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Asian Journal of Biochemistry

Year: 2008  |  Volume: 3  |  Issue: 2  |  Page No.: 99 - 108

Protective Effect of Metformin on Cardiac and Hepatic Toxicity Induced by Adriamycin in Swiss Albino Mice

A.M. Aleisa, S.S. Al-Rejaie, S.A. Bakheet, A.M. Al-Bekairi, O.A. Al-Shabanah, Abdulhakeem Al-Majed, Abdulaziz A. Al-Yahya and S. Qureshi

Abstract

Diabetes Mellitus (DM) is a chronic disease that is characterized by deterioration of glycemic control. The disease is known to be caused by imbalance between Reactive Oxygen Species (ROS) and antioxidant defense systems. Hyperglycemia is commonly observed in a wide variety of diseases, including cancer. Although, therapy against glycemic control is used in all these diseases, the diabetic cancer patients are on additional therapy with anticancer drugs. The objective of present study was to investigate if metformin, a very popular antidiabetic agent can avert the cardiac and hepatic toxicity caused by Adriamycin (ADR), which is a commonly used cytotoxic drug. The experimental protocol included oral treatment of mice with different doses (62.5, 125 and 250 mg kg-1 day-1) of metformin for 7 days. Some mice in each group were injected i.p. with ADR (15 mg kg-1), 24 h prior to sacrifice. In each case animals were killed, 24 h after the last treatment, blood sample was collected and plasma was separated for analysis of AST, ALT and CK-MB. Liver and heart from the same animals were excised for analysis of proteins, nucleic acids, MDA and NP-SH. The results obtained revealed that pretreatment with metformin (i) reduced the ADR-induced increase in the concentrations of AST, ALT and CK-MB (ii) protected against the ADR-induced increase of MDA and decrease of DNA and NP-SH in both cardiac and hepatic tissues. These results demonstrate that the treatment with metformin might be useful to protect cardiac and hepatic toxicity. The exact mechanism of action is not known, however; the inhibition of ADR-induced increase of plasma enzymes and MDA and depletion of DNA and NP-SH by metformin may be attributed to its antioxidant potentials, which are well known for the reduction of glycotoxins and general improvement in cellular dysfunction. The use of Metformin by cancerous diabetic patients on cytotoxic therapy will be a boon to avert the cardiac and hepatic toxicity.

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