Empagliflozin attenuates radiation-induced hematopoietic damage via NOX-4/ROS/p38 pathway.

Autor: Huo Q; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China., Yue T; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China., Li W; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China., Wang X; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China., Dong Y; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China. Electronic address: dongyinping@irm-cams.ac.cn., Li D; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China. Electronic address: lideguan@irm-cams.ac.cn.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2024 Mar 15; Vol. 341, pp. 122486. Date of Electronic Publication: 2024 Feb 06.
DOI: 10.1016/j.lfs.2024.122486
Abstrakt: Purpose: Damage to the hematopoietic system and functional inhibition are severe consequences of radiation exposure. In this study, we have investigated the effect of empagliflozin on radiation-induced hematopoietic damage, with the aim of providing new preventive approach to such injuries.
Methods and Materials: Mice were given 4 Gy total body irradiation (TBI) 1 h after the oral administration of empagliflozin, followed by the continuous administration of the same dose of empagliflozin for 6d, and then sacrificed on the 10th day after irradiation. The reactive oxygen species (ROS) levels in hematopoietic cells and their regulatory mechanisms were also been investigated. Colony forming unit granulocyte macrophage assay and bone marrow transplantation assays were performed to detect the function of the bone marrow cells.
Key Findings: Empagliflozin increased the cell viability, reduced ROS levels, and attenuated apoptosis in vitro after the bone marrow cells were exposed to 1 Gy radiation. Empagliflozin significantly attenuated ionizing radiation injuries to the hematopoietic system, increased the peripheral blood cell count, and enhanced the proportion and function of hematopoietic stem cells in mice exposed to 4 Gy TBI. These effects may be related to the NOX-4/ROS/p38 pathway-mediated suppression of MAPK in hematopoietic stem cells. Empagliflozin also influenced the expression of Nrf-2 and increased glutathione peroxidase activity, thereby promoting the clearance of reactive oxygen species. Furthermore, empagliflozin mitigated metabolic abnormalities by inhibiting the mammalian target of rapamycin.
Significance: Our study has demonstrated that empagliflozin can reduce radiation-induced injury in hematopoietic stem cells. This finding suggests that empagliflozin is a promising novel agent for preventing radiation-induced damage to the hematopoietic system.
Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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