Modulation of NADPH oxidase and Nrf2/HO‐1 pathway by vanillin in cisplatin‐induced nephrotoxicity in rats.

Younis, Nahla N.; Elsherbiny, Nehal M; Shaheen, Mohamed A.; Elseweidy, Mohamed M.

Objectives: To investigate the protective effect of vanillin in cisplatin (CP)‐induced nephrotoxicity in rats and elucidate the role of nrf‐2 and its downstream antioxidant molecules. Methods: Rats received vanillin (100 mg/kg orally) for 10 constitutive days and CP (7.5 mg/kg, once, ip) on day 6 of vanillin administration. Key findings: Cisplatin suppressed body weight gain, increased serum urea and creatinine and renal malondialdehyde and nitric oxide while decreased renal total antioxidant capacity. Up‐regulation of NADPH oxidase‐4 (NOX‐4) was marked in renal tissue of CP‐treated rats along with down‐regulation of the antioxidant genes (nuclear factor erythroid 2‐related factor2 (NRF2) and haem oxygenase‐1(HO‐1)). Increased tumour necrosis factor‐α and decreased interleukin‐10 with increased myeloperoxidase activity were apparent in renal tissue of CP‐treated rats along with marked tubular injury, neutrophil infiltration and increased apoptosis (caspase‐3) and some degree of interstitial fibrosis. Vanillin prophylactic administration prevented the deterioration of kidney function, oxidative and nitrosative stress. It also suppressed NOX‐4 and up‐regulated NRF2 and HO‐1 expression in renal tissue. Inflammation, apoptosis and tubular injury were also inhibited by vanillin. Conclusions: The antioxidant mechanism by which vanillin protected against CP‐induced nephrotoxicity involved the inhibition of NOX‐4 along with the stimulation of Nrf2/HO‐1 signalling pathway. These in turn inhibited inflammation and apoptosis.

NADPH oxidase; NEPHROTOXICOLOGY; OXIDANT status; RATS; WEIGHT gain; NEUTROPHILS; FETAL hemoglobin

Journal of Pharmacy & Pharmacology, 2020, Vol 72, Issue 11, p1546

0022-3573

Academic Journal

10.1111/jphp.13340