Sulforaphane Protects Against Sodium Valproate-Induced Acute Liver Injury

Can J Physiol Pharmacol. 2017 Apr;95(4):420-426. doi: 10.1139/cjpp-2016-0447. Epub 2016 Nov 1.

Abstract

Drug-induced hepatotoxicity is one of the most commonly encountered obstacles in the field of medical practice. Sodium valproate (VPA) is among many drugs with reported hepatotoxic effects. Sulforaphane (SFN) is a thiol compound found in wide abundance in cruciferous plants that has numerous reported therapeutic efficacies. The current investigation sheds light on the potential hepatoprotective effect of SFN against VPA-induced liver injury in rats. Twice daily VPA (700 mg/kg, i.p.) for 7 days induced significant biochemical alterations and hepatic histopathological damage. SFN (0.5 mg/kg, orally) for 7 days significantly boosted liver function biomarkers; it reduced serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase, and restored serum albumin concentration in a significant manner. Meanwhile, SFN significantly mitigated VPA-induced histopathological alterations. To highlight the mechanisms implicated in the observed hepatoprotective action, hepatic malondialdehyde and tumour necrosis factor α content significantly declined with concomitant increase in hepatic heme oxygenase-1 content and glutathione concentration with SFN treatment. In conclusion, SFN can significantly ameliorate VPA-induced hepatotoxicity and liver injury primarily by direct association between antioxidant and anti-inflammatory properties.

Keywords: TNFα; heme oxygenase-1; hème oxygénase 1; liver injury; lésions hépatiques; sodium valproate; sulforaphane; valproate de sodium.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Anticarcinogenic Agents / therapeutic use*
  • Anticonvulsants / adverse effects*
  • Anticonvulsants / therapeutic use
  • Antioxidants / therapeutic use
  • Aspartate Aminotransferases / blood
  • Biomarkers / analysis
  • Brassica / chemistry
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Epilepsy / drug therapy
  • Glutathione / metabolism
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Isothiocyanates / therapeutic use*
  • Liver Function Tests
  • Male
  • Malondialdehyde / metabolism
  • Phytochemicals / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / metabolism
  • Valproic Acid / adverse effects*
  • Valproic Acid / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Anticarcinogenic Agents
  • Anticonvulsants
  • Antioxidants
  • Biomarkers
  • Isothiocyanates
  • Phytochemicals
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Valproic Acid
  • Heme Oxygenase-1
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • sulforafan
  • Glutathione