Rapamycin enhances whole gland homeostasis and alleviates irradiation-induced parotid injury: Study

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

Reference:

Zhu, Z., Song, J., Zhang, C., Zhang, J., & Shan, Z. (2024). Rapamycin alleviates irradiation-induced parotid injury by enhancing the whole gland homeostasis. Oral Diseases, 30, 5050–5061. https://doi.org/10.1111/odi.14948