title: Beneficial Effects of Silymarin After the Discontinuation of CCl4-Induced Liver Fibrosis.
abstract: Silymarin (Si) is a herbal product with hepatoprotective potential, well-known for its antioxidant, anti-inflammatory, and immunomodulatory properties. We have recently demonstrated that the usual therapeutic doses of Si are capable of inhibiting the progression of incipient liver fibrosis. We aimed at further investigating the benefits of Si administration upon liver alterations after the hepatotoxin discontinuation, using CCl4 to induce liver injuries on rats. CCl4 administration induces first of all oxidative stress, but other mechanisms, such as inflammation and liver fibrosis are also triggered. Fifty Wistar rats were randomly divided into five groups (n = 10). The control group received sunflower oil twice a week for 8 weeks. Carboxymethyl cellulose group received sunflower oil twice a week, for 8 weeks and CMC daily, for the next 2 weeks. CCl4 group received CCl4 in sunflower oil, by gavage, twice a week, for 8 weeks. CCl4 + Si 50 group received CCl4 twice a week, for 8 weeks, and then 50 mg/body weight (b.w.) Silymarin for the next 2 weeks. CCl4 + Si 200 group was similar to the previous group, but with Si 200 mg/b.w. Ten weeks after the experiment had begun, we assessed inflammation (IL-6, MAPK, NF-κB, pNF-κB), fibrosis (hyaluronic acid), TGF-β1, MMP-9, markers of hepatic stellate cell activation (α-SMA expression), and proliferative capacity (proliferating cell nuclear antigen). Our data showed that Silymarin administered after the toxic liver injury is capable of reducing inflammation and liver fibrosis. The benefits were more important for the higher dose than for the usual therapeutic dose.
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.affiliation: 1 Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca, Romania .
authors.forename: Diana
authors.initials: D
authors.lastname: Olteanu
authors.affiliation: 1 Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca, Romania .
authors.forename: Adriana
authors.initials: A
authors.lastname: Filip
authors.affiliation: 2 Department of Pathology, University of Agricultural Sciences and Veterinary Medicine , Cluj-Napoca, Romania .
authors.forename: Andras-Laszlo
authors.initials: AL
authors.lastname: Nagy
authors.affiliation: 3 Department of Veterinary Toxicology, University of Agricultural Sciences and Veterinary Medicine , Cluj-Napoca, Romania .
authors.forename: Adrian
authors.initials: A
authors.lastname: Oros
authors.affiliation: 4 Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca, Romania .
authors.forename: Petru A
authors.initials: PA
authors.lastname: Mircea
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000150:complications* / Q000473:pathology; D006820:Hyaluronic Acid / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008297:Male; D020944:Silybum marianum / Q000737:chemistry; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D017208:Rats, Wistar; D012838:Silymarin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D018836:Inflammation Mediators; D010936:Plant Extracts; D012838:Silymarin; D006820:Hyaluronic Acid; D002251:Carbon Tetrachloride
keywords: NF-κB; anti-inflammatory; antioxidant; hepatic toxicity; liver fibrosis