Telmisartan Modulates the Oral Mucositis Induced by 5-Fluorouracil in Hamsters

Abstract

Oral mucositis (OM) is a common adverse effect resulting from cancer therapy. The OM it has implications that may compromise oncologic treatment and decrease the patient’s quality of life. The therapeutic options to prevent or treat the symptoms of OM are scarce; there is no effective therapy that improves the symptoms. Based on the need for further research for the treatment of OM, the present study objective was to evaluate the effect of telmisartan (TELM) on the OM induced by 5-fluorouracil (5-FU), using as animal model Golden Syrian hamsters. 5-FU followed by mechanical trauma on day 4 was used to induce OM in hamsters. Euthanasia occurred on the day 10. The experiments were constituted by the groups saline, mechanical trauma, 5-FU, and TELM in three doses (1, 5, or 10 mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The samples also were used for analysis enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reactions (qPCR). TELM (5 or 10 mg/kg) was able to reduce the inflammatory ulceration and infiltration in the oral mucosa of the animals, decreasing the levels of the cytokines TNF-α and IL-1β. These treatments was minimize the immunostaining for cyclooxygenase-2, matrix metalloproteinase-9, transforming growth factor-β, and smad 2/3. The nuclear transcription factor kappa B (NFκB) p65 and inducible nitric oxide synthase were reduced in the oral mucosa. Finally, TELM (10 mg/kg) increased the PPARγ gene expression and reduced STAT1 and NFκB p65 gene expression relative to the 5-FU group. Therefore, TELM prevents the OM produced by 5-FU on animal model.

Effect of Gold Nanoparticle on 5-Fluorouracil-Induced Experimental Oral Mucositis in Hamsters

“…Oral mucositis is induced with 5-fluorouracil (5-FU) followed by mechanical trauma (MT) [5,[22][23][24]. The induced mechanical trauma simulates irritating damages suffered by the oral mucosa of humans, which occur due to constant contact of the oral cavity with orthodontic appliances, maladaptive dental prostheses, and frequently used objects for hydration and feeding.…”

“…On day 10, the oral mucosa was exposed and clinically classified according to 6 score points: Score 0: Completely healthy mucosa, without erosion or vasodilation; score 1: The presence of erythema, with no evidence of mucosal erosion; score 2: Severe erythema, vasodilatation, and superficial erosion; score 3: Ulcer formation on one or more faces, affecting no more than 25% of the surface area of the mucosa, severe erythema, and vasodilation; score 4: Cumulative formation of ulcers, reaching about 50% of the surface area of the mucosa; and scale 5: Complete ulceration, making mucosal exposure impossible [5,25].…”

“…This method analyzes the gene expression of the sample in relation to the control (PVP group), using the Ct values. Expression data were standardized using the reference gene GADPH in formula 2-∆∆Ct [5,33].…”

“…The use of anti-inflammatory drugs for the prevention and treatment of oral mucositis has been extensively described in the literature [4][5][6]. Nuclear factor kappa B (NF-κB) is the most studied classical pathway involved in the pathophysiology of OM.…”

Mucoadhesive formulation containing Curcuma longa L. reduces oral mucositis induced by 5‐fluorouracil in hamsters

“…Among them, cryotherapy, recombinant human keratinocyte growth factor‐1 (KGF‐1/palifermin), low‐level laser therapy, and benzydamine mouthwash were reported. In addition, other anti‐inflammatory agents have also been studied in the management of OM (Barbosa et al, ). Herbal medicines have been considered as new modalities to be studied for the management of inflammatory conditions, including mucositis (Baharvand, Jafari, & Mortazavi, ; Cinausero et al, ), because they are safe, easily accessible, and inexpensive.…”