Rosmarinic acid attenuates hepatic ischemia and reperfusion injury in rats |
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| Affiliation: | 1. Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil;2. Pontifical Catholic University of Paraná, Londrina, PR, Brazil;3. Department of Pathological Sciences, State University of Londrina, Londrina, PR, Brazil;1. Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China;2. Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA;1. Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran 14359-16471, Iran;2. Research Group on Community Nutrition and Oxidative Stress (NUCOX) and CIBEROBN (Physiopathology of Obesity and Nutrition CB12/03/30038), University of Balearic Islands, Palma de Mallorca E-07122, Balearic Islands, Spain;3. Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran;4. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran;5. School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran;6. National Institute for Agricultural and Veterinary Research (INIAV), I.P., Vairão, Vila do Conde 4480, Portugal;7. Center for Study in Animal Science (CECA), ICETA, University of Oporto, Oporto 4051-401, Portugal;8. Department of Biotechnology, Alagappa University, Karaikudi, Tamil Nadu 630 003, India;9. Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan;10. Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela 15782, Spain;11. Instituto de Investigación e Innovación en Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago, Chile;12. Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Pavia 27100, Italy;13. Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Australia;14. Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy;15. Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies National Council of Research, Bari, Italy |
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| 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. |
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