Pretreatment with magnesium ameliorates lipopolysaccharide-induced liver injury in mice

Background: Lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, is involved in the pathogenesis of sepsis. LPS administration induces systemic inflammation that mimics many of the initial clinical features of sepsis and has deleterious effects on several organs including the liver and eventually leading to septic shock and death. The present study aimed to investigate the protective effect of magnesium (Mg), a well known cofactor in many enzymatic reactions and a critical component of the antioxidant system, on hepatic damage associated with LPS-induced endotoxima in mice. Methods: Mg (20 and 40 mg/kg, po) was administered for 7 consecutive days. Systemic inflammation was induced 1 h after the last dose of Mg by a single dose of LPS (2 mg/kg, ip) and 3 h thereafter plasma was separated, animals were sacrificed and their livers were isolated. Results: LPS-treated mice suffered from hepatic dysfunction revealed by histological observation, elevation in plasma transaminases activities, C-reactive protein content and caspase-3, a critical marker of apoptosis. Liver inflammation was evident by elevation in liver cytokines contents (TNF-alpha and IL-10) and MPO activity. Additionally, oxidative stress was manifested by increased liver lipoperoxidation, glutathione depletion, elevated total nitrate/nitrite (NOx) content and glutathione peroxidase (GPx) activity. Pretreatment with Mg largely mitigated these alternations. Conclusion: Pretreatment with Mg protects the liver from the acute injury which occurs shortly after septicemia. (C) 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z.o.o. All rights reserved.