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

Research output: Contribution to journalArticlepeer-review

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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