A hyaluronic acid-based compound inhibits fibroblast senescence induced by oxidative stress in vitro and prevents oral mucositis in vivo

• Published in: Journal of cellular physiology 2015-07, Vol.230 (7), p.1421-1429
• Main Authors: Cirillo, Nicola, Vicidomini, Antonio, McCullough, Michael, Gambardella, Antonio, Hassona, Yazan, Prime, Stephen S., Colella, Giuseppe
• Format: Article
• Language: English
• Subjects: Aged; Amino acids; Antineoplastic Agents - adverse effects; Cell Movement - drug effects; Chemoradiotherapy - adverse effects; Chemotherapy; Cisplatin - administration & dosage; Cisplatin - therapeutic use; Doxorubicin - administration & dosage; Doxorubicin - therapeutic use; Female; Fibroblasts - drug effects; Humans; Hyaluronic Acid - analogs & derivatives; Hyaluronic Acid - chemistry; Hyaluronic Acid - pharmacology; Hydrogen peroxide; Keratinocytes - drug effects; Male; Middle Aged; Mouth Neoplasms - drug therapy; Mouth Neoplasms - radiotherapy; Oxidative Stress; Radiotherapy - adverse effects; Stomatitis - etiology; Stomatitis - prevention & control; Time Factors
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.24908

Virtually all patients receiving radio‐ and chemotherapy for cancer develop oral mucositis, a severe and highly debilitating condition. The onset of mucositis is thought to involve the production of reactive oxygen species (ROS) in the submucosa. Here we investigated a possible protective effect of a commercial formulation of hyaluronic acid (HA) enriched with amino acids (Mucosamin®) against the damage induced by oxidative stress both in vitro and in vivo. Transient exposure of normal human oral fibroblasts to hydrogen peroxide (H2O2) led to irreversible senescence, as demonstrated by sustained increase in the levels of p16INK4A and SA‐βGal. Conditioned media from senescent fibroblasts induced detrimental effects on keratinocytes, as shown by reduced metabolic activity and migration capability. Pre‐treatment with Mucosamin® prevented H2O2‐induced, but not TGF‐β‐induced, fibroblast senescence with a concomitant reduction of fibroblast‐induced loss of keratinocyte vitality and functional activity. Finally, data from a case‐series of patients undergoing radio/chemotherapy strongly suggested that prophylactic use of the hyaluronic acid‐based compound in the form of a spray may be effective in preventing the onset of oral mucositis. J. Cell. Physiol. 230: 1421–1429, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company