POTENTIAL PROTECTIVE EFFECT OF METFORMIN AND L-CARNITINE IN RAT MODEL OF CARBOPLATIN-INDUCED MYELOSUPPRESSION, COMPARATIVE STUDY | ||||
| Bulletin of Pharmaceutical Sciences Assiut University | ||||
| Volume 45, Issue 2, December 2022, Page 975-988 PDF (1.42 MB) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/bfsa.2022.271778 | ||||
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| Authors | ||||
Rania H. Shalaby  1; Fatma MKh Ibrahim2; Sarah Ibrahim3; Nadia E. helal4; Dina M. El-Guindy2; Eman F. Eltabaa5; Mohamed A. Safa6; Hanem Mohamed Rabah7; Norhan Ahmed AbuoHashish1
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| 1Pharmacology Department, Faculty of Medicine, Tanta University | ||||
| 2Pathology Department, Faculty of Medicine, Tanta University | ||||
| 3Anatomy Department, Faculty of Medicine, Tanta University | ||||
| 4Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Tanta University | ||||
| 5Physiology Department, Faculty of Medicine, Tanta University | ||||
| 6Internal Medicine Department, Faculty of Medicine, Tanta University | ||||
| 7Biochemistry Department, Faculty of Medicine, Tanta University | ||||
| Abstract | ||||
| Background: Carboplatin (CP), a well-known second-generation platinum compound, is effective against various malignancies including ovarian, lung, neck, breast, cervix and bladder cancer. However, myelosuppression is the most overwhelming toxic effect which results in leucopenia, thrombocytopenia and anemia. L-Carnitine (LCR) is a well-known antioxidant, cardioprotective, neuroprotective, and immunostimulant natural chemical compound. Metformin (MF) is a well-known drug approved for type 2 DM treatment. The aim of this work was to compare the potential protective effect of metformin and L-carnitine in a rat model of CP-induced myelosuppression. Methods and results: This study was performed on 40 adult male albino rats which were divided into four groups: control group, Carboplatin (CP) group, metformin (MF+CP) group and L-Carnitine (LCR+CP) group. Serum was used for measurement of TNF-α alpha, malondialdehyde (MDA), glutathione peroxidase (Gpx), glutathione reductase, catalase and superoxide dismutase (SOD) levels. Histopathological and immunohistochemical changes analyses were done in bone marrow. Carboplatin group showed redox status imbalance which was reversed by metformin and l-carnitine treatment corrected redox status balance. RBCs, WBCs and platelets counts were decreased in carboplatin treated group. Metformin and l-carnitine increased RBCs, WBCs and platelets counts significantly. TGF-β1 and caspase 3 expression were high in carboplatin treated group. Metformin and l-carnitine treatment significantly decreased their expression. Conclusions: Metformin and L-Carnitine have a possible protective role in myelosuppression induced by carboplatin and this effect is more potent with LCR treatment so we could recommend using L-Carnitine during Carboplatin treatment to prevent developing myelosuppression. | ||||
| Keywords | ||||
| Carboplatin; Myelosuppression; Metformin; L-Carnitine; TGF-β1; caspase 3 | ||||
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