<abstract xmlns="http://www.w3.org/1999/xhtml"><p>The redox cycle triggered by one electron reduction of doxorubicin and tirapazamine - both anticancer agents - leads to superoxide production. This superoxide production itself removes one iron atom from the [4Fe-4S] cluster, being an active center of aconitase. In addition, the incurred changes in cell redox equilibrium may affect lipid metabolism. The aim of the study was to evaluate a concomitant effect of both drugs on hepatic aconitase activity and triglycerides level. In our study, doxorubicin (1.8 mg/kg b.w.) was administered intraperitoneal (i.p.) six times, once a week, within male Wistar rats, to achieve a cumulative dose of 10.8 mg/kg b.w. Two hours before every doxorubicin administration, tirapazamine in the dose of either 5 or 10 mg/kg b.w. was also i.p. injected. A week after withdrawing drug administration, the liver was taken for biochemical analysis. Therein, an increase in aconitase activity and a decrease in triglycerides level was seen in all groups exposed to doxorubicin. Our work demonstrated that tirapazamine administration had no influence on both tested parameters, but its higher dose rate normalized aconitase activity affected by doxorubicin.</p></abstract>

The redox cycle triggered by one electron reduction of doxorubicin and tirapazamine - both anticancer agents - leads to superoxide production. This superoxide production itself removes one iron atom from the [4Fe-4S] cluster, being an active center of aconitase. In addition, the incurred changes in cell redox equilibrium may affect lipid metabolism. The aim of the study was to evaluate a concomitant effect of both drugs on hepatic aconitase activity and triglycerides level. In our study, doxorubicin (1.8 mg/kg b.w.) was administered intraperitoneal (i.p.) six times, once a week, within male Wistar rats, to achieve a cumulative dose of 10.8 mg/kg b.w. Two hours before every doxorubicin administration, tirapazamine in the dose of either 5 or 10 mg/kg b.w. was also i.p. injected. A week after withdrawing drug administration, the liver was taken for biochemical analysis. Therein, an increase in aconitase activity and a decrease in triglycerides level was seen in all groups exposed to doxorubicin. Our work demonstrated that tirapazamine administration had no influence on both tested parameters, but its higher dose rate normalized aconitase activity affected by doxorubicin.

The effect of one-electron reduced drugs on hepatic aconitase activity and triglycerides level

Independent Medical Biology Unit, Medical University of Lublin, Jaczewskiego 8, 20-950 Lublin, Poland

Department of Pneumology, Oncology and Alergology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland

Department of Histology and Embryology, Medical University of Lublin, Radziwillowska 11, 20-080 Lublin, Poland

Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland

St. John’s Cancer Center, Jaczewskiego 7, 20-090 Lublin, Poland

Chair and Department of Toxicology, Medical University of Lublin, Chodzki 8, 20-093 Lublin, Poland

Current Issues in Pharmacy and Medical Sciences

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

The redox cycle triggered by one electron reduction of doxorubicin and tirapazamine - both anticancer agents - leads to superoxide production. This superoxide...

The effect of one-electron reduced drugs on hepatic aconitase activity and triglycerides level

Data publikacji: 09 maj 2015

Zakres stron: 5 - 7

Otrzymano: 03 gru 2014

Przyjęty: 22 gru 2014

DOI: https://doi.org/10.1515/cipms-2015-0031

Słowa kluczowe
doxorubicin, thyroxin, liver, redox equilibrium, lipid metabolism

© 2015

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

The effect of one-electron reduced drugs on hepatic aconitase activity and triglycerides level

Data publikacji: 09 maj 2015

Zakres stron: 5 - 7

Otrzymano: 03 gru 2014

Przyjęty: 22 gru 2014

DOI: https://doi.org/10.1515/cipms-2015-0031

Słowa kluczowedoxorubicin, thyroxin, liver, redox equilibrium, lipid metabolism

© 2015

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Słowa kluczowe
doxorubicin, thyroxin, liver, redox equilibrium, lipid metabolism