High molecular weight hyaluronic acid drastically reduces chemotherapy-induced mucositis and apoptotic cell death

Mohammed, AI; Celentano, A; Paolini, R; Low, JT; Silke, J; O&#39; Reilly LA; McCullough, M; Cirillo, N

Author(s): Mohammed, AI; Celentano, A; Paolini, R; Low, JT; Silke, J; O' Reilly LA; McCullough, M; Cirillo, N;
Details: Publication Year 2023-07-21,Volume 14,Issue #7,Page 453
Journal Title: Cell Death & Disease
Abstract: Oral and intestinal mucositis (OIM) are debilitating inflammatory diseases initiated by oxidative stress, resulting in epithelial cell death and are frequently observed in cancer patients undergoing chemo-radiotherapy. There are currently few preventative strategies for this debilitating condition. Therefore, the development of a safe and effective mucositis mitigating strategy is an unmet medical need. Hyaluronic acid (HA) preparations have been tentatively used in oral mucositis. However, the protective effects of HA in chemotherapy-induced mucositis and their underlying mechanisms remain to be fully elucidated. This study aimed to assess these mechanisms using multiple formulations of enriched HA (Mucosamin(®)), cross-linked (xl-), and non-crosslinked high molecular weight HA (H-MW-HA) in an oxidative stress-induced model of human oral mucosal injury in vitro and an in vivo murine model of 5-flurouracil (5-FU)-induced oral/intestinal mucositis. All tested HA formulations protected against oxidative stress-induced damage in vitro without inducing cytotoxicity, with H-MW-HA also significantly reducing ROS production. Daily supplementation with H-MW-HA in vivo drastically reduced the severity of 5-FU-induced OIM, prevented apoptotic damage and reduced COX-2 enzyme activity in both the oral and intestinal epithelium. In 5-FU-injected mice, HA supplementation also significantly reduced serum levels of IL-6 and the chemokine CXCL1/KC, while the serum antioxidant activity of superoxide dismutase was elevated. Our data suggest that H-MW-HA attenuates 5-FU-induced OIM, at least partly, by impeding apoptosis, inhibiting of oxidative stress and suppressing inflammatory cytokines. This study supports the development of H-MW-HA preparations for preventing OIM in patients receiving chemotherapy.
Publisher: NPG
Research Division(s): Inflammation
PubMed ID: 37479691
Publisher's Version: https://doi.org/10.1038/s41419-023-05934-6
Open Access at Publisher's Site: https://doi.org/10.1038/s41419-023-05934-6
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: s41419-023-05934-6.pdf - (6.11MB, application/pdf)

Creation Date: 2023-08-04 12:44:07

Last Modified: 2023-08-04 01:30:58