Heavy-ion radiation received during radiotherapy as well as the heavy-ion radiation received during space flight are equally considered harmful. Our previous study showed that TLR4 low toxic agonist, monophosphoryl lipid A (MPLA), alleviated radiation injury resulting from exposure to low-LET radiation. However, the role and mechanism of MPLA in heavy-ion-radiation injury are unclear. This study aimed to investigate the role of MPLA on radiation damage. Our data showed that MPLA treatment alleviated the heavy-ion-induced damage to microstructure and the spleen and testis indexes. The number of karyocytes in the bone marrow from the MPLA-treated group was higher than that in the irradiated group. Meanwhile, western blotting analysis of intestine proteins showed that pro-apoptotic proteins (cleaved-caspase3 and Bax) were downregulated while anti-apoptotic proteins (Bcl-2) were upregulated in the MPLA-treated group. Our in vitro study demonstrated that MPLA significantly improved cell proliferation and inhibited cell apoptosis after irradiation. Moreover, immunofluorescence staining and quantification of nucleic γ-H2AX and 53BP1 foci also suggested that MPLA significantly attenuated cellular DNA damage repair. Collectively, the above evidence supports the potential ability of MPLA to protect against heavy-ion-radiation injury by inhibiting apoptosis and alleviating DNA damage in vivo and vitro, which could be a promising medical countermeasure for the prevention of heavy-ion-radiation injury.
TLR4 Agonist MPLA Ameliorates Heavy-Ion Radiation Damage via Regulating DNA Damage Repair and Apoptosis
Tingting Liu, Hang Wang, Hui Shen, Zhipeng Du, Zhijie Wan, Junshi Li, Xide Zhang, Zhuqing Li, Nan Yang, Yanyong Yang, Yuanyuan Chen, Fu Gao, Kun Cao; TLR4 Agonist MPLA Ameliorates Heavy-Ion Radiation Damage via Regulating DNA Damage Repair and Apoptosis. Radiat Res 1 August 2023; 200 (2): 127–138. doi: https://doi.org/10.1667/RADE-22-00200.1
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