Title: Targeting Oxidative Stress: A Comparative Study on the Effects of Doxorubicin on Antioxidant Enzymes Activities in Heart and Tumor Tissues in Mice
Authors: Almohktar A. Adwas, Azab Elsayed Azab, Ahamed A. A. Adous, Mohamed A. A. Adous
Volume: 8
Issue: 11
Pages: 70-81
Publication Date: 2024/11/28
Abstract:
Background: Oxidative stress is a key component in linking environmental toxicity to the multistage carcinogenic process. Reactive oxygen species (ROS) are generated in response to both endogenous and exogenous stimuli. To counterbalance ROS-mediated injury, an endogenous antioxidants defense system exists; however, when oxidation exceeds the control mechanisms, oxidative stress arises. Doxorubicin (DOX) belongs to the class of anthracycline antibiotics that is widely used in the treatment protocols of a wide range of malignancies. The major deleterious effect of doxorubicin use is the possible occurrence of cardiotoxicity. Purpose: The present study aimed to investigate the effect of DOX on antioxidant enzymes activity in the cardiac and tumor tissues in mice. Methods: Sixty BALB/c male mice were used in this study. Except for mice in the control group, each mouse was implanted subcutaneously with 0.2 ml of the ascites fluid containing 1x106 Ehrlich carcinoma cells (ECCs) into the thigh of the hind limb. Mice were divided into three groups (20 mice per group) as follow: Control group, in which mice received an intraperitoneal (i.p.) injection of 0.2 ml normal saline once weekly on days 0, 7, 14, 21 (for 21 days), Solid Ehrlich carcinoma (SEC) control group, in which mice received an intraperitoneal injection of 0.2 ml normal saline once weekly on days 0, 7, 14, 21 (for 21 days) starting one hour after tumor inoculation, Doxorubicin (DOX+ SEC) group, in which mice received DOX (4 mg/kg, i.p.) once weekly on days 0, 7, 14, 21 (for 21 days) starting one hour after tumor inoculation. Serum creatine kinase (CK-MB), lactate dehydrogenase (LDH) and troponin I (cTn-I) levels activities, which are cardiac function markers were determined. Also, the levels of malondialdehyde (MDA) was assessed and enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPx) were assessed to determine the effect of DOX on antioxidant enzymes activity in the cardiac and tumor tissues in mice. Results: Administration of DOX to ECCs-bearing mice resulted in a significant increase in serum levels of CK-MB, LDH, cTnI, tissue SOD, CAT, GR and GPx with significant decrease in tissue MDA compared to SEC group. Administration of DOX to ECCs-bearing mice resulted in a significant decrease in cardiac tissue SOD, CAT, GR and GPx with significant increase in tissue MDA compared to control group. Conclusion: In tumor tissues, DOX was found to increase the activity of antioxidant enzymes, whereas in heart tissues, it reduced their activity. This variation might be due to the specific type of tissue affected by DOX. In cardiac tissues, DOX affects the cardiac adriamycin-responsive protein (CARP), which is exclusively found in these tissues and functions as a negative regulator of cardiac-specific gene expression.