Protective effect of adenosine triphosphate against cisplatin-induced necrotic and degenerative oral mucositis in rats

Abstract

Inflammation, oxidative damage, and adenosine triphosphate (ATP) depletion play a role in the pathogenesis of cisplatin (CIS)-induced oral mucositis. Objective:  The purpose of this research is to examine the impact of ATP against potential oral mucositis development in cisplatin-treated rats. Methodology All rats were randomly assigned to four groups, namely healthy control group (HG), ATP group (ATPG), Cisplatin group (CISG), and ATP + Cisplatin group (ATCS). Firstly, ATP 4 mg/kg was administered via intraperitoneal injection (IP) to both ATPG and ATCS groups. The same volume of normal saline was injected into HG and CISG groups. After 1 h, cisplatin 5 mg/kg was administered via IP to CISG and ATCS groups. The drugs were taken 1x1 for 7 d. Later, tongue tissues were collected from all groups. Biochemical, macroscopic, and histopathological examinations were performed on all tissues. Results:  ATP inhibited cisplatin-induced oxidative damage and pro-inflammatory cytokines levels in tongue tissue. In the CIS group, a significant number of distinct sulcus formations were found in the apex and corpus, as well as a few ulcer foci in the corpus, significant papilla loss, and bleeding. Meanwhile, in the ATP group, a similar appearance to healthy tissue was observed. Histopathologically, it was determined that in cisplatin-aggravated tongue tissue damage, filiform papillae decreased when ATP was administered, and the arrangement and structures of the epithelium, blood capillaries, muscle groups, and adipose cell groups were normal. Conclusions:  Oral mucositis caused by cisplatin is alleviated by ATP. These findings may be useful for developing new therapeutic approaches to prevent or treat mucositis, a side effect so severe that can lead to treatment discontinuation.