title: The angiotensin-converting enzyme inhibitor captopril rescues mice from endotoxin-induced lethal hepatitis.
abstract: The renin-angiotensin system is classically regarded as a crucial regulator of circulatory homeostasis, but recent studies also revealed its pro-inflammatory roles. The beneficial effects of the angiotensin-converting enzyme inhibitor (ACEI) in severe inflammatory injury in the lung and heart have been previously reported, but its potential effects on lethal hepatitis were unknown. In this study, a mouse model with LPS/d-galactosamine (GalN)-induced fulminant hepatitis were used to test the protective potential of captopril, a representative ACEI. The results indicated that treatment with captopril significantly decreased the plasma level of alanine aminotransferase and aspartate aminotransferase, alleviated the histopathological damage of the liver tissue and improve the survival rate of LPS/GalN-challenged mice. These effects were accompanied by reduced mRNA levels of TNF-α and IL-6 in the liver, and decreased protein level of TNF-α and IL-6 in the plasma. In addition, the activation of caspases 3, 8 and 9, and the presence of TUNEL-positive apoptotic cells, were also suppressed by captopril treatment. The above evidence suggested that the renin-angiotensin system might be involved in the development of LPS/GalN-induced fulminant hepatitis and ACEI might have potential value in lethal hepatitis.
authors.affiliation: 1 Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Ge
authors.affiliation: 2 Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: 1 Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
authors.affiliation: 1 Department of Pathophysiology, Chongqing Medical University, Chongqing, China.|2 Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: 3 Hospital of Chongqing University of Arts and Sciences, Chongqing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Dai
authors.affiliation: 1 Department of Pathophysiology, Chongqing Medical University, Chongqing, China.|2 Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 4 Department of Pathogenic Biology, Chongqing Medical University, Chongqing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Ye
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D002216:Captopril / Q000627:therapeutic use*; D005688:Galactosamine / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006520:Hepatitis, Animal / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D002216:Captopril; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D007703:Peptidyl-Dipeptidase A
keywords: Hepatitis; angiotensin-converting enzyme inhibitor; captopril; inflammation; lipopolysaccharide