Conjunction of mitochondrial targeting nutrients for the management of heart dysfunctions associated with type 2 diabetes

Abstract

Backgrounds and aims 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. Material and methods 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. Results After 14 wks diabetic animals had not lost weight compared with control and treatment did not affect it, P P P P P Conclusion 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.