Authors
Yu Min, Kun Gao, Yingtong Liu, Lei Dai, Xingchen Peng
Published in
MedComm. Volume 7. Issue 8. Pages e70862. Epub Jul 15, 2026.
Abstract
Radiotherapy for head and neck cancer commonly induces salivary gland dysfunction, resulting in xerostomia that substantially impairs quality of life after treatment. To identify protective strategies, we established the irradiation-induced submandibular glands (SMG) injury mice model and performed integrated proteomic and metabolomic profiling of gland tissue and saliva. Spermidine levels were significantly altered in irradiated SMG during the postradiotherapy recovery phase. Oral spermidine supplementation restored salivary flow, preserved acinar aquaporin-5 expression, and attenuated vacuolization, apoptosis, and fibrosis in vivo; these effects were validated in SMG organoids. Single-cell RNA transcriptomic analysis further showed that spermidine increased the proportion of acinar cells, enhanced Golgi-mediated secretory gene expression, and suppressed inflammatory cytokine signaling. In the randomized, double-blind, proof-of-concept clinical trial, oral spermidine supplementation during peri-radiotherapy significantly reduced the incidence of xerostomia at 3 months compared with placebo (48.28 vs. 79.31%, p = 0.0391), while increasing salivary output and improving quality of life without serious adverse events. These findings highlight the potential of spermidine as a safe, metabolite-based strategy for preserving salivary gland function and alleviating radiation-induced xerostomia. Clinical trial registration: The RCT has been registered in Clinical. gov (NCT07035626).
PMID:
42460130
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.
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