Protective Role Of Alpha 2-Macroglobulin Against Jaw Osteoradionecrosis In A Preclinical Rat Model

Objective We have previously demonstrated the effect of alpha-2-macroglobulin (alpha 2M) in the remediation of radiation-induced cellular damage. Here, we investigated the protective effects of alpha 2M in a preclinical rat model of jaw osteoradionecrosis (ORN). Methods Eighteen rats were divided randomly into three groups: the control group, the radiation therapy (RT) alone group, and the radiated mandibles pretreated with alpha 2M (alpha 2M + RT) group. One month after radiation, all left molar teeth were extracted. After another 3 months, the animals were sacrificed and body weight, histopathology, microcomputed tomography and immunofluorescence were evaluated in all groups. Results The RT group showed serious alopecia, bone exposure, inflammation, necrosis, fibrosis, and the absence of new bone formation within the socket. The alpha 2M + RT group exhibited less alopecia than the RT group and slight inflammation and fibrosis in the bone marrow cavity. The cortical bone was similar to normal bone tissue. Interestingly, compared with RT group, serum superoxide dismutase levels in the alpha 2M + RT group increased at the 1th day (P = 0.037), 14th day (P = 0.012), while reactive oxygen species levels clearly decreased at the 1th day (P< 0.001), 14th day (P = 0.007), and 28th day (P = 0.013). Conclusions A clinically translational model of jaw ORN was successfully established and the application of alpha 2M prior to radiation protected the bone from being injured by the radiation, possibly related to oxidative stress.