Protective agent, erdosteine, against cisplatin-induced hepatic oxidant injury in rats
Protective agent, erdosteine, against cisplatin-induced hepatic oxidant injury in rats
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DOI：
10.1007/s11010-005-6630-z
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发表时间：
2005-10-01
影响因子：
4.3
通讯作者：
Sogut, S
中科院分区：
文献类型：
--
作者：
Koc, A;Duru, M;Sogut, S
顺铂是最有效的抗癌细胞毒药物之一，但有几种毒性。肝毒性是高剂量给药时发生的毒性反应之一。本研究的目的是通过组织氧化/抗氧化参数和光学显微镜评价来确定厄多司坦对顺铂诱导的肝损伤的影响。将大鼠随机分为对照组（n=5）、顺铂（10 mg/kg，n=6）和顺铂+厄多司坦（50 mg/kg/d，口服厄多司坦，n=8）组。在顺铂治疗的第5天处死大鼠。光镜下观察肝组织形态学变化，并检测氧化/抗氧化生化指标。顺铂组丙二醛（MDA）和一氧化氮（NO）水平较对照组和顺铂+厄多司坦组升高（P < 0.05）。对照组与顺铂+厄多司坦组MDA、NO水平无显著性差异。顺铂+厄多司坦组超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）活性均高于顺铂组（p < 0.05）。顺铂组CAT和GSH-Px活性明显低于对照组（p < 0.05）。光镜下顺铂组可见细胞质改变，尤其是中央静脉细胞周围。这些细胞中可见肝细胞空泡化。与顺铂组相比，厄多司坦联合顺铂组肝细胞胞浆改变减少，中央静脉细胞周围窦状隙减少。根据显微镜和生化结果，可以得出结论，高剂量顺铂引起的肝损伤和厄多司坦通过其抗氧化和清除自由基的作用来防止这种毒副作用。
Cisplatin, one of the most active cytotoxic agents against cancer, has several toxicities. Hepatotoxicity is one of them occurred during high doses treatment. The aim of this study was to determine the effects of erdosteine against cisplatin-induced liver injury through tissue oxidant/antioxidant parameters and light microscopic evaluation. The rats were randomly divided into three groups: control (n=5), cisplatin (10 mg/kg, n=6) and cisplatin+erdosteine (50 mg/kg/day oral erdosteine, n=8) groups. The rats were sacrificed at the 5th day of cisplatin treatment. The liver tissues were examined with light microscopy and oxidant/antioxidant biochemical parameters. The malondialdehyde (MDA) and nitric oxide (NO) levels were increased in the cisplatin group in comparison with the control and cisplatin+erdosteine groups (p < 0.05). There was no significant difference in MDA and NO levels between control and cisplatin+erdosteine groups. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were higher in cisplatin+erdosteine group than cisplatin group (p < 0.05). However, the CAT and GSH-Px activities were significantly lower in cisplatin group than in control group (p < 0.05). The light microscopic examination revealed that cytoplasmic changes especially around cells of central vein were observed in cisplatin group. Hepatocellular vacuolization was seen in these cells. In the cisplatin plus erdosteine group, a decrease in cytoplasmic changes with the hepatocytes and sinusoidal dilatations around cells of central vein were noticed in as compared to cisplatin group. In the light of microscopic and biochemical results, it was concluded that cisplatin-induced liver damage in high dose and erdosteine prevented this toxic side effect by the way of its antioxidant and radical scavenging effects.