Abstract

Silymarin (Silybum marianum) has some protective effects against drug toxicity (cisplatin, acetaminophen, adriamycin, gentamicin etc.). Colistin is a strong antimicrobial, which is frequently used in the treatment of resistant gram-negative bacterial infections in recent years although it has nephrotoxic potential. This study was aimed to determine the role of silymarin against colistin-induced acute nephrotoxicity (CIN). Rats were randomly divided into four groups. The control group was treated with tap water whereas groups 2 and 3 received silymarin (orally, 100 mg/kg/day) and colistin (intraperitoneally, 750.000 IU/kg/day) for seven days, respectively. Group 4 received both 750,000 IU/kg/day colistin and 100 mg/kg/day silymarin for seven days. After euthanasia, histopathological and biochemical examinations were completed for the kidney tissue specimens and blood samples. All parameters of the control and silymarin groups were similar. Severe weight loss was seen in the groups receiving colistin (groups 3 and 4). Silymarin significantly increased glutathione peroxidase and superoxide dismutase levels when administered with colistin in group 4 only. Acute tubular injury, tubular necrosis, meduller congestion, interstitial inflammation and apoptotic indices of colistin group were significantly higher than the control group. The administration of colistin with silymarin (group 4) was able to make some improvements in tubular necrosis and significant increase in antioxidant capacity. Silymarin increased antioxidant enzyme activity only when used in combination with colistin. The effects of silymarin may become more pronounced when used at higher doses or with a longer duration of treatment and may prevent nephrotoxicity.

 抽象的

水飞蓟素（Silybum marianum）对药物毒性（顺铂、对乙酰氨基酚、阿霉素、庆大霉素等）有一定的保护作用。粘菌素是一种强效抗菌剂，尽管具有潜在的肾毒性，但近年来常用于​​治疗耐药革兰氏阴性细菌感染。本研究旨在确定水飞蓟素对抗粘菌素诱导的急性肾毒性（CIN）的作用。将大鼠随机分为四组。对照组用自来水治疗，而第2组和第3组分别接受水飞蓟素（口服，100毫克/公斤/天）和粘菌素（腹膜内注射，750.000国际单位/公斤/天），持续7天。第 4 组接受 750,000 IU/kg/天的粘菌素和 100 mg/kg/天的水飞蓟素，持续 7 天。安乐死后，对肾组织标本和血液样本进行组织病理学和生化检查。对照组和水飞蓟素组的所有参数均相似。在接受粘菌素的组（第 3 组和第 4 组）中观察到体重严重减轻。仅在第 4 组中与粘菌素一起施用时，水飞蓟素显着增加了谷胱甘肽过氧化物酶和超氧化物歧化酶水平。粘菌素组急性肾小管损伤、肾小管坏死、髓质充血、间质炎症及细胞凋亡指数均显着高于对照组。给予粘菌素和水飞蓟素（第4组）能够在一定程度上改善肾小管坏死并显着提高抗氧化能力。水飞蓟素仅在与粘菌素联合使用时才能提高抗氧化酶活性。当使用较高剂量或治疗时间较长时，水飞蓟素的作用可能会变得更加明显，并且可以预防肾毒性。