Partial protection by 18β Glycrrhetinic acid against Cisplatin induced oxidative intestinal damage in wistar rats: Possible role of NFkB and caspases

Pharmacol Rep. 2017 Oct;69(5):1007-1013. doi: 10.1016/j.pharep.2017.02.013. Epub 2017 Feb 20.

Abstract

Background: Cisplatin (CP) is a potent chemotherapeutic agent commonly used for the treatment of various malignancies. It has varied undesirable effects such as nephrotoxicity, intestinal toxicity which limit its wide and extensive clinical usage. 18β-Glycyrrhetinic acid (GA) is a pentacyclic triterpenoid derivative, obtained from the herb liquorice having pharmacological properties such as anti-inflammatory, hepatoprotective and antioxidant. The present study was designed to investigate in vivo efficacy of GA against CP induced small intestinal toxicity.

Methods: Rats were subjected to prophylactic oral treatment of GA (50 and 100mg/kg body weight) for 21days against intestinal toxicity induced by single intra peritoneal injection of CP (10mg/kg body weight) on day 18th and sacrificed on 21st day.

Results: The plausible mechanism of CP induced small intestinal toxicity is via deficit in anti-oxidant armory, induction of oxidative stress; TNF-α, NFkB, activation of apoptotic pathway proteins by up regulation of caspases. However prophylactic treatment of GA diminished oxidative stress markers, TNF-α, NFkB expression and enhanced anti-oxidant status, down regulated apoptosis, recovered histopatholgical alterations in small intestine.

Conclusion: Therefore, results of the present finding provide strong evidence that GA may be a useful modulator in alleviating CP induced intestinal toxicity.

Keywords: Apoptosis; CP; GA; Inflammation; Oxidative stress.

MeSH terms

  • Animals
  • Biomarkers
  • Caspases / metabolism*
  • Cisplatin / toxicity*
  • Gene Expression Regulation / drug effects
  • Glutathione / metabolism
  • Glycyrrhetinic Acid / analogs & derivatives*
  • Glycyrrhetinic Acid / pharmacology
  • Intestinal Diseases / chemically induced*
  • Male
  • NF-kappa B / metabolism*
  • Oxidative Stress
  • Random Allocation
  • Rats
  • Rats, Wistar

Substances

  • Biomarkers
  • NF-kappa B
  • 18alpha-glycyrrhetinic acid
  • Caspases
  • Glutathione
  • Glycyrrhetinic Acid
  • Cisplatin