Faculty of Pharmacy, Department of Pharmacology and Toxicology, Mansoura University, 35516 Mansoura, Egypt.
Fundam Clin Pharmacol. 2013 Apr;27(2):186-91. doi: 10.1111/j.1472-8206.2011.00996.x. Epub 2011 Oct 11.
Effect of montelukast on the renal dysfunction induced by cisplatin was investigated. A single dose of cisplatin (7 mg/kg, i.p.) induced nephrotoxicity, which was manifested by increasing the sensitivity of isolated urinary bladder rings to acetylcholine (ACh) together with a significant elevation of serum creatinine, blood urea nitrogen, and lactate dehydrogenase. On the other hand, serum albumin was significantly decreased. Moreover, renal dysfunction was further confirmed by a significant increase in lipid peroxides that were measured as malondialdehyde (MDA) in kidney tissue homogenate. Kidney reduced glutathione (GSH) content and superoxide dismutase (SOD) activity were measured, which were decreased and increased, respectively. Administration of montelukast (10 mg/kg/day, p.o.) 5 days before and 5 days after cisplatin injection significantly ameliorated the renotoxic effects of cisplatin, as judged by a significant reduction in the responses of isolated bladder rings to ACh. The deleterious changes induced by cisplatin treatment in kidney function parameters and oxidative stress markers were significantly mitigated by montelukast treatment.
Montelukast may be a beneficial remedy for cisplatin-induced renal dysfunction.
研究孟鲁司特对顺铂诱导的肾功能障碍的影响。
单次腹腔注射顺铂(7mg/kg)可诱导肾毒性,表现为增加分离的膀胱环对乙酰胆碱(ACh)的敏感性,同时血清肌酐、血尿素氮和乳酸脱氢酶显著升高。另一方面,血清白蛋白显著降低。此外,肾功障碍进一步通过测量肾组织匀浆中的丙二醛(MDA)来证实脂质过氧化物的显著增加。还测量了肾还原型谷胱甘肽(GSH)含量和超氧化物歧化酶(SOD)活性,分别降低和增加。顺铂注射前 5 天和后 5 天每天给予孟鲁司特(10mg/kg,po)治疗,可显著改善顺铂的肾毒性作用,这可通过分离的膀胱环对 ACh 的反应显著降低来判断。孟鲁司特治疗可显著减轻顺铂治疗引起的肾功能参数和氧化应激标志物的有害变化。
孟鲁司特可能是治疗顺铂诱导的肾功能障碍的有益药物。