Mechanism of the prevention effect of a free radical scavenger, Tempol, on radiation-induced dysfunction in the submandibular gland of mouse

Objective: To explore the possible mechanism of the prevention effect of Tempol (TPL) on radiation-induced submandibular gland dysfunction using a C57bl/6 mouse model. Methods: One-hundred twenty male C57bl/6 mice were randomly divided into six groups: blank control group, radiation group, 25 mg/kg TPL group, 200 mg/kg TPL group, 25 mg/kg TPL+ radiation group and 200 mg/kg TPL+ radiation group. 25 mg/kg and 200 mg/kg TPL was injected to mice enterocoelia 10 min before 15 Gy X-ray radiation. Survival rate and weight change of the mice were observed 30 d after radiation. Salivary flow rate and mandibular gland apoptosis were detected at 3 and 30 d after radiation. Total superoxide dismutase activity, total glutathione and malondialdehyde content and Bcl-2, Bax, Caspase 3 expression levels were detected at 3 d after radiation. Results: Salivary flow rates at 3 and 30 days in the radiation group were 5.67±1.05 and 5.27±1.34, lower than that of 200 mg/kg TPL + radiation group (13.12±1.17, 13.09±2.71) significantly (F = 226.4, 215.3, P < 0.05) but had no significant difference (P > 0.05) compared with 25 mg/kg TPL + radiation group (6.44±1.09, 5.48±1.79). Pretreatment of mice with 200 mg/kg TPL could reduce radiation induced apoptosis and the content of MDA in tissue but increased the GSH content. The TPL also increased the activity of SOD, the expression of Bcl-2 protein level, but reduced the levels of Bax and cleaved Caspase-3 protein. Conclusions: 200 mg/kg TPL could protect C57bl/6 mice salivary glands from radiation injury probably by alleviating oxidative stress and regulating the mitochondrial pathway of apoptosis except 25 mg/kg TPL. (authors)