Efeito protetor da l-cisteína exógena no modelo de mucosite oral induzido por 5-fluorouracil em hamsters golden syrian (Mesocricetus auratus)

Abstract

Mucositis is an inflammation that occurs in the lining of the oral cavity resulting from the cytotoxic effect of 5-Fluorouracil (5-FU) treatment. There are studies that show that, through the administration of L-Cysteine, the production of Hydrogen Sulphide (H2S) occurs, having gastroprotective, anti-inflammatory and cicatricial action. In view of these properties, the objective of this research was to investigate the protective effect of L-cysteine on the oral mucositis model induced by 5-FU in hamsters. We selected 30 hamsters divided into 5 groups (n = 6): (Normal, received 0.9% saline solution, i.p), (Mechanical Trauma); (5- (FU)); (L-cysteine 10mg); (L-cysteine 40mg) and NaHs (27μg) (these received doses of 60 and 40 mg / kg of 5-FU on days 1 and 2, and on the 4

th day the right oral mucosa was excoriated in the 5th and 6th animals received L- cysteine intraperitoneally at concentrations of 10, 40, 27 mg, μg / kg, respectively).

Macroscopic, histological, survival, weight, dermal thickness, mast cell counts, MDA, GSH, MPO, Nitrite / Nitrate, collagen percentage, Cox2 immunohistochemistry and H2S levels were evaluated. It was observed that L-cysteine at doses of 10 and 40 mg / kg were able to prevent and reverse the changes promoted by 5-FU. Therefore, the elective L-cysteine dose was 40 mg / kg because it showed a significant increase in the thickness of the dermis, collagen percentage, decreased levels of: MDA, GSH, MPO and increased levels of GSH and H2S when compared to 5-FU group (p <0.005). Concerning Cox2 levels in the 40 mg / kg L-cysteine group, a statistically significant (p <0.005) decrease in Cox2 immunolabeling was observed when compared to the 5-FU group, as well as the decrease in the number of mast cells (p <0.005). Thus, our results suggest that L- cysteine may probably be an enzymatic substrate, which increases the endogenous production of H2S that has anti-inflammatory and antioxidant action against 5-FU injury.