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.