Document Type : Research article
Authors
1
Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt.
2
Department of Biochemistry, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt.
3
Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt. and School of Veterinary Medicine, Badr University, Assiut, Egypt
4
Department of Histology and Cell Biology, Faculty of Medicine, Assiut University, Egypt.
5
4 School of Veterinary Medicine, Badr University, Assiut, Egypt and Department of Pharmacology, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt.
Abstract
Doxorubicin (DOX) is a potent cytotoxic drug for treating various types of tumors. However, the limitation of its use is due to its potential for cumulative and dose-dependent cardiotoxicity. Recently, it has been suggested that the accumulation of damaged mitochondria, through dysregulation of the mitochondrial fission/fusion dynamic process, may be a critical mechanism contributing to DOX-induced cardiotoxicity. Metformin (Met), an antihyperglycemic drug, has been reported to exert cardio protection against DOX- induced Cardiotoxicity. We supposed that metformin medication could protect the heart from DOX induced cardiotoxicity via modulating mitochondrial dynamics. 32 adult male rats (190–210 g) were haphazardly separated into four groups. Control group was taken 1 ml of normal saline orally every day; DOX group: taken 3 mg/kg twice a week; Met group taken metformin (250 mg/kg/day) orally; and DOX+ Met group: received Met and DOX. After two weeks, the heart muscle of each rat was extracted, and each left ventricle was dissected out and cut into two parts. The primary part was placed in formic aldehyde for histology examinations. The other part was stored at −80°C for measurements of proteins of mitochondrial fusion expression, mitofusin 1 and mitofusin 2 (MFN1 and MFN2), which were estimated by real-time PCR. The results admit that Met medication affected the interpretation of MNF1 and MFN2, which significantly increased in the DOX+ Met group, compared to the DOX group. In conclusion, we discovered that metformin treatment could improve the mitochondrial dysregulation created by DOX.
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