Differential effects of eugenol against hepatic inflammation and overall damage induced by ischemia/re-perfusion injury

J Immunotoxicol. Jul-Sep 2014;11(3):238-45. doi: 10.3109/1547691X.2013.832444. Epub 2013 Oct 7.

Abstract

Liver injuries, liver tumor resection, and liver transplantation are known to be responsible for ischemia/reperfusion (I/R) injury that, in turn, gives rise to liver damage. This study was undertaken to investigate the possible protective effect of eugenol against the damage induced by I/R in rat livers as well as to explore possible mechanisms of action. Male rats were divided into four groups: sham-operated, I/R only, and two groups that received 10 or 100 mg eugenol/kg/day (Eug10 and Eug100, respectively) for 15 days by gavage and were then subjected to I/R, i.e. an ischemia induced for 45 min followed by re-perfusion for 6 h. The rats were euthanized and liver tissues and blood collected for examination. The results showed that I/R induced massive hepatic structural and functional damage. Eug10-treated rats had improvement in both liver function and structure, and inhibition of I/R-induced increases in serum myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, as well as hepatic nuclear factor-κB (NF-κB) p65 and caspase-3 expression. Eug10 treatment also inhibited the degree of loss in reduced glutathione (GSH) and of rise in malondialdehyde (MDA) levels in liver tissues induced by I/R. In contrast, augmentation of liver damage induced by I/R was noted in Eug100-treated rats, with these hosts displaying significant increases in oxidant, inflammatory, and apoptotic markers relative to levels seen in I/R-only rats. The results of the present study provide the first evidence that a low dose of eugenol may protect the liver against I/R injury in part by decreasing levels of lipid peroxidation, down-regulating inflammatory mediators, and inhibiting apoptosis, and that a larger dose amplifies the liver injury via oxidant and inflammatory effects.

Keywords: Caspase-3; MDA; NF-κB; eugenol; hepatic I/R.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Drug Dosage Calculations
  • Eugenol / administration & dosage*
  • Glutathione / metabolism
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / immunology
  • Liver / pathology
  • Male
  • Malondialdehyde / metabolism
  • NF-kappa B / metabolism
  • Peroxidase / blood
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / immunology
  • Tumor Necrosis Factor-alpha / blood

Substances

  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Eugenol
  • Malondialdehyde
  • Peroxidase
  • Caspase 3
  • Glutathione