Histological and Immunohistochemical analysis of possible ameliorative effect of Ashwagandha on Methotrexate-Induced Oral Mucositis in Albino Rats

Abstract

Introduction: Oral mucositis is a common side effect of methotrexate chemotherapy; it represents a challenge for a successful cancer treatment, as it may lead to discontinuity of the chemotherapy. Ashwagandha is one of the most familiar Ayurveda herbs in India. Recently, it has gained attention due to its favorable biological effects. Aim: Investigation of the possible protective effect of Ashwagandha roots extract on methotrexate-induced oral mucositis in albino rats. Materials and methods: 40 rats were divided equally into 4 groups: (C): received distilled water, (ASH): received 300mg/kg ashwagandha root extract for 8 days, (MTX): received single dose of 60 mg/kg intraperitoneal injection of methotrexate on day 4, and (MTX/ASH): received 300mg/kg ashwagandha root extract daily for 8 days interrupted with 60 mg/kg i.p injection of methotrexate on day 4. Results: Histopathological examination revealed normal appearance of tongue and buccal mucosa in C and ASH groups. In MTX group there was atrophy of tongue papilla, decrease of epithelial thickness, flattening of rete pegs, nuclear pyknosis, nuclear hyperchromatism, karyorrhexis, disruption of basement membrane, inflammatory cells infiltrate, blood vessels congestion, muscle atrophy in both mucosae. In MTX/ASH group, both mucosae maintained normal appearance. Immunohistochemical results revealed significant decrease of Ki67 staining in MTX group compared to C and MTX/ASH groups in both mucosae, COX2 staining revealed significant increase in MTX group compared to C and MTX/ASH groups. Conclusion: Prophylactic administration of Ashwagandha root extract ameliorated the oral mucositis induced by methotrexate chemotherapy, therefore it could be a good adjuvant therapy during chemotherapeutic treatment.