Effect of selective versus non-selective cyclooxygenase inhibitors on ischemia-reperfusion-induced hepatic injury in rats

Seham A. Abdel-Gaber, Mohamed A. Ibrahim, Entesar F. Amin, Salwa A. Ibrahim, Rehab K. Mohammed, Aly M. Abdelrahman

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)42-48
Number of pages7
JournalLife Sciences
Volume134
Issue number1
DOIs
Publication statusPublished - 2015

Fingerprint

Celecoxib
Cyclooxygenase Inhibitors
Liver
Reperfusion
Rats
Ischemia
Nitric Oxide Synthase
Indomethacin
Caspase 3
Tissue
Wounds and Injuries
Oxidative stress
Cyclooxygenase 2 Inhibitors
Cyclooxygenase 2
Alanine Transaminase
Reperfusion Injury
Tumor Necrosis Factor-alpha
Modulation
Cyclooxygenase 1
Nitric Oxide Synthase Type III

Keywords

  • Celecoxib-ischemia-reperfusion
  • Cyclooxygenase inhibitors
  • Hepatic ischemia-reperfusion
  • Indomethacin-ischemia-reperfusion

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Effect of selective versus non-selective cyclooxygenase inhibitors on ischemia-reperfusion-induced hepatic injury in rats. / Abdel-Gaber, Seham A.; Ibrahim, Mohamed A.; Amin, Entesar F.; Ibrahim, Salwa A.; Mohammed, Rehab K.; Abdelrahman, Aly M.

In: Life Sciences, Vol. 134, No. 1, 2015, p. 42-48.

Research output: Contribution to journalArticle

Abdel-Gaber, Seham A. ; Ibrahim, Mohamed A. ; Amin, Entesar F. ; Ibrahim, Salwa A. ; Mohammed, Rehab K. ; Abdelrahman, Aly M. / Effect of selective versus non-selective cyclooxygenase inhibitors on ischemia-reperfusion-induced hepatic injury in rats. In: Life Sciences. 2015 ; Vol. 134, No. 1. pp. 42-48.
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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.

PY - 2015

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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.

AB - 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.

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KW - Indomethacin-ischemia-reperfusion

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