Damage to the cell antioxidative system in human erythrocytes incubated with idarubicin and glutaraldehyde.
Encapsulation of antineoplastic drugs within erythrocytes is one of the studied strategies to diminish the toxic side effects of anthracycline antibiotics. Glutaraldehyde is often used as crosslinking agent to link the drugs, including idarubicin (IDA) to the cells. The previous studies indicated that in glutaraldehyde-treated human erythrocytes the elevated level of drug was observed but also the various changes in the organization of the red cells were noted. In this study, we continue our investigations and now we concentrate on the effect of these compounds on antioxidative system in erythrocytes. We determined reactive oxygen species (ROS) production, glutathione content and alterations in the activity of enzymes responsible for maintaining glutathione in reduced form in human erythrocytes. Measurements of both reduced and total glutathione levels and the activity of glutathione reductase and glucose-6-phosphate dehydrogenase were performed spectrophotometrically. The results show that ROS were produced in erythrocytes treated with IDA and with IDA and glutaraldehyde. IDA at a concentration of 10 microg/ml did not cause any changes in total or reduced glutathione levels. When IDA-preincubated erythrocytes were treated with glutaraldehyde, significant changes in the determined parameters were observed in a glutaraldehyde concentration dependent manner. It was correlated with decreased activity of glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD). Together with the significant changes in reduced form of glutathione (GSH)/total glutathione ratio, the exposure of phosphatidylserine at the cell surface was also observed.
Marczak
Agnieszka
A
Department of Thermobiology, University of Łódź, 90-237 Łódź, Poland. aszwar@biol.uni.lodz.pl
Jóźwiak
Zofia
Z
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity; D000975:Antioxidants / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D005976:Glutaral / Q000008:administration & dosage / Q000633:toxicity*; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000633:toxicity*; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013053:Spectrophotometry
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D003432:Cross-Linking Reagents; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D005954:Glucosephosphate Dehydrogenase; D005980:Glutathione Reductase; D005978:Glutathione; D005976:Glutaral; D015255:Idarubicin