The effect of ascorbic acid on the efficiency of cytotoxic therapy with cytostatic drugs in combination with NaNO3 and hydroxamic acids

Abstract

The present investigation is based on the paradoxical dichotomy of the biological action of nitric oxide (NO). Depending on its concentration in the organism, it can have therapeutic or pathogenic effect. It was shown that during the treatment with cisplatin (cPt) or cyclophospamide (CP), adjunct therapy with ascorbic acid (AA) known to increase the NO content in the organism extended the average lifespan (ALS) by 20—30% as compared to cytostatic monotherapy. Combination of cytostatics with sodium nitrate extended ALS by 20—38% depending on the concentration of the nitrate. The efficiency of cytotoxic therapy in combination with two chemo sensitizers (NaNO₃ and hydroxamic acid) also depends on the concentration of injected NaNO₃. Addition of AA to these combinations extended ALS by 16%, or inhibited it by 40%. Variation of the dose of injected NaNO₃ that is a NO donor in combination with endogenous NO stimulated with AA controls the action of cytostatics and combinations thereof.