The possible protective effect of CoQ10 enzyme on Methotrexate-induced cerebellar toxicity in adult male albino rats : A histological and immunohistochemical study / Rana Maged Yakout ; Supervised Soad Jimmy Tadros , Mary Attia Morcos , Abeer Ibraheem Abdallah

Thesis (M.Sc.) - Cairo University - Faculty of Medicine - Department of Histology

Background : Methotrexate (MTX), as an antineoplastic agent, can cause serious side effects including neurotoxicity. The most common mechanism of MTX induced damage is oxidative stress. CoenzymeQ10 (CoQ10) is a potent antioxidant that protects cells from damage and plays an important role in metabolism. Aim: This study was designed to evaluate the possible therapeutic effect of CoQ10 on the cerebellar histological changes induced by MTX in the brain of adult male albino rats.Materials and methods: Fourty eight adult male albino rats were divided into three groups namely, Control group (I), MTX group (II),which received single intraperitoneal dose of MTX (20mg/kg) and MTX+CoQ10 (III) which received MTX (as group II) and CoQ10 in a dose of 200mg daily orally by gastric tube.They were subdivided into subgroups a and b, then sacrificed 3 and 5 weeks from the start of the experiment, respectively. Cerebellar specimens were processed for histological (H&E and Toluidine blue stains) and immunohistochemical [anti-Glial Fibrillary Acidic Protein (GFAP)] antibodies studies. Mean area percent of GFAP positive reaction and mean number of Purkinje cells were detected, then the data were statistically analyzed. Results: Methotrexate treatment (group II) caused degenerative changes in Purkinje cells as many cells appeared shrunken with dark pyknotic nuclei. Vaculations in the molecular layer (ML) and splitting of myelinated nerve fibers were detected in the white matter. The Mean area percent of GFAP immunoreaction showed significant increase as compared to control group. CoQ10 treatment ( group III) resulted in amelioration of cell degeneration which was more evident in subgroup IIIb. Moreover, there was significant decrease in GFAP immunoreactivity. Conclusion: CoQ10 enzyme oral administration in rats following MTX-induced cerebellar toxicity, could ameliorate the neurodegenerative changes occurring in the cerebellum especially when administration continue for long period

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