Current Issues of Pharmacy and Medical Sciences

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

Curr Issues Pharm Med Sci., Vol. 28, No. 1, Pages 5-7

Magdalena Wnukowska1 , Slawomir Mandziuk2, Agnieszka Korga1*,
Barbara Jodlowska-Jedrych3, Wlodzimierz Matysiak3, Justyna Halasa4,
Franciszek Burdan4,5, Magdalena Iwan1, Renata Gieroba1, Jaroslaw Dudka1,6

1 Independent Medical Biology Unit, Medical University of Lublin, Jaczewskiego 8, 20-950 Lublin, Poland
2 Department of Pneumology, Oncology and Alergology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland
3 Department of Histology and Embryology, Medical University of Lublin, Radziwillowska 11, 20-080 Lublin, Poland
4 Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland
5 St. John’s Cancer Center, Jaczewskiego 7, 20-090 Lublin, Poland
6 Chair and Department of Toxicology, Medical University of Lublin, Chodzki 8, 20-093 Lublin, Poland


DOI: 10.1515/cipms-2015-0031

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.

 

Full Text

Keywords

doxorubicin, thyroxin, liver, redox equilibrium, lipid metabolism.

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