Protective Role of Hepatocyte Cyclooxygenase-2 Expression Against Liver Ischemia-Reperfusion Injury in Mice

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Omar MotiñoPaloma Martín-Sanz

Abstract

Liver ischemia and reperfusion injury (IRI) remains a serious clinical problem affecting liver transplantation outcomes. IRI causes up to 10% of early organ failure and predisposes to chronic rejection. Cyclooxygenase-2 (COX-2) is involved in different liver diseases, but the significance of COX-2 in IRI is a matter of controversy. This study was designed to elucidate the role of COX-2 induction in hepatocytes against liver IRI. In the present work, hepatocyte-specific COX-2 transgenic mice (hCOX-2-Tg) and their wild-type (Wt) littermates were subjected to IRI. hCOX-2-Tg mice exhibited lower grades of necrosis and inflammation than Wt mice, in part by reduced hepatic recruitment and infiltration of neutrophils, with a concomitant decrease in serum levels of proinflammatory cytokines. Moreover, hCOX-2-Tg mice showed a significant attenuation of the IRI-induced increase in oxidative stress and hepatic apoptosis, an increase in autophagic flux, and a decrease in endoplasmic reticulum stress compared to Wt mice. Interestingly, ischemic preconditioning of Wt mice resembles the beneficial effects observed in hCOX-2-Tg mice against IRI due to a preconditioning-derived increase in endogenous COX-2, which is mainly localized in hepatocy...Continue Reading

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Citations

Mar 1, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shuji NakamotoMasataka Majima
Jan 24, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Guoming ChenHua Xu
Apr 29, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·San-Yang ChenShui-Jun Zhang
Mar 26, 2021·Frontiers in Immunology·Jiaojiao TangHongyang Wang
May 7, 2020·Journal of Hepatology·Hui HanNatalia Nieto
Aug 14, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Momoka YamaguchiTomohisa Ishikawa
Aug 20, 2021·Biochemical Pharmacology·María de Luján Alvarez, Florencia Lorenzetti
Sep 13, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Naroa Goikoetxea-UsandizagaMaría Luz Martínez-Chantar
Dec 22, 2021·Expert Review of Gastroenterology & Hepatology·Jinglin WangXiaolei Shi

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