Objective::To investigate the effects of lactoferrin (Lf) on hepatic pyroptosis (an inflammatory form of programmed cell death) in mice exposed to radiation.Methods::A total of thirty-six BALB/c male mice were randomly divided into four groups, namely the control group, 5 Gy group, 5 Gy + 2 mg Lf group, and 5 Gy + 4 mg Lf group. The mice were administered whole-body ionizing radiation using a PRIMUS accelerator, with a single dose of 5 Gy and an absorbed dose rate of 2.0 Gy/min at a source-skin distance of 100 cm. Lf solution was intraperitoneally injected into the mice 2 h before and per day after radiation. The mice were sacrificed 1, 3, and 9 d after radiation, and their livers were used for histopathologic examination, immunohistochemistry analysis, and Western blot analysis for absent in melanoma 2 (AIM2) inflammasome pathway.Results::Histopathologic examination showed the disorder of the hepatocellular structure and the accumulation of inflammatory cells after radiation. Lf intervention inhibited hepatocellular proliferation and decreased the infiltration of inflammatory cells. Immunohistochemistry analysis indicated that AIM2 overexpression was significantly attenuated by 4 mg of Lf ( t =3.065, P < 0.05) 3 d after radiation and by 2 mg and 4 mg of Lf ( t= 4.032, t =2.786, P < 0.05) 9 d after radiation. Western blot analysis showed that Lf downregulated the hepatic overexpression of AIM2, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), IL-1β, and IL-18. 2 mg of Lf significantly downregulated the abovementioned protein expression 3 d ( t =7.934, 4.092, 5.193, 2.916, P < 0.05) and 9 d after radiation ( t=5.016, 3.882, 9.528, P < 0.05 for AIM2, ASC, IL-1β). Conclusions::Lf intervention suppressed the hepatic pyroptosis in mice exposed to ionizing radiation by down-regulating the protein expression of AIM2 inflammasome.

Lactoferrin;Irradiation;Liver;Pyroptosis;Absent in melanoma 2 (AIM2)

Zhang Ru;Gu Jia;Wei Yulu;Guo Yaxing;Qin Liqiang;Xu Jiaying

Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou 215123, China;Suzhou National High-tech District Center for Disease Prevention and Control, Suzhou 215011, China;State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China

放射医学与防护（英文）

[1]Zhang Ru;Gu Jia;Wei Yulu;Guo Yaxing;Qin Liqiang;Xu Jiaying-.Lactoferrin improves hepatic pyroptosis in mice after irradiation)[J].放射医学与防护（英文）,2022(01):16-21

Lactoferrin,PRIMUS,Histopathologic

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