Hepatoprotective Role of Thymol in Drug-Induced Gastric Ulcer Model

Ann Hepatol. 2018 Oct 16;17(6):980-991. doi: 10.5604/01.3001.0012.7198.

Abstract

Introduction and aim: Indo is widely one of the non-steroidal anti-inflammatory drugs and one of the common toxic effects of this drug is hepatic failure. Thymol is a monoterpene phenol with many different pharmacological activities. However, up to now its hepatoprotective effects on Indo-induced gastric ulcer model in rats have not been explored yet.

Material and methods: Thirty five Sprague-Dawley rats were divided into seven groups: control, ulcer control (30 mg/kg Indo), Indo + reference standard (50 mg/kg Rantidine), Indo + Thymol (75, 100, 250 and 500 mg/kg) groups. 10 minutes after the induction of ulcer with Indo; Thymol was orally administered to the rats. Liver function enzymes (AST, ALT and LDH) were measured from serum samples. TOS/TAC, TNF-α and PGE2 levels, eNOS and Caspase-3 activity were assessed from tissue homogenate samples. In addition, histopathologic analysis on liver sections was performed.

Results: Indo significantly increased the levels of hepatic enzymes, TNF-α and eNOS, and caspase-3 activation, while decreased PGE2 levels. Furthermore, it induced oxidative stress as evidenced by elevated TOS and decreased TAC levels. However, Thymol treatment induced a significant improvement in these parameters, especially in 250 mg/kg dose. On the other hand, treatment with Thymol 500 mg/kg dramatically affected the parameters much worse than the Indo treated group.

Conclusion: The findings of the current study demonstrated that Thymol administration significantly ameliorated liver injury due to Indo toxicity. This effect of Thymol (250 mg/kg) may be mediated by its anti-oxidative or anti-inflammatory effect, and up-regulation the synthesis of PGE2.

Keywords: Apoptosis; Cytokines; Histopathology; Oxidative stress; Prostaglandin E2.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Cytoprotection
  • Dinoprostone / metabolism
  • Female
  • Indomethacin*
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / pathology
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidative Stress / drug effects
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Stomach Ulcer / chemically induced*
  • Thymol / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Tumor Necrosis Factor-alpha
  • Thymol
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Casp3 protein, rat
  • Caspase 3
  • Dinoprostone
  • Indomethacin