Ellagic acid attenuates liver toxicity induced by valproic acid in rats

J Pharmacol Sci. 2020 May;143(1):23-29. doi: 10.1016/j.jphs.2020.01.007. Epub 2020 Jan 29.

Abstract

Valproic acid is a commonly used drug for many psychiatric disorders, particularly for epilepsy. However, it has been reported that its use is associated with possible side effects including hepatotoxicity. The present study investigated the hepatoprotective effect of ellagic acid against valproic acid-induced hepatotoxicity in rats. Ellagic acid (60 mg/kg/day; p.o) was treated for one week, followed by concomitant injection of valproic acid (250 mg/kg/day; i.p.) for another 14 consecutive days to induce hepatocellular damage in adult Sprague-Dawley rats. Valproic acid showed a marked increase in serum enzyme activities, AST, ALT, ALP and GGT. In addition, it significantly increased MDA and NO along with a marked decline in reduced GSH content. At the same time, valproic acid administration resulted in marked elevation in hydroxyproline, TNF-α production and NF-kB expression. These results were confirmed by histopathological examination. Treatment with ellagic acid markedly attenuated valproic acid-induced hepatic injury in rats.

Keywords: Ellagic acid; Hepatocellular damage; Hepatotoxicity; Oxidative stress; Valproic acid.

MeSH terms

  • Alanine Transaminase / metabolism
  • Alkaline Phosphatase / metabolism
  • Animals
  • Aspartate Aminotransferases / metabolism
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Ellagic Acid / administration & dosage
  • Ellagic Acid / pharmacology*
  • Ellagic Acid / therapeutic use
  • Glutathione / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects
  • Phytotherapy
  • Rats, Sprague-Dawley
  • Valproic Acid / administration & dosage
  • Valproic Acid / adverse effects
  • Valproic Acid / toxicity*

Substances

  • Ellagic Acid
  • Nitric Oxide
  • Valproic Acid
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Alkaline Phosphatase
  • Glutathione