is both sought and gained. In this article, I explore the reasons why young men engage in specific types of heterosexual practice in order to gain social approval. A central question is the extent to which heterosexuality is compelling for young men. That young men do feel compelled to behave in certain ways sexually, behaviours that they may be uncomfortable with and/or dislike, and the fact that they feel they are restricted in terms of how they can talk about their experiences within their peer group networks, demonstrates the power of dominant discourses of masculinity in everyday life. This is addressed through an examination of the restrictive effects of normative discourses about male heterosexuality, including their privatizing effects, which suggest that youth masculinities are often experienced in ways that are highly contradictory requiring young men to adopt a range of strategies to deal with this.

  15. Paget disease of the male nipple.

    El Harroudi, T; Tijami, F; El Otmany, A; Jalil, A

    2010-01-01

    Breast cancer occurring in the mammary gland of men is infrequent. It accounts for 0.8% of all breast cancers, which is less than one per cent of all newly diagnosed male cancers and 0.2% of male cancer deaths. However, Paget disease of the male nipple is extremely rare. We report a single case of Paget disease with infiltrative ductal carcinoma of the breast in a 61-year-old man.

  16. Would male hormonal contraceptives affect cardiovascular risk?

    Michael Zitzmann

    2018-01-01

    Full Text Available The aim of hormonal male contraception is to prevent unintended pregnancies by suppressing spermatogenesis. Hormonal male contraception is based on the principle that exogenous administration of androgens and other hormones such as progestins suppress circulating gonadotropin concentrations, decreasing testicular Leydig cell and Sertoli cell activity and spermatogenesis. In order to achieve more complete suppression of circulating gonadotropins and spermatogenesis, a progestin has been added testosterone to the most recent efficacy trials of hormonal male contraceptives. This review focusses on the potential effects of male hormonal contraceptives on cardiovascular risk factors, lipids and body composition, mainly in the target group of younger to middle-aged men. Present data suggest that hormonal male contraception can be reasonably regarded as safe in terms of cardiovascular risk. However, as all trials have been relatively short (< 3 years, a final statement regarding the cardiovascular safety of hormonal male contraception, especially in long-term use, cannot be made. Older men with at high risk of cardiovascular event might not be good candidates for hormonal male contraception. The potential adverse effects of hormonal contraceptives on cardiovascular risk appear to depend greatly on the choice of the progestin in regimens for hormonal male contraceptives. In the development of prospective hormonal male contraception, data on longer-term cardiovascular safety will be essential.

  17. Testosterone and reproductive effort in male primates.

    Muller, Martin N

    2017-05-01

    Considerable evidence suggests that the steroid hormone testosterone mediates major life-history trade-offs in vertebrates, promoting mating effort at the expense of parenting effort or survival. Observations from a range of wild primates support the "Challenge Hypothesis," which posits that variation in male testosterone is more closely associated with aggressive mating competition than with reproductive physiology. In both seasonally and non-seasonally breeding species, males increase testosterone production primarily when competing for fecund females. In species where males compete to maintain long-term access to females, testosterone increases when males are threatened with losing access to females, rather than during mating periods. And when male status is linked to mating success, and dependent on aggression, high-ranking males normally maintain higher testosterone levels than subordinates, particularly when dominance hierarchies are unstable. Trade-offs between parenting effort and mating effort appear to be weak in most primates, because direct investment in the form of infant transport and provisioning is rare. Instead, infant protection is the primary form of paternal investment in the order. Testosterone does not inhibit this form of investment, which relies on male aggression. Testosterone has a wide range of effects in primates that plausibly function to support male competitive behavior. These include psychological effects related to dominance striving, analgesic effects, and effects on the development and maintenance of the armaments and adornments that males employ in mating competition. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Sexy faces in a male paper wasp.

    de Souza, André Rodrigues; Alberto Mourão Júnior, Carlos; do Nascimento, Fabio Santos; Lino-Neto, José

    2014-01-01

    Sexually selected signals are common in many animals, though little reported in social insects. We investigated the occurrence of male visual signals mediating the dominance relationships among males and female choice of sexual partner in the paper wasp Polistes simillimus. Males have three conspicuous, variable and sexually dimorphic traits: black pigmentation on the head, a pair of yellow abdominal spots and body size differences. By conducting behavioral assays, we found that none of the three visual traits are associated with male-male dominance relationship. However, males with higher proportion of black facial pigmentation and bigger yellow abdominal spots are more likely chosen as sexual partners. Also, after experimentally manipulating the proportion of black pigment on males' face, we found that females may evaluate male facial coloration during the choice of a sexual partner. Thus, the black pigmentation on P. simillimus male's head appears to play a role as a sexually selected visual signal. We suggest that sexual selection is a common force in Polistes and we highlight the importance of this group as a model for the study of visual communication in insects.

  19. Sexy faces in a male paper wasp.

    André Rodrigues de Souza

    Full Text Available Sexually selected signals are common in many animals, though little reported in social insects. We investigated the occurrence of male visual signals mediating the dominance relationships among males and female choice of sexual partner in the paper wasp Polistes simillimus. Males have three conspicuous, variable and sexually dimorphic traits: black pigmentation on the head, a pair of yellow abdominal spots and body size differences. By conducting behavioral assays, we found that none of the three visual traits are associated with male-male dominance relationship. However, males with higher proportion of black facial pigmentation and bigger yellow abdominal spots are more likely chosen as sexual partners. Also, after experimentally manipulating the proportion of black pigment on males' face, we found that females may evaluate male facial coloration during the choice of a sexual partner. Thus, the black pigmentation on P. simillimus male's head appears to play a role as a sexually selected visual signal. We suggest that sexual selection is a common force in Polistes and we highlight the importance of this group as a model for the study of visual communication in insects.

  20. Both male and female identity influence variation in male signalling effort

    Svensson P Andreas

    2011-08-01

    Full Text Available Abstract Background Male sexual displays play an important role in sexual selection by affecting reproductive success. However, for such displays to be useful for female mate choice, courtship should vary more among than within individual males. In this regard, a potentially important source of within male variation is adjustment of male courtship effort in response to female traits. Accordingly, we set out to dissect sources of variation in male courtship effort in a fish, the desert goby (Chlamydogobius eremius. We did so by designing an experiment that allowed simultaneous estimation of within and between male variation in courtship, while also assessing the importance of the males and females as sources of courtship variation. Results Although males adjusted their courtship depending on the identity of the female (a potentially important source of within-male variation, among-male differences were considerably greater. In addition, male courtship effort towards a pair of females was highly repeatable over a short time frame. Conclusion Despite the plasticity in male courtship effort, courtship displays had the potential to reliably convey information about the male to mate-searching females. Our experiment therefore underscores the importance of addressing the different sources contributing to variation in the expression of sexually-selected traits.

  1. [Mechanisms of electromagnetic radiation damaging male reproduction].

    Xue, Lei; Chen, Hao-Yu; Wang, Shui-Ming

    2012-08-01

    More and more evidence from over 50 years of researches on the effects of electromagnetic radiation on male reproduction show that a certain dose of electromagnetic radiation obviously damages male reproduction, particularly the structure and function of spermatogenic cells. The mechanisms of the injury may be associated with energy dysmetabolism, lipid peroxidation, abnormal expressions of apoptosis-related genes and proteins, and DNA damage.

  2. Male versus Female Attitudes toward Stuttering

    St. Louis, Kenneth O.

    2012-01-01

    Purpose: The study investigated the extent to which differences existed between public attitudes of males versus females. Method: One hundred adults, 50 males and 50 females, were chosen at random from each of 50 study samples comprising a total of 3371 respondents in a database archive who had completed the "Public Opinion Survey of Human…

  3. A review of eating disorders in males

    Raevuori, Anu; Keski-Rahkonen, Anna; Hoek, Hans W.

    2014-01-01

    Purpose of review Research in eating disorders in males has been active lately compared to the past. This review aims to provide an overview of the recently published studies of eating disorders in males. Recent findings Publication of the Diagnostic and Statistical Manual of Mental Disorders, 5th

  4. Exogenous melatonin administration is beneficial for male ...

    ABSTRACT. Background: A concern in the use of exogenous melatonin as a therapeutic intervention is that it may interfere with reproductive function. Herein, we report that chronic exogenous melatonin administration does not impair male reproductive function during ageing and at old age in male Sprague Dawley rats.

  5. Exogenous melatonin administration is beneficial for male ...

    Background: A concern in the use of exogenous melatonin as a therapeutic intervention is that it may interfere with reproductive function. Herein, we report that chronic exogenous melatonin administration does not impair male reproductive function during ageing and at old age in male Sprague Dawley rats. Methods: ...

  6. External morphology of the cycliophoran dwarf male

    Neves, Ricardo Cardoso; da Cunha, Maria Ribeiro; Funch, Peter

    2010-01-01

    the phylum was first described, the dwarf male has a remarkably complex bodyplan albeit its very small size (approx. 30–40 lm in length). Aiming to increase the knowledge on the gross morphology of the cycliophoran dwarf male, specimens from S. pandora and S. americanus were analyzed by scanning electron...

  7. Communities for and with Black Male Students

    Jett, Christopher C.; Stinson, David W.; Williams, Brian A.

    2015-01-01

    The social and educational status of black male youth in the United States has been receiving increasing attention. In February 2014, President Barack Obama announced a new national initiative--My Brother's Keeper--for helping black boys and male youth or, to speak more generally, boys and young men of color, to "stay on track; providing the…

  8. Endogenous retrovirus sequences expressed in male mammalian ...

    Objectives: To review the research findings on the expression of endogenous retroviruses and retroviral-related particles in male mammalian reproductive tissues, and to discuss their possible role in normal cellular events and association with disease conditions in male reproductive tissues. Data sources: Published ...

