title: Silymarin inhibits the progression of fibrosis in the early stages of liver injury in CCl₄-treated rats.
abstract: Liver fibrosis, a common condition occurring during the evolution of almost all chronic liver diseases, is the consequence of hepatocyte injury that leads to the activation of Kupffer cells and hepatic stellate cells (HSC). Silymarin (Si) is a herbal product widely used for its hepatoprotective potential. Our study aims to investigate the effects of two different doses of Silymarin on a CCl4-induced model of liver fibrosis with a focus on the early stages of liver injury. Fifty Wistar rats were randomly divided into five groups (n=10): control group (sunflower oil twice a week); CMC group (carboxymethyl cellulose five times a week, sunflower oil twice a week); CCl4 group (CCl4 in sunflower oil, by gavage, twice a week); CCl4+Si 50 group (CCl4 twice a week, Silymarin 50 mg/b.w. in CMC five times a week); and CCl4+Si 200 group (similar to the previous group, with Si 200 mg/b.w.). One month after the experiment began we explored hepato-cytolysis (aminotransferases and lactate dehydrogenase), oxidative stress, fibrosis (histological score, hyaluronic acid), markers of HSC activation (transforming growth factor β1 [TGF-β1], and α-smooth muscle actin [α-SMA] expression by western blot) and activation of Kupffer cells by immunohistochemistry. Our data showed that Si 50 mg/b.w. had the capacity of reducing oxidative stress, hepato-cytolysis, fibrosis, activation of Kupffer cells, and the expression of α-SMA and TGF-β1 with better results than Si 200 mg/b.w. Thus, the usual therapeutic dose of Silymarin, administered in the early stages of fibrotic changes is capable of inhibiting the fibrogenetic mechanism and the progression of initial liver fibrosis.
authors.affiliation: 1 Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca, Romania .
authors.forename: Simona
authors.initials: S
authors.lastname: Clichici
authors.forename: Diana
authors.initials: D
authors.lastname: Olteanu
authors.forename: Andras-Laszlo
authors.initials: AL
authors.lastname: Nagy
authors.forename: Adrian
authors.initials: A
authors.lastname: Oros
authors.forename: Adriana
authors.initials: A
authors.lastname: Filip
authors.forename: Petru A
authors.initials: PA
authors.lastname: Mircea
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000187:drug effects; D007728:Kupffer Cells / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D020944:Silybum marianum / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D017208:Rats, Wistar; D012838:Silymarin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D000975:Antioxidants; D010936:Plant Extracts; D012838:Silymarin; D053773:Transforming Growth Factor beta1; D002251:Carbon Tetrachloride
keywords: Silymarin; liver fibrosis; oxidative stress