Melamine Nephrotoxicity is Mediated by Hyperuricemia

发布时间：2018-01-20 07:22

本文关键词： Melamine Nephrotoxicity Hyperuricemia Urolithiasis　出处：《Biomedical and Environmental Sciences》2015年12期 　论文类型：期刊论文

【摘要】：Objective We tested whether melamine nephrotoxicity was exacerbated by urate(a typical component of renal stones in humans)in rats with hyperuricemiainduced by the uricase inhibitor,potassium oxonate(Oxo).Methods Rats were exposed to melamine or Oxo alone or combinations of melamine(200-400 mg/kg)and Oxo(200-600 mg/kg)for 3 consecutive days.Kidney injury was evaluated by renal biochemical functions,histomorphology,and lipid peroxidation.Kidney crystals were analyzed for their composition.Results Nephrotoxicity was minimal in animals administered melamine or Oxo alone,but it was demonstrable in animals administered at least 800 mg/kg of the two compounds combined.All rats in the 400+600(melamine+Oxo)and 400+400 mg/kg groups and 4 out of 6 in the 200+600 mg/kg group died within 3 days;no rat died in the 200+400 or 200+200 mg/kg group.Dose-dependent renal damage resembling clinical findings in affected patients was observed in rats administered the two compounds.Crystal composition determination revealed the existence of melamine and uric acid in the affected kidneys,resembling human stones.Conclusion Our findings suggest that uric acid plays a key role in melamine-related kidney injury in humans.Future studies should consider uric acid together with melamine when examining adverse effects in humans.
[Abstract]:Objective We tested whether melamine nephrotoxicity was exacerbated by urate(a typical component of renal stones in humans)in rats with hyperuricemiainduced by the uricase inhibitor,potassium oxonate(Oxo).Methods Rats were exposed to melamine or Oxo alone or combinations of melamine(200-400 mg/kg)and Oxo(200-600 mg/kg)for 3 consecutive days.Kidney injury was evaluated by renal biochemical functions,histomorphology,and lipid peroxidation.Kidney crystals were analyzed for their composition.Results Nephrotoxicity was minimal in animals administered melamine or Oxo alone,but it was demonstrable in animals administered at least 800 mg/kg of the two compounds combined.All rats in the 400+600(melamine+Oxo)and 400+400 mg/kg groups and 4 out of 6 in the 200+600 mg/kg group died within 3 days;no rat died in the 200+400 or 200+200 mg/kg group.Dose-dependent renal damage resembling clinical findings in affected patients was observed in rats administered the two compounds.Crystal composition determination revealed the existence of melamine and uric acid in the affected kidneys,resembling human stones.Conclusion Our findings suggest that uric acid plays a key role in melamine-related kidney injury in humans.Future studies should consider uric acid together with melamine when examining adverse effects in humans.
【作者单位】： Institute
【基金】：supported by National Natural Science Foundation of China(grant number:81072372)
【分类号】：R114
【正文快照】： INTRODUCTIONT he melamine-adulteration event in Chinahas received substantial public healthattention,with approximately 300,000affected children suffering from urinary tract abnormalities[1-3].Although most of the affectedchildren have recovered[1,4],co

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