Chemoprotective effect of ascorbic acid on cyclophosphomide induced oral toxicity

Abstract

Background and objective: Oral mucositis is currently considered to be the most severe complication of anticancer therapy such as cyclophosphamide (CTX). Ascorbic acid is a well-known antioxidant, which can protect the body from damage caused by free radicals that can be generated during normal metabolism as well as through exposure to toxins and carcinogens. This study aimed to evaluate the effectiveness of ascorbic acid as a treatment for CTX induced oral mucositis. Methods: Forty Wister-albino rats, age about 6-8 weeks and weighing 150-200 g were used. The rats were randomly divided by simple random allocation into two groups (20 animals each). The control group was intraperitoneally injected with physiological saline and the animals were grouped randomly into two groups: Saline/Water treated group which were daily received intraperitoneal injection of distilled water, while the Saline/Ascorbic acid treated group received a daily intraperitoneal injection of ascorbic acid (12mg/kg/day). For the induction of mucositis, a single dose (300 mg/kg) of CTX was administered intraperitoneally to each animal in the study group, and the animals were grouped randomly into two groups: CTX /Water treated group which was daily received intraperitoneal injection of distilled water, while the CTX /Ascorbic acid treated group were daily received intraperitoneal injection of 12 mg/kg /day of ascorbic acid. The animals were sacrificed at day four and eight (five animals each) and the tongue was dissected from the jaw for histological and immunohistochemical analysis.Results: Ascorbic acid decreased the severity of the induced CTX oral mucositis by a significant increase in epithelial thickness, significant decrease in damage score, and significant increase in PCNA immune expression at day four and eight respectively (P <0.05). Conclusion: CTX chemotherapy has a deleterious effect on the oral mucosa leading to marked morphometric and microscopic changes. Ascorbic acid can protect the oral mucosa from CTX-induced cytotoxicity, and attenuate or decrease the associated injury.