The effect of celecoxib, a selective COX-2 inhibitor, on liver ischemia/reperfusion-induced oxidative stress in rats

Öztürk, Hayrettin; Gezici, Ayten; Öztürk, Hülya

doi:10.1016/j.hepres.2005.11.003

Cited by 54 publications

(37 citation statements)

References 40 publications

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“…Our observation that the lack of COX-2 confers a protective role in liver I/R injury is supported by our own celecoxib studies, in which selective COX-2 inhibition ameliorated mouse liver I/R injury. This observation is also supported by other publications, in which COX-2 inhibition was beneficial in rat liver I/R injury (22,23). Bcl-2 and Bcl-x L play an important role in inhibition of apoptotic cell death and are essential for maintenance of major organ systems (49).…”

Section: Discussionsupporting

confidence: 89%

“…Mice treated with celecoxib before I/R injury showed a marked decrease in liver damage at 6 h after I/R injury (sGPTs (U/L): 4944 Ϯ 3177 vs 14,523 Ϯ 700; p Ͻ 0.003; and sGOTs (IU/L): 2796 Ϯ 1425 vs 13,700 Ϯ 735; p Ͻ 0.002; n ϭ 5/gr) as compared with respective vehicle-treated control mice. Therefore, these results support our observations in COX-2-deficient mice and are in agreement with previous studies in rats (22,23) showing that COX-2 inhibition ameliorates liver I/R injury.…”

Section: Cox-2 Inhibition With Celecoxib Was Effective In Protecting supporting

confidence: 94%

“…We have previously observed that COX-2 expression is up-regulated in damaged livers after I/R (20). Moreover, COX-2 inhibition has been shown to ameliorate liver I/R injury (21)(22)(23) and to reduced liver injury and hepatic microcirculatory dysfunction in response to LPS (24). In contrast, inhibition of COX-2 failed to attenuate hepatocellular injury in rats with endotoxemia (25), and COX-2-deficient mice showed more susceptibility to Con A-induced hepatitis (26).…”

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confidence: 98%

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Cyclooxygenase-2 Deficiency Enhances Th2 Immune Responses and Impairs Neutrophil Recruitment in Hepatic Ischemia/Reperfusion Injury

Hamada

Tsuchihashi

Avanesyan

et al. 2008

The Journal of Immunology

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Cyclooxygenase-2 (COX-2) is a prostanoid-synthesizing enzyme that is critically implicated in a variety of pathophysiological processes. Using a COX-2-deficient mouse model, we present data that suggest that COX-2 has an active role in liver ischemia/reperfusion (I/R) injury. We demonstrate that COX-2-deficient mice had a significant reduction in liver damage after I/R insult. The inability of COX-2−/− to elaborate COX-2 products favored a Th2-type response in these mice. COX-2−/− livers after I/R injury showed significantly decreased levels of IL-2, as well as IL-12, a cytokine known to have a central role in Th1 effector cell differentiation. Moreover, such livers expressed enhanced levels of the anti-inflammatory cytokine IL-10, shifting the balance in favor of a Th2 response in COX-2-deficient mice. The lack of COX-2 expression resulted in decreased levels of CXCL2, a neutrophil-activating chemokine, reduced infiltration of MMP-9-positive neutrophils, and impaired late macrophage activation in livers after I/R injury. Additionally, Bcl-2 and Bcl-xL were normally expressed in COX-2−/− livers after injury, whereas respective wild-type controls were almost depleted of these two inhibitors of cell death. In contrast, caspase-3 activation and TUNEL-positive cells were depressed in COX-2−/− livers. Therefore, our data support the concept that COX-2 is involved in the pathogenic events occurring in liver I/R injury. The data also suggest that potential valuable therapeutic approaches in liver I/R injury may result from further studies aimed at identifying specific COX-2-derived prostanoid pathways.

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Section: Discussionsupporting

confidence: 89%

Section: Cox-2 Inhibition With Celecoxib Was Effective In Protecting supporting

confidence: 94%

mentioning

confidence: 98%

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Cyclooxygenase-2 Deficiency Enhances Th2 Immune Responses and Impairs Neutrophil Recruitment in Hepatic Ischemia/Reperfusion Injury

Hamada

Tsuchihashi

Avanesyan

et al. 2008

The Journal of Immunology

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“…The blocks were cut into 4-µm sections and stained with hematoxylin-eosin, using standard protocols. The severity of hepatic injury in the sections was evaluated using a point-counting method on an ordinal scale as follows: grade 0, minimal or no evidence of injury; grade 1, mild injury consisting of cytoplasmic vacuolation and focal nuclear pyknosis; grade 2, moderate to severe injury with extensive nuclear pyknosis, cytoplasmic hypereosinophilia, and loss of intercellular borders; and grade 3, severe necrosis with disintegration of hepatic cords, hemorrhage, and neutrophil infiltration [18] .…”

