The effect of treatment with high dose melphalan, cisplatin or carboplatin on levels of glutathione in plasma, erythrocytes, mononuclear cells and urine

Glutathione (GSH) has been implicated as an important factor in the detoxification of many electrophilic xenobiotics, including agents used in cytotoxic chemotherapy. Maintenance of high levels of GSH in normal tissues is believed to be important in the prevention of drug-induced toxicity. Previous studies have indicated that exposure of cells to some toxic electrophiles both in vitro and in vivo can cause a temporary decrease in intracellular levels of GSH. In this paper we report that in a series of 22 children and young adults treated with high dose melphalan (ten courses studied, all 200 mg/m(2)), cisplatin (eight courses, 80-104 mg/m(2)) or carboplatin (seven courses, 507-750 mg/m(2)) there was no significant alteration in the level of plasma, erythrocyte or urine GSH in the period immediately following drug administration. Fluctuations in the level of GSH in mononuclear cells were observed in some patients but did not follow any consistent pattern and were similar to those observed in a series of nine normal adult controls over the same time course. These results suggest that for melphalan, cisplatin and carboplatin, drug-GSH adduct formation is insufficient to cause a measurable decrease in intracellular GSH levels in normal peripheral haematopoietic cells during the course of treatment.