title: Effect of selective versus non-selective cyclooxygenase inhibitors on ischemia-reperfusion-induced hepatic injury in rats.
abstract: OBJECTIVE
  Ischemia-reperfusion (IR) injury represents an important pathological process of liver injury during major hepatic surgery. The role of cyclooxygenase (COX) enzymes in the pathogenesis of ischemia-reperfusion (IR)-induced liver injury is not clear. This study investigated the effect of a selective COX-2 inhibitor, celecoxib, versus non-selective, indomethacin, on hepatic IR injury in rats.
  
  
  METHODS
  Hepatic IR was induced in adult male rats. The animals were divided into 4 groups: normal control (sham group), IR non-treated group; IR-indomethacin-treated group; and IR-celecoxib-treated group. Liver injury was evaluated by serum alanine aminotransferase (ALT) and a histopathological examination of liver tissues. Hepatic tissue content of oxidative stress parameters glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase, malondialdehyde (MDA), nitric oxide (NO) and the inflammatory marker, tumor necrosis factor-alpha, (TNF-α) were measured. Moreover, the immunohistochemical detection of endothelial NO synthase (eNOS), inducible NO synthase (iNOS), and caspase-3 in the hepatic tissue was performed.
  
  
  RESULTS
  Celecoxib, but not indomethacin, significantly attenuated hepatic IR injury as evidenced by reduction in serum ALT as well as by improvement in the histopathological scoring. Such effect was associated with attenuation in oxidative stress and TNF-α, along with modulation of immunohistochemical expression of eNOS, iNOS and caspase-3 in the hepatic tissue.
  
  
  CONCLUSIONS
  The present study concluded that selective COX-2 inhibition (but not non-selective), is hepatoprotective against liver IR injury; indicating a differential role of COX-1 versus COX-2. Modulation of iNOS, eNOS and caspase-3 might participate in the protective effect of selective COX-2-inhibitors.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Minia University, Egypt.
authors.forename: Seham A
authors.initials: SA
authors.lastname: Abdel-Gaber
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Minia University, Egypt. Electronic address: maim69@yahoo.com.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Ibrahim
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Minia University, Egypt.
authors.forename: Entesar F
authors.initials: EF
authors.lastname: Amin
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Minia University, Egypt.
authors.forename: Salwa A
authors.initials: SA
authors.lastname: Ibrahim
authors.affiliation: Department of Pathology, Faculty of Medicine, Minia University, Egypt.
authors.forename: Rehab K
authors.initials: RK
authors.lastname: Mohammed
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Minia University, Egypt.
authors.forename: Aly M
authors.initials: AM
authors.lastname: Abdelrahman
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D010088:Oxidoreductases; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D000410:Alanine Transaminase; C505410:Casp3 protein, rat; D053148:Caspase 3; D000068579:Celecoxib; D007213:Indomethacin
keywords: Celecoxib-ischemia–reperfusion; Cyclooxygenase inhibitors; Hepatic ischemia–reperfusion; Indomethacin-ischemia–reperfusion