Affiliation:
1. Department of Pharmacology Medical Research and Clinical Studies Institute, National Research Centre Giza Egypt
2. Department of Pathology, Faculty of Veterinary Medicine Cairo University Giza Egypt
3. Department of Molecular Food Chemistry and Food Development, Institute of Food Science and Human Nutrition Gottfried Wilhelm Leibniz University Hannover Hannover Germany
4. Pharmacognosy Department, Faculty of Pharmacy University of Sadat City Sadat City Egypt
Abstract
AbstractLiver fibrosis is a common chronic hepatic disease. This study aimed to investigate the effect of pitavastatin (Pit) against thioacetamide (TAA)‐induced liver fibrosis. Rats were divided into four groups: (1) control group; (2) TAA group (100 mg/kg, i.p.) three times weekly for 2 weeks; (3 and 4) TAA/Pit‐treated group, in which Pit was administered orally (0.4 and 0.8 mg/kg/day) for 2 weeks following TAA injections. TAA caused liver damage manifested by elevated serum transaminases, reduced albumin and histological alterations. Hepatic malondialdehyde (MDA) was increased, and glutathione (GSH) and superoxide dismutase (SOD) were decreased in TAA‐administered rats. TAA upregulated the inflammatory markers NF‐κB, NF‐κB p65, TNF‐α and IL‐6. Treatment with Pit ameliorated serum transaminases, elevated serum albumin and prevented histopathological changes in TAA‐intoxicated rats. Pit suppressed MDA, NF‐κB, NF‐κB p65, the inflammatory cytokines and PI3K mRNA in TAA‐intoxicated rats. In addition, Pit enhanced hepatic antioxidants and boosted the nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) mRNA. Moreover, immunohistological studies supported the ability of Pit to reduce liver fibrosis via suppressing p‐AKT expression. In conclusion, Pit effectively prevents TAA‐induced liver fibrosis by attenuating oxidative stress and the inflammatory response. The hepatoprotective efficacy of Pit was associated with the upregulation of Nrf2/HO‐1 and downregulation of NF‐κB and PI3K/Akt signalling pathways.
Funder
Gottfried Wilhelm Leibniz Universität Hannover
Subject
Cell Biology,Molecular Medicine