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Article: Effect of indole-3-carbinol on ethanol-induced liver injury and acetaldehyde-stimulated hepatic stellate cells activation using precision-cut rat liver slices

TitleEffect of indole-3-carbinol on ethanol-induced liver injury and acetaldehyde-stimulated hepatic stellate cells activation using precision-cut rat liver slices
Authors
KeywordsAcetaldehyde
Ethanol
Hepatic stellate cells
Indole-3-carbinol
Precision-cut liver slice
Issue Date2010
PublisherBlackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/CEP
Citation
Clinical And Experimental Pharmacology And Physiology, 2010, v. 37 n. 12, p. 1107-1113 How to Cite?
Abstract1. Indole-3-carbinol (I3C), a major indole compound found in high levels in cruciferous vegetables, shows a broad spectrum of biological activities. However, few studies have reported the effect of I3C on alcoholic liver injury. In the present study, we investigated the protective effect of I3C on acute ethanol-induced hepatotoxicity and acetaldehyde-stimulated hepatic stellate cells (HSC) activation using precision-cut liver slices (PCLS). 2. Rat PCLS were incubated with 50 mmol/L ethanol or 350 μmol/L acetaldehyde, and different concentrations (100-400 μmol/L) of I3C were added into the culture system of these two liver injury models, respectively. Hepatotoxicity was assessed by measuring enzyme leakage and malondialdehyde (MDA) content in tissue. Activities of alcoholic enzymes were also determined. α-Smooth muscle actin (α-SMA), transforming growth factor (TGF-β1) and hydroxyproline (HYP) were used as indices to evaluate the activation of HSC. In addition, matrix metalloproteinase-1 (MMP-1) and the tissue inhibitor of metalloproteinase (TIMP-1) were observed to estimate collagen degradation. 3. I3C significantly reduced the enzyme leakage in ethanol-treated slices. In I3C groups, cytochrome P450 (CYP) 2E1 activities were inhibited by 40.9-51.8%, whereas alcohol dehydrogenase (ADH) activity was enhanced 1.6-fold compared with the ethanol-treated group. I3C also showed an inhibitory effect against HSC activation and collagen production stimulated by acetaldehyde. After being incubated with I3C (400 μmol/L), the expression of MMP-1 was markedly enhanced, whereas TIMP-1 was decreased. 4. These results showed that I3C protected PCLS against alcoholic liver injury, which might be associated with the regulation of ethanol metabolic enzymes, attenuation of oxidative injury and acceleration of collagen degradation. © 2010 The Authors. Clinical and Experimental Pharmacology and Physiology © 2010 Blackwell Publishing Asia Pty Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/138925
ISSN
2012 Impact Factor: 2.16
2015 SCImago Journal Rankings: 0.944
ISI Accession Number ID
Funding AgencyGrant Number
National Nature Sciences Foundation of China30371666
Funding Information:

This work was supported by a grant of the National Nature Sciences Foundation of China (No. 30371666).

References

 

DC FieldValueLanguage
dc.contributor.authorGuo, Yen_HK
dc.contributor.authorWu, XQen_HK
dc.contributor.authorZhang, Cen_HK
dc.contributor.authorLiao, ZXen_HK
dc.contributor.authorWu, Yen_HK
dc.contributor.authorXia, ZYen_HK
dc.contributor.authorWang, Hen_HK
dc.date.accessioned2011-09-23T05:42:11Z-
dc.date.available2011-09-23T05:42:11Z-
dc.date.issued2010en_HK
dc.identifier.citationClinical And Experimental Pharmacology And Physiology, 2010, v. 37 n. 12, p. 1107-1113en_HK
dc.identifier.issn0305-1870en_HK
dc.identifier.urihttp://hdl.handle.net/10722/138925-
dc.description.abstract1. Indole-3-carbinol (I3C), a major indole compound found in high levels in cruciferous vegetables, shows a broad spectrum of biological activities. However, few studies have reported the effect of I3C on alcoholic liver injury. In the present study, we investigated the protective effect of I3C on acute ethanol-induced hepatotoxicity and acetaldehyde-stimulated hepatic stellate cells (HSC) activation using precision-cut liver slices (PCLS). 2. Rat PCLS were incubated with 50 mmol/L ethanol or 350 μmol/L acetaldehyde, and different concentrations (100-400 μmol/L) of I3C were added into the culture system of these two liver injury models, respectively. Hepatotoxicity was assessed by measuring enzyme leakage and malondialdehyde (MDA) content in tissue. Activities of alcoholic enzymes were also determined. α-Smooth muscle actin (α-SMA), transforming growth factor (TGF-β1) and hydroxyproline (HYP) were used as indices to evaluate the activation of HSC. In addition, matrix metalloproteinase-1 (MMP-1) and the tissue inhibitor of metalloproteinase (TIMP-1) were observed to estimate collagen degradation. 3. I3C significantly reduced the enzyme leakage in ethanol-treated slices. In I3C groups, cytochrome P450 (CYP) 2E1 activities were inhibited by 40.9-51.8%, whereas alcohol dehydrogenase (ADH) activity was enhanced 1.6-fold compared with the ethanol-treated group. I3C also showed an inhibitory effect against HSC activation and collagen production stimulated by acetaldehyde. After being incubated with I3C (400 μmol/L), the expression of MMP-1 was markedly enhanced, whereas TIMP-1 was decreased. 4. These results showed that I3C protected PCLS against alcoholic liver injury, which might be associated with the regulation of ethanol metabolic enzymes, attenuation of oxidative injury and acceleration of collagen degradation. © 2010 The Authors. Clinical and Experimental Pharmacology and Physiology © 2010 Blackwell Publishing Asia Pty Ltd.en_HK
dc.languageengen_US
dc.publisherBlackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/CEPen_HK
dc.relation.ispartofClinical and Experimental Pharmacology and Physiologyen_HK
dc.rightsThe definitive version is available at www.blackwell-synergy.com-
dc.subjectAcetaldehydeen_HK
dc.subjectEthanolen_HK
dc.subjectHepatic stellate cellsen_HK
dc.subjectIndole-3-carbinolen_HK
dc.subjectPrecision-cut liver sliceen_HK
dc.subject.meshAcetaldehyde - pharmacology-
dc.subject.meshEthanol - administration and dosage-
dc.subject.meshHepatic Stellate Cells - drug effects - metabolism-
dc.subject.meshIndoles - pharmacology-
dc.subject.meshLiver Diseases, Alcoholic - enzymology - metabolism - pathology - prevention and control-
dc.titleEffect of indole-3-carbinol on ethanol-induced liver injury and acetaldehyde-stimulated hepatic stellate cells activation using precision-cut rat liver slicesen_HK
dc.typeArticleen_HK
dc.identifier.emailXia, ZY:zyxia@hkucc.hku.hken_HK
dc.identifier.authorityXia, ZY=rp00532en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1440-1681.2010.05450.xen_HK
dc.identifier.pmid20880187-
dc.identifier.scopuseid_2-s2.0-78649730559en_HK
dc.identifier.hkuros193388en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78649730559&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume37en_HK
dc.identifier.issue12en_HK
dc.identifier.spage1107en_HK
dc.identifier.epage1113en_HK
dc.identifier.isiWOS:000284768900002-
dc.publisher.placeAustraliaen_HK
dc.identifier.citeulike8375173-

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