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Changes in glutathione-related enzymes in tumor-bearing mice after cisplatin treatment

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Abstract

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 (~24%) mainly at 72 h of treatment. An increase in glutathione reductase (~1.5–2.5 times), glutathione peroxidase (significant at 24 h, 47%), and superoxide dismutase (~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 (~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 (~60%) during later periods (72–96 h) of treatment. Cisplatin treatment caused a decrease in glutathione level in Dalton lymphoma cells (~14–20%) and kidney (~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.

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Khynriam, D., Prasad, S. Changes in glutathione-related enzymes in tumor-bearing mice after cisplatin treatment. Cell Biol Toxicol 18, 349–358 (2002). https://doi.org/10.1023/A:1020899221192

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