Effect of tirapazamine on oxidative stress and metabolic parameters in skeletal muscle of rats treated with classic anticancer drugs
DOI:
https://doi.org/10.12923/Abstract
Tirazapamine is a drug that has been shown to be a selective anticancer compound which was proved, in the latest studies, more efficient in concomitant treatment with other chemotherapeutic agents. In previous studies evidence suggested that the predominant mechanism DOX and TPZ cell toxicity is linked with the generation of reactive oxygen species. Moreover, under normal cell condition, CP decreased the level of reduced glutathione changing red-ox status. Then Red-ox equilibrium differences may have an impact on lipids, hydrocarbons and proteins metabolic transformations. In our study we tested the effect of TPZ in combination with DOX, CP and 5-FU on myocytes oxidative stress, triglycerides, glucose and proteins levels. The rats were treated (i.p.) with two doses (5 i 10 mg/kg b.w.) of tirapazamine, 2h before administration of 1.8 mg/kg b.w. of doxorubicin, 2 mg/kg b.w of cisplatin or 10 mg/kg b.w. of 5-fluorouracil. All tested drugs were administered once a week over a period of 6 weeks and a week after the last dose was given, and the obtained skeletal muscle samples were taken to be tasted. The data presented in this study support the assumption that TPZ changed the red-ox equilibrium in skeletal muscle of rats treated at the same time with DOX or FU. TPZ also caused metabolic disorders in rats treated simultaneously with CP. On the other hand, the lack of relationship between oxidative stress and metabolic disorders in the tested pairs of drugs suggested that these phenomena are independent under experimental conditions.
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