Biochemical effects of niridazole. I. In vitro and in vivo effect of niridazole on the rate of gluconeogenesis and oxidation of pyruvate and some Krebs cycle intermediates in mice.

Abstract

The effects of the antischistosomal drug, niridazole, on the rate of gluconeogenesis in kidney cortex slices and on the rate of oxidation of pyruvate and some Krebs cycle intermediates in liver homogenate of non infected mice were determined. In vitro, niridazole was found to inhibit the succinate and pyruvate oxidation at the high concentration tested (10(-3)M). The rate of gluconeogenesis from alpha-ketoglutarate was unaffected. In vivo, niridazole showed a stimulatory effect on the rate of gluconeogenesis from alpha-ketoglutarate and on the rate of oxidation of pyruvate at a dosage level of 100 mg/kg for 5 days. The observed changes were discussed and the differences observed between the in vivo and in vitro work were assumed to be due to exposure of the tissues to the unmetabolized drug in vitro and to the drug and its metabolites in vivo.