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Combined effects of an antioxidant and caspase inhibitor on the reversal of hepatic fibrosis in rats

Authors
 Do Young Kim  ;  Sook In Chung  ;  Simon Weonsang Ro  ;  Yong Han Paik  ;  Jung Il Lee  ;  Man Kil Jung  ;  Min Goo Lee  ;  Young Nyun Park  ;  Kwan Sik Lee  ;  Jung Gyu Park  ;  Hee Dong Park  ;  Kwang-Hyub Han 
Citation
 Apoptosis, Vol.18(12) : 1481-1491, 2013 
Journal Title
 Apoptosis 
ISSN
 1360-8185 
Issue Date
2013
Abstract
We sought to determine the hepatic fibrosis-reversal effects upon simultaneous administration of lithospermate B (LAB), an anti-oxidant, and nivocasan, a caspase inhibitor, to rats compared with each compound alone. Liver fibrosis was induced in Sprague–Dawley rats by thioacetamide (TAA). Rats were treated with TAA and then given LAB and (or) nivocasan. Fibrotic areas were evaluated quantitatively by computerized morphometry. Apoptosis was assessed using a TUNEL assay, and immunohistochemical staining for malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4HNE) was performed to assess oxidative stress levels. Real-time quantitative PCR was used to quantify expression of fibrosis-related genes. The degree of hepatic fibrosis was significantly reduced in rats treated with LAB and nivocasan compared to either treatment alone (P < 0.001). Treatment with each compound significantly decreased expression of fibrosis-related genes, such as type I collagen α1 (col1α1), α-SMA and TGF-β1 (P < 0.05). Co-treatment with LAB and nivocasan further reduced col1α1 expression compared to treatment with either compound. A TUNEL assay revealed that hepatocyte apoptosis was significantly decreased in the group treated with nivocasan compared to other groups (P < 0.01). Immunohistochemistry showed a decrease in MDA and 4HNE, reflecting amelioration of oxidative stress, when LAB or LAB+nivocasan was administered compared to nivocasan alone (P < 0.01). Nivocasan was found to inhibit caspase-1, -3, -7, -9 and gliotoxin-induced death of rat-derived hepatic stellate cells was inhibited by nivocasan administration without overexpression of α-SMA. Conclusions: Co-incidental administration of LAB and nivocasan suppressed oxidative stress and apoptosis, resulting in enhanced reversal of hepatic fibrosis in rat.
Full Text
http://link.springer.com/article/10.1007%2Fs10495-013-0896-5
DOI
10.1007/s10495-013-0896-5
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Liver Cirrhosis Clinical Research Center (간경변증임상연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
김도영(Kim, Do Young)
노원상(Ro, Simon Weonsang) ORCID logo https://orcid.org/0000-0003-2187-3698
박영년(Park, Young Nyun) ORCID logo https://orcid.org/0000-0003-0357-7967
이관식(Lee, Kwan Sik) ORCID logo https://orcid.org/0000-0002-3672-1198
이민구(Lee, Min Goo) ORCID logo https://orcid.org/0000-0001-7436-012X
이정일(Lee, Jung Il) ORCID logo https://orcid.org/0000-0002-0142-1398
정숙인(Chung, Sook In) ORCID logo https://orcid.org/0000-0002-7915-9203
한광협(Han, Kwang-Hyub) ORCID logo https://orcid.org/0000-0003-3960-6539
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/88460
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