Prevention of sodium valproate-induced hepatotoxicity by curcumin, rosiglitazone and N-acetylcysteine in rats

Arzneimittelforschung. 2010;60(11):647-53. doi: 10.1055/s-0031-1296342.

Abstract

The present study was designed to examine the potential preventive effect of curcumin (CMN; CAS 458-37-7), rosiglitazone (RGN; CAS 155141-29-0), N-acetylcysteine (NAC; CAS 616-91-1), resveratrol (RSV; CAS 501-36-0), and losartan (LOS; CAS 114798-26-4) on sodium valproate-induced hepatotoxicity. Sodium valproate (SVP; CAS 1069-66-5) was given at a dose of 250 mg/kg i. p. 3 times daily for one week. The tested compounds were given simultaneously with SVP for one week. The results demonstrate that CMN, RGN and NAC treatment can confer protection from SVP-induced hepatotoxicity. The second part of the study includes an evaluation of the effect of CMN, RGN and NAC on the anticonvulsant activity of SVP against pentetrazole-induced seizures in mice. The results demonstrate that CMN, RGN and NAC do not affect the anticonvulsant activity of SVP. Combined administration of either of CMN, RGN and NAC with valproate appears to be beneficial in reducing valproate-induced hepatotoxicity.

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Animals
  • Anticonvulsants / antagonists & inhibitors
  • Anticonvulsants / therapeutic use
  • Anticonvulsants / toxicity*
  • Body Weight / drug effects
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Convulsants
  • Curcumin / therapeutic use*
  • Eating / drug effects
  • Fatty Liver / chemically induced
  • Fatty Liver / pathology
  • Fatty Liver / prevention & control
  • Free Radical Scavengers / therapeutic use*
  • Hypoglycemic Agents / therapeutic use*
  • Liver / pathology
  • Liver Function Tests
  • Male
  • Mice
  • Pentylenetetrazole
  • Rats
  • Rats, Sprague-Dawley
  • Rosiglitazone
  • Seizures / chemically induced
  • Seizures / prevention & control
  • Thiazolidinediones / therapeutic use*
  • Valproic Acid / antagonists & inhibitors
  • Valproic Acid / therapeutic use
  • Valproic Acid / toxicity*

Substances

  • Anticonvulsants
  • Convulsants
  • Free Radical Scavengers
  • Hypoglycemic Agents
  • Thiazolidinediones
  • Rosiglitazone
  • Valproic Acid
  • Curcumin
  • Pentylenetetrazole
  • Acetylcysteine