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Changes in glutathione-related enzymes in tumor-bearing mice after cisplatin treatment
1Cell and Tumor Biology Laboratory, Department of Zoology, North-Eastern Hill University, Shillong, India.
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 (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.
Insights
Cisplatin alters glutathione-related enzymes in liver, kidney, and tumor cells, impacting antioxidant defense and potentially contributing to toxicity and anticancer effects.
Area of Science:
- Biochemistry
- Pharmacology
- Toxicology
Background:
- Cisplatin is a widely used chemotherapeutic agent.
- Glutathione-related enzymes play a crucial role in cellular defense against oxidative stress.
- Understanding the impact of cisplatin on these enzymes is vital for managing its toxicity and efficacy.
Purpose of the Study:
- To investigate the effect of cisplatin on key glutathione-related enzymes in different tissues.
- To assess the impact of cisplatin on cellular antioxidant defense mechanisms.
- To explore the correlation between enzyme activity changes and cisplatin-induced toxicity.
Main Methods:
- Tumor-bearing mice were treated with cisplatin.
- Activities of glutathione S-transferase, glutathione peroxidase, catalase, glutathione reductase, and superoxide dismutase were measured in liver, kidney, and Dalton lymphoma cells.
- Glutathione levels were also determined in these tissues.
Main Results:
- Cisplatin treatment significantly altered the activities of glutathione-related enzymes across liver, kidney, and lymphoma cells.
- Notable decreases in antioxidant enzymes were observed in liver and lymphoma cells, while kidney showed mixed changes.
- Glutathione levels decreased in kidney and lymphoma cells but remained unchanged in the liver.
Conclusions:
- Cisplatin significantly modulates glutathione-related enzyme activities and glutathione levels in a tissue-specific manner.
- These alterations in cellular antioxidant defense may contribute to cisplatin's anticancer activity and its associated toxicities, particularly nephrotoxicity.
- Further research is needed to establish a direct correlation between specific enzyme changes and clinical outcomes.
