Possible Interaction: Glutathione and Misonidazole

“Some biochemical repair processes, in particular those concerned with the rejoining of breaks induced by radiation in the presence of oxygen or misonidazole , appear also to be critically dependent on glutathione.”

“The protective effects of glutathione and thiourea were diminished by the addition of misonidazole.”

“Depletion of intracellular glutathione GSH ) can enhance misonidazole (MISO) radiosensitizing efficacy both in vivo and in vitro.”

“When CHO cells were incubated with misonidazole in the presence of added GSH , a substantial increase in the amount of the conjugate was detected.”

“When extracts of CHO cells exposed to misonidazole under hypoxia were subsequently exposed to GSH , an increased formation of the conjugate was observed.”

“However, glutathione depletion caused a profound change in the radiosensitizing efficiency of misonidazole , with a decrease in Km of about sevenfold from 0.6 to 0.09 mM. In contrast, only a 2.5-fold decrease was found in the Km for radiosensitization by oxygen with diethylmaleate pretreatment.”

“The possible involvement of glutathione depletion in chemosensitization by MISO was investigated by comparison with the effect of diethyl maleate (DEM), a known thiol-depleting reagent.”

“Although … glutathione (GSH) occurs during … pretreatments with MISO , simulating the same magnitude of GSH depletion with the GSH depleter, diethylmaleate, gave a dose reduction factor of only 1.4, … GSH depletion would not be expected to contribute to the sensitization which occurs when MISO is given after L-PAM.”

“These results demonstrate that glutathione protects against the cytotoxic effect of MIS.”

“ Glutathione reduced the binding of misonidazole to microsomal protein below the level observed for boiled microsomes while ascorbic acid had no effect.”

“ Misonidazole (MISO) depletes intracellular glutathione and is more toxic in glutathione depleted cells.”