Background: Methotrexate (MTX) is an anti-metabolite most commonly used in chemotherapy and immunosuppressant in auto-immune diseases. Thymoquinone (TQ) is the principal component of Nigella sativa (N. Sativa). It has prominent therapeutic actions as it possesses antiapoptotic, antioxidant activities.
Objective: This study aimed to clarify the possible effect of TQ on the histological changes of the cerebellar cortex of MTX –treated adult male albino rats and to assess the restoration of the normal histological structure after cessation of MTX.
Materials and Methods: Thirty six adult healthy male albino rats were divided into four groups; group I (Control group), group II (MTX group). Group III (MTX and TQ group), and group IV (recovery group. At the end of the experiment, all rats were anesthetized and cerebellar specimens were obtained and processed.
Results: Microscopic examinationof MTX group displayed shrunken Purkinje cells with darkly stained pyknotic nuclei. Cresyl fast violet-stained cerebellar sections showed ill-defined purple Nissl granules in the perikarya of Purkinje cells and other neurons.Immunohistochemical-stained sections for GFAP showed a strong positive reaction in the processes of astrocytes, weak positive reaction for Bcl-2 in neuronal cytoplasm. MTX and TQ-treated groups showed no deterioration in their motor activities. Signs of degeneration were still present in the cerebellar cortex of the recovery group.
Conclusion: The cerebella of MTX- treated albino rats showed evident structural alterations seen indicating its neurotoxicity. Co-administration of TQ attenuated these changes more than cessation of MTX. This indicates TQ neuroprotective effect which can be considered clinically.