Nicorandil and atorvastatin attenuate carbon tetrachloride - induced liver fibrosis in rats.

Autor: Abdel-Sattar AR; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt., Abo-Saif AA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt., Aboyoussef AM; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Jazyk: angličtina
Zdroj: Immunopharmacology and immunotoxicology [Immunopharmacol Immunotoxicol] 2020 Dec; Vol. 42 (6), pp. 582-593. Date of Electronic Publication: 2020 Oct 19.
DOI: 10.1080/08923973.2020.1830104
Abstrakt: Purpose: The present study aimed to evaluate the possible hepatoprotective effects of nicorandil and atorvastatin against experimentally induced liver fibrosis.
Materials and Methods: Wistar male rats wereassigned tofivegroups; control group, fibrosis group, the remaining three groups received in addition to CCl 4 , N-acetyl cysteine (300 mg/kg), nicorandil(15 mg/kg) and atorvastatin (20 mg/kg), respectively. Liver fibrosis was induced by intraperitoneal injection of rats with CCl 4 (2 ml/kg), twice weekly for five consecutive weeks. All treatments were administered daily starting from the first day of fibrosis induction for five consecutive weeks. By the end of the experiment, fibrosis biomarkers [hepatic transforming growth factor β1 (TGF-β 1 ) and hydroxyproline (HYP)], liver function [serum alanine transaminase (ALT), aspartate transaminase (AST), albumin and total bilirubin] were assessed. Moreover, lipid profile [total cholesterol, serum triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)], inflammatory biomarkers [hepatic myeloperoxidase (MPO), serum tumor necrosis factor alpha (TNF-α)], relative liver weight] and oxidative stress biomarkers [malondialdehyde (MDA), glutathione (GSH) and catalase (CAT)] were evaluated. In support, histopathological and immunohistochemical examination of liver alpha smooth muscle actin (α-SMA) were performed.
Results: Nicorandil and atorvastatin effectively reduced fibrosis and liver function biomarkers. They both restored serum lipid profile, TNF-α, MPO, relative liver weight, and hepatic MDA content. Alternatively, they markedly elevated albumin, HDL-C and hepatic content of GSH and CAT. Additionally, a marked histopathological and immunohistochemical improvement of α-SMA was observed.
Conclusion: Nicorandil and atorvastatin might be promising protective agents against liver fibrosis through amelioration of liver function, modulation of fibrous formation, anti-inflammatory and antioxidant potentials.
Databáze: MEDLINE
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