EJMS

Abstract

Introduction: Methotrexate is a chemotherapeutic agent used in the treatment of many types of cancer diseases. However, its clinical use was associated with neurotoxicity in the cerebellar cortex. The mechanism of Methotrexate degeneration was proved to be due to oxidative stress. Dantrolene has an antioxidant effect against the free radicals released during the oxidation process. Aim of work: to investigate the possible protective role of Dantrolene on cerebellar toxicity induced experimentally in rats with Methotrexate treatment. Material & Methods: the present study was carried out on forty eight adult male albino rats divided into 4 equal groups: group I (control group), group II (Dantrolene treated group) received Dantrolene at a dose 10 mg/kg body weight diluted in 15 ml of water given orally by gavage daily for four weeks, group IIІ (Methotrexate treated group) received 20 mg/kg body weight Methotrexate administered intraperitoneally once weekly for four weeks and group VI (Dantrolene and Methotrexate treated group) were concomitantly treated with Methotrexate and Dantrolene as the same previous doses, period and route of administration. The animals were sacrificed at the end of the experiment; the cerebellum was excised and prepared for histological and ultrastructural study. Results: Histological examination displayed severe degenerative changes in the cerebellar cortex after Methotrexate administration. Necrosis of Purkinje cells with areas of degenerative changes of the myelinated axons such as disruption and loss of the lamellar compact structure of myelin layers was shown. Many axons showed complete absence of myelin. Concomitant administration of Dantrolene with Methotrexate revealed an observable protection against such pathological changes. Conclusion: Dantrolene protects the cerebellum against the neurotoxic effect of Methotrexate in adult male albino rats.