title: 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.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. framalho@fmrp.usp.br
authors.forename: Leandra Naira Z
authors.initials: LN
authors.lastname: Ramalho
authors.forename: Ângelo Augusto C
authors.initials: ÂA
authors.lastname: Pasta
authors.forename: Vânia Aparecida
authors.initials: VA
authors.lastname: Terra
authors.forename: Marlei  Josiele
authors.initials: M
authors.lastname: Augusto
authors.forename: Sheila Cristina
authors.initials: SC
authors.lastname: Sanches
authors.forename: Fernando P
authors.initials: FP
authors.lastname: Souza-Neto
authors.forename: Rubens
authors.initials: R
authors.lastname: Cecchini
authors.forename: Francine
authors.initials: F
authors.lastname: Gulin
authors.forename: Fernando Silva
authors.initials: FS
authors.lastname: Ramalho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D002934:Cinnamates / Q000627:therapeutic use*; D053630:Depsides / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008107:Liver Diseases / Q000188:drug therapy* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D020556:Neutrophil Infiltration; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097123:Rosmarinic Acid
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002934:Cinnamates; D053630:Depsides; D005978:Glutathione; D053583:Interleukin-1beta; D009569:Nitric Oxide; D009195:Peroxidase; D014409:Tumor Necrosis Factor-alpha; D000097123:Rosmarinic Acid