Abstract
Radioiodine (RI) therapy is known to cause salivary gland (SG) dysfunction. The effects of antioxidants on RI-induced SG damage have not been well described. This study was performed to investigate the radioprotective effects of alpha lipoic acid (ALA) administered prior to RI therapy in a mouse model of RI-induced sialadenitis. Four-week-old female C57BL/6 mice were divided into four groups (n = 10 per group): group I, normal control; group II, ALA alone (100 mg/kg); group III, RI alone (0.01 mCi/g body weight, orally); and group IV, ALA + RI (ALA at 100 mg/kg, 24 h and 30 min before RI exposure at 0.01 mCi/g body weight). The animals in these groups were divided into two subgroups and euthanized at 30 or 90 days post-RI treatment. Changes in salivary 99mTc pertechnetate uptake and excretion were tracked by single-photon emission computed tomography. Salivary histological examinations and TUNEL assays were performed. The 99mTc pertechnetate excretion level recovered in the ALA treatment group. Salivary epithelial (aquaporin 5) cells of the ALA + RI group were protected from RI damage. The ALA + RI group exhibited more mucin-containing parenchyma and less fibrotic tissues than the RI only group. Fewer apoptotic cells were observed in the ALA + RI group compared to the RI only group. Pretreatment with ALA before RI therapy is potentially beneficial in protecting against RI-induced salivary dysfunction.
Highlights
The standard treatment for differentiated thyroid cancer is thyroidectomy followed by high-dose radioiodine (RI) treatment to completely ablate thyroid remnants
The mean body weight of the RI-treated mice group was significantly lower than the control group at 90 days, while the weight in the RI +alpha lipoic acid (ALA) and ALA groups were similar to the control group (Figure 1A)
The salivary lag time improved in the RI + ALA group compared to the RI only group at 90 days post treatment (Figure 1C)
Summary
The standard treatment for differentiated thyroid cancer is thyroidectomy followed by high-dose radioiodine (RI) treatment to completely ablate thyroid remnants. SGs are known to exhibit irreversible radiation-induced damage—such as sialoadenitis, xerostomia, and neoplasia—as seen in patients with differentiated thyroid cancer after high-dose RI therapy [2,3]. High-dose RI treatment is regularly performed under SG stimulation to minimize SG dysfunction, this treatment has shown only limited success [4,5]. The acinar and ductal cells in the SG are damaged by RI. Amifostine is the only drug reported to date that is capable of reducing the side effects of ionizing radiation in SGs, and the US FDA has approved its clinical use as a radioprotector [7]. Research is underway regarding the protection of SGs after RI therapy, ideal radioprotective agents have yet to be found
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