Alleviation of Splenic Injury by CB001 after Low-Dose Irradiation Mediated by NLRP3/Caspase-1-BAX/Caspase-3 Axis

Author:

Hu Changkun12,Liao Zebin2,Zhang Liangliang2,Ma Zengchun2,Xiao Chengrong2,Shao Shuai3,Gao Yue12

Affiliation:

1. a State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, P.R. China

2. b Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, P.R. China

3. c Institute of Radiation Protection and Nuclear Safety Medicine, Chinese Center for Disease Control and Prevention, Beijing, P.R. China

Abstract

Low-dose radiation has been extensively employed in clinical practice, including tumor immunotherapy, chronic inflammation treatment and nidus screening. However, the damage on the spleen caused by low-dose radiation significantly increases the risk of late infection-related mortality, and there is currently no corresponding protective strategy. In the present study, a novel compound preparation named CB001 mainly constituted of Acanthopanax senticosus (AS) and Oldenlandia diffusa (OD) was developed to alleviate splenic injury caused by fractionated low-dose exposures. As our results show that, white pulp atrophy and the excessive apoptosis in spleen tissue induced by radiation exposure were significantly ameliorated by CB001. Mechanistically, BAX-caspase-3 signaling and nucleotide-binding domain and leucine-rich-repeat-containing family pyrin 3 (NLRP3) inflammasome signaling were demonstrated to be involved in the radio-protective activity of CB001 with the selective activators. Furthermore, the crosstalk between apoptosis signaling and NLRP3 inflammasome signaling in mediating the radio-protective activity of CB001 was clarified, in which the pro-apoptotic protein BAX but not the anti-apoptotic protein Bcl2 was found to be downstream of NLRP3. Our study demonstrated that the use of a novel drug product CB001 can potentially facilitate the alleviation of radiation-induced splenic injury for patients receiving medical imaging diagnosis or fractionated radiation therapy.

Publisher

Radiation Research Society

Subject

Radiology, Nuclear Medicine and imaging,Radiation,Biophysics

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