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

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Wnukowska M., Mandziuk S., Korga A., Jodlowska-Jedrych B., Matysiak W., Halasa J., Burdan F., Iwan M., Gieroba R., Dudka J.

Current Issues in Pharmacy and Medical Sciences

2015

vol. 28

issue 1

5-7

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 thyroxin on hepatic redox equilibrium and lipid metabolism in rats treated with doxorubicin

100%

Czuba B., Fituch M., Mandziuk S., Jodlowska-Jedrych B., Matysiak W., Halasa J., Burdan F., Korga A., Iwan M., Luszczewska-Sierakowska I., Dudka J.

Current Issues in Pharmacy and Medical Sciences

2014

vol. 27

issue 4

220-223

The main side effects of the administration of doxorubicin, a widely used anticancer drug, is the generation of a reactive oxygen species (ROS) in normal cells. As a result, redox disorders and secondary oxidative stress are developed. Doxorubicin ROS generation is attributed to enzymes that are produced abundantly in hepatocytes. Oxidative stress has been a well-known risk factor of doxorubicin-related toxicity. However, in addition, according to the data collected in the last decade, changes in thyroxin status can propagate ROS generation, and, thus, initiate the doxorubicin hepatic effect. Moreover, both compounds have an impact on the cell metabolism. The aim of the study was to verify the thesis that thyroxin can modulate the effect of doxorubicin with regard to redox status and lipid metabolism disorders. In our work, we determined the ratio of NADP+/ NADPH and NAD+/NADH in liver homogenates, blood ketone bodies and triglycerides in the liver and blood in rats treated with doxorubicin and thyroxin. Our results indicate that thyroxin has an insignificant effect on NAD+/NADH, NADP+/NADPH ratios and on hepatic and blood triglycerides. Moreover, thyroxin administration normalized the level of blood ketone bodies that was disturbed by doxorubicin.

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2 Current Issues in Pharmacy and Medical Sciences

1 2015

1 2014

2 Burdan F.

2 Dudka J.

2 Halasa J.

2 Iwan M.

2 Jodlowska-Jedrych B.

2 Korga A.

2 Mandziuk S.

2 Matysiak W.

1 Czuba B.

1 Fituch M.

1 Gieroba R.

1 Luszczewska-Sierakowska I.

1 Wnukowska M.

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

The effect of thyroxin on hepatic redox equilibrium and lipid metabolism in rats treated with doxorubicin