Nephrotoxicity is a major adverse effect of the widely used anticancer
drug cisplatin. Oxidative stress,
inflammation and apoptosis are implicated in the pathophysiology of
cisplatin-induced
acute renal injury. Moreover,
cisplatin activates many signal transduction pathways involved in cell injury and death, particularly
mitogen activated protein kinase (MAPK) pathway. With this background, we aimed to investigate the protective effect of
telmisartan, a widely used
antihypertensive drug, in
cisplatin-induced nephrotoxicity model in rats. To accomplish this, male albino wistar rats (150-200 g) were divided into 6 groups: Normal,
cisplatin-control,
telmisartan (2.5, 5 and 10 mg/kg) and
telmisartan per se treatment groups.
Normal saline or
telmisartan was administered orally to rats for 10 days and
cisplatin was given on 7th day (8 mg/kg; i.p.) to induce nephrotoxicity. On 10th day, rats were killed and both the kidneys were harvested for biochemical, histopathological and molecular studies.
Cisplatin injected rats showed depressed renal function, altered proxidant-
antioxidant balance and acute tubular
necrosis which was significantly normalized by
telmisartan co-treatment. Furthermore,
cisplatin administration activated MAPK pathway that caused tubular
inflammation and apoptosis in rats.
Telmisartan treatment significantly prevented MAPK mediated
inflammation and apoptosis. Among the three doses studied
telmisartan at 10 mg/kg dose showed maximum nephroprotective effect which could be due to maintenance of cellular redox status and inhibition of MAPK activation.