Busari Abdulwasiu A, Adejare Abdullahi A, Shodipe Abiodun F, Oduniyi Oludaisi A, Ismail-Badmus Khadijah B, Oreagba Ibrahim A
Department of Pharmacology, Therapeutics and Toxicology , Lagos, Nigeria.
Department of Physiology, College of Medicine of the University of Lagos, Lagos, Nigeria.
Drug Res (Stuttg). 2018 Dec;68(12):696-703. doi: 10.1055/a-0626-7003. Epub 2018 Jun 26.
Cisplatin is an anti-cancer drug that causes nephrotoxicity and oxidative stress. Extracts of Nigella sativa is nephroprotective. Vitamin E is also a potent antioxidant. This study sought to determine a possible synergistic effect of administering the two agents prior to cisplatin use on nephrotoxicity and oxidative stress.
48 male Wistar rats were randomly divided into 6 groups of 8 rats each. Group I served as the control. Group II received cisplatin without any treatment for 6 days. Groups III, IV, V and VI received 100 mg/kg Nigella sativa (NS), 200 mg/kg NS, 100 mg/kg Vitamin E and 200 mg/kg NS+100 mg/kg Vitamin E respectively for 5 days prior to 6 days administration of cisplatin. On the last day of the experiment, all the animals were sacrificed and serum samples collected for analysis.
Cisplatin administration caused a significant increase in creatinine level (p<0.01), urea level (p<0.01), sodium concentration and malondialdehyde level (p<0.001). Pre-administration with NS caused a significant reduction in creatinine level (p<0.001), urea level (p<0.001), sodium concentration (p<0.001) and malondialdehyde (p<0.01) level. Pre-administration with vitamin E caused a significant reduction in creatinine level (p<0.001), urea level (p<0.01), sodium concentration (p<0.001) and malondialdehyde level. They both also caused a significant increase in superoxide dismutase, reduced glutathione and catalase (CAT) levels. The combination of NS and vitamin E however did not show significant synergistic effects.
These results suggest that even though pre-administration of the two agents protect against renal toxicity and oxidative stress, the effects are however not collaborative.
顺铂是一种会导致肾毒性和氧化应激的抗癌药物。黑种草提取物具有肾保护作用。维生素E也是一种有效的抗氧化剂。本研究旨在确定在使用顺铂之前给予这两种药物对肾毒性和氧化应激是否可能具有协同作用。
48只雄性Wistar大鼠随机分为6组,每组8只。第一组作为对照组。第二组接受顺铂治疗,未进行任何处理,持续6天。第三组、第四组、第五组和第六组在给予顺铂6天之前,分别接受100mg/kg黑种草(NS)、200mg/kg NS、100mg/kg维生素E和200mg/kg NS + 100mg/kg维生素E治疗5天。在实验的最后一天,处死所有动物并收集血清样本进行分析。
给予顺铂导致肌酐水平(p<0.01)、尿素水平(p<0.01)、钠浓度和丙二醛水平(p<0.001)显著升高。预先给予NS导致肌酐水平(p<0.001)、尿素水平(p<0.001)、钠浓度(p<0.001)和丙二醛(p<0.01)水平显著降低。预先给予维生素E导致肌酐水平(p<0.001)、尿素水平(p<0.01)、钠浓度(p<0.001)和丙二醛水平显著降低。它们还都导致超氧化物歧化酶、还原型谷胱甘肽和过氧化氢酶(CAT)水平显著升高。然而,NS和维生素E的组合并未显示出显著的协同作用。
这些结果表明,尽管预先给予这两种药物可预防肾毒性和氧化应激,但其效果并非协同作用。