Rosmarinic acid attenuates hepatic ischemia and reperfusion injury in rats

Food Chem Toxicol. 2014 Dec:74:270-8. doi: 10.1016/j.fct.2014.10.004.

Abstract

Rosmarinic acid (RosmA) demonstrates antioxidant and anti-inflammatory properties. We investigated the effect of RosmA on liver ischemia/reperfusion injury. Rats were submitted to 60 min of ischemia plus saline or RosmA treatment (150 mg/kg BW intraperitoneally) followed by 6 h of reperfusion. Hepatocellular injury was evaluated according to aminotransferase activity and histological damage. Hepatic neutrophil accumulation was also evaluated. Oxidative/nitrosative stress was estimated by measuring the reduced glutathione, lipid hydroperoxide and nitrotyrosine levels. Endothelial and inducible nitric oxide synthase (eNOS/iNOS) and nitric oxide (NO) were assessed with immunoblotting and chemiluminescence assays. Hepatic tumor necrosis factor-alpha (TNF-α) and interleukin-1beta mRNA were assessed using real-time PCR, and nuclear factor-kappaB (NF-κB) activation was estimated by immunostaining. RosmA treatment reduced hepatocellular damage, neutrophil infiltration and all oxidative/nitrosative stress parameters. RosmA decreased the liver content of eNOS/iNOS and NO, attenuated NF-κB activation, and down-regulated TNF-α and interleukin-1beta gene expression. These data indicate that RosmA exerts anti-inflammatory and antioxidant effects in the ischemic liver, thereby protecting hepatocytes against ischemia/reperfusion injury. The mechanisms underlying these effects may be related to the inhibitory potential of RosmA on the NF-κB signaling pathway and the reduction of iNOS and eNOS expressions and NO levels, in addition to its natural antioxidant capability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / therapeutic use*
  • Cinnamates / therapeutic use*
  • Depsides / therapeutic use*
  • Glutathione / metabolism
  • Interleukin-1beta / metabolism
  • Lipid Peroxidation / drug effects
  • Liver Diseases / drug therapy*
  • Liver Diseases / pathology
  • Liver Function Tests
  • Male
  • Neutrophil Infiltration
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects
  • Peroxidase / analysis
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / pathology
  • Rosmarinic Acid
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cinnamates
  • Depsides
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Peroxidase
  • Glutathione