Department of Nephrology, Gazi University Faculty of Medicine, Ankara, Turkey.
Department of Medical Pharmacology, Kirikkale University Faculty of Medicine, Kirikkale, Turkey.
Drug Chem Toxicol. 2022 Mar;45(2):568-575. doi: 10.1080/01480545.2020.1733003. Epub 2020 Mar 16.
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.
水飞蓟素(水飞蓟)对一些药物毒性(顺铂、对乙酰氨基酚、阿霉素、庆大霉素等)具有保护作用。多粘菌素是一种强有力的抗菌药物,近年来常用于治疗耐药革兰氏阴性菌感染,尽管它有肾毒性的潜力。本研究旨在确定水飞蓟素对多粘菌素诱导的急性肾毒性(CIN)的作用。大鼠随机分为四组。对照组给予自来水,而第 2 组和第 3 组分别给予水飞蓟素(口服,100mg/kg/天)和多粘菌素(腹腔内,750000IU/kg/天),共 7 天。第 4 组同时给予 750000IU/kg/天多粘菌素和 100mg/kg/天水飞蓟素,共 7 天。安乐死后,对肾脏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。接受多粘菌素治疗的组(第 3 组和第 4 组)体重明显减轻。只有在第 4 组中,当给予水飞蓟素时,多粘菌素才显著增加谷胱甘肽过氧化物酶和超氧化物歧化酶的水平。与对照组相比,多粘菌素组的急性肾小管损伤、肾小管坏死、髓质充血、间质炎症和细胞凋亡指数明显升高。多粘菌素联合水飞蓟素(第 4 组)治疗可改善肾小管坏死,并显著增加抗氧化能力。只有当与多粘菌素联合使用时,水飞蓟素才能增加抗氧化酶的活性。当使用更高的剂量或更长的治疗时间时,水飞蓟素的作用可能会更加明显,并可能预防肾毒性。