An Engineered Biopolymer Prevents Mucositis Induced by 5-Fluorouracil in Hamsters

Abstract

Oral mucositis is a common, treatment-limiting, and costly side effect of cancer treatments whose biological underpinnings remain poorly understood. In this study, mucositis induced in hamsters by 5-fluorouracil (5-FU) was observed after cheek-pouch scarifications, with and without administration of RGTA (RG1503), a polymer engineered to mimic the protective effects of heparan sulfate. RG1503 had no effects on 5-FU-induced decreases in body weight, blood cell counts, or cheek-pouch and jejunum epithelium proliferation rates, suggesting absence of interference with the cytotoxic effects of 5-FU. Extensive mucositis occurred in all of the untreated animals, and consisted of severe damage to cheek pouch tissues (epithelium, underlying connective tissue, and muscle bundles). Only half of the RG1503-treated animals had mucositis, over a mean area 70% smaller than in the untreated animals. Basement membranes were almost completely destroyed in the untreated group but was preserved in the RG1503 group. Mucositis is a common and debilitating side effect of radiation therapy and chemotherapy for cancer.1 The lesions develop in the oral and gastrointestinal tract mucosae, most notably at nonkeratinized sites. Mucositis of the oral cavity affects the cheeks, lips, soft palate, ventral surface of the tongue, and mouth floor. The ulcerative lesions are painful, restrict food intake, and often act as a portal of entry for indigenous oral flora.2 Mucositis is a source of morbidity, adversely affects quality of life, and incurs substantial economic cost. The risk of mucositis is influenced by the diagnosis, patient age, pre-existing oral health, and type and frequency of treatment administration.3

A New Matrix Therapy Agent for Faster Corneal Healing and Less Ocular Discomfort Following Epi-off Accelerated Corneal Cross-linking in Progressive Keratoconus

“…RGTAs have been shown to modulate collagen synthesis in several cell culture and tissue explant models, as well as affect the enzymatic activities of various proteases involved in extracellular matrix remodeling. 12,23,24 Briefly, RGTA facilitates the healing of injured corneas via a reduction of proteolytic, oxidative, and nitrosative damage. 25 In the literature, in vivo and in vitro experimental models concluded that various RGTAs significantly improved the speed and quality of wound repair in different tissues such as skin and also decreased woundrelated pain.…”

Insights on a new path of pre-mitochondrial apoptosis regulation by a glycosaminoglycan mimetic

“…11,[15][16][17] RGTAs are characterized by their capacity to surrogate natural GAGs destroyed by glycanase activities during stress. As expected, the GAG-mimetic decreased lipid peroxidation of cell membranes and restored the activity of aconitase close to control level (Figure 1) indicating that, at low concentrations, L929 were used for their sensitivity to TNF-a mediated cytotoxicity.…”

“…[14][15][16][17] Therefore they were also named RGTA s for ReGeneraTing Agents. Here, we postulate that GAG-mimetics can participate to regulation of apoptosis in a mechanism implicating cathepsins activation and lysosomal membrane permeabilization.…”

Effect of Eriobotrya japonica Seed Extract on 5-Fluorouracil-Induced Mucositis in Hamsters

“…[20][21][22][23][24] In this model, mucositis was induced by scraping the oral mucosa after bone marrow suppression was induced by massive 5-FU administration. Therefore, it has been reported that the leukocyte count after 5-FU administration decreased.…”