Nitroimidazole inhibition of lactate production in CHO cells

Misonidazole (MISO) and desmethylmisonidazole (DMM) inhibit lactate production in CHO cells under aerobic conditions. This inhibition is time and dose dependent. At the 20 mM level DMM is stronger in producing this inhibition of lactate than is MISO. This inhibiton of lactate production suggests that these compounds are capable of inhibiting the glycolytic pathway. The resultant energy deficiency may be an explantation for the toxicity of these compounds under hypoxic as well as aerobic conditions. The increased dependency on glycolysis of hypoxic cells may correspond to the analogous increase in toxicity of hypoxic cells to nitroimidazoles.