Abrogation of 5-Fluorouracil (5-FU) Induced Myelosuppression Model in Sprague Dawley Rats by Carvedilol and Vitamin D as Monotherapy or Double Therapy

Abstract

Myelosuppression is the most common and seriousside effect of chemotherapy. Oxidative stress, inflammation, and apoptosis are the primary cause of toxicity.This study was designed to evaluate and compare effects of carvedilol and vitamin D when used either alone or together for the abrogation of 5-fluorouracil (5-FU) induced myelosuppression. Carvedilol and vitamin D effects on myelosuppression were not assessed before.This study was carried out on 50 female Sprague Dawley rats divided into five equal groups. The bodyweight and blood film were assessed weekly, vitamin D levels wereassessed at the start and at the end. At the end of the experiment, blood was collected to perform complete blood count(CBC) and assessreduced glutathione (GSH), malondialdehyde (MDA) and tumor necrosis factor alpha (TNFα).The right femurs and tibiae were processed for examination of histopathological changes and immunohistochemistry of Bcl-2, while left femurs and tibiae were prepared for bone marrow cell count.Combination of both carvedilol and vitamin D provide a significant decrease in MDA, TNF α and a significant increase in GSH, Bcl-2 expression, with significant improvement in CBC, bone marrow cell count and histopathological finding when compared to other groups.Carvedilol and vitamin D were found to be promising candidates for the abrogation of 5-Fu inducedmyelosuppression. Their combination is superior to treatment by each one alone.