Co-administration of metformin and N-acetylcysteine with dietary control improves the biochemical and histological manifestations in rats with non-alcoholic fatty liver

Theodor Bilharz Research Institute

Bibliographic Information

Authors: El-Lakkany N.M.; Seif El-Din S.H.; Abdel-Aal Sabra A.-N.; Hammam O.A.; Ebeid F.A.-L.

Journal: Research in Pharmaceutical Sciences

Publisher: Medknow Publications

Publication Date: 2016

Volume / Issue: Volume 11 / Issue 5

Pages: 374–382

ISSN: 17355362

DOI: 10.4103/1735-5362.192487

Scopus: View on Scopus

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access


Authors and Affiliations

El-Lakkany N.M., Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, Giza, Egypt; Seif El-Din S.H., Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, Giza, Egypt; Abdel-Aal Sabra A.-N., Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, Giza, Egypt; Hammam O.A., Department of Pathology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba,Giza, Egypt; Ebeid F.A.-L., Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, Giza, Egypt


Abstract

Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem that affects 1/3 of the adult population and an increasing number of children in developed countries. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. This study was conceived in a NAFLD rat model to evaluate the efficacy of both metformin (MTF) and N-acetylcysteine (NAC) with dietary control on biochemical and histologic liver manifestations. Rats were classified into nine groups; normal (I), NAFLD-induced by feeding high-fat diet (HFD; II) for 12 weeks, NAFLD switched to regular diet (RD; III), NAFLD-HFD or -RD treated with MTF in a dose of 150 mg/kg (IV, V), NAC in a dose of 500 mg/kg (VI, VII) or MTF+NAC (VIII, IX) respectively for 8 weeks. After 20 weeks, the rats in group II showed notable steatosis, lobular inflammation, fibrosis accompanied with elevated (P < 0.05) serum alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (β-GT), cholesterol, triglycerides, LDL, VLDL, leptin, tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1) and hepatic malondialdehyde (MDA) compared with group I. Meanwhile, hepatic superoxide dismutase (SOD), glutathione GSH with serum HDL, adiponectin were significantly decreased (P < 0.05). These changes were to a less extent in group III. MTF or NAC individually resulted in improvement of most of these biochemical and histological parameters. These improvements were more pronounced in the combined groups VIII and IX versus each drug alone. NAC supplementation concomitant with MTF could be beneficial for the treatment of NAFLD and prevention of nonalcoholic steatohepatitis (NASH).


Keywords

Adipocytokines; Metformin; N-acetylcysteine; NAFLD; Oxidative stress; TNF-β; acetylcysteine; adiponectin; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; cholesterol; gamma glutamyltransferase; glutathione; high density lipoprotein; leptin; low density lipoprotein; malonaldehyde; superoxide dismutase; transforming growth factor beta1; triacylglycerol; tumor necrosis factor; very low density lipoprotein; alanine aminotransferase blood level; animal experiment; animal model; animal tissue; Article; biochemistry; cholesterol blood level; controlled study; diet therapy; drug effect; drug efficacy; fatty liver; hepatitis; histopathology; liver fibrosis; male; nonalcoholic fatty liver; nonhuman; rat; Sprague Dawley rat


Citation Information

Scopus Citations: 37


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