Possible Involvement of Nitric Oxide in Enhanced Liver Injury and Fibrogenesis during Cholestasis in Cytoglobin-deficient Mice

• DOI: 10.1038/srep41888
• Publication Date: 2017-02-03T14:24:42Z
• Authors: Tuong Thi Van Thuy; Le Thi Thanh Thuy; Katsutoshi Yoshizato; Norifumi Kawada
• Keywords: Liver Cirrhosis; Male; 0303 health sciences; Cholestasis; Membrane Glycoproteins; Caspase 3; Cytoglobin; Cytochromes c; Nitric Oxide; Article; Globins; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Hepatocytes; Animals; Neprilysin; Carrier Proteins

Abstract This study clarified the role of Cygb, fourth globin in mammals originally discovered rat hepatic stellate cells (HSCs), cholestatic liver disease. Bile duct ligation (BDL) augmented inflammatory reactions as revealed by increased infiltrating neutrophils, CD68 + -macrophages, and chemokine expression Cygb −/− mice. In these mice, impairment bile canalicular indicated loss CD10 expression, down-regulation salt transporters, total acid, massive apoptotic necrotic hepatocytes occurred with release cytochrome c, activation caspase 3, resulting reduced animal survival compared to wild-type mouse liver, all NO metabolites oxidative stress were increased. Treatment inhibitor restrained above phenotypes restored BDL while administration donor aggravated damage BDL-wild type mice same extent BDL-Cygb N-acetylcysteine had a negligible effect groups. for 1–3 weeks, fibrosis-related markers was significantly Thus, deficiency HSCs enhances hepatocyte inflammation early phase fibrosis development late subjected BDL, presumably via altered metabolism.