  9. Genotyping and Phenotyping of Male Breast Cancer

    Kornegoor, R.

    2012-01-01

    Male breast cancer is a rare disease and most of the knowledge has been extrapolated from females, although these entities are likely different. A better understanding of male breast carcinogenesis is crucial for developing novel targets suitable for personalized treatment. A major problem in

  10. Looking at the Male Librarian Stereotype.

    Dickinson, Thad E.

    2002-01-01

    Discussion of library profession stereotypes focuses on academic male librarians. Topics include the position of the early academic librarians and the environment in which they worked; the beginnings of reference service; women in academic libraries; men in a feminized profession; and current images of male librarians in motion pictures and…

  11. The Sexual Stereotype of the Black Male.

    Davis, Gary L.; Cross, Herbert J.

    This paper presents the results of a study to examine the existence of sexual stereotyping of black males by white college students. Subjects were 180 male and 180 female white undergraduates; they were tested in sexually segregated groups. Each read one of three types of pornographic stories (hard-core, erotic realism, or sexual fantasy). The…

  12. Male reproductive health after childhood cancer

    Lähteenmäki, P M; Arola, M; Suominen, J

    2008-01-01

    Twenty-five male patients were investigated to elucidate the correlation of semen parameters and other related parameters in the assessment of spermatogenesis after childhood cancer treatment.......Twenty-five male patients were investigated to elucidate the correlation of semen parameters and other related parameters in the assessment of spermatogenesis after childhood cancer treatment....

  13. Male sterile mutant in Vigna radiata

    Pande, Kalpana; Raghuvanshi, S.S.

    1987-01-01

    Single and combined treatment of γ-rays and 0.25 per cent EMS were tried on Vigna radiata variety K851. A male sterile mutant was isolated in M 2 generation. Experiments indicated male sterility to be recessive and monogenic in nature. 6 figures. (author)

  14. Approaches to male hypogonadism in primary care

    Lawrence, Kristi L.; Stewart, Felicia; Larson, Brandi M.

    2017-01-01

    Abstract: Evidence suggests that providers are not adhering to current testosterone replacement therapy guidelines when treating male hypogonadism. Understanding the diagnosis and management of this condition is further complicated by conflicting recommendations among available guidelines. NPs must select and follow the best guideline recommendations available to optimally treat male hypogonadism.

  15. A consumer study of entire male pigs

    Godt, Jannik; Kristensen, Kai; Poulsen, Carsten Stig

    1996-01-01

    made in-home by consumers, thus bringing the analysis out of the laboratory and into the market place. The vast majority of the population of uncastrated male pigs have low concentrations of skatole and androstenone. The cutlets that were evaluated in this study were selected from uncastrated male pigs...... on a number of castrated male pigs and gilts. No difference was found in the way the odour components affected the eating quality determined by men and women. A total of 5.4% of the consumers in the study reacted negatively in their evaluation of the eating quality of the cutlets selected for the study......Former studies of the unpleasant odour of meat from certain uncastrated male pigs have been based mainly on evaluations made by trained sensory panellists. This study analyses the effect of the two dominating male pig odour components, skatole and androstenone, on the evaluation of eating quality...

  16. Male infertility and its causes in human.

    Miyamoto, Toshinobu; Tsujimura, Akira; Miyagawa, Yasushi; Koh, Eitetsu; Namiki, Mikio; Sengoku, Kazuo

    2012-01-01

    Infertility is one of the most serious social problems facing advanced nations. In general, approximate half of all cases of infertility are caused by factors related to the male partner. To date, various treatments have been developed for male infertility and are steadily producing results. However, there is no effective treatment for patients with nonobstructive azoospermia, in which there is an absence of mature sperm in the testes. Although evidence suggests that many patients with male infertility have a genetic predisposition to the condition, the cause has not been elucidated in the vast majority of cases. This paper discusses the environmental factors considered likely to be involved in male infertility and the genes that have been clearly shown to be involved in male infertility in humans, including our recent findings.

  17. A Consumer Study of Entire Male Pigs

    Poulsen, Carsten Stig; Godt, J.; Kristensen, K.

    1996-01-01

    Former studies of the unpleasant odour of meat from certain uncastrated male pigs have been based mainly on evaluations made by trained sensory panellists. This study analyses the effect of the two dominating male pig odour components, skatole and androstenone, on the evaluation of eating quality...... made in-home by consumers, thus bringing the analysis out of the laboratory and into the market place. The vast majority of the population of uncastrated male pigs have low concentrations of skatole and androstenone. The cutlets that were evaluated in this study were selected from uncastrated male pigs...... on a number of castrated male pigs and gilts. No difference was found in the way the odour components affected the eating quality determined by men and women. A total of 5.4% of the consumers in the study reacted negatively in their evaluation of the eating quality of the cutlets selected for the study...

  18. Male Infertility and Its Causes in Human

    Toshinobu Miyamoto

    2012-01-01

    Full Text Available Infertility is one of the most serious social problems facing advanced nations. In general, approximate half of all cases of infertility are caused by factors related to the male partner. To date, various treatments have been developed for male infertility and are steadily producing results. However, there is no effective treatment for patients with nonobstructive azoospermia, in which there is an absence of mature sperm in the testes. Although evidence suggests that many patients with male infertility have a genetic predisposition to the condition, the cause has not been elucidated in the vast majority of cases. This paper discusses the environmental factors considered likely to be involved in male infertility and the genes that have been clearly shown to be involved in male infertility in humans, including our recent findings.

  19. Sneaker Males Affect Fighter Male Body Size and Sexual Size Dimorphism in Salmon.

    Weir, Laura K; Kindsvater, Holly K; Young, Kyle A; Reynolds, John D

    2016-08-01

    Large male body size is typically favored by directional sexual selection through competition for mates. However, alternative male life-history phenotypes, such as "sneakers," should decrease the strength of sexual selection acting on body size of large "fighter" males. We tested this prediction with salmon species; in southern populations, where sneakers are common, fighter males should be smaller than in northern populations, where sneakers are rare, leading to geographical clines in sexual size dimorphism (SSD). Consistent with our prediction, fighter male body size and SSD (fighter male∶female size) increase with latitude in species with sneaker males (Atlantic salmon Salmo salar and masu salmon Oncorhynchus masou) but not in species without sneakers (chum salmon Oncorhynchus keta and pink salmon Oncorhynchus gorbuscha). This is the first evidence that sneaker males affect SSD across populations and species, and it suggests that alternative male mating strategies may shape the evolution of body size.

  20. Male size composition affects male reproductive variance in Atlantic cod Gadus morhua L. spawning aggregations

    Bekkevold, Dorte

    2006-01-01

    Estimates of Atlantic cod Gadus morhua reproductive success, determined using experimental spawning groups and genetic paternity assignment of offspring, showed that within-group variance in male size correlated positively with the degree of male mating skew, predicting a decrease in male reprodu...

  1. The decline in Australian young male suicide.

    Morrell, Stephen; Page, Andrew N; Taylor, Richard J

    2007-02-01

    Since the late 1990s there has been a sharp downward trend in Australian young male suicide. It is possible that a major government youth suicide prevention initiative, the National Youth Suicide Prevention Strategy (NYSPS), implemented during 1995-1999 may have influenced the decline. In this article, we examine time trends in age- and means-specific male and female Australian suicide rates in relation to unemployment rates and the NYSPS. Based on Australian suicide data over the period 1966-2003, we assess secular changes in the 20-24 year male suicide to total (crude) male suicide rate ratio in relation to the NYSPS, using interrupted time series analysis (ARIMA), since this was previously found to be significantly associated with the 20-24 year male unemployment to total employment ratio. Results show that a dramatic reduction in Australian young male (aged 20-34 years) suicide has occurred since 1997-1998, declining from approximately 40 per 100,000 in 1997-1998 to approximately 20 per 100,000 in 2003. Most of the decline is due to a decrease in suicide by hanging and to a lesser extent from motor vehicle carbon monoxide and other gases. Further, the previously established strong secular association (lasting over 3 decades from 1966) between the rate ratio of 20-24 year male suicide to total (crude) male suicide, and the rate ratio of 20-24 year male unemployment to total unemployment, appears to have been disrupted. ARIMA modelling of the suicide ratio against the initiative indicates a highly significant statistical association between the NYSPS and the suicide ratio reduction but not between the NYSPS and the unemployment indicator trend, suggesting a break in the link between young male suicide and unemployment. The recent sudden turnaround in Australian young male suicide trends and its extent appears to preclude explanations centring on slow-moving social indices traditionally associated with suicide, or on possible cohort effects. This sudden decrease

  2. Male microchimerism in the human female brain.

    William F N Chan

    Full Text Available In humans, naturally acquired microchimerism has been observed in many tissues and organs. Fetal microchimerism, however, has not been investigated in the human brain. Microchimerism of fetal as well as maternal origin has recently been reported in the mouse brain. In this study, we quantified male DNA in the human female brain as a marker for microchimerism of fetal origin (i.e. acquisition of male DNA by a woman while bearing a male fetus. Targeting the Y-chromosome-specific DYS14 gene, we performed real-time quantitative PCR in autopsied brain from women without clinical or pathologic evidence of neurologic disease (n=26, or women who had Alzheimer's disease (n=33. We report that 63% of the females (37 of 59 tested harbored male microchimerism in the brain. Male microchimerism was present in multiple brain regions. Results also suggested lower prevalence (p=0.03 and concentration (p=0.06 of male microchimerism in the brains of women with Alzheimer's disease than the brains of women without neurologic disease. In conclusion, male microchimerism is frequent and widely distributed in the human female brain.

  3. Sexually antagonistic selection in human male homosexuality.

    Andrea Camperio Ciani

    Full Text Available Several lines of evidence indicate the existence of genetic factors influencing male homosexuality and bisexuality. In spite of its relatively low frequency, the stable permanence in all human populations of this apparently detrimental trait constitutes a puzzling 'Darwinian paradox'. Furthermore, several studies have pointed out relevant asymmetries in the distribution of both male homosexuality and of female fecundity in the parental lines of homosexual vs. heterosexual males. A number of hypotheses have attempted to give an evolutionary explanation for the long-standing persistence of this trait, and for its asymmetric distribution in family lines; however a satisfactory understanding of the population genetics of male homosexuality is lacking at present. We perform a systematic mathematical analysis of the propagation and equilibrium of the putative genetic factors for male homosexuality in the population, based on the selection equation for one or two diallelic loci and Bayesian statistics for pedigree investigation. We show that only the two-locus genetic model with at least one locus on the X chromosome, and in which gene expression is sexually antagonistic (increasing female fitness but decreasing male fitness, accounts for all known empirical data. Our results help clarify the basic evolutionary dynamics of male homosexuality, establishing this as a clearly ascertained sexually antagonistic human trait.

  4. Beyond the Condom: Frontiers in Male Contraception.

    Roth, Mara Y; Amory, John K

    2016-05-01

    Nearly half of all pregnancies worldwide are unplanned, despite numerous contraceptive options available. No new contraceptive method has been developed for men since the invention of condom. Nevertheless, more than 25% of contraception worldwide relies on male methods. Therefore, novel effective methods of male contraception are of interest. Herein we review the physiologic basis for both male hormonal and nonhormonal methods of contraception. We review the history of male hormonal contraception development, current hormonal agents in development, as well as the potential risks and benefits of male hormonal contraception options for men. Nonhormonal methods reviewed will include both pharmacological and mechanical approaches in development, with specific focus on methods which inhibit the testicular retinoic acid synthesis and action. Multiple hormonal and nonhormonal methods of male contraception are in the drug development pathway, with the hope that a reversible, reliable, safe method of male contraception will be available to couples in the not too distant future. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. Technology, normalisation and male sex work.

    MacPhail, Catherine; Scott, John; Minichiello, Victor

    2015-01-01

    Technological change, particularly the growth of the Internet and smart phones, has increased the visibility of male escorts, expanded their client base and diversified the range of venues in which male sex work can take place. Specifically, the Internet has relocated some forms of male sex work away from the street and thereby increased market reach, visibility and access and the scope of sex work advertising. Using the online profiles of 257 male sex workers drawn from six of the largest websites advertising male sexual services in Australia, the role of the Internet in facilitating the normalisation of male sex work is discussed. Specifically we examine how engagement with the sex industry has been reconstituted in term of better informed consumer-seller decisions for both clients and sex workers. Rather than being seen as a 'deviant' activity, understood in terms of pathology or criminal activity, male sex work is increasingly presented as an everyday commodity in the market place. In this context, the management of risks associated with sex work has shifted from formalised social control to more informal practices conducted among online communities of clients and sex workers. We discuss the implications for health, legal and welfare responses within an empowerment paradigm.

  6. Trichloroethylene and trichloroethanol-induced formic aciduria and renal injury in male F-344 rats following 12 weeks exposure

    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

  7. Trichloroethylene and trichloroethanol-induced formic aciduria and renal injury in male F-344 rats following 12 weeks exposure.

    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

  8. A Case of Male Goltz Syndrome

    Bhaswati Ghoshal

    2012-01-01

    Full Text Available We present the case of a boy with a clinical diagnosis of Goltz syndrome (focal dermal hypoplasia, a rare genodermatosis characterized by widespread dysplasia of mesodermal and ectodermal tissues. A 9-year-old male patient with Goltz syndrome presented with typical skin lesions along with progressive dimness of vision and mental retardation since birth. It is inherited in an X-linked dominant fashion and is normally lethal in male patients, and so very few male patients, like the index case, have been reported.

  9. Haemorrhagic SLE In A Young Male

    Rajagopal R

    2002-01-01

    Full Text Available Systemic lupus erythematous (SLE is a systemic autoimmune disease that tends to occur in early adult life. The peak age of onset of the first symptom or sign in females is about 38 years and later in men, at about 44 years. Females outnumber men in this illness in a ratio of about 8 : 1. Cutaneous lesions in male have not been properly investigated and some studies in male with SLE have shown that the illness may present with atypical skin lesions. A case of SLE in a 20 year male who developed sudden onset of haemorrhagic vesiculobullous butterfly rash is described.

  10. Solitary neurofibroma in the male breast

    Smith Mark EF

    2007-02-01

    Full Text Available Abstract Background Neurofibroma of the male breast outside of neurofibromatosis is extremely rare with only one previous case having been reported. Case presentation A 48 year old male patient with a neurofibroma in the breast presenting with gynaecomastia is reported. Clinical and mammogram findings with fine needle aspiration cytology and full histology are presented. Conclusion To our knowledge this is only the second case of a neurofibroma in a male breast in the English literature and the first report to include the mammographic findings.

  11. Sport fans' impressions of gay male athletes.

    Campbell, Jamonn; Cothren, Denise; Rogers, Ross; Kistler, Lindsay; Osowski, Anne; Greenauer, Nathan; End, Christian

    2011-01-01

    The purpose of this study was to examine sport fans' impressions of gay male athletes. Participants formed impressions of a fictional athlete from their favorite team after reading a short scenario about the player. The scenarios described the athlete as being gay or straight, and either becoming a distraction or not causing a distraction to the team. While males' ratings of the athlete did not significantly differ, female fans formed significantly more positive impressions of the gay male player than the straight athlete. These results are discussed in terms of the ingroup bias and the shifting culture of homophobia in sport.

  12. Finasteride treatment and male breast cancer

    Meijer, Mathias; Thygesen, Lau Caspar; Green, Anders

    2018-01-01

    A potential link has been suggested between dispensed finasteride and increased risk of male breast cancer (MBC). Due to the rare occurrence of MBC, it remains to be established if such a relationship exists. The purpose of this study was to combine nationwide registers in four countries to assess...... the potential association between dispensed finasteride and MBC. A cohort of all males with dispensed finasteride in Denmark, Finland, Norway, and Sweden (1,365,088 person years) was followed up for up to 15 years for breast cancer, and compared to a cohort of males unexposed to finasteride. Individual...

  13. Genital size: a common adolescent male concern.

    Lee, Peter A; Reiter, Edward O

    2002-02-01

    Long before adolescence, males hear insinuations about adequacy of penis size. This concern may heighten during teen years and persist to varying degrees into adulthood. Men tend to underestimate their own penis size. This chapter provides objective information about anatomy and growth of the penis, including data about normal sizes. Published data indicate that, although full growth may be reached at different ages during adolescence, size is similar for most adult males. Hopefully, this information will provide the basis for teenaged males to develop a healthy perspective and to avoid intimidation by unfounded claims about sexual enhancement or size enlargement techniques.

  14. Reduction of dopamine level enhances the attractiveness of male Drosophila to other males.

    Liu, Tong; Dartevelle, Laurence; Yuan, Chunyan; Wei, Hongping; Wang, Ying; Ferveur, Jean-François; Guo, Aike

    2009-01-01

    Dopamine is an important neuromodulator in animals and its roles in mammalian sexual behavior are extensively studied. Drosophila as a useful model system is widely used in many fields of biological studies. It has been reported that dopamine reduction can affect female receptivity in Drosophila and leave male-female courtship behavior unaffected. Here, we used genetic and pharmacological approaches to decrease the dopamine level in dopaminergic cells in Drosophila, and investigated the consequence of this manipulation on male homosexual courtship behavior. We find that reduction of dopamine level can induce Drosophila male-male courtship behavior, and that this behavior is mainly due to the increased male attractiveness or decreased aversiveness towards other males, but not to their enhanced propensity to court other males. Chemical signal input probably plays a crucial role in the male-male courtship induced by the courtees with reduction of dopamine. Our finding provides insight into the relationship between the dopamine reduction and male-male courtship behavior, and hints dopamine level is important for controlling Drosophila courtship behavior.

  15. Sneaker "jack" males outcompete dominant "hooknose" males under sperm competition in Chinook salmon (Oncorhynchus tshawytscha).

    Young, Brent; Conti, David V; Dean, Matthew D

    2013-12-01

    In a variety of taxa, males deploy alternative reproductive tactics to secure fertilizations. In many species, small "sneaker" males attempt to steal fertilizations while avoiding encounters with larger, more aggressive, dominant males. Sneaker males usually face a number of disadvantages, including reduced access to females and the higher likelihood that upon ejaculation, their sperm face competition from other males. Nevertheless, sneaker males represent an evolutionarily stable strategy under a wide range of conditions. Game theory suggests that sneaker males compensate for these disadvantages by investing disproportionately in spermatogenesis, by producing more sperm per unit body mass (the "fair raffle") and/or by producing higher quality sperm (the "loaded raffle"). Here, we test these models by competing sperm from sneaker "jack" males against sperm from dominant "hooknose" males in Chinook salmon. Using two complementary approaches, we reject the fair raffle in favor of the loaded raffle and estimate that jack males were ∼1.35 times as likely as hooknose males to fertilize eggs under controlled competitive conditions. Interestingly, the direction and magnitude of this skew in paternity shifted according to individual female egg donors, suggesting cryptic female choice could moderate the outcomes of sperm competition in this externally fertilizing species.

  16. Hybrid male sterility and genome-wide misexpression of male reproductive proteases.

    Gomes, Suzanne; Civetta, Alberto

    2015-07-06

    Hybrid male sterility is a common barrier to gene flow between species. Previous studies have posited a link between misregulation of spermatogenesis genes in interspecies hybrids and sterility. However, in the absence of fully fertile control hybrids, it is impossible to differentiate between misregulation associated with sterility vs. fast male gene regulatory evolution. Here, we differentiate between these two possibilities using a D. pseudoobscura species pair that experiences unidirectional hybrid sterility. We identify genes uniquely misexpressed in sterile hybrid male reproductive tracts via RNA-seq. The sterile male hybrids had more misregulated and more over or under expressed genes relative to parental species than the fertile male hybrids. Proteases were the only gene ontology class overrepresented among uniquely misexpressed genes, with four located within a previously identified hybrid male sterility locus. This result highlights the potential role of a previously unexplored class of genes in interspecific hybrid male sterility and speciation.

  17. Condition-dependent female preference for male genitalia length is based on male reproductive tactics.

    Hernandez-Jimenez, Armando; Rios-Cardenas, Oscar

    2017-12-06

    There is extensive morphological variation of male genitalia across animals with internal fertilization, even among closely related species. Most studies attempting to explain this extraordinary diversity have focused on processes that occur post-copula (e.g. sperm competition, cryptic female choice). Only a few studies have focused on the pre-copula process of female preference. In addition, the extent to which this variation could be associated with the use of different reproductive tactics has yet to be explored. Here, we show that female preference for male genitalia length in two livebearing fishes depends on the type of reproductive tactic of the males being evaluated as well as the body condition of the female. In a species where all males coax females to acquire matings (courters), females preferred males with short genitalia. In a species with genetically influenced alternative reproductive tactics (courter males that only court and produce courter sons, sneaker males that use the coercive tactic of sneak chase and produce sneaker sons), female preference depended on an interaction between male tactic and female condition: females in good condition preferred courter males with short genitalia, and sneaker males with long genitalia. Our results suggest that female preference for male traits favourable to their sons may be an important factor contributing to the diversification of male genitalia. Despite the contrasting selection for genitalia length that our female preference tests suggest, we found no significant differences in genitalia length between coaxing (courters) and coercive (sneakers) males. Our study represents a starting point to more clearly understand the role of alternative reproductive tactics and variation in female mate preference in the evolution of male genitalia. © 2017 The Author(s).

  18. Reproductive physiology of the male camelid.

    Bravo, P W; Johnson, L W

    1994-07-01

    The physiology of reproduction with emphasis on endocrinology of llamas and alpacas is addressed. Information regarding male anatomy, puberty, testicular function, semen description, and sexual behavior is also included.

  19. Sociodemographic Findings in an Infertile Male Population

    Tayfun Güngör

    2008-08-01

    CONCLUSION: This study claims that the previously established risk factors which are considered to be associated with infertility might influence less or interfere with male infertility in more subtle ways.

  20. Zika Virus in the Male Reproductive Tract

    Liesel Stassen

    2018-04-01

    Full Text Available Arthropod-borne viruses (arboviruses are resurging across the globe. Zika virus (ZIKV has caused significant concern in recent years because it can lead to congenital malformations in babies and Guillain-Barré syndrome in adults. Unlike other arboviruses, ZIKV can be sexually transmitted and may persist in the male reproductive tract. There is limited information regarding the impact of ZIKV on male reproductive health and fertility. Understanding the mechanisms that underlie persistent ZIKV infections in men is critical to developing effective vaccines and therapies. Mouse and macaque models have begun to unravel the pathogenesis of ZIKV infection in the male reproductive tract, with the testes and prostate gland implicated as potential reservoirs for persistent ZIKV infection. Here, we summarize current knowledge regarding the pathogenesis of ZIKV in the male reproductive tract, the development of animal models to study ZIKV infection at this site, and prospects for vaccines and therapeutics against persistent ZIKV infection.

  1. Subtotal obstruction of the male reproductive tract

    Pierik, F.H.; Dohle, G.R.; Roijen, J.H. van; Vreeburg, J.T.M.; Weber, R.F.A.

    2003-01-01

    Bilateral obstruction of the male reproductive tract is suspected in men with azoospermia, normal testicular volume and normal FSH. A testicular biopsy is required to differentiate between an obstruction and a testicular insufficiency. Unilateral or subtotal bilateral obstructions and epididymal

  2. Hyperprolactinaemia in male infertility: Clinical case scenarios

    Zeinab Dabbous

    2018-03-01

    Full Text Available Objective: To explore the evaluation, treatment and impact of hyperprolactinaemia on male infertility and testicular function, as hyperprolactinaemia is commonly detected during the evaluation of infertile men. Methods: A literature search was performed using MEDLINE/PubMed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines to identify all studies exploring hyperprolactinaemia in male infertility. Results: Elevated levels of serum prolactin have a detrimental effect on male reproduction through inhibition of the pulsatile release of gonadotrophins from the anterior pituitary gland, and a direct effect on spermatogenesis. Treatment of confirmed hyperprolactinaemia with dopamine agonists leads to significant improvements in both semen parameters and hormone levels. Conclusion: Hyperprolactinaemia, both directly and indirectly, has a negative effect on sperm production, and its detection and management in men seeking fertility is mandatory. Keywords: Prolactin, Male infertility, Dopamine agonists, Testosterone, Pituitary adenoma

  3. New frontiers in nonhormonal male contraception.

    Cheng, C Yan; Mruk, Dolores D

    2010-11-01

    The world's population is nearing 6.8 billion, and we are in need of a male contraceptive that is safe, effective, reversible and affordable. Hormonal approaches, which employ different formulations of testosterone administered in combination with other hormones, have shown considerable promise in clinical trials, and they are currently at the forefront of research and development. However, the long-term effects of using hormones throughout a male's reproductive life for contraception are unknown, and it may take decades before this information becomes available. Because of this, many investigators are aiming to bring a nonhormonal male contraceptive to the consumer market. Indeed, there are several distinct but feasible avenues in which fertility can be regulated without affecting the hypothalamus-pituitary-testis axis. In this review, we discuss several approaches for fertility control involving the testis that one day may lead to the development of a nonhormonal male contraceptive. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. A Profile Gonococcal Uretheritis in Male

    D D Ganguli

    1982-01-01

    Full Text Available A study of 125 uncomplicated urethritis in males were selected at and analysed from different angles in view the changing facets of gonococcal infection and its impact at the present time.

  5. EXPERIMENTAL MODEL OF THE PRIMARY MALE HYPOGONADISM

    P. A. Kulikova

    2014-01-01

    Full Text Available Background: Development of the new methods of treatment of primary male hypogonadism is an urgent medical problem. Its solution requires a suitable experimental model of the disease. Aim: The creation of new experimental model of primary male hypogonadism. Materials and methods: The study was conducted on the male Wistar rats, hypogonadism was modeled by temporary ligation of the distal part of the spermatic cord. Results: It was shown that three-day ligation of the spermatic cord led to persistent disturbance of the testosterone-producing and reproductive functions. These manifestations were reversible at shorter duration of the exposure. Conclusion: The created model of primary male hypogonadism is characterized by the persistent testosterone-producing and reproductive functions disturbance, technical availability, non-toxicity to the other organs and systems. Availability of the model provides new opportunities for the development of approaches to treating diseases of the reproductive organs in men.

  6. Male Fertility After Inguinal Hernia Mesh Repair

    Kohl, Andreas Pagh; Andresen, Kristoffer; Rosenberg, Jacob

    2017-01-01

    OBJECTIVE:: To determine whether patients who receive an inguinal hernia repair father the same number of children as the background population. BACKGROUND:: Although the effect of inguinal hernia repair on male fertility has previously been investigated through indirect measures, no previous...... studies have evaluated the final measure of male fertility, which is the number of children fathered by patients. METHODS:: Prospectively collected data on 32,621 male patients between the ages of 18 and 55 years who received 1 or more inguinal hernia repairs during the years 1998 to 2012 were found in 5...... hernia repair using Lichtenstein technique or laparoscopic approach did not father fewer children than expected. Thus, inguinal hernia repair using Lichtenstein or laparoscopic approach did not impair male fertility....

  7. Male Infertility: MedlinePlus Health Topic

    ... Spanish Testicular biopsy (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Male Infertility updates ... analysis Sperm release pathway Testicular biopsy Related Health Topics Assisted Reproductive Technology Female Infertility Infertility National Institutes ...

  8. God as Father: The maleness of God

    D. T. Williams

    1990-03-01

    Full Text Available It is fashionable today to try to avoid sexist language in theology, despite the Bible’s consistent use of the masculine pronoun when referring to God. Although such an attempt has largely been engendered by modem culture, the maleness of God is not simply a hangover from a patriarchal society, but reflects a fundamental maleness in God’s dealing with man. It emphasises the idea of redemption by grace alone over against creation, and such aspects as the adoption of Christians as sons. The maleness of Christ likewise has not simply been cultural, but is significant theologically. This is not to deny any femininity in God, but to assert that male features predominate. Such an idea does not reduce the status of women, but rather an emphasis on redemption raises it. Raising the status of women in society would in fact reduce the pressure to demasculinize God.

  9. Congenital anomalies of the male urethra

    Levin, Terry L.; Han, Bokyung; Little, Brent P.

    2007-01-01

    The spectrum of congenital anomalies of the male urethra is presented. The embryologic basis of each anomaly, when known, is discussed. Clinical and imaging features of each entity are presented. (orig.)

  10. The Male Gender Role and Depression

    Liljegren, Tom

    2010-01-01

    Although depression is a common mental health disorder, less research has been devoted to men's experience with depression compared to women's experiences. Although men may exhibit similar patterns of depression as women, men often have unique pattern of exhibiting depression characterized by substance abuse, irritability, aggression, and interpersonal conflict. The paper presents a review of the relevant literature on male depression and, in particular, how it is potentially affected by male...

  11. Ectopic ureterocele in the male infant

    Ekloef, O.; Loehr, G.; Ringertz, H.; Thomasson, B.

    1978-01-01

    An account is given of a series of ectopic ureterocele present in 14 male infants. The malformation is found to be more complex than in the female. The ipsilateral renal function is severely impaired or abolished and obstruction to the bladder outflow common. Associated dilatation and elongation of the posterior urethra during micturition may result in a valvelike appearance. Eversion of the male ureterocele is common and possible mechanisms to account for this event are discussed. (Auth.)

  12. Male microchimerism and survival among women

    Kamper-Jørgensen, Mads; Hjalgrim, Henrik; Andersen, Anne-Marie Nybo

    2014-01-01

    During pregnancy, woman and fetus exchange small quantities of cells, and their persistence at later times is termed microchimerism. Microchimerism is known to substantially impact on women's later health. This study examined the survival of women according to male microchimerism status.......During pregnancy, woman and fetus exchange small quantities of cells, and their persistence at later times is termed microchimerism. Microchimerism is known to substantially impact on women's later health. This study examined the survival of women according to male microchimerism status....

  13. Role of Ultrasound in Male Infertility

    Moon, Min Hoan; Sung, Chang Kyu [Dept. of Radiology, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2012-06-15

    US evaluation is the mainstay of diagnostic imaging of infertile men. In this editorial, we review the spectrum of diseases responsible for male infertility, discuss the way in which US imaging studies can be used for evaluation of male infertility, and illustrate characteristic US imaging features that allow for specific diagnosis. The discussion will be divided into three main categories: obstruction in sperm passage, impairment of sperm function, and defect in sperm genesis.

  14. Role of Ultrasound in Male Infertility

    Moon, Min Hoan; Sung, Chang Kyu

    2012-01-01

    US evaluation is the mainstay of diagnostic imaging of infertile men. In this editorial, we review the spectrum of diseases responsible for male infertility, discuss the way in which US imaging studies can be used for evaluation of male infertility, and illustrate characteristic US imaging features that allow for specific diagnosis. The discussion will be divided into three main categories: obstruction in sperm passage, impairment of sperm function, and defect in sperm genesis.

  15. Aesthetic surgery of the male genitalia.

    Alter, Gary J; Salgado, Christopher J; Chim, Harvey

    2011-08-01

    Appearance of the male genitalia is linked with self-esteem and sexual identity. Aesthetic surgery of the male genitalia serves to correct perceived deficiencies as well as physical deformities, which may cause psychological distress. Attention to patient motivation for surgery and to surgical technique is key to achieving optimal results. In this review, the authors describe aesthetic surgical techniques for treatment of penile and scrotal deficiencies. They also discuss techniques for revision in patients with previous surgery.

  16. TRADISI LISAN MALE-MALE: NYANYIAN KEMATIAN DALAM MASYARAKAT CIACIA: KAJIAN SOSIOLOGIS DAN UPAYA PEWARISAN

    Asrif Asrif

    2016-08-01

      Oral Tradition of Male-Male: Death Anthem Ciacia: Sosiological Studies and an Effort to Pass It On to the next Generation. Male-Male is lyrics sung upon the death of a member of the society who is considered a perfect person. This oral tradition shows the society appreciation towards the person through the expression of sadness, longing, partience and praises. Male-Male serves various functions; both private functions (the singer and host, and societal function (the guests. For th singer and the host, this tradition serves as consolation, caring towards other members, dissemination of social values and religion, prestige, and passing on a tradition. For the society, Male-Male functions as a self remainder of death, strengthening faith, increasing empathy and solidarity. Efforts to guarantee the continuity of this tradition by the next generation are required. Formal effortcan be made through schools, and the informal ones can be made through the strengthening of tradition bodies. Keywords: Oral tradition, Male-Male, Sociology, and Passing the tradition

  17. Concomitant gentamicin-induced nephrotoxicity and bilateral ...

    2015-11-20

    Nov 20, 2015 ... author is credited and the new creations are licensed under the identical terms. For reprints .... of aminoglycosides varies from center to center. The ... underlying age‑related reduced renal reserve and impaired hearing ability.

  18. Effects of protein restriction, melatonin administration, and short daylength on brain benzodiazepine receptors in prepubertal male rats

    Kennaway, D.J.; Royles, P.; Webb, H.; Carbone, F.

    1988-01-01

    The possibility that there are changes in brain benzodiazepine binding sites controlled by photoperiod was investigated in two strains of male rats. The hypothesis was tested by 3H-diazepam binding studies in various brain regions of prepubertal rats maintained in 14 or 10 h of light or treated with late-afternoon injections of melatonin (50 micrograms/day). Protein restriction was applied during the experiment to sensitize the animals to the treatments. Under the conditions employed, rats kept in short daylength throughout or kept on long photoperiod and given late-afternoon melatonin injections showed evidence of delayed puberty (seminal vesicle, ventral prostate, and testis weight decreased by 45%, 55%, and 60% respectively, compared to control rats). Binding measurements were made 1 h before and 2 and 5 h after the onset of darkness in the pubertal (42-day-old) or experimentally prepubertal rats. In the rats of the Porton strain (for which protein restriction was obligatory for the gonadal response) there was no consistent treatment or time effects on specific binding of 3H-diazepam to washed membranes of the hypothalamus, midbrain, or striatum. Similarly, there were no differences in the stimulation of 3H-diazepam binding by 100 microM GABA or the inhibition of binding by 50 microM N-acetyl 5 methoxy kynurenamine. By contrast, in Wistar rats, specific binding to midbrain membranes was reduced 5 h after dark compared to 2 h (37% saline; 20% melatonin) and the extent of stimulation by GABA in the hypothalamus was increased 5 h after darkness (35.6% to 46.7% saline; 37.4% to 50% melatonin). Melatonin treatment resulted in significantly higher specific binding in the hypothalamus 2 h after dark (10%, control fed; 20%, protein restricted) but reduced the GABA induced stimulation of binding in the midbrain (35.5% to 25%, control fed; 33.7% to 23.5%, protein restricted)

  19. Seasonal variation in male alternative reproductive tactics.

    Monroe, M J; Amundsen, T; Utne-Palm, A C; Mobley, K B

    2016-12-01

    Genetic parentage analyses reveal considerable diversity in alternative reproductive behaviours (e.g. sneaking) in many taxa. However, little is known about whether these behaviours vary seasonally and between populations. Here, we investigate seasonal variation in male reproductive behaviours in a population of two-spotted gobies (Gobiusculus flavescens) in Norway. Male two-spotted gobies guard nests, attract females and care for fertilized eggs. We collected clutches and nest-guarding males early and late in the breeding season in artificial nests and used microsatellite markers to reconstruct parentage from a subset of offspring from each nest. We hypothesized that mating, reproductive success and sneaking should be more prevalent early in the breeding season when competition for mates among males is predicted to be higher. However, parentage analyses revealed similar values of mating, reproductive success and high frequencies of successful sneaking early (30% of nests) and late (27% of nests) in the season. We also found that multiple females with eggs in the same nest were fertilized by one or more sneaker males, indicating that some males in this population engage in a satellite strategy. We contrast our results to previous work that demonstrates low levels of cuckoldry in a population in Sweden. Our results demonstrate marked stability in both the genetic mating system and male alternative reproductive tactics over the breeding season. However, sneaking rates may vary geographically within a species, likely due to local selection influencing ecological factors encountered at different locations. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  20. Seminal fluid enhances competitiveness of territorial males' sperm in a fish with alternative male reproductive tactics.

    Poli, Federica; Locatello, Lisa; Rasotto, Maria B

    2018-05-29

    The most common adaptation to sperm competition in males is represented by an increase in the sperm number and/or quality released at mating, to raise their probability of egg fertilization. However, rapidly mounting evidence highlights that seminal fluid may directly influence the competitive fertilization success of a male by affecting either own and/or rival sperm performances. In the black goby, Gobius niger , an external fertilizer with guard-sneaker mating tactics and high sperm competition level, sneaker males' ejaculates contain less seminal fluid and more sperm, that are also of better quality, than those of territorial males. However, territorial males, gain a higher paternity success inside natural nests. Here, we ask whether the seminal fluid can contribute to territorial males' reproductive success by enhancing their sperm performances and/or by decreasing those of sneaker males. Using sperm and seminal fluid manipulation and in vitro fertilization tests, we found that own seminal fluid influences the velocity and fertilization ability of sperm only in territorial males, making them as faster as those of sneakers and with similar fertilization rate. Moreover, both sneaker and territorial males' sperm remain unaffected by the seminal fluid of rival males. Thus, black goby males respond to the different level of sperm competition faced by differently allocating in sperm and non-sperm components of the ejaculate, with sneakers primarily investing in sperm of intrinsic high quality and territorial males relying on the effect of seminal fluid to increase the lower intrinsic quality of their sperm. © 2018. Published by The Company of Biologists Ltd.

  1. Promotores��� perspectives on a male-to-male peer network

    Macia, Laura; Ruiz, Hector Camilo; Boyzo, Roberto; Documet, Patricia Isabel

    2016-01-01

    Little documentation exists about male community health workers (promotores) networks. The experiences of promotores can provide input on how to attract, train, supervise and maintain male promotores in CHW programs. We present the experience and perspectives of promotores who participated in a male promotores network assisting Latino immigrant men in an emerging Latino community. All promotores in this community-based participatory study received payment for work 10 hours a week. We conducte...

  2. Male-Male Mounting Behaviour in Free-Ranging Golden Snub-Nosed Monkeys (Rhinopithecus roxellana).

    Fang, Gu; Dixson, Alan F; Qi, Xiao-Guang; Li, Bao-Guo

    2018-01-01

    An all-male band of golden snub-nosed monkeys (Rhinopithecus roxellana) was observed for 3 months in the Qinling Mountains of China, in order to collect data on the frequencies and contextual significance of male-male mounting behaviour. Mounts occurred in a variety of affiliative, dominance-related and sexual contexts, which differed depending upon the ages of the males involved. Mounting behaviour in this group was mainly initiated by adults. Juveniles mounted each other in affiliative contexts (during play and prior to grooming). Adult males mounted subadult and juvenile partners in a greater variety of sociosexual contexts (dominance/rank-related interactions; reconciliation following agonistic encounters, and sometimes as a prelude to receiving grooming). However, subadults and juveniles were never observed to mount adults. In one dyad, involving an adult male and a subadult partner, mounting was more frequent and prolonged, and included bouts of deep pelvic thrusting. Two mounts resulted in anal intromissions and, in 1 case, the subadult partner exhibited seminal emission. Given that the study took place during the annual mating peak period of R. roxellana, it is possible that this unusual male-male sexual activity was related to the absence of mating opportunities for those adults that were excluded from 1-male units. © 2018 S. Karger AG, Basel.

  3. Repeated Bout Effect Was More Expressed in Young Adult Males Than in Elderly Males and Boys

    Giedrius Gorianovas

    2013-01-01

    Full Text Available This study investigated possible differences using the same stretch-shortening exercise (SSE protocol on generally accepted monitoring markers (dependent variables: changes in creatine kinase, muscle soreness, and voluntary and electrically evoked torque in males across three lifespan stages (childhood versus adulthood versus old age. The protocol consisted of 100 intermittent (30 s interval between jumps drop jumps to determine the repeated bout effect (RBE (first and second bouts performed at a 2-week interval. The results showed that indirect symptoms of exercise-induced muscle damage after SSE were more expressed in adult males than in boys and elderly males, suggesting that the muscles of boys and elderly males are more resistant to exercise-induced damage than those of adult males. RBE was more pronounced in adult males than in boys and elderly males, suggesting that the muscles of boys and elderly males are less adaptive to exercise-induced muscle damage than those of adult males.

  4. Female sticklebacks use male coloration in mate choice and hence avoid parasitized males

    Milinski, Manfred; Bakker, Theo C. M.

    1990-03-01

    AN important problem in evolutionary biology since the time of Darwin has been to understand why females preferentially mate with males handicapped by secondary sexual ornaments1-3. One hypothesis of sexual selection theory is that these ornaments reliably reveal the male's condition4-6, which can be affected for example by parasites4,7-13. Here we show that in the three-spined stickleback (Gasterosteus aculeatus) the intensity of male red breeding coloration positively correlates with physical condition. Gravid females base their active mate choice on the intensity of the male's red coloration. Choice experiments under green light prevent the use of red colour cues by females, and males that were previously preferred are now chosen no more than randomly, although the courtship behaviour of the males remains unchanged. Parasitieation causes a deterioration in the males' condition and a decrease in the intensity of their red coloration. Tests under both lighting conditions reveal that the females recognize the formerly parasitized males by the lower intensity of their breeding coloration. Female sticklebacks possibly select a male with a good capacity for paternal care14 but if there is additive genetic variation for parasite resistance, then they might also select for resistance genes, as proposed by Hamilton and Zuk4.

  5. Progesterone impairs social recognition in male rats.

    Bychowski, Meaghan E; Auger, Catherine J

    2012-04-01

    The influence of progesterone in the brain and on the behavior of females is fairly well understood. However, less is known about the effect of progesterone in the male system. In male rats, receptors for progesterone are present in virtually all vasopressin (AVP) immunoreactive cells in the bed nucleus of the stria terminalis (BST) and the medial amygdala (MeA). This colocalization functions to regulate AVP expression, as progesterone and/or progestin receptors (PR)s suppress AVP expression in these same extrahypothalamic regions in the brain. These data suggest that progesterone may influence AVP-dependent behavior. While AVP is implicated in numerous behavioral and physiological functions in rodents, AVP appears essential for social recognition of conspecifics. Therefore, we examined the effects of progesterone on social recognition. We report that progesterone plays an important role in modulating social recognition in the male brain, as progesterone treatment leads to a significant impairment of social recognition in male rats. Moreover, progesterone appears to act on PRs to impair social recognition, as progesterone impairment of social recognition is blocked by a PR antagonist, RU-486. Social recognition is also impaired by a specific progestin agonist, R5020. Interestingly, we show that progesterone does not interfere with either general memory or olfactory processes, suggesting that progesterone seems critically important to social recognition memory. These data provide strong evidence that physiological levels of progesterone can have an important impact on social behavior in male rats. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Dispersal of Engineered Male Aedes aegypti Mosquitoes.

    Winskill, Peter; Carvalho, Danilo O; Capurro, Margareth L; Alphey, Luke; Donnelly, Christl A; McKemey, Andrew R

    2015-11-01

    Aedes aegypti, the principal vector of dengue fever, have been genetically engineered for use in a sterile insect control programme. To improve our understanding of the dispersal ecology of mosquitoes and to inform appropriate release strategies of 'genetically sterile' male Aedes aegypti detailed knowledge of the dispersal ability of the released insects is needed. The dispersal ability of released 'genetically sterile' male Aedes aegypti at a field site in Brazil has been estimated. Dispersal kernels embedded within a generalized linear model framework were used to analyse data collected from three large scale mark release recapture studies. The methodology has been applied to previously published dispersal data to compare the dispersal ability of 'genetically sterile' male Aedes aegypti in contrasting environments. We parameterised dispersal kernels and estimated the mean distance travelled for insects in Brazil: 52.8 m (95% CI: 49.9 m, 56.8 m) and Malaysia: 58.0 m (95% CI: 51.1 m, 71.0 m). Our results provide specific, detailed estimates of the dispersal characteristics of released 'genetically sterile' male Aedes aegypti in the field. The comparative analysis indicates that despite differing environments and recapture rates, key features of the insects' dispersal kernels are conserved across the two studies. The results can be used to inform both risk assessments and release programmes using 'genetically sterile' male Aedes aegypti.

  7. Does Halitosis Effect Sexual Life in Males?

    Gul Soylu Ozler

    2014-03-01

    Full Text Available Aim: Halitosis is an unpleasant alteration of the halitus. The aim of the study is to assess the quality of sexual life of males with and without halitosis. Material and Method: Males between 20-50 years old; with a complaint of halitosis; married and able to complete the study were included in the study. The control group were healthy, adult, married males who have normal otorhinolaryngologic examination. The International Index of Erectile Function questionnaire(IIEF were used to assess the quality of sexual life  of males with halitosis and the results were compared with a similar group of healthy men. Results: A total of 80 adult subjects completed the study. When the groups were compared in terms of age, body mass index(BMI and duration of marriage, they were similar (p=0.65, p= 0.20, p= 0.08 respectively.The halitosis group had significantly lower scores for all function domains (p=0.0001.There was no correlation between degree of halitosis and the scores of IIEF (p< 0.05. Discussion: This is the first study investigating the sexual health of males with halitosis. Halitosis not only effects oral health status but also strongly declines quality of life. The otorhinolaryngologist must not only treat halitosis but also help the patient to stand up to social and sexual problems concomitting halitosis.

  8. Psychological aspects of male fertility treatment.

    Mikkelsen, Alice Toft; Madsen, Svend Aage; Humaidan, Peter

    2013-09-01

    To explore and to identify the possible need for psychological communicative support in men undergoing fertility treatment. Male infertility affects many aspects of a man's life and may cause a life crisis. Although infertility treatment is now commonplace in men, they often feel remote and disconnected from the treatment process. A descriptive survey. A questionnaire with structured and open-ended questions was completed by 210 Danish men undergoing fertility treatment. The questionnaire covered three issues: individual perception of male infertility, gender equality issues, and communication with health professionals in the clinic. Data were collected during 2008. Of the participants, 28% believed that their reduced sperm quality affected their perception of masculinity. 46% stated that equal involvement between partners was a very important element of the treatment; however, 63% said that the health professionals communicated primarily with their female partner. Finally, 62% found that there was a need for a deeper dialogue with the nurses concerning male infertility and 72% lacked information about the psychological consequences of male infertility. In general, participants wanted a more open and balanced dialogue about infertility treatment and the role of the male partner during this process. Infertile men want health professionals to view them on equal terms with their partner. When treating the infertile man, there is a further need to develop more inclusive communication skills. © 2012 Blackwell Publishing Ltd.

  9. Male reproductive health and environmental xenoestrogens

    Toppari, J; Larsen, J C; Christiansen, Peter

    1996-01-01

    that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common......Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias...... and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest...

  10. Mechanisms of male sterility in higher plants

    Ohta, Yasuo [Tsukuba Univ., Sakura, Ibaraki (Japan)

    1982-03-01

    The mechanisms causing male sterility in higher plants were classified into two major categories: genetic and non-genetic. The former was further divided into six classes: 1) Anomality in spindle mechanism during meiosis, 2) chromosomal anomality such as haploidy, polyploidy, aneuploidy, chromosome some deficiency, inversion and reciprocal translocation, 3) presence of male sterile genes, 4) cytoplasmic abnormality, 5) the combination of some specific cytoplasm with particular genes, and 6) infections of microorganisms or viruses. Each mechanism was briefly explained, and the methods for the maintenance of parent lines for heterosis breeding and hybrid seed production were described. The non-genetic male sterility was classified into four types, which are caused by 1) low or high temperature, 2) water deficiency, 3) application of chemicals, and 4) radiation, with a brief explanation given for each of them.

  11. Female perception of male body odor.

    Sergeant, Mark J T

    2010-01-01

    Olfaction is one of the most crucial forms of communication among nonhuman animals. Historically, olfaction has been perceived as being of limited importance for humans, but recent research has documented that not only do humans have sensitive olfactory abilities, but also odors have the potential to influence our physiology and behavior. This chapter reviews research on olfactory communication among humans, focusing on the effects of male bodily odors on female physiology and behavior. The process of body odor production and the detection of olfactory signals are reviewed, focusing on potential sex differences in these abilities. The effects of male body odors on female physiological and behavioral effects of body odors are considered. Finally, with specific regard to female mate choice, evidence regarding the influence of the major histocompatibility complex and fluctuating asymmetry on male olfactory cues is reviewed. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Interventional Radiology of Male Varicocele: Current Status

    Iaccarino, Vittorio; Venetucci, Pietro

    2012-01-01

    Varicocele is a fairly common condition in male individuals. Although a minor disease, it may cause infertility and testicular pain. Consequently, it has high health and social impact. Here we review the current status of interventional radiology of male varicocele. We describe the radiological anatomy of gonadal veins and the clinical aspects of male varicocele, particularly the physical examination, which includes a new clinical and ultrasound Doppler maneuver. The surgical and radiological treatment options are also described with the focus on retrograde and antegrade sclerotherapy, together with our long experience with these procedures. Last, we compare the outcomes, recurrence and persistence rates, complications, procedure time and cost-effectiveness of each method. It clearly emerges from this analysis that there is a need for randomized multicentre trials designed to compare the various surgical and percutaneous techniques, all of which are aimed at occlusion of the anterior pampiniform plexus.

  13. Male reproductive health and environmental xenoestrogens

    Toppari, J; Larsen, J C; Christiansen, Peter

    1996-01-01

    Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias...... and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest...... that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common...

  14. Sexual Homicide by Older Male Offenders.

    Myers, Wade C; Chan, Heng Choon Oliver; Mariano, Timothy Y; Safarik, Mark E; Geberth, Vernon J

    2017-07-01

    Recent research has expanded our understanding of sexual homicide offenders (SHOs). However, little exists beyond case reports for older SHOs. We characterized male SHOs ≥ 55 years, comparing them to typical adult male SHOs who are in their 20s. Analysis of 37 years (1976-2012) of US Supplementary Homicide Reports data provided a large SHO sample (N = 3453). Three case reports provide clinical context for the diverse nature and patterns of older SHOs. Only 32 older male SHOs and no older female SHOs were identified. Murders by older SHOs accounted for only 0.5% of US sexual homicides. Unlike typical SHOs that generally target young adult females, over two-thirds of older SHO victims were ≥40 years, and one-third were ≥55 years. Sexual homicides by older SHOs, like sexual homicide in general, decreased over the study period. These crimes, while exceedingly rare, do occur, warranting special consideration. © 2017 American Academy of Forensic Sciences.

  15. Mechanisms of male sterility in higher plants

    Ohta, Yasuo

    1982-01-01

    The mechanisms causing male sterility in higher plants were classified into two major categories: genetic and non-genetic. The former was further divided into six classes: 1) Anomality in spindle mechanism during meiosis, 2) chromosomal anomality such as haploidy, polyploidy, aneuploidy, chromosome some deficiency, inversion and reciprocal translocation, 3) presence of male sterile genes, 4) cytoplasmic abnormality, 5) the combination of some specific cytoplasm with particular genes, and 6) infections of microorganisms or viruses. Each mechanism was briefly explained, and the methods for the maintenance of parent lines for heterosis breeding and hybrid seed production were described. The non-genetic male sterility was classified into four types, which are caused by 1) low or high temperature, 2) water deficiency, 3) application of chemicals, and 4) radiation, with a brief explanation given for each of them. (Kaihara, S.)

  16. Interventional Radiology of Male Varicocele: Current Status

    Iaccarino, Vittorio, E-mail: vittorio.iaccarino@unina.it; Venetucci, Pietro [University of Naples ' Federico II' , Diagnostic Imaging Department-Cardiovascular and Interventional Radiology, School of Medicine (Italy)

    2012-12-15

    Varicocele is a fairly common condition in male individuals. Although a minor disease, it may cause infertility and testicular pain. Consequently, it has high health and social impact. Here we review the current status of interventional radiology of male varicocele. We describe the radiological anatomy of gonadal veins and the clinical aspects of male varicocele, particularly the physical examination, which includes a new clinical and ultrasound Doppler maneuver. The surgical and radiological treatment options are also described with the focus on retrograde and antegrade sclerotherapy, together with our long experience with these procedures. Last, we compare the outcomes, recurrence and persistence rates, complications, procedure time and cost-effectiveness of each method. It clearly emerges from this analysis that there is a need for randomized multicentre trials designed to compare the various surgical and percutaneous techniques, all of which are aimed at occlusion of the anterior pampiniform plexus.

  17. Aesthetic facial surgery for the asian male.

    Lam, Samuel M

    2005-11-01

    Cosmetic surgery of the Asian face has become increasingly popular in the Far East and the West. The Asian male identity has undergone an evolution in Western media toward a more positive change. The standards of beauty have also changed, being defined by more multicultural models and styles of dress than before. To undertake cosmetic surgery of the Asian face, particularly of the Asian male, requires a different psychological understanding of the individual as well as an entirely different surgical technique in most cases. This brief article does not delve into the technical details of each procedure but concentrates on the salient differences in how to approach the Asian male patient for each of the different procedures, including Asian blepharoplasty, augmentation rhinoplasty, lip reduction, dimple fabrication, otoplasty, facial contouring and aging face procedures, and hair restoration.

  18. Breast Abscess Mimicking Breast Carcinoma in Male.

    Gochhait, Debasis; Dehuri, Priyadarshini; Umamahesweran, Sandyya; Kamat, Rohan

    2018-01-01

    Male breast can show almost all pathological entities described in female breast. Inflammatory conditions of the breast in male are not common; however, occasionally, it can be encountered in the form of an abscess. Clinically, gynecomastia always presents as a symmetric unilateral or bilateral lump in the retroareolar region, and any irregular asymmetric lump raises a possibility of malignancy. Radiology should be used as a part of the triple assessment protocol for breast lump along with fine-needle aspiration cytology for definite diagnosis and proper management.

  19. Breast Abscess Mimicking Breast Carcinoma in Male

    Debasis Gochhait

    2018-01-01

    Full Text Available Male breast can show almost all pathological entities described in female breast. Inflammatory conditions of the breast in male are not common; however, occasionally, it can be encountered in the form of an abscess. Clinically, gynecomastia always presents as a symmetric unilateral or bilateral lump in the retroareolar region, and any irregular asymmetric lump raises a possibility of malignancy. Radiology should be used as a part of the triple assessment protocol for breast lump along with fine-needle aspiration cytology for definite diagnosis and proper management.

  20. Is male infertility a forerunner to cancer?

    Whitney R. Burns

    2010-10-01

    Full Text Available PURPOSE: The frequency of testicular cancer and male infertility has been increasing in the past several decades. This article examines the relationship between male infertility and testicular cancer, concentrating particularly on causal links. RESULTS: Both of these disorders are associated with testicular dysgenesis syndrome and have also been traced to mutations in genes involving DNA repair and tumor suppression, as well as environmental exposure. CONCLUSION: The identification and examination of these common points of origin supports the integration of testicular cancer screenings into the routine evaluation of infertile men.

  1. Decline in male circumcision in South Korea.

    Kim, DaiSik; Koo, Sung-Ae; Pang, Myung-Geol

    2012-12-11

    To investigate the changing circumcision rate in South Korea in the last decade and to propose underlying causes for this change, in the context of the present fluctuating world-wide trends in circumcision. From 2009 to 2011, 3,296 South Korean males (or their parents) aged 0-64 years were asked about their circumcision status, their age at circumcision, and their information level regarding circumcision. We employed non-probability sampling considering the sensitive questions on the study theme. Currently the age-standardized circumcision rate for South Korean males aged 14-29 is found to be 75.8%. In an earlier study performed in 2002, the rate for the same age group was 86.3%. Of particular interest, males aged 14-16 show a circumcision rate of 56.4%, while the same age group 10 years ago displayed a much higher percentage, at 88.4%. In addition, the extraordinarily high circumcision rate of 95.2% found 10 years ago for the 17-19 age group is now reduced to 74.4%. Interestingly, of the circumcised males, the percentage circumcised in the last decade was only 25.2%; i.e., the majority of the currently circumcised males had undergone the operation prior to 2002, indicating that the actual change in the last decade is far greater. Consistent with this conjecture, the 2002 survey showed that the majority of circumcised males (75.7%) had undergone the operation in the decade prior to that point. Focusing on the flagship age group of 14-16, this drop suggests that, considering the population structure of Korean males, approximately one million fewer circumcision operations have been performed in the last decade relative to the case of non-decline. This decline is strongly correlated with the information available through internet, newspapers, lectures, books, and television: within the circumcised population, both the patients and their parents had less prior knowledge regarding circumcision, other than information obtained from person to person by oral communication

  2. Clinical trials in male hormonal contraception.

    Nieschlag, Eberhard

    2010-11-01

    Research has established the principle of hormonal male contraception based on suppression of gonadotropins and spermatogenesis. All hormonal male contraceptives use testosterone, but only in East Asian men can testosterone alone suppress spermatogenesis to a level compatible with contraceptive protection. In Caucasians, additional agents are required of which progestins are favored. Clinical trials concentrate on testosterone combined with norethisterone, desogestrel, etonogestrel or depot-medroxyprogesterone acetate. The first randomized, placebo-controlled clinical trial performed by the pharmaceutical industry demonstrated the effectiveness of a combination of testosterone undecanoate and etonogestrel in suppressing spermatogenesis in volunteers. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Male and Female Differences in Nonconscious Mimicry

    Lehane, Christine Marie

    2015-01-01

    , thus neglecting a discussion regarding the role of sex or gender as a moderator of nonconscious mimicry. This article reviews the research on nonconscious mimicry – facial, behavioural, and verbal, in order to identify whether or not there are male and female differences. The results indicate...... that mimicry may be moderated by participant sex or gender depending upon, among others, choice of mimicry measurement, stimulus exposure length, and social context. However, few studies address male and female differences in mimicry and many have methodological limitations. The review concludes...

  4. Noninvasive Body Contouring: A Male Perspective.

    Wat, Heidi; Wu, Douglas C; Goldman, Mitchel P

    2018-01-01

    Noninvasive body contouring is an attractive therapeutic modality to enhance the ideal male physique. Men place higher value on enhancing a well-defined, strong, masculine jawline and developing a V-shaped taper through the upper body. An understanding of the body contour men strive for allows the treating physician to focus on areas that are of most concern to men, thus enhancing patient experience and satisfaction. This article discusses noninvasive body contouring techniques, taking into account the unique aesthetic concerns of the male patient by combining an analysis of the existing literature with our own clinical experience. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Systemic lupus erythematosus in a male patient

    Sibarani, H.; Zubir, Z.

    2018-03-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with a broad spectrum of clinical presentations. Female to male ratio is approximately 9:1.A 20 years old male was admitted to HAM Hospital 3 months ago with chief complaint pain in both knees joint. After anamneses, physical examination and laboratory test the patient was diagnosed with systemic lupus erythematosus. The patient tested positive for ANA and anti-ds-DNA antibody test. The patient was with giving non-biologic DMARDS @myfortic 360mg, methylprednisolone, chloroquine and other symptomatic drugs.

  6. Vulnerable discipline: experiences of male competitive bodybuilders.

    Bjørnestad, Jone; Kandal, Øyvind; Anderssen, Norman

    2014-09-01

    The aim was to understand experiences of male competitive bodybuilders from a non-pathologizing perspective. Six male Norwegian competitive bodybuilders were interviewed. The interviews were analysed using a meaning condensation procedure resulting in five themes: being proud of capacity for discipline, seeing a perfectionist attitude as a necessary evil, experiencing recognition within the bodybuilding community, being stigmatized outside the bodybuilding community and going on stage to display a capacity for willpower and discipline. We suggest that bodybuilders may be stigmatized for breaking social norms: by their distinctive appearance, by the way they handle suspected drug use and by challenging gender norms. © The Author(s) 2013.

  7. Steroid sulfatase gene in XX males.

    Mohandas, T K; Stern, H J; Meeker, C A; Passage, M B; Müller, U; Page, D C; Yen, P H; Shapiro, L J

    1990-01-01

    The human X and Y chromosomes pair and recombine at their distal short arms during male meiosis. Recent studies indicate that the majority of XX males arise as a result of an aberrant exchange between X and Y chromosomes such that the testis-determining factor gene (TDF) is transferred from a Y chromatid to an X chromatid. It has been shown that X-specific loci such as that coding for the red cell surface antigen, Xg, are sometimes lost from the X chromosome in this aberrant exchange. The ste...

  8. Knowledge, Perception and Level of Male Partner Involvement in ...

    AJRH Managing Editor

    establishing the level of male partner involvement and influence of couple knowledge and perception on male involvement in choice of ... access to care and provision of emotional and ..... although the male partners are key decision makers.

  9. Genetics Home Reference: familial male-limited precocious puberty

    ... male-limited precocious puberty Familial male-limited precocious puberty Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Familial male-limited precocious puberty is a condition that causes early sexual development ...

  10. Sex-Fair Education and the Male Experience.

    Scott, Kathryn P.

    1982-01-01

    Describes how the traditional, agressive male role has been reinforced by social studies textbooks. The author recommends that teachers teach about new roles for males by presenting images of males in caring, nurturing, and expressive roles. (AM)

  11. Genetics Home Reference: CATSPER1-related nonsyndromic male infertility

    ... related nonsyndromic male infertility CATSPER1-related nonsyndromic male infertility Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description CATSPER1 -related nonsyndromic male infertility is a condition that affects the function of ...

  12. Genetics Home Reference: sensorineural deafness and male infertility

    ... deafness and male infertility Sensorineural deafness and male infertility Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Sensorineural deafness and male infertility is a condition characterized by hearing loss and ...

  13. Behavior of ergatoid males in the ant, Cardiocondyla nuda

    Heinze, Jürgen; Künholz, S.; Schilder, K.; Hölldobler, B.

    1993-01-01

    Ergatoid males of the ant, Cardiocondyla nuda, attack and frequently kill young males during or shortly after eclosion. Smaller colonies therefore contain typically only one adult male, which may inseminate all alate queens which are reared in the colony over a few weeks. In larger colonies, several males may be present, however, fighting among adult males was not observed. We discuss the significance of male fighting behavior in ants.

  14. Female qualities in males: vitellogenin synthesis induced by ovary transplants into the male silkworm, Bombyx mori.

    Yang, Congwen; Lin, Ying; Shen, Guanwang; Chen, Enxiang; Wang, Yanxia; Luo, Juan; Zhang, Haiyan; Xing, Runmiao; Xia, Qingyou

    2014-10-10

    Female qualities in males are common in vertebrates but have not been extensively reported in insects. Vitellogenin (Vg) is highly expressed in the female fat body and is generally required for the formation of yolk proteins in the insect egg. Vg upregulation is generally regarded as a female quality in female oviparous animals. In this study, we found that Bombyx mori Vg (BmVg) is especially highly expressed in the female pupa. Downregulation of the BmVg gene in the female pupa by RNA interference (RNAi) interfered with egg formation and embryonic development, showing the importance of BmVg in these processes. So, we used BmVg as a biomarker for female qualities in the silkworm. Hematoxylin-eosin staining and immunofluorescence histochemistry showed that ovary transplants induced BmVg synthesis in the male pupa fat body. Ovaries transplanted into male silkworms produced only a few eggs with deformed yolk granules. These results suggested that the amount of BmVg in the male silkworm was insufficient for eggs to undergo complete embryonic development. After 17-beta-estradiol was used to treat male pupae and male pupal fat bodies, BmVg was upregulated in vivo and in vitro. These findings indicated that the male silkworm has innate female qualities that were induced by a transplanted ovary and 17β-estradiol. However, in silkworms, female qualities in males are not as complete as in females. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Male-male aggression peaks at intermediate relatedness in a social spider mite

    Sato, Y.; Egas, M.; Sabelis, M.W.; Mochizuki, A.

    2013-01-01

    Theory predicts that when individuals live in groups or colonies, male-male aggression peaks at intermediate levels of local average relatedness. Assuming that aggression is costly and directed toward nonrelatives and that competition for reproduction acts within the colony, benefits of aggressive

  16. Diploid male dynamics under different numbers of sexual alleles and male dispersal abilities.

    Faria, Luiz R R; Soares, Elaine Della Giustina; Carmo, Eduardo do; Oliveira, Paulo Murilo Castro de

    2016-09-01

    Insects in the order Hymenoptera (bees, wasps and ants) present an haplodiploid system of sexual determination in which fertilized eggs become females and unfertilized eggs males. Under single locus complementary sex-determination (sl-CSD) system, the sex of a specimen depends on the alleles at a single locus: when diploid, an individual will be a female if heterozygous and male if homozygous. Significant diploid male (DM) production may drive a population to an extinction scenario called "diploid male vortex". We aimed at studying the dynamics of populations of a sl-CSD organism under several combinations of two parameters: male flight abilities and number of sexual alleles. In these simulations, we evaluated the frequency of DM and a genetic diversity measure over 10,000 generations. The number of sexual alleles varied from 10 to 100 and, at each generation, a male offspring might fly to another random site within a varying radius R. Two main results emerge from our simulations: (i) the number of DM depends more on male flight radius than on the number of alleles; (ii) in large geographic regions, the effect of males flight radius on the allelic diversity turns out much less pronounced than in small regions. In other words, small regions where inbreeding normally appears recover genetic diversity due to large flight radii. These results may be particularly relevant when considering the population dynamics of species with increasingly limited dispersal ability (e.g., forest-dependent species of euglossine bees in fragmented landscapes).

  17. Bodice Rippers without the Bodice: Ten Male-on-Male Romances for a Core Collection

    Thomas, Devon

    2011-01-01

    One of the hottest growing segments of the romance genre is male-on-male (M/M) romance--gay romantic fiction mostly written and read by straight women. Featuring traditional romance conventions, including mistaken identities, star-crossed lovers, and happy endings, these stories show both physical and emotional intimacy between men. M/M builds on…

  18. Why Are Males Bad for Females? Models for the Evolution of Damaging Male Mating Behavior

    Lessells, C.M.

    2005-01-01

    One explanation for the cost to mating for females caused by damaging male mating behavior is that this causes the females to adaptively modify their subsequent life histories in a way that also increases male fitness. This might occur because the reduction in residual reproductive value of the

  19. Negotiating the "White Male Math Myth": African American Male Students and Success in School Mathematics

    Stinson, David W.

    2013-01-01

    This article shows how equity research in mathematics education can be decentered by reporting the "voices" of mathematically successful African American male students as they recount their experiences with school mathematics, illustrating, in essence, how they negotiated the White male math myth. Using post-structural theory, the…

  20. Empowering Young Black Males--III: A Systematic Modular Training Program for Black Male Children & Adolescents.

    Lee, Courtland C.

    This series of five interrelated modules is an update and revision of "Saving the Native Son: Empowerment Strategies for Young Black Males (1996)." It offers specific strategies for empowering young African American males to help them achieve optimal educational and social success. Empowerment is a developmental process by which people who are…