title: Endogenous carbon monoxide downregulates hepatic cystathionine-γ-lyase in rats with liver cirrhosis.
abstract: The aim of the present study was to investigate the effect of endogenous carbon monoxide (CO) on the hydrogen sulfide/cystathionine-γ-lyase (H2S/CSE) pathway in cirrhotic rat livers. The rats were allocated at random into four groups: Sham, cirrhosis, cobalt protoporphyrin (CoPP) and zinc protoporphyrin IX (ZnPP). The expression of hepatic CSE mRNA was evaluated using a quantitative polymerase chain reaction, while CSE protein expression was determined using immunohistochemical analysis. Hematoxylin and eosin staining was performed for the histological evaluation of liver fibrosis. The levels of H2S, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and carboxyhemoglobin (COHb) in the arterial blood were determined, in addition to the portal vein pressure. The mRNA and protein expression levels of hepatic CSE and the serum levels of H2S were significantly decreased in the cirrhosis group compared with those in the sham group (P<0.05). Compared with the cirrhosis group, rats in the ZnPP group had significantly lower levels of serum ALT, AST and TBIL, arterial COHb and hepatic fibrosis, while hepatic CSE expression and the production of H2S were significantly increased (P<0.05). The CoPP group exhibited decreased hepatic CSE expression and H2S production, but aggravated hepatic function and fibrosis (P<0.05). In conclusion, the H2S/CSE pathway is involved in the formation of liver cirrhosis and serves a crucial function in protecting liver cells against the progression of liver fibrosis. Endogenous CO downregulates hepatic CSE mRNA and protein expression and the production of H2S in rats with liver cirrhosis.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Shi-Bin
authors.initials: SB
authors.lastname: Guo
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Duan
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China ; Department of Gastroenterology, Affiliated Beijing Chinese Medicine Hospital, Capital Medical University, Beijing 100000, P.R. China.
authors.forename: Qiu-Ming
authors.initials: QM
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, Liaoning 116001, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Dalian Friendship Hospital, Dalian, Liaoning 116001, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Sun
keywords: biliary cirrhosis; carbon monoxide; cobalt protoporphyrin; cystathionine-γ-lyase; heme oxygenase-1; hydrogen sulfide; zinc protoporphyrin