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

Abstract

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.