Protective effects of magnesium supplementation on metabolic energy derangements in lipopolysaccharide induced cardiotoxicity in mice

Abstract

Endotoxic shock is a major factor that contributes to morbidity and mortality in critically ill patients in intensive care units. Metabolic derangements and bioenergetic failure are major contributors to sepsis induced cardiotoxicity. The present investigation was directed to estimate the cardioprotective effect of magnesium (Mg), a cofactor in many enzymatic reactions that involve energy creation and utilization, in lipopolysaccharide (LPS)-induced metabolic energy changes in mice. Oral doses of Mg aspartate (20 or 40 mg/kg) were administered once daily for 7 days. Mice were then subjected to a single intraperitoneal injection of LPS (2 mg/kg). Three hours after LPS injection, plasma was separated for determination of creatine kinase-MB activity. Animals were then sacrificed and hearts were separated for estimation of tissue thiobarbituric acid reactive substances, reduced glutathione, lactate, pyruvate, adenine nucleotides,creatine phosphate and cardiac Na+,K+-ATPase activity. Finally, electron microscopic examination was performed to visualize the effect of Mg pretreatment on mitochondrial ultrastructure. The higher dose of Mg was more effective than the lower dose in ameliorating creatine kinase-MB elevation, the state of oxidative stress, lactate accumulation, pyruvate reduction as well as preserving creatine phosphate, adenine nucleotides and Na+,K+-ATPase activity. Moreover, the higher dose of Mg provided a significant cardioprotection against mitochondrial ultrastructure changes. Mg therapy can afford a significant protection against metabolic energy derangements and mitochondrial ultrastructure changes induced by LPS cardiotoxicity. Clinical studies are required to establish the effectiveness of magnesium as an adjunctive therapy in critically ill patients suffering from sepsis.