Protective Role of α2‐Macroglobulin against Jaw Osteoradionecrosis in a Preclinical Rat Model

Abstract

Objective

We have previously demonstrated the effect of alpha‐2‐macroglobulin (α2M) in the remediation of radiation‐induced cellular damage. Here, we investigated the protective effects of α2M 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 α2M (α2M + RT) group. One month after radiation, all left molar teeth were extracted. After another three 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 absence of new bone formation within the socket. The α2M + 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 α2M + RT group increased at the 1^th day (p= 0.037), 14^th day (p= 0.012), while reactive oxygen species levels clearly decreased at the 1^th day (p< 0.001), 14^th day (p= 0.007), and 28^th day (p= 0.013).

Conclusions

A clinically translational model of jaw ORN was successfully established and the application of α2M prior to radiation protected the bone from being injured by the radiation, possibly related to oxidative stress.

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