1. Rapamycin alleviates irradiation‐induced parotid injury by enhancing the whole gland homeostasis.
- Author
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Zhu, Zhao, Song, Jiaxin, Zhang, Chunmei, Zhang, Jing, and Shan, Zhaochen
- Subjects
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PAROTID gland physiology , *SWINE , *HOMEOSTASIS , *AUTOPHAGY , *HEAD & neck cancer , *RADIATION injuries , *APOPTOSIS , *CELL physiology , *MESENCHYMAL stem cells , *REVERSE transcriptase polymerase chain reaction , *TUMOR markers , *DESCRIPTIVE statistics , *FIBROSIS , *GENE expression , *ANIMAL experimentation , *WESTERN immunoblotting , *STAINS & staining (Microscopy) , *INFLAMMATION , *DATA analysis software , *PAROTID glands , *RAPAMYCIN , *PHARMACODYNAMICS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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