title: Role of the heme oxygenase/carbon monoxide pathway in the pathogenesis and prevention of hepatic encephalopathy.
abstract: Hepatic encephalopathy (HE) is a severe complication of liver cirrhosis and its pathogenesis has yet to be fully elucidated. Previous studies have demonstrated that heme oxygenase-1 (HO-1) is important in the induction of liver cirrhosis. The present study aimed to investigate the role of HO-1 in the pathogenesis of HE. Rats were divided into 5 treatment groups; sham, bile duct ligation (BDL), HE, zinc protoporphyrin (ZnPP) and cobalt protoporphyrin (CoPP). The levels of HO-1 were examined by western blotting and quantitative real-time PCR (qRT-PCR). Serum levels of carboxyhemoglobin (COHb), ammonia levels in the plasma and brain, brain water content and portal vein pressure (PVP) were also quantified. Aquaporin-4 expression levels were measured by immunohistochemistry and qRT-PCR. The results demonstrated that the levels of HO-1 in the brain and the serum levels of COHb were significantly increased in the HE group compared with the BDL group. Brain water content, PVP and ammonia levels in the plasma and brain were increased in the HE and CoPP groups; however, these were reduced following the treatment with ZnPP. The levels of AQP-4 expression and oxidative stress in the brain were reduced following treatment with ZnPP and increased following treatment with CoPP. In conclusion, following the inhibition of HO-1 expression, treatment with ZnPP improved HE due to reducing the expression levels of AQP-4 and oxidative stress. Therefore, ZnPP treatment may represent a novel therapeutic approach for HE.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, PR China.
authors.forename: Qiu-Ming
authors.initials: QM
authors.lastname: Wang
authors.forename: Xue-Ying
authors.initials: XY
authors.lastname: Yin
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Duan
authors.forename: Shi-Bin
authors.initials: SB
authors.lastname: Guo
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Sun
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002248:Carbon Monoxide / Q000378:metabolism*; D004032:Diet / Q000009:adverse effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000209:etiology / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D015398:Signal Transduction
chemical_list: D051401:Aquaporin 4; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1