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辅酶 Q10 治疗可改善小鼠顺铂急性肾毒性。

Coenzyme Q10 treatment ameliorates acute cisplatin nephrotoxicity in mice.

机构信息

Department of Biomedical Sciences, Pharmacology Division, College of Medicine, Al-Ahsa, King Faisal University, 31982 Saudi Arabia.

出版信息

Toxicology. 2010 Jul-Aug;274(1-3):49-56. doi: 10.1016/j.tox.2010.05.007. Epub 2010 May 25.

Abstract

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-alpha, 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-kappaB, 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.

摘要

辅酶 Q10 对顺铂诱导的急性肾损伤的肾保护作用研究

本研究旨在探讨辅酶 Q10 对顺铂诱导的急性肾损伤的肾保护作用。顺铂(5mg/kg,ip)单次注射诱导急性肾损伤模型,辅酶 Q10(10mg/kg/day,ip)连续给药 6 天,于顺铂给药前 1 天开始。结果显示,辅酶 Q10 可降低顺铂诱导的血尿素氮和血清肌酐水平升高。辅酶 Q10 可显著补偿抗氧化防御机制的缺陷(还原型谷胱甘肽水平和超氧化物歧化酶活性降低),抑制脂质过氧化,降低肿瘤坏死因子-α、一氧化氮和铂离子浓度的升高,并减轻顺铂给药引起的肾组织中硒和锌离子的降低。此外,辅酶 Q10 可改善顺铂介导的肾组织病理损伤。免疫组化分析显示,辅酶 Q10 可显著降低顺铂诱导的诱导型一氧化氮合酶、核因子-κB、半胱氨酸天冬氨酸蛋白酶-3 和 p53 在肾组织中的过度表达。综上所述,辅酶 Q10 可能是一种有潜力的治疗选择,可用于预防临床实践中常见的顺铂肾毒性。

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