Efficacy of silymarin on calprotectin and S100A12/EN-RAGE in chemotherapy-induced oral mucositis.

Abstract

Background: Oral mucositis (OM) is an oral complication of chemotherapy with agents such as 5-fluorouracil (5-FU). Silymarin (SM) has been utilized therapeutically as a cytoprotective medication.

Objectives: The aim of the study was to evaluate the efficacy of SM as a mucoprotective agent in the treatment of chemotherapy-induced oral mucositis (CIOM) induced by 5-FU, and to assess calprotectin (CP) and S100A12/EN-RAGE levels as novel biomarkers for the evaluation of mucositis.

Material and methods: Fifty Wistar albino rats of both sexes were divided randomly into 5 groups. Three groups were treated with different doses of SM (2 mg/kg, 4 mg/kg, 6 mg/kg) for 10 days. Subsequently, the animals from groups I-III received intraperitoneal injections of 5-FU (60 mg/kg) on days 11-14. The 4th group was treated with dimethyl sulfoxide (DMSO) as a control for 10 days, followed by 2 doses of 5-FU, and the 5th group served as a second control and received 5-FU only. The buccal mucosa of the animals was gently injured with a 0.8-mm orthodontic wire (2×6 strokes) under anesthesia. The efficacy of SM treatment on CP and S100A12/EN-RAGE levels in CIOM was evaluated. Macroscopic and histopathological findings were analyzed, and the correlation coefficients between the studied parameters were calculated.

Results: The study demonstrated a significant protective effect of SM in chemotherapy-induced buccal mucositis in a dose-dependent manner. Mucositis ulceration was not observed, in contrast to severe OM lesions noted in the control groups. Analysis using a 95% confidence interval (CI) showed highly significant differences between the groups regarding the levels of CP and S100A12/EN-RAGE, as well as very strong correlations with OM ulcers.

Conclusions: Based on the macroscopic and histopathological appearance, the study confirmed the dose-dependent protective efficacy of SM treatment in CIOM. In addition, the findings suggest a novel mucoprotective mechanism of SM mediated through its effects on CP and S100A12/EN-RAGE levels. A very strong positive correlation was found between plasma CP and S100A12/EN-RAGE levels and the presence of OM ulcers, suggesting that these biomarkers may be useful in the clinical assessment of CIOM.