Changes in glutathione-related enzymes in tumor-bearing mice after cisplatin treatment.
The effect of cisplatin on five glutathione-related enzymes was studied in liver, kidney, and Dalton lymphoma cells of tumor-bearing mice. In liver, the activities of glutathione S-transferase, glutathione peroxidase, catalase, and superoxide dismutase decreased approximately 30-40%, 60-67%, 35-50% and 70-80% respectively, while glutathione reductase increased about 36-45% after cisplatin treatment. In kidney, catalase activity decreased by 47-82% at all time points (24-96 h) of cisplatin treatment, while glutathione S-transferase activity decreased significantly (approximately 24%) mainly at 72 h of treatment. An increase in glutathione reductase (approximately 1.5-2.5 times), glutathione peroxidase (significant at 24 h, 47%), and superoxide dismutase (approximately 15-60%) was noted in kidney after the treatment. In Dalton lymphoma cells, the activities of glutathione S-transferase, glutathione peroxidase, and catalase decreased very distinctly (approximately 2-5, 2-5 and 5-11 times, respectively) at all time points, but glutathione reductase decreased significantly only at 72 h of cisplatin treatment. Interestingly, the superoxide dismutase activity in Dalton lymphoma cells increased initially at 24-48 h and then decreased (approximately 60%) during later periods (72-96 h) of treatment. Cisplatin treatment caused a decrease in glutathione level in Dalton lymphoma cells (approximately 14-20%) and kidney (approximately 18-28%) but no change in liver. In view of the results, a definite correlation with the changes in glutathione concentrations and enzymatic activities in a tissue could not be firmly derived. It is suggested that the changes in various glutathione-related enzymes and glutathione levels in the tissues of the host during cisplatin-mediated chemotherapy could affect cellular antioxidant defense potential, which may play an important contributory role in cisplatin-mediated toxicity, particularly nephrotoxicity, and anticancer activity in the host.
Khynriam
D
D
Cell and Tumor Biology Laboratory, Department of Zoology, North-Eastern Hill University, Shillong, India.
Prasad
S B
SB
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008223:Lymphoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D010544:Peroxidases / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010544:Peroxidases; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D002945:Cisplatin