Mitigating Effects of 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) on Hematopoietic Acute Radiation Syndrome after Total-Body Ionizing Irradiation in Mice

Abstract

Acute radiation syndrome (ARS) occurs as a result of partial-or whole-body, high-dose exposure to radiation in a very short period of time. Survival is dependent on the severity of the hematopoietic sub-syndrome of ARS. In this study, we investigated the mitigating effects of a lipid molecule, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), on the kinetics of hematopoietic cells, including absolute neutrophil count (ANC), red blood cells (RBCs) and platelet counts, in mice after gamma-ray total-body irradiation (TBI). Male and female BALB/c mice (11 weeks old) received a LD 70/30 dose of TBI. PLAG significantly and dosedependently attenuated radiation-induced mortality (P ¼ 0.0041 for PLAG 50 mg/kg; P , 0.0001 for PLAG 250 mg/kg) and body weight loss (P , 0.0001 for PLAG 50 and 250 mg/ kg) in mice. Single-fraction TBI sharply reduced ANC within 3 days postirradiation and maintained the neutropenic state (ANC , 500 cells/ll) by approximately 26.8 6 0.8 days. However, administration of PLAG attenuated radiationinduced severe neutropenia (ANC , 100 cells/ll) by effectively delaying the mean day of its onset and decreasing its duration. PLAG also significantly mitigated radiationinduced thrombocytopenia (P , 0.0001 for PLAG 250 mg/kg) and anemia (P ¼ 0.0023 for PLAG 250 mg/kg) by increasing mean platelet and RBC counts, as well as hemoglobin levels, in peripheral blood. Moreover, delayed administration of PLAG, even at 48 and 72 h after gamma-ray irradiation, significantly attenuated radiation-induced mortality in a time-dependent manner. When compared to olive oil and palmitic linoleic hydroxyl (PLH), only PLAG effectively attenuated radiation-induced mortality, indicating that it has a distinctive mechanism of action. Based on these preclinical observations, we concluded that PLAG has high potential as a radiation countermeasure for the improvement of survivability and the treatment of hematopoietic injury in gamma-rayinduced ARS.

Mitigating Effect of 1-Palmitoyl-2-Linoleoyl-3-Acetyl-Rac-Glycerol (PLAG) on a Murine Model of 5-Fluorouracil-Induced Hematological Toxicity

“…Previously, PLAG has been demonstrated in various inflammatory diseases, such as hepatitis, asthma, rheumatoid arthritis, and oral mucositis [26,27,28,29]. Recently, we showed that administration of PLAG effectively mitigates hematopoietic acute radiation syndrome of mice following a lethal dose of gamma-ray irradiation [30]. Besides, PLAG effectively reduced the incidence of gemcitabine-induced neutropenia by attenuating IL-8-induced neutrophil extravasation in clinical and nonclinical settings [31,32].…”

Radioprotective effect of radiation-induced Lactococcus lactis cell-free extract against 60Coγ injury in mice

“…The hematopoietic system is one of the systems most sensitive to IR, and it is vulnerable to radiation (Kim et al, 2019). Hematopoietic stem cells are very sensitive to radiation, and they are sharply decreased after radiation, which makes the source of mature blood cells in peripheral blood deficient.…”

Protective effect of coix seed seedling extract on 60Co‐γ radiation‐induced oxidative stress in mice

“…The hematopoietic system is sensitive to radiation (Kim et al., 2019). The decrease of the number of WBC in the peripheral blood and the contents of DNA in bone marrow can reflect the damage degree of hematopoietic system (Shao et al., 2018).…”