Rapamycin alleviates irradiation-induced parotid injury by enhancing the whole gland homeostasis

© 2024 Wiley Periodicals LLC..

OBJECTIVES: Salivary gland injury is one of the most common complications of radiotherapy in head-and-neck cancers. This study investigated the mechanism by which rapamycin prevents irradiation (IR)-induced injury in the parotid glands.

MATERIALS AND METHODS: Miniature pigs either received (a) no treatment (NT), (b) IR in the right parotid gland for 5 consecutive days (IR), or intraperitoneal administration of rapamycin (Rap) 1 h prior to IR (IR + Rap). Tissues were collected at three distinct time points (24 h, 4 weeks, and 16 weeks) after IR. Histological analyses, western blot, and real-time reverse transcriptase-polymerase chain reaction were performed to explore the mechanisms of IR-induced injury in the parotid gland.

RESULTS: Rapamycin treatment maintained parotid salivary flow 16 weeks post-IR, preserved the number of acinar cells, and reduced parotid tissue fibrosis, as well as reduced apoptosis levels, decreased cleaved caspase-3 expression, and increased the Bcl-2/Bax ratio in the parotid glands. Autophagy marker LC3B was upregulated by rapamycin after IR, while P62 expression was downregulated. Rapamycin reduced the expression of pro-inflammatory factors and the mesenchymal tissue fibrosis following IR.

CONCLUSIONS: Rapamycin maintains gland homeostasis after IR by decreasing apoptosis, reducing the expression of pro-inflammatory factors, and enhancing autophagy.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

Oral diseases - (2024) vom: 03. Apr.

Sprache:

Englisch

Beteiligte Personen:

Zhu, Zhao [VerfasserIn]
Song, Jiaxin [VerfasserIn]
Zhang, Chunmei [VerfasserIn]
Zhang, Jing [VerfasserIn]
Shan, Zhaochen [VerfasserIn]

Links:

Volltext

Themen:

Acinar cells
Head‐and‐neck cancers
Homeostasis
Irradiation
Journal Article
Parotid
Rapamycin

Anmerkungen:

Date Revised 03.04.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.1111/odi.14948

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM370585011