Effect of indole-3-carbinol on ethanol-induced liver injury and acetaldehyde-stimulated hepatic stellate cells activation using precision-cut rat liver slices.
1. 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-β(1) ) 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.
Guo
Yu
Y
Department of Pharmacology, School of Basic Medical Science, Wuhan University, Wuhan, China.
Wu
Xiao-Qian
XQ
Zhang
Chun
C
Liao
Zhang-Xiu
ZX
Wu
Yong
Y
Xia
Zheng-Yuan
ZY
Wang
Hui
H
D000079:Acetaldehyde / Q000494:pharmacology*; D000199:Actins / Q000096:biosynthesis; D000818:Animals; D001937:Brassica / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000378:metabolism
D000079:Acetaldehyde; D000199:Actins; D003094:Collagen; D000431:Ethanol; D007211:Indoles; D020781:Matrix Metalloproteinase 1; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat; C016517:indole-3-carbinol