Nicorandil mitigates folic acid-induced nephrotoxicity in mice: Role of iNOS and eNOS.

Folic acid (FA)-induced acute kidney injury (AKI) is a commonly used model in experimental animals for studying renal injury. This study aimed to investigate the probable protecting impact of nicorandil against FA-induced renal dysfunction. A mouse model was executed by a single injection of FA (250 mg/kg). Nicorandil was orally administrated in two doses (50 and 100 mg/kg) for 10 days. Nicorandil repressed the progression of FA-induced AKI as evidenced by the improvement of histopathological alterations and the substantial decrease of serum levels of creatinine, urea, blood urea nitrogen, malondialdehyde (MDA), and urinary protein levels. Moreover, nicorandil resulted in a profound reduction in oxidative stress as manifested by decreased MDA and increased reduced glutathione and superoxide dismutase in renal tissue. Notably, nicorandil suppressed FA-induced inflammation; it reduced renal levels of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6. Furthermore, nicorandil decreased renal levels of nitric oxide, inducible nitric oxide synthase, and increased endothelial nitric oxide synthase. Lastly, nicorandil efficiently decreased expression of the proapoptotic protein (Bax) and caspase 3. Nicorandil confers dose-dependent protection against FA-induced AKI by alleviating oxidative stress, inflammation besides modulating nitric oxide synthase and reducing apoptosis.