Efeito da clorexidina, iodopovidona e eritromicina na mucosite oral e no reparo de úlceras traumáticas induzidas na língua de ratos submetidos à quimioterapia: avaliação clínica, histológica e bioquímica

Abstract

Oral mucositis is an important and frequent adverse event associated with cancer treatment. This condition presents high morbidity and may lead to the suspension of cancer treatment, negatively interfering with the patient's prognosis. Management includes therapeutic interventions for the prevention or treatment of oral mucositis. Thus, in the first article of this thesis, we reviewed the literature on the pathobiology of oral mucositis and the properties of erythromycin, to consider the possibility of its use for the prevention and treatment of oral mucositis. Erythromycin has particular characteristics, independent of its antimicrobial effect, which can limit oxidative stress, the activation of nuclear transcription factors and suppress the production of several pro-inflammatory cytokines that are directly associated with oral mucositis. However, there are no studies in the literature, so far, related to the use of this macrolide for the management of oral lesions secondary to anticancer therapy. The second article deals with an experimental study developed in an animal model, with the objective of evaluating the topical effect of 0.12% chlorhexidine, 10% povidone-iodine and 50% erythromycin, on oral mucositis and on the healing of traumatic ulcers made on the ventral surface of the tongue of rats undergoing chemotherapy by means of clinical, histological and biochemical analysis. Seventy-seven Wistar rats were randomly divided into five groups: control (n = 13), 5-FU (n = 16), chlorhexidine (n = 16), povidone-iodine (n = 16) and erythromycin (n = 16). Oral mucositis was induced with two intraperitoneal injections of 5-fluorouracil, performed on the first and third day of the experiment. On the 4th day, an ulcer 5 mm in diameter was produced on the ventral surface of the tongue of each animal. After 24 hours, the rats received topical application of the substances twice a day. On the 10th day, the animals were euthanized. Clinical, histological and biochemical evaluation was carried out. During of experiment, eight rats died. The control showed the least area of residual ulcer (p ≤ 0.01) and lowest inflammation scores (p = 0.027). The erythromycin group displayed the lowest incidence of OM (p = 0.046). In the histological analysis, the area of newly formed epithelium in the control was significantly greater (p < 0.05). Among the animals undergoing chemotherapy with 5-fluorouracil, the erythromycin group showed the highest values for newly formed epithelial area (p = 0.05) and lowest expression levels of interleukin 6 and tumor necrosis factor-α (p < 0.01). In the biochemical analysis of catalase and reduced glutathione, there was no significant difference between the groups. Topical erythromycin exhibited positive effects on the clinical and histopathological status of oral mucositis induced by 5-fluorouracil in rats. However, more clinical studies are needed to evaluate the effect of erythromycin on the oral mucosa in humans.