Section: Histopathological Studymentioning

confidence: 99%

Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats

Gedik¹,

Gırgın²,

Öztürk³

et al. 2008

WJG

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AIM:To investigate the effects of resveratrol on liver ischemia/reperfusion (I/R) injury in rats. METHODS: A total of 40 male Sprague-Dawley rats weighing 240-290 g were randomized into four groups of ten: (1) controls: data from unmanipulated animals; (2) sham group: rats subjected to the surgical procedure, except for liver I/R, and given saline; (3) I/R group: rats underwent liver ischemia for 45 min followed by reperfusion for 45 min; (4) I-R/Resveratrol group: rats pretreated with resveratrol (10 µmol/L, iv). Liver tissues were obtained to determine antioxidant enzyme levels and for biochemical and histological evaluation. RESULTS: Plasma aminotransferase activities were higher in the I/R group than in the I-R/Resveratrol group. Malondialdehyde levels and the hepatic injury score decreased, while superoxide dismutase, catalase, and glutathione peroxidase levels increased in group 4 compared to group 3. In group 4, histopathological changes were significantly attenuated in resveratroltreated livers. CONCLUSION: These results suggest that resveratrol has protective effects against hepatic I/R injury, and is a potential therapeutic drug for ischemia reperfusionrelated liver injury.

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“…Hepatic ischemia/reperfusion (Hepatic I/R) injury is an important non-immunologic problem and a limitating factor in liver transplantation and it may result in liver dysfunction, liver failure, and even death [2] . Hepatic I/R injury is one of the major complications of hepatic resection, hemorrhagic shock with fluid resuscitation, and liver transplantation, particularly with grafts from marginal donors [3] . The mechanisms underlying ischemia/ reperfusion induced organ damage are likely multifactorial and interdependent.…”

Section: Basic Researchmentioning

confidence: 99%

Protection ofVeratrum nigrum L. var. ussuriense Nakai alkaloidsagainst ischemia-reperfusion injury of the rat liver

Wang

Zhao²,

Tian³

et al. 2007

WJG

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AIM:To investigate the protective effects and possible mechanisms of Veratrum nigrum L.var. ussuriense Nakai alkaloids (VnA) on hepatic ischemia/reperfusion (I/R) injury in rats. METHODS:Forty male Wistar rats were randomly divided into four experimental groups (n = 10 in each): (A) Control group (the sham operation group); (B) I/R group (pretreated with normal saline); (C) Small-dose (10 mg/kg) VnA pretreatment group; (D) Large-dose (20 mg/kg) VnA pretreatment group. Hepatic ischemia/ reperfusion (Hepatic I/R) was induced by occlusion of the portal vein and the hepatic artery for 90 min, followed by reperfusion for 240 min. The pretreatment groups were administered with VnA intraperitoneally, 30 min before surgery, while the control group and I/R group were given equal volumes of normal saline. Superoxide dismutase (SOD) activity, myeloperoxidase (MPO) activity and nitric oxide (NO) content in the liver tissue at the end of reperfusion were determined and liver function was measured. The expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin (ES) were detected by immunohistochemical examinations and Western blot analyses. RESULTS:The results showed that hepatic I/R elicited a significant increase in the plasma levels of alanine .4 IU/L, P < 0.01, P < 0.01; MPO: 2.57 ± 0.13 U/g vs 2.13 ± 0.13 U/g, 2.07 ± 0.05 U/g, P < 0.01, P < 0.01; NO: 78.39 ± 2.28 mmol/g protein vs 71.11 ± 1.73 mmol/g protein, 68.58 ± 1.95 mmol/g protein, P < 0.05, P < 0.01). The activity of SOD (361.75 ± 16.22 U/mg protein vs 263.19 ± 12.10 U/mg protein, P < 0.01) in the liver tissue was decreased after I/R, which was enhanced by VnA pretreatment (263.19 ± 12.10 U/mg protein vs 299.40 ± 10.80 U/mg protein, 302.09 ± 14.80 U/mg protein, P < 0.05, P < 0.05). Simultaneously, the histological evidence of liver hemorrhage, polymorphonuclear neutrophil infiltration and the overexpression of ICAM-1 and E-selectin in the liver tissue were observed, all of which were attenuated in the VnA pretreated groups. CONCLUSION:The results demonstrate that VnA pretreatment exerts significant protection against hepatic I/R injury in rats. The protective effects are possibly associated with enhancement of antioxidant capacity, reduction of inflammatory responses and suppressed expression of ICAM-1 and E-selectin.

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The effect of celecoxib, a selective COX-2 inhibitor, on liver ischemia/reperfusion-induced oxidative stress in rats

Cited by 54 publications

References 40 publications

Cyclooxygenase-2 Deficiency Enhances Th2 Immune Responses and Impairs Neutrophil Recruitment in Hepatic Ischemia/Reperfusion Injury

Cyclooxygenase-2 Deficiency Enhances Th2 Immune Responses and Impairs Neutrophil Recruitment in Hepatic Ischemia/Reperfusion Injury

Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats

Protection ofVeratrum nigrum L. var. ussuriense Nakai alkaloidsagainst ischemia-reperfusion injury of the rat liver

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