Oxidative stress induced in rat liver by anticancer drugs doxorubicin, paclitaxel and docetaxel
Section snippets
INTRODUCTION
Chemotherapy is one of the principal methods employed in the treatment of several types of cancer, allowing for use of a combination of different types of antineoplastic drugs to increase its efficiency [1]. Both cancer and chemotherapyassociated complications, cause, however, substantial mortality. The objective of chemotherapy is to eliminate exclusively tumour cells. Most of the antineoplastic agents act, however, non-specifically, harming both malignant and normal cells. Toxicity of
Animals
Two months old 180 – 220 g male Wistar rats of outbred strain Imp:WIST were obtained from Nofer Institute of Occupational Medicine in Lodz. Animals were kept under standard conditions with free access to pellet diet and clean drinking water.
All experiments were performed according to the guidelines of the European Community for the Use of Experimental Animals (L358-86/609/EEC) and the Guiding Principles in the Use of Animals in Toxicology (1989) and were approved by the Local Ethics Committee
RESULTS
No animal deaths were observed in the course of the experiments.
The activities of superoxide dismutase (EC. 1.15.1.1) and catalase (EC. 1.11.1.6) are essential biomarkers of induction of oxidative stress in the liver tissue. SOD is an enzyme which catalyses the dismutation of superoxide anion to hydrogen peroxide and oxygen, while the role of catalase is the decomposition of hydrogen peroxide (H2O2) to water and oxygen and protection of cells against the toxic effects of ROS. Changes in SOD and
DISCUSSION
Taxanes, paclitaxel and docetaxel, are microtubule active drugs and one of the most potent cancer chemotherapeutics. Both of these drugs are employed in the therapy of a variety of human tumours, including ovarian carcinomas, breast and lung cancers [21, 22, 23]. Moreover, paclitaxel and docetaxel maintain substantial antitumour activity in anthracycline-resistant breast cancer [24]. Taxanes are also used in combined chemotherapy, which is superior to single drug use. PTX or DTX in conjugation
CONCLUSION
Our results indicate the hepatotoxic effects of doxorubicin and taxanes – paclitaxel and docetaxel, in experimental rat model in vivo. Combination of doxorubicin with any of the taxanes enhanced oxidative stress and caused greater changes in investigated parameters of oxidative stress compared to monotherapy treatment. This indicates the development of considerable oxidative stress in liver tissue during treatment with doxorubicin-taxane chemotherapy and possible involvement of oxidative stress
ACKNOWLEDGEMENTS
This work was supported in part by Grant N 401 2337 33 of Ministry of Science and Higher Education (Poland).
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