Cisplatin impairs antioxidant system and causes oxidation in rat kidney tissues:: possible protective roles of natural antioxidant foods
Cisplatin impairs antioxidant system and causes oxidation in rat kidney tissues:: possible protective roles of natural antioxidant foods
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DOI：
10.1002/jat.1103
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发表时间：
2006-01-01
影响因子：
3.3
通讯作者：
Durak, I
中科院分区：
文献类型：
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作者：
Çetin, R;Devrim, E;Durak, I
本研究旨在阐明顺铂肾毒性的分子机制(S)以及抗氧化剂食品对顺铂肾毒性的可能保护作用。在整个研究过程中使用了28只老鼠。顺铂腹腔注射(Ip)。单次给药(10 mg kg(-1))。在顺铂治疗前3天开始补充抗氧化剂食物。每组(对照组、顺铂、顺铂+黑葡萄干、顺铂+番茄汁)各7只。治疗72h后处死大鼠。取出肾脏，准备进行生化和组织病理学检查。测定各组大鼠肾组织的抗氧化剂(氧化敏感性、黄嘌呤氧化酶和丙二醛水平)和抗氧化剂(超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶、抗氧化剂潜能值)参数。同时进行组织病理学检查。肾脏过氧化氢酶和谷胱甘肽过氧化物酶活性显著降低。然而，与对照组相比，顺铂处理组动物的黄嘌呤氧化物酶活性显著增加。顺铂组大鼠肾组织丙二醛水平升高，但氧化敏感性和抗氧化潜能值降低。在食物添加组中，观察到黑葡萄通过提高抗氧化能力来消除氧化应激，而西红柿则没有。组织病理学检查结果还显示，顺铂治疗的大鼠肾脏组织有明显的损害。在黑葡萄组中，与顺铂组相比，观察到显著改善。西红柿组也有一些改善，但与黑葡萄组相比程度较小。结果提示，顺铂通过激活黄嘌呤氧化酶和损伤抗氧化剂防御系统，导致肾脏组织氧化反应加速，从而导致肾脏的氧化负荷增加。有人建议，补充一些食物，如含有白藜芦醇作为抗氧化剂的黑葡萄，可以对顺铂的肾毒性起到明显的保护作用。版权所有(C)2005 John Wiley&Sons，Ltd.
This study aims to elucidate the molecular mechanism(s) of cisplatin nephrotoxicity and the possible protective effects of antioxidant food supplementation on this toxicity. Twenty eight rats were used throughout the study. Cisplatin was administered intraperitoneally (i.p.) in a single dose (10 mg kg(-1)). Antioxidant food supplementation was started 3 days before cisplatin treatment. In each group (control, cisplatin, cisplatin plus dried black grape and cisplatin plus tomato juice), there were seven animals. Rats were killed 72 h after treatment. The kidneys were removed and prepared for biochemical and histopathological investigations. Oxidant (sensitivity to oxidation, xanthine oxidase enzyme and malondialdehyde level) and antioxidant (superoxide dismutase, glutathione peroxidase and catalase enzymes, and antioxidant potential value) parameters were measured in kidney tissues of the groups. Histopathological examination was also performed. Significant decreases were measured in the renal activities of catalase and glutathione peroxidase enzymes. There was, however, a significant increase in the activity of xanthine oxidase enzyme in the cisplatin-treated animals compared with the control group. The kidney tissue malondialdehyde levels were found to be increased, but sensitivity to oxidation and antioxidant potential values to be decreased in the cisplatin group. In the food supplemented groups, it has been observed that black grape eliminated oxidant stress by increasing antioxidant potential, but tomato did not. Histopathological examination results also revealed significant damage in the kidney tissues from the cisplatin-treated rats. In the black grape group, significant improvements were observed compared with the cisplatin group. In the tomato group, there were also some improvements but to a lesser degree compared with the black grape group. The results suggest that cisplatin treatment causes significant oxidant load to the kidneys through both xanthine oxidase activation and impaired antioxidant defense system, which resulted in accelerated oxidation reactions in the kidney tissue. It is proposed that supplementation of some foods such as black grape which has resveratrol as an antioxidant can provide significant protection against cisplatin nephrotoxicity. Copyright (c) 2005 John Wiley & Sons, Ltd.