Histological & Immunohistochemical Study on the Effect of Methotrexate on the Cerebellum of Adult Male Albino Rats and The Possible Protective Role of Lepidium Sativum

Introduction: Methotrexate is a cytotoxic chemotherapeutic agent, vastly utilized not only for malignancies but also for variousinflammatory diseases, but it had hazardous effects on cerebellum. Lepidium sativum aherbal medication seemed to have neuroprotective effects.Objectives: This study was done to assess the effects of methotrexate on thecerebellum of adult male albino rats and the possible neuroprotective effect of lepidium sativum. Material and methods:Sixty (60) adult male albino rats, weighing nearly 170-200gms were used in the current study. The first group (n=10) was the control group. Ratsof second group(n=10)were given lepidium sativum aqueous extract (150mg/kg/day) by gastric tube daily for 4 weeks. Rats of third group (n=20)were given methotrexate (20mg/kg) on the 14th day then left without treatment for 2 weeks. Rats of fourth group (n=20)were given both Methotrexate and Lepidium Sativum as groups II and III. After 4 weeks, animals were sacrificed then the cerebellum was excised and processed for histological, immunohistochemical and quantitative studies. Results:Rats given lepidium sativum aquous extract was nearly similar to control group. Methotrexate treated rats showed significant decrease in number of Purkinje cells, significant increase in mean area % of GFAP positive immuno-staining and destructive changes of Purkinje cells with marked reduction of Nissl's granules. This was confirmed by electron microscopic examination and strong positive reaction for GFAP and caspase -3 reactions. Rats treated by Methotrexate and Lepidium Sativum showed nearly normal histological appearance of Purkinje cells with less vacuolated cytoplasm. This was confirmed by a significantrise in the number of Purkinje cells, significantdiminution in caspase-3 positive cells and in GFAP immunostaining.Conclusion:Lepidium Sativum aqueous extract ameliorates the neurotoxic effects of methotrexate. So, it is recommended to use Lepidium Sativum, whenever methotrexate treatment is needed.

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