engleski

Diazenes as modificators of intracellular glutathione levels

Glutathione (GSH) is a ubiquitous non-protein thiol essential for cellular homeostasis. It plays an important role in protecting cells against free radical induced oxydant injury, as well as in the detoxification of numerous endogenous and foreign electrophilic compounds. Most studies indicate that modulation of glutathione metabolism may be one of the most promising means of reversing clinical drug-resistance, which is the major obstacle to effective chemotherapy of cancer. Ten new diazenecarboxamides (diazenes) have been synthesized that should, according to their structure and biochemical properties, lower the intracellular GSH content. In the present study we determined intracellular GSH levels in human cervical carcinoma cells following 48 h incubation with equitoxic (the highest non-toxic concentrations) of these diazenes. GSH concentrations were determined spectrophotometrically by the procedure developed by Tietze. The results show that diazene RL-625 lowered significantly the GSH level, diazenes JK-918 and JK-1013 increased significantly the level of GSH, while remaining 7 diazenes (JK-914, UP-11, UP-39, UP-91, RL-338, RL-514 and BR-25) were in this respect inefficient. These results suggest that chemical structure of diazenes is essential for their influence on the intracellular GSH content.

cell cultures; glutathione; diazene

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