Effects of different doses of hyperbaric oxygen on cisplatin-induced nephrotoxicity
Effects of different doses of hyperbaric oxygen on cisplatin-induced nephrotoxicity
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DOI：
10.1080/08860220601166487
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发表时间：
2007-01-01
期刊：
影响因子：
3
通讯作者：
Evrenkaya, Rifki
中科院分区：
文献类型：
--
作者：
Aydinoz, Seed;Uzun, Gunalp;Evrenkaya, Rifki
顺铂是一种有效的治疗药物，常引起动物和人类的急性肾功能衰竭。高压氧（HBO）已被证明可以预防顺铂诱导的大鼠肾毒性。本研究探讨了两种不同的高压氧治疗方案对顺铂治疗后大鼠肾功能、氧化应激和组织病理学变化的影响。Wistar大鼠分为对照组、HBO组、顺铂组、顺铂+HBO组和顺铂+HBO组。顺铂以6 mg/kg的剂量单次腹腔注射，并在2.5atm下施加HBO 60 min，持续6天。与对照组相比，单独HBO没有改变任何生化参数或组织病理学结果。顺铂增加血清尿素和肌酐水平，并造成严重的组织病理学损伤。此外，顺铂增加脂质过氧化和损害超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）在肾组织中的活性。顺铂治疗后每日一次HBO可轻微降低血清尿素和肌酐水平，减轻组织病理学损伤。HBO还能显著降低脂质过氧化反应，提高SOD和GSH-Px活性。虽然每天两次HBO被确定为比每天一次HBO对氧化应激参数更有效，但与顺铂组相比，它增加了血清肌酐水平和组织病理学损伤。得出的结论是，HBO单独不诱导大鼠肾脏的肾毒性和氧化应激;每日一次HBO可以防止顺铂诱导的肾毒性，这种作用部分是通过肾脏中氧化剂/抗氧化剂系统的修饰介导的;每日两次HBO通过ROS独立机制增强顺铂肾毒性。
Cisplatin, an effective antineoplastic agent, frequently induces acute renal failure in animals and humans. Hyperbaric oxygen (HBO) has been shown to prevent cisplatin-induced nephrotoxicity in rats. This study investigated the effect of two different HBO regimes on renal functions, oxidative stress, and histopathological changes in rat kidneys after cisplatin treatment. Wistar rats were divided into five groups: control, HBO, cisplatin, cisplatin plus once daily HBO, and cisplatin plus twice daily HBO. Cisplatin was given as a single intraperitoneal dose of 6 mg/kg, and HBO was applied for 60 min at 2.5 atm for six days. HBO alone did not alter any biochemical parameters or histopathological findings compared with the control group. Cisplatin increased serum urea and creatinine levels and caused severe histopathological injury. In addition, cisplatin increased lipid peroxidation and impaired superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in kidney tissue. Once daily HBO after cisplatin treatment slightly reduced serum urea and creatinine levels and attenuated histopathological injury. HBO also reduced lipid peroxidation and increased SOD and GSH-Px activities significantly. Although twice daily HBO was determined to be more effective than once daily HBO on oxidative stress parameters, it increased serum creatinine levels and histopathological injury compared with the cisplatin group. It was concluded that HBO alone does not induce nephrotoxicity and oxidative stress in rat kidneys; once daily HBO may prevent cisplatin-induced nephrotoxicity, an effect that is partially mediated by the modification of oxidant/antioxidant systems in the kidneys; and twice daily HBO potentiates cisplatin nephrotoxicity by a ROS-independent mechanism.