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Effect of selective versus non-selective cyclooxygenase inhibitors on ischemia-reperfusion-induced hepatic injury in rats.
Life Sci. 2015 Aug 01; 134:42-8.LS

Abstract

AIM

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.

MATERIALS AND 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.

KEY FINDINGS

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.

SIGNIFICANCE

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+Show Affiliations

Department of Pharmacology, Faculty of Medicine, Minia University, Egypt.Department of Pharmacology, Faculty of Medicine, Minia University, Egypt. Electronic address: maim69@yahoo.com.Department of Pharmacology, Faculty of Medicine, Minia University, Egypt.Department of Pharmacology, Faculty of Medicine, Minia University, Egypt.Department of Pathology, Faculty of Medicine, Minia University, Egypt.Department of Pharmacology, Faculty of Medicine, Minia University, Egypt.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26006041

Citation

Abdel-Gaber, Seham A., et al. "Effect of Selective Versus Non-selective Cyclooxygenase Inhibitors On Ischemia-reperfusion-induced Hepatic Injury in Rats." Life Sciences, vol. 134, 2015, pp. 42-8.
Abdel-Gaber SA, Ibrahim MA, Amin EF, et al. Effect of selective versus non-selective cyclooxygenase inhibitors on ischemia-reperfusion-induced hepatic injury in rats. Life Sci. 2015;134:42-8.
Abdel-Gaber, S. A., Ibrahim, M. A., Amin, E. F., Ibrahim, S. A., Mohammed, R. K., & Abdelrahman, A. M. (2015). Effect of selective versus non-selective cyclooxygenase inhibitors on ischemia-reperfusion-induced hepatic injury in rats. Life Sciences, 134, 42-8. https://doi.org/10.1016/j.lfs.2015.04.025
Abdel-Gaber SA, et al. Effect of Selective Versus Non-selective Cyclooxygenase Inhibitors On Ischemia-reperfusion-induced Hepatic Injury in Rats. Life Sci. 2015 Aug 1;134:42-8. PubMed PMID: 26006041.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of selective versus non-selective cyclooxygenase inhibitors on ischemia-reperfusion-induced hepatic injury in rats. AU - Abdel-Gaber,Seham A, AU - Ibrahim,Mohamed A, AU - Amin,Entesar F, AU - Ibrahim,Salwa A, AU - Mohammed,Rehab K, AU - Abdelrahman,Aly M, Y1 - 2015/05/23/ PY - 2014/12/25/received PY - 2015/04/22/revised PY - 2015/04/25/accepted PY - 2015/5/27/entrez PY - 2015/5/27/pubmed PY - 2015/9/17/medline KW - Celecoxib-ischemia–reperfusion KW - Cyclooxygenase inhibitors KW - Hepatic ischemia–reperfusion KW - Indomethacin-ischemia–reperfusion SP - 42 EP - 8 JF - Life sciences JO - Life Sci VL - 134 N2 - AIM: 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. MATERIALS AND 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. KEY FINDINGS: 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. SIGNIFICANCE: 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. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/26006041/Effect_of_selective_versus_non_selective_cyclooxygenase_inhibitors_on_ischemia_reperfusion_induced_hepatic_injury_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(15)00278-7 DB - PRIME DP - Unbound Medicine ER -