Nicotinamide attenuates cyclophosphamide-induced hepatotoxicity in SD rats by reducing oxidative stress and apoptosis

J Biochem Mol Toxicol. 2020 Oct;34(10):e22558. doi: 10.1002/jbt.22558. Epub 2020 Jul 1.

Abstract

Cyclophosphamide (CP) is a widely used anticancer and immunosuppressant drug. Nevertheless, clinical utilization of CP is limited due to considerable adverse effects and toxicities. Nicotinamide (NMD) is a micronutrient and the effect of NMD against CP-induced hepatotoxicity is yet unexplored. The present study was designed to evaluate the chemoprotective effect of NMD against CP-induced hepatic injury in Sprague-Dawley rats. Hepatotoxicity was induced by the administration of CP (30 mg/kg/day) for 10 consecutive days by intraperitoneal injection. The chemoprotective effect of NMD treatment (200 mg/kg) against CP-induced hepatotoxicity was evaluated by the oxidative stress, liver function, histopathological changes, and DNA damage. NMD cotreatment significantly reduced CP-induced oxidative stress, histological changes, and apoptosis in the liver. The present study demonstrated that NMD treatment ameliorated CP-induced hepatic damage by improving the antioxidant system and reducing DNA damage. The present findings revealed that NMD supplementation might be useful to reduce CP-associated hepatotoxicity, and thereby can increase the therapeutic utility of CP.

Keywords: apoptosis; cyclophosphamide; hepatotoxicity; nicotinamide; oxidative stress.

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / toxicity*
  • Apoptosis / drug effects*
  • Body Weight / drug effects
  • Cyclophosphamide / toxicity*
  • Female
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / metabolism
  • Liver Function Tests
  • Liver Glycogen / metabolism
  • Niacinamide / pharmacology*
  • Organ Size / drug effects
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antineoplastic Agents, Alkylating
  • Liver Glycogen
  • Niacinamide
  • Cyclophosphamide