Avaliação do efeito de polifenóis derivados da Olea Europaea L. na prevenção e tratamento da mucosite oral induzida por quimioterapia em camundongos

Abstract

Oral mucositis (OM) is an acute and frequent adverse effect of antineoplastic therapy. This disorder deserves significant attention, as it affects the quality of life of patients and can become a limiting factor to treatment. Management of OM includes therapeutic interventions aimed at preventing and treating injuries. In the first article of this dissertation, a literature review was carried out, investigating the properties of polyphenols derived from Olea Europaea L. and their potential for the treatment of OM. Studies have shown that oleuropein, hydroxytyrosol (HT) and tyrosol modulate the release of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and cyclooxygenase-2 (COX-2), which are directly associated with development inflammatory diseases. In addition, polyphenols showed antioxidant and antimicrobial activity, demonstrated in vitro and in vivo. The second article describes an experimental study that evaluated the topical and systemic effect of HT in ulcerated lesions, mechanically induced on the tongue of mice treated with 5-fluourouracil (5-FU). Fifty-nine male mice received injections of 5-FU (days 0, 2 and 4), in addition to trauma to the ventral toungue (bottom surface of the tongue) (days 3, 4 and 5). All groups, except the control, were treated with 5-FU. The animals received the respective treatments, daily, according to the distribution of the groups: control group (saline), group 5-FU (saline), glycerin group (topically applied glycerin, and saline), systemic HT group (hydroxytyrosol 10 mg/kg), Oli Ola® group (3% hydroxytyrosol, 10mg/kg) and topical HT group (5% concentration, applied in topical form). The animals were euthanized after nine days of treatment. Clinical and histological analyzes of the oral mucosa were performed, in addition to evaluation of the myeloperoxidase (in the intenstine) and glutathione (in the liver) enzymes. The weight of the systemic HT group was significantly lower (P = 0.000) than that of the control group at the end of the study. In the clinical evaluation of the oral mucosa, no clinical signs of oral mucositis were observed and the ulcerated lesions were healed. In the histological evaluation of the tongue, in previously ulcerated regions, there was no difference between the groups regarding the inflammation scores (P = 0.139). The group that received treatment with HT in topical form presented all epithelialized samples, differing significantly from the group 5-FU (P = 0.012). The levels of the myeloperoxidase and glutathione enzymes did not differ significantly between the groups (P = 0.837 and 0.748, respectively). This study demonstrated that treatment with HT did not have positive effects on the healing of ulcerated oral lesions in animals treated with 5-FU. The HT did not reduce the intensity of the inflammatory process in the lesions, nor did it alter markers of intestinal inflammation or oxidative stress in the model used. In topical form, HT had a beneficial effect on the epithelial tissue, favoring the epithelialization of wounds. It is suggested to investigate this substance in topical form in other models of oral mucositis.