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

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.

SUBMITTER: Mohammed AI

PROVIDER: S-EPMC10362044 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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

Mohammed Ali I AI Celentano Antonio A Paolini Rita R Low Jun T JT Silke John J O' Reilly Lorraine A LA McCullough Michael M Cirillo Nicola N

Cell death & disease 20230721 7

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 ...[more]

PMID: 37479691

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

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

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