The Effect of 5-Fluorouracil on the tongue mucosa of adult male albino rat and the possible protective role of melatonin: A light and scanning electron microscopic study

Abstract

Background:5-Fluorouracil(5-FU)is a common anti-tumor drug that is used in the management of different forms of malignancies. Mucosal inflammation of the oral cavity is the most common adverse effect of its administration. Melatonin has valuable activities like antioxidant and anti-inflammatory effects. Melatonin has protective effects on different organs against various side effects caused by anti-cancer treatments.Aim: To evaluate the protective effect of melatonin against 5-fluorouracil –induced changes in the tongue mucosa of rats using different histological techniques.Materials and Methods: Forty adult male rats were randomly divided into four main groups: group I acted as control, group II was given melatonin at a dose 10 mg/kg/day, group III was given 5-FU at a dose 60 mg/kg on day 0 and 40 mg/kg on day 2, and group IV was given melatonin one hour before 5-FU administration. The specimens of the tongue were processed for light and scanning electron microscopic study. Immunohistochemical study was done by employing the nuclear marker for proliferation of the cells(Ki67)antibody.Results: 5-FU induced structural changes in the tongue mucosa in the form of focal loss of lingual papillae, marked thinning and shortening of the filiform papillae, separation of the keratin layer from the underlying epithelium, vacuolated cytoplasm of the basal and suprabasal epithelial cells, and congestion of blood vessels with cellular infilteration in the lamina propria. A significant decrease in the papillae height, papillae width, ventral epithelial thickness, and percentage of Ki67 immunopositive cells were also detected. Scanning electron microscopy exhibited atrophy of the filiform papillae with desquamation of their epithelial covering. Deformed fungiform papillae with ill-defined taste pores were also revealed. On the other hand, these changes were less pronounced in rats received melatonin before 5-FU administration. Conclusion: 5-FU induced significant structural changes in the tongue mucosa of albino rats. Melatonin attenuated these mucosal changes.