Oxytocin inhibits NADPH oxidase and P38 MAPK in cisplatin-induced nephrotoxicity
Oxytocin inhibits NADPH oxidase and P38 MAPK in cisplatin-induced nephrotoxicity
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DOI：
10.1016/j.biopha.2011.07.001
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发表时间：
2011-10-01
影响因子：
7.5
通讯作者：
Soliman, Hala M.
中科院分区：
文献类型：
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作者：
Rashed, Laila A.;Hashem, Reem M.;Soliman, Hala M.
氧化应激显著促进顺铂（CP）相关的细胞毒性，使用抗氧化剂可以抵消CP的这种细胞毒性作用。活性氧（reactive oxygen species，ROS）形成的主要生化途径是NADPH氧化酶产生O（2）（-），这种氧化应激可激活p38 MAPK，增强CP的细胞毒作用。我们的主要目的是研究催产素（OT）对CP诱导的肾毒性的保护作用，而它以前被证明在不同的炎症模型中具有抗炎作用。给药OT可显著降低NADPH氧化酶和P38 MAPK、一氧化氮（NO）、髓过氧化物酶（MPO）和TBARS的基因表达，并增加肾组织抗氧化剂、还原型谷胱甘肽（GSH）和超氧化物歧化酶（SOD）的水平。在组织学上，OT减少CP引起的肾毒性的单细胞浸润以及肾小管损伤。结论OT具有较强的抗氧化作用，可通过抑制NADPH氧化酶和P38 MAPK而减轻CP所致的肾毒性，从而改善肾功能。(C)2011年Elsevier Masson SAS。All rights reserved.
Oxidative stress significantly contributes to cisplatin (CP)-associated cytotoxicity, and use of antioxidants could counteract such cytotoxic effects of CP. The major biochemical pathway for reactive oxygen species (ROS) formation proceeds through O(2)(-) production, which is generated by NADPH oxidase, such oxidative stress can activate p38 MAPK to intensify the cytotoxic effect of CP. We mainly aimed to study the protective effect of oxytocin (OT) on CP-induced nephrotoxicity whereas; it was previously shown to have anti-inflammatory effects in different inflammation models. Administration of OT significantly decreased the gene expression of both NADPH oxidase and P38 MAPK, nitric oxide (NO), myloperoxidase (MPO), and TBARS, furthermore it increased the renal tissue levels of antioxidants; reduced glutathione (GSH), and superoxide dismutase (SOD). Histologically, OT reduced the monocellular infiltration as well as the tubular damage in CP-induced nephrotoxicity. In conclusion OT has a powerful antioxidant effect that can alleviate the CP-induced nephrotoxicity through inhibition of NADPH oxidase and P38 MAPK resulting in improvement of kidney functions. (C) 2011 Elsevier Masson SAS. All rights reserved.