Hydrogen peroxide induces midzonal heat shock protein 72 and apoptosis in sinusoidal endothelial cells of hypoxic rat liver

Objective: To investigate the heat shock protein (HSP) 72 expression and ap optosis induced by hydrogen peroxide in hypoxic rat liver, Design: Prospective control study using the isolated rat liver. Setting: Animal research facility. Subjects: Fasted, pathogen-free specific, male Sprague-Dawley rats, Interventions: A low-flow hypoxia model was made by reducing an afferent pr essure from 10 to 2.5 cm H2O, and by perfusing the isolated rat liver for 2 hrs, Measurement and Main Results: We investigated the hydrogen peroxide product ion by using the 2'-7' dichlorofluorescein image, the induction of HSP 72 b y using immunohistochemistry, and apoptosis by using terminal deoxynucleoti dyl transferase-mediated dUTP-digoxigenin nick end-labeling method in the l ow flow hypoxic rat liver. In low-flow hypoxia, hydrogen peroxide productio n, HSP 72 expression, and apoptosis were induced in the midzone of rat live r. Prevalence of HSP 72 expression was higher in the sinusoidal endothelial cells (SEC) than in the hepatocytes, Ail apoptotic cells were SEC with exp ression of HSP 72, Hydrogen peroxide was derived from hepatocytes, Pretreat ment with the specific xanthine oxidase inhibitor, sodium(-)-8-(3-methoxy-4 -phenylsulfinylphenyl) pyrazolo [1,5-a]-1,3,5-triazine-4-olate monohydrate significantly attenuated hydrogen peroxide production, HSP 72 expression, a nd apoptosis of SEC in the midzone, Conclusion: Xanthine oxidase-dependent hydrogen peroxide induces midzonal a nd SEC-dominant HSP 72 expression and apoptosis in hypoxic rat liver.