Combined effect of lipoic acid and doxorubicin in murine leukemia

Our experiments indicate that administration of a toxic drug with high rate of free-radical formation (doxorubicin, DOX) combined with an antioxidant (alpha-lipoic acid, LA) may lead to a decrease in drug-toxicity. However, t he effects of antioxidant may be concentration-dependent and it is therefor e crucial to choose its appropriate dosage. LA at a low concentration (1 mu mol/l) acts as a growth factor and at a higher concentration (100 mu mol/l ) acts as an antiproliferation agent. Both concentrations of LA in combinat ion with DOX were examined in cytotoxic and antitumor effects in L1210 mous e leukemia cells employing a MTT chemosensitivity assay. In most concentrat ion combinations, DOX and LA effect were antagonistic and synergistic actio n was only found at the higher concentration of both agents (DOX 2.5 mu mol /l and LA 100 mu mol/l). Use of LA in doxorubicin therapy lead to an increase (though marginally sig nificant) in survival of animals. Combined single-dose administration of DO X (5 mg/kg) and LA (16 mg/kg) lead to super-additive effect of the combinat ion on survival of leukemic mice.