Rosmarinic acid attenuates hepatic ischemia and reperfusion injury in rats.

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.

• Authors: Leandra Naira Z Ramalho, Ângelo Augusto C Pasta, Vânia Aparecida Terra, Marlei Josiele Augusto, Sheila Cristina Sanches, Fernando P Souza-Neto, Rubens Cecchini, Francine Gulin, Fernando Silva Ramalho
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 74 Pg. 270-8 (Dec 2014) ISSN: 1873-6351 [Electronic] England
• PMID: 25455894 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, pathology)
• Liver Function Tests
• Male
• Neutrophil Infiltration
• Nitric Oxide (metabolism)
• Oxidative Stress (drug effects)
• Peroxidase (analysis, metabolism)
• Rats
• Rats, Wistar
• Reperfusion Injury (drug therapy, pathology)
• Tumor Necrosis Factor-alpha (metabolism)