Underlying protective mechanism of α1-adrenoceptor activation against irradiation-induced damage in rat submandibular gland

Objectives: Damage to salivary gland after radiotherapy for head and neck malignant tumours can lead to irreversible oral complaints, which severely impair quality of life. The protective effect of alpha(1)-adrenoceptor activation on the salivary glands after irradiation has previously been demonstrated. However, the exact mechanism remains unclear. In this study, we investigated the underlying cytoprotective mechanism of alpha(1)-adrenoceptor activation in rat submandibular glands after irradiation. Study design: Rats were locally irradiated using a linear accelerator in the head and neck region with a dose of 20 Gy. After irradiation, phenylephrine (5 mg/kg) was injected intra-peritoneally for 7 successive days and the submandibular glands were then collected. The antiapoptotic effect of phenylephrine on the gland was examined by TUNEL, the proliferative cellular nuclei antigen (PCNA) was determined by immunohistochemistry, and the activation of c-Jun N-terminal kinase (INK) was detected by Western blot. Results: The irradiation only group showed severe atrophy, increased apoptosis, enhanced cell proliferation, and the phosphorylation of JNK was markedly increased by 26.89% (P < 0.05), compared to the control. The phenylephrine-treated group, however, showed remarkably alleviated atrophy, decreased apoptosis, and further increased cell proliferation, and the phosphorylation of JNK was markedly decreased by 36.00% (P < 0.05), compared to the irradiation only group. Conclusions: The data showed that the underlying protective mechanism of alpha(1)-adrenoceptor activation in irradiated gland might be related to improved cell proliferation, inhibited cell apoptosis, and depressed activation of JNK. It could be helpful in protecting salivary glands against irradiation damage. (C) 2013 Elsevier Ltd. All rights reserved.