Mechanism of the protective effect of phenylephrine pretreatment against irradiation-induced damage in the submandibular gland

Irradiation is a fundamental treatment modality for head and neck malignancies. However, a significant drawback of irradiation treatment is the irreversible damage to salivary glands in the radiation field. Although the protective effect of phenylephrine pretreatment on salivary glands following irradiation has previously been demonstrated, the exact mechanism remains unclear. In this study, we investigated the cytoprotective mechanisms of phenylephrine pretreatment in rat submandibular glands following irradiation. Rats were locally irradiated using a linear accelerator in the head and neck region with a single dose of 20 Gy. Phenylephrine (5 mg/kg) was injected intraperitoneally 30 min prior to irradiation and the submandibular glands were collected on day 7 after irradiation. In comparison with the control group, the irradiation-only group demonstrated severe atrophy, enhanced cell proliferation and increased apoptosis. The phenylephrine-pretreated group, however, demonstrated markedly alleviated atrophy, further increased cell proliferation and decreased apoptosis compared with the irradiation-only group. The data indicated that the cytoprotective mechanisms of phenylephrine pretreatment in the submandibular gland following irradiation may be related to improved cell proliferation and inhibition of cell apoptosis.