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

DC FieldValueLanguage
dc.contributor.author김도영-
dc.contributor.author노원상-
dc.contributor.author박영년-
dc.contributor.author이관식-
dc.contributor.author이민구-
dc.contributor.author이정일-
dc.contributor.author정숙인-
dc.contributor.author한광협-
dc.date.accessioned2014-12-18T09:35:34Z-
dc.date.available2014-12-18T09:35:34Z-
dc.date.issued2013-
dc.identifier.issn1360-8185-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/88460-
dc.description.abstractWe 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.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfAPOPTOSIS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHAntioxidants/administration & dosage*-
dc.subject.MESHApoptosis/drug effects*-
dc.subject.MESHCaspase Inhibitors/administration & dosage*-
dc.subject.MESHCaspases/genetics-
dc.subject.MESHCaspases/metabolism-
dc.subject.MESHCollagen Type I/genetics-
dc.subject.MESHCollagen Type I/metabolism-
dc.subject.MESHDrug Therapy, Combination-
dc.subject.MESHDrugs, Chinese Herbal/administration & dosage*-
dc.subject.MESHHumans-
dc.subject.MESHLiver Cirrhosis/drug therapy*-
dc.subject.MESHLiver Cirrhosis/genetics-
dc.subject.MESHLiver Cirrhosis/metabolism-
dc.subject.MESHLiver Cirrhosis/physiopathology-
dc.subject.MESHMale-
dc.subject.MESHOxidative Stress/drug effects-
dc.subject.MESHRats-
dc.subject.MESHRats, Sprague-Dawley-
dc.subject.MESHTransforming Growth Factor beta1/genetics-
dc.subject.MESHTransforming Growth Factor beta1/metabolism-
dc.titleCombined effects of an antioxidant and caspase inhibitor on the reversal of hepatic fibrosis in rats-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학)-
dc.contributor.googleauthorDo Young Kim-
dc.contributor.googleauthorSook In Chung-
dc.contributor.googleauthorSimon Weonsang Ro-
dc.contributor.googleauthorYong Han Paik-
dc.contributor.googleauthorJung Il Lee-
dc.contributor.googleauthorMan Kil Jung-
dc.contributor.googleauthorMin Goo Lee-
dc.contributor.googleauthorYoung Nyun Park-
dc.contributor.googleauthorKwan Sik Lee-
dc.contributor.googleauthorJung Gyu Park-
dc.contributor.googleauthorHee Dong Park-
dc.contributor.googleauthorKwang-Hyub Han-
dc.identifier.doi10.1007/s10495-013-0896-5-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA01563-
dc.contributor.localIdA02666-
dc.contributor.localIdA02781-
dc.contributor.localIdA03640-
dc.contributor.localIdA04268-
dc.contributor.localIdA03122-
dc.contributor.localIdA00385-
dc.contributor.localIdA01286-
dc.relation.journalcodeJ00195-
dc.identifier.eissn1573-675X-
dc.identifier.pmid24045874-
dc.identifier.urlhttp://link.springer.com/article/10.1007%2Fs10495-013-0896-5-
dc.subject.keywordAnimals-
dc.subject.keywordAntioxidants/administration & dosage*-
dc.subject.keywordApoptosis/drug effects*-
dc.subject.keywordCaspase Inhibitors/administration & dosage*-
dc.subject.keywordCaspases/genetics-
dc.subject.keywordCaspases/metabolism-
dc.subject.keywordCollagen Type I/genetics-
dc.subject.keywordCollagen Type I/metabolism-
dc.subject.keywordDrug Therapy, Combination-
dc.subject.keywordDrugs, Chinese Herbal/administration & dosage*-
dc.subject.keywordHumans-
dc.subject.keywordLiver Cirrhosis/drug therapy*-
dc.subject.keywordLiver Cirrhosis/genetics-
dc.subject.keywordLiver Cirrhosis/metabolism-
dc.subject.keywordLiver Cirrhosis/physiopathology-
dc.subject.keywordMale-
dc.subject.keywordOxidative Stress/drug effects-
dc.subject.keywordRats-
dc.subject.keywordRats, Sprague-Dawley-
dc.subject.keywordTransforming Growth Factor beta1/genetics-
dc.subject.keywordTransforming Growth Factor beta1/metabolism-
dc.contributor.alternativeNameKim, Do Young-
dc.contributor.alternativeNameRo, Simon Weonsang-
dc.contributor.alternativeNamePark, Young Nyun-
dc.contributor.alternativeNameLee, Kwan Sik-
dc.contributor.alternativeNameLee, Min Goo-
dc.contributor.alternativeNameLee, Jung Il-
dc.contributor.alternativeNameChung, Sook In-
dc.contributor.alternativeNameHan, Kwang Hyup-
dc.contributor.affiliatedAuthorPark, Young Nyun-
dc.contributor.affiliatedAuthorLee, Kwan Sik-
dc.contributor.affiliatedAuthorLee, Min Goo-
dc.contributor.affiliatedAuthorChung, Sook In-
dc.contributor.affiliatedAuthorHan, Kwang Hyup-
dc.contributor.affiliatedAuthorLee, Jung Il-
dc.contributor.affiliatedAuthorKim, Do Young-
dc.contributor.affiliatedAuthorRo, Simon Weonsang-
dc.rights.accessRightsnot free-
dc.citation.volume18-
dc.citation.number12-
dc.citation.startPage1481-
dc.citation.endPage1491-
dc.identifier.bibliographicCitationAPOPTOSIS, Vol.18(12) : 1481-1491, 2013-
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

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