The heart is known to be susceptible to oxidative damage from high ambient oxidant levels, hypercoagulation and hypofibrinolysis associated with diabetes. It is also likely that poly(ADP-ribose)polymerase-1 (PARP-1) activation plays a crucial role in the pathogenesis of heart dysfunctions induced by diabetes. The study was performed to evaluate cardioprotective efficacy of a combined supplementation of mitochondria-specific antioxidants [acetyl-L-carnitine (ALC) and alpha-lipoic acid (ALA)] and nicotinamide (NAm), as a multiple-action drug in prevention of metabolic and haemostatic system's abnormalities induced by diabetes.

Neonatal diabetes was induced by STZ (80mg/kg b. w., i.p.) on the 2nd day of male Wistar rats’ life. Rats were treated for 2 wks with or without combination of ALC, ALA and NAm (respectively 100, 50 and 100mg/kg b.w., i.p.) after 12 wks of STZ-induced diabetes. PARP-1 activity in heart was measured by the incorporation of radioactivity from NAD+ (labeled in the adenine moiety) into nuclei proteins. The metabolic and hemostatic system's parameters were also assessed.

After 14 wks diabetic animals had not lost weight compared with control and treatment did not affect it, P<0.05. At the end of term it was found that the development of diabetes leads to insulin resistance of rat tissues, increases blood glucose and glycated hemoglobin levels in 1.8 and 2 times, respectively as compared to control, P<0.05. Tryptophan (precursor of NAD+ and serotonin) and serotonin levels were decreased in blood from diabetic rats by 40% and 45% respectively, P<0.05 suggesting that the lack of NAD+ in heart by 32% vs. control, P<0.05 is likely to be due to deficiency of precursors of its biosynthesis. Metabolic alterations in diabetic rats are accompanied by increase of fibrinogen plasma level in 1.5 time, plasminogen activator inhibitor-1 in 1.7 times respectively, appearance of soluble-fibrin-monomers complexes, decrease of activated protein C by 15%, factor X activity by 19%, P<0.05 and slight decrease of tissue-type plasminogen activator that may contribute to cardiovascular dysfunctions and intensification of inflammatory processes. Combined treatment caused reduction of glucose and glycated hemoglobin levels in 1.3 and 1.7 times respectively, normalized serotonin levels and improved the content of tryptophan in blood and NAD+ level and PARP-1 activity in heart which was increased in 1.6 times in diabetic rats vs. control. All haemostatic system's abnormalities were partly improved after treatment.

The findings suggest that combined supplement of naturally occurring biologically active compounds such as ALC, ALA and NAm offer a non-toxic, well tolerated and rational option for heart dysfunctions associated with type 2 diabetes improving metabolic and haemostatic system's alterations.