Mg-Supplementation Protects Against Oxidative Stress And Cardiac Dysfunction In Chronic Highly Active Antiretroviral Therapy-Treated Rats

Highly active antiretroviral therapy (HAART) agents, azidothymidine (AZT), ritonavir (RTV), and efavirenz (EFV), were assessed in vivo for oxidative stress, cardiac injury, and dysfunction in rats, and dietary Mg-supplementation (Mg-Sup sixfold higher) was evaluated for antioxidant benefits. Three weeks AZT or up to 8 weeks of RTV- and EFV treatments led to substantial elevations in neutrophil basal superoxide production, plasma 8-isoprostane, and RBC oxidized glutathione (GSSG) levels. Echocardiography revealed that AZT had minimal impact on left ventricular systolic function but depressed diastolic function. RTV and EFV led to diastolic and systolic dysfunction >= 5 weeks and decreased left ventricular posterior wall thickness (LVPW), suggesting onset of dilated cardiomyopathy; RTV and EFV caused ventricular fibrosis at 8 weeks. Mg-Sup suppressed HAART-induced neutrophil superoxide production, isoprostane, and GSSG elevations, attenuated systolic and diastolic dysfunction, lessened LVPW wall thinning, and reduced fibrosis. Mg-Sup provided protection against oxidative cardiac toxicity associated with different classes of HAART agents.