Peroxynitrite decomposition catalyst ameliorates renal damage and protein nitration in cisplatin-induced nephrotoxicity in rats
Peroxynitrite decomposition catalyst ameliorates renal damage and protein nitration in cisplatin-induced nephrotoxicity in rats
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DOI：
10.1186/1471-2210-4-20
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发表时间：
2004-09-30
期刊：
影响因子：
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通讯作者：
Pedraza-Chaverri, Jose
中科院分区：
文献类型：
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作者：
Chirino, Yolanda I.;Hernandez-Pando, Rogelio;Pedraza-Chaverri, Jose
背景：氧化应激参与顺铂肾毒性。然而，这一实验模型中是否涉及活性氮物种和亚硝化应激还没有完全确定。本工作的目的是利用能代谢过亚硝酸根的可溶性络合物5，10，15，20-四(4-磺酸苯基)卟啉合铁(FeTPPS)，研究活性氮物种过氧亚硝酸根在顺铂肾毒性中的作用。结果：在顺铂(单次注射7.5 mg/kg体重)治疗的大鼠中，3-硝基酪氨酸在第3天出现明显的肾脏亚硝化应激。此外，顺铂引起的肾毒性表现为近端肾小管细胞的组织学损害和(A)血清肌酸、(B)血氮、尿素的增加。和(C)尿N-乙酰-β-D-氨基葡萄糖苷酶和总蛋白的排泄。FeTPPS(15 mg/kg体重，每12小时一次，连续3天)可减轻顺铂诱导的亚硝化应激和肾毒性。结论：亚硝化应激参与了顺铂诱导的大鼠肾毒性。我们的数据表明，过氧亚硝酸盐至少部分参与了顺铂引起的肾毒性和蛋白质硝化。
Background: Oxidative stress is involved in cisplatin-nephrotoxicity. However, it has not completely established if reactive nitrogen species and nitrosative stress are involved in this experimental model. The purpose of this work was to study the role of peroxynitrite, a reactive nitrogen specie, in cisplatin-nephrotoxicity using the compound 5,10,15,20-tetrakis ( 4-sulfonatophenyl) porphyrinato iron ( III) ( FeTPPS), a soluble complex able to metabolize peroxynitrite.Results: In rats treated with cisplatin ( a single intraperitoneal dose of 7.5 mg/kg body weight), renal nitrosative stress was made evident by the increase in 3-nitrotyrosine on day 3. In addition, cisplatin-induced nephrotoxicity was evident by the histological damage of proximal tubular cells and by the increase in ( a) serum creatinine, ( b) blood urea nitrogen, and ( c) urinary excretion of N-acetyl-beta-D-glucosaminidase and total protein. Cisplatin-induced nitrosative stress and nephrotoxicity were attenuated by FeTPPS-treatment ( 15 mg/kg body weight, intraperitoneally, every 12 hours for 3 days).Conclusions: Nitrosative stress is involved in cisplatin-induced nephrotoxicity in rats. Our data suggest that peroxynitrite is involved, at least in part, in cisplatin-induced nephrotoxicity and protein nitration.