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Changes in GSH-antioxidant system induced by daunorubicin in human normal and diabetic fibroblasts
Agnieszka Zatorska1, Janusz Maszewski, Zofia Jóźwiak
1Department of Thermobiology, University of Łódź, Poland. lgebicka@mitr.p.lodz.pl
Abstract:
We investigated the effect of daunorubicin on glutathione content and activity of GSH-related enzymes in cultured normal and diabetic human fibroblasts. Cells were incubated with 4 microM daunorubicin (DNR) for 2 h followed by culture in drug-free medium for up to 72 h. Treatment of diabetic cells with the drug caused a time-dependent depletion of intracellular GSH and a decrease of the GSH to total glutathione ratio. GSH depletion was accompanied by apoptotic changes in morphology of the nucleus. Analysis of GSH-related enzymes showed a significant increase of the activities of Se-dependent and Se-independent peroxidases and glutathione S-transferase. In contrast, glutathione reductase activity was reduced by 50%. Significant differences between normal and diabetic cells exposed to DNR were observed in the level of GST and Se-dependent glutathione peroxidase activities. These findings indicated that daunorubicin efficiently affects the GSH antioxidant defense system both in normal and diabetic fibroblasts leading to disturbances in glutathione content as well as in the activity of GSH-related enzymes.
Insights
Daunorubicin treatment depletes glutathione (GSH) and alters GSH-related enzyme activity in human fibroblasts. Diabetic cells showed more pronounced effects, indicating daunorubicin disrupts antioxidant defenses.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Glutathione (GSH) is a critical intracellular antioxidant.
- Diabetic conditions can impair cellular antioxidant defenses.
- Daunorubicin is an anticancer drug with potential cellular toxicity.
Purpose of the Study:
- To investigate the impact of daunorubicin on GSH levels and GSH-related enzyme activity in normal and diabetic human fibroblasts.
- To compare the cellular response to daunorubicin between normal and diabetic fibroblast models.
Main Methods:
- Human fibroblasts (normal and diabetic) were exposed to daunorubicin (4 microM) for 2 hours.
- Cells were subsequently cultured in drug-free medium for up to 72 hours.
- Intracellular GSH content, GSH ratio, and activities of GSH-related enzymes (peroxidases, glutathione S-transferase, glutathione reductase) were analyzed.
Main Results:
- Daunorubicin induced a time-dependent decrease in intracellular GSH and the GSH/total glutathione ratio in diabetic fibroblasts.
- GSH depletion correlated with nuclear apoptotic changes.
- Activities of Se-dependent/independent peroxidases and glutathione S-transferase increased, while glutathione reductase activity decreased by 50%.
- Diabetic cells exhibited significant differences in glutathione S-transferase and Se-dependent glutathione peroxidase activities compared to normal cells.
Conclusions:
- Daunorubicin significantly disrupts the glutathione antioxidant defense system in both normal and diabetic human fibroblasts.
- Diabetic fibroblasts show altered responses to daunorubicin, suggesting a compromised antioxidant system.
- These findings highlight the drug's impact on cellular redox balance and potential implications in diabetic patients.