Diabetes-induced metabolic abnormalities in myocardium: Effect of antioxidant therapy

Effects of hyperglycemia (both diabetes and experimental galactosemia) on c ardiac metabolism have been determined. In addition, the effect of suppleme ntal antioxidants on these hyperglycemia-induced abnormalities of cardiac m etabolism has been investigated. Diabetes or experimental galactosemia of 2 months duration in rats significantly increased oxidative stress in myocar dium, as demonstrated by elevation of thiobarbituric acid reactive substanc es (TBARS) and lipid fluorescent products in left ventricle. Activity of pr otein kinase C (PKC) was elevated in the myocardium, and the activities of (Na,K)-ATPase and calcium ATPases were subnormal. Administration of supplem ental antioxidants containing a mixture of ascorbic acid, Trolox; alpha-toc opherol acetate, N-acetyl cysteine, beta-carotene, and selenium prevented b oth the diabetes-induced and galactosemia-induced elevation of oxidative st ress and PKC activity, and inhibited the decreases of myocardial (Na,K)-ATP ase and calcium ATPases. The results show that these metabolic abnormalitie s are not unique to diabetes per se, but are secondary to elevated blood he xose levels, and supplemental antioxidants inhibit these metabolic abnormal ities. Our findings suggest that antioxidants inhibit abnormal metabolic pr ocesses that may contribute to the development of cardiac disease in diabet es, and offer a potential clinical means to inhibit cardiac abnormalities i n diabetes.