title: Effect of preischemic treatment with fenofibrate, a peroxisome proliferator-activated receptor-α ligand, on hepatic ischemia-reperfusion injury in rats.
abstract: Liver ischemia/reperfusion (I/R) injury is a serious clinical problem. The reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α) are important mediators in liver I/R injury. This study was designed to investigate the effect of preischemic treatment with fenofibrate (Peroxisome proliferator-activated receptor- α agonist) on the oxidative stress and inflammatory response to hepatic I/R injury in rats. Hepatic I/R was induced by clamping the blood supply of the left lateral and median lobes of the liver for 60 min, followed by reperfusion for 4 h. Each animal group was pretreated with a single dose of fenofibrate (50 mg/kg body weight) intraperitoneally 1 h before ischemia. At the end of reperfusion, blood samples and liver tissues were obtained to assess serum alanine aminotransferase (ALT), TNF-α, hepatic malondialdehyde (MDA) and superoxide dismutase activity (SOD). Liver specimens were obtained and processed for light and electron microscopic study. Hepatic I/R induced a significant elevation of serum ALT and TNF-α with significant elevation of hepatic MDA and reduction of SOD activity. Histopathological examination revealed hepatic inflammation, necrosis and apoptosis. Preischemic treatment with fenofibrate at a dose of 50 mg/kg significantly attenuated the biochemical and structural alterations of I/R-induced liver injury.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. vivianboshra@hotmail.com
authors.forename: Vivian
authors.initials: V
authors.lastname: Boshra
authors.forename: Amal M
authors.initials: AM
authors.lastname: Moustafa
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004727:Endothelium / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D007511:Ischemia / Q000517:prevention & control*; D007728:Kupffer Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D047493:PPAR alpha; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D000410:Alanine Transaminase; D011345:Fenofibrate