Antifibrotic activity of anthocyanidin delphinidin in carbon tetrachloride-induced hepatotoxicity in mice.
The aim of this study was to investigate the hepatoprotective effects of anthocyanidin delphinidin in carbon tetrachloride (CCl(4))-induced liver fibrosis in mice. Male Balb/C mice were treated with CCl(4) dissolved in olive oil (20%, v/v, 2mL/kg) intraperitoneally (i.p.), twice a week for 7 weeks. Delphinidin was administered i.p. once daily for next 2 weeks, in doses of 10 and 25mg/kg of body weight. The CCl(4) control group has been observed for spontaneous reversion of fibrosis. CCl(4)-administration induced an elevation in serum transaminase and alkaline phosphatase levels and increased oxidative stress in the liver. Delphinidin has successfully attenuated oxidative stress, increased matrix metalloproteinase-9 and metallothionein I/II expression and restored hepatic architecture. Furthermore, the overexpression of tumor necrosis factor-alpha and transforming growth factor-beta1 has been withdrawn by delphinidin. Concomitantly, the expression of alpha-smooth muscle actin indicated returning of hepatic stellate cells (HSC) into inactive state. Our results suggest the therapeutic effects of delphinidin in CCl(4)-induced liver fibrosis by promoting extracellular matrix degradation, HSC inactivation and down-regulation of fibrogenic stimuli, with strong enhancement of hepatic regenerative capability.
Domitrović
Robert
R
Department of Chemistry and Biochemistry, School of Medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia. robertd@medri.hr
Jakovac
Hrvoje
H
D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000009:adverse effects*; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy*; D015536:Down-Regulation / Q000187:drug effects; D064420:Drug-Related Side Effects and Adverse Reactions / Q000188:drug therapy; D005355:Fibrosis / Q000188:drug therapy / Q000473:pathology; D055166:Hepatic Stellate Cells / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D000069463:Olive Oil; D010938:Plant Oils / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000872:Anthocyanins; D000069463:Olive Oil; D010938:Plant Oils; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D008668:Metallothionein; D002251:Carbon Tetrachloride; D020780:Matrix Metalloproteinase 9; C017185:delphinidin