Radioprotective and radiomitigative effects of BP-C2, a novel lignin-derived polyphenolic composition with ammonium molybdate, in two mouse strains exposed to total body irradiation

Быков, В. Н.; Драчев, И. С.; Kraev, Sergey Yu; Maydin, Mikhail; Губарева, Е. А.; Pigarev, Sergey E.; Anisimov, Vladimir N.; Балдуева, Ирина; Fedoros, Elena I.; Panchenko, Andrey

doi:10.1080/09553002.2018.1416204

Cited by 23 publications

(16 citation statements)

References 41 publications

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“…A novel lignin-derived polyphenolic composition with ammonium molybdate, BP-C2 mitigates radiation-induced damage in midlethal range of radiation doses. Effects are mediated by the enhancement of extramedullar hematopoiesis in the spleen and a protective effect on the intestinal epithelium [ 54 ]. Tea polyphenols, particularly in the combination in TP50 as the radioprotector in mice, have antioxidant potential activity and can reduce inflammatory cytokines especially during the recovery of the hematopoietic system [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of JXT Ethanol Extract on Radiation‐Induced Hematopoietic Alteration and Oxidative Stress in the Liver

Dong

Wang

Xiao

et al. 2018

Oxidative Medicine and Cellular Longevity

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This study aims at investigating the radioprotective effect of ethanol extract from Ji-Xue-Teng (JXT, Spatholobus suberectus) on radiation-induced hematopoietic alteration and oxidative stress in the liver. Mice were exposed to a single acute γ-radiation for the whole body at the dose of 6.0 Gy, then subjected to administration of amifostine (45 mg/kg) or JXT (40 g crude drug/kg) once a day for 28 consecutive days, respectively. Bone marrow cells and hemogram including white cells, red cells, platelet counts, and hemoglobin level were examined. The protein expression levels of pJAK2/JAK2, pSTAT5a/STAT5a, pSTAT5b/STAT5b, and Bcl-2 in bone marrow tissue; levels of reactive oxygen species (ROS); and the activity of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in serum and liver tissue were determined. At the end of the experiment, the effect of JXT on cell viability and G-CSF and G-CSFR levels in NFS-60 cells were tested by CCK-8 assay, ELISA, and flow cytometry. The results showed that the mice exposed to γ-radiation alone exhibited a typical hematopoietic syndrome. In contrast, at the end of the 28-day experiment, irradiated mice subjected to oral administration of JXT showed an obvious improvement on blood profile with reduced leucopenia, thrombocytopenia (platelet counts), RBC, and hemoglobin levels, as well as bone marrow cells. The expression of pJAK2/JAK2, pSTAT5a/STAT5a, and Bcl-2 in bone marrow tissue was increased after JXT treatment. The elevation of ROS was due to radiation-induced toxicity, but JXT significantly reduced the ROS level in serum and liver tissue, elevated endogenous SOD and GSH-PX levels, and reduced the MDA level in the liver. JXT could also increase cell viability and G-CSFR level in NFS-60 cells, which was similar to exogenous G-CSF. Our findings suggested that oral administration of JXT effectively facilitated the recovery of hematopoietic bone marrow damage and oxidative stress of the mice induced by γ-radiation.

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Section: Discussionmentioning

confidence: 99%

Protective Effect of JXT Ethanol Extract on Radiation‐Induced Hematopoietic Alteration and Oxidative Stress in the Liver

Dong

Wang

Xiao

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…Hematopoietic stresses are well known to mobilize hematopoietic stem cells from the bone marrow to the spleen, which induces extramedullary hematopoiesis [16]. Bykov et al also reported that lignin-derived polyphenolic composition with ammonium molybdate improved the 30-day survival rate and increased the formation of endogenous splenic colony-forming units, indicating that the radio-mitigative effects are mediated by the enhancement of extramedullary hematopoiesis in the spleen [29]. It is therefore possible that the administration of combination #4 also enhanced the hematopoietic function in the spleen instead of the damaged bone marrow of mice exposed to lethal TBI.…”

Section: Discussionmentioning

confidence: 99%

Mitigative Efficacy of the Clinical Dosage Administration of Granulocyte Colony-stimulating Factor and Romiplostim in Mice With