Copper chelation reduces early collagen deposition and preserves saliva secretion in irradiated salivary glands.

Autor:	Nam K; Christopher S. Bond Life Sciences Center, United States.; School of Medicine Department of Otolaryngology-Head and Neck Surgery, United States., Dos Santos HT; Christopher S. Bond Life Sciences Center, United States.; School of Medicine Department of Otolaryngology-Head and Neck Surgery, United States., Maslow FM; Christopher S. Bond Life Sciences Center, United States.; School of Medicine Department of Otolaryngology-Head and Neck Surgery, United States., Small T; Christopher S. Bond Life Sciences Center, United States.; School of Medicine Department of Otolaryngology-Head and Neck Surgery, United States., Shanbhag V; Christopher S. Bond Life Sciences Center, United States.; Department of Biochemistry, United States., Petris MJ; Christopher S. Bond Life Sciences Center, United States.; Department of Biochemistry, United States.; Department of Ophthalmology, University of Missouri, Columbia, MO, 65211, United States., Baker OJ; Christopher S. Bond Life Sciences Center, United States.; School of Medicine Department of Otolaryngology-Head and Neck Surgery, United States.; Department of Biochemistry, United States.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 Jan 11; Vol. 10 (2), pp. e24368. Date of Electronic Publication: 2024 Jan 11 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e24368
Abstrakt:	Radiation therapy is a first-line treatment for head and neck cancer; however, it typically leads to hyposalivation stemming from fibrosis of the salivary gland. Current strategies to restore glandular function are dependent on the presence of residual functional salivary gland tissue, a condition commonly not met in patients with extensive fibrotic coverage of the salivary gland resulting from radiation therapy. Fibrosis is defined by the pathological accumulation of connective tissue ( i.e., extracellular matrix) and excessive deposition of crosslinked (fibrillar) collagen that can impact a range of tissues and given that collagen crosslinking is necessary for fibrosis formation, inhibiting this process is a reasonable focus for developing anti-fibrotic therapies. Collagen crosslinking is catalyzed by the lysyl oxidase family of secreted copper-dependent metalloenzymes, and since that copper is an essential cofactor in all lysyl oxidase family members, we tested whether localized delivery of a copper chelator into the submandibular gland of irradiated mice could suppress collagen deposition and preserve the structure and function of this organ. Our results demonstrate that transdermal injection of tetrathiomolybdate into salivary glands significantly reduced the early deposition of fibrillar collagen in irradiated mice and preserved the integrity and function of submandibular gland epithelial tissue. Together, these studies identify copper metabolism as a novel therapeutic target to control radiation induced damage to the salivary gland and the current findings further indicate the therapeutic potential of repurposing clinically approved copper chelators as neoadjuvant treatments for radiation therapy. Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Olga J. Baker reports financial support was provided by 10.13039/100000072National Institute of Dental and Craniofacial Research, National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors.)
Databáze:	MEDLINE
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