Melatonin inhibits nuclear factor kappa B activation and oxidative stress and protects against thioacetamide induced liver damage in rats

Rafael Bruck*, Hussein Aeed, Yona Avni, Haim Shirin, Zipora Matas, Mark Shahmurov, Ilana Avinoach, Galina Zozulya, Nir Weizman, Ayala Hochman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

165 Scopus citations

Abstract

Background/Aims: Free radical-mediated oxidative stress has been implicated in the pathogenesis of acute liver injury. The aim of our study was to investigate whether melatonin, a potent free radical scavenger could prevent fulminant hepatic failure in rats. Methods: Liver damage was induced by two consecutive injections of thioacetamide (TAA, 300 mg/kg/i.p.) at 24 h intervals. Treatment with melatonin (3 mg/kg/daily, i.p) was initiated 24 h prior to TAA. Results: Twenty-four h after the second TAA injection, serum liver enzymes and blood ammonia were lower in rats treated with TAA + melatonin compared to TAA (P < 0.001). Liver histology was significantly improved and the mortality in the melatonin-treated rats was decreased (P < 0.001). The increased nuclear binding of nuclear factor κB in the livers of the TAA-treated rats, was inhibited by melatonin. The hepatic levels of thiobarbituric acid reactive substances, protein carbonyls and inducible nitric oxide synthase were lower in the TAA + melatonin-treated group (P < 0.01), indicating decreased oxidative stress and inflammation. Conclusions: In a rat model of TAA-induced fulminant hepatic failure, melatonin improves survival and reduces liver damage and oxidative stress. The results suggest a causative role of oxidative stress in TAA-induced hepatic damage and suggest that melatonin may be utilized to reduce liver injury associated with oxidative stress.

Original languageEnglish
Pages (from-to)86-93
Number of pages8
JournalJournal of Hepatology
Volume40
Issue number1
DOIs
StatePublished - Jan 2004

Keywords

  • Fulminant hepatitis
  • Melatonin
  • Oxidative stress
  • Thioacetamide

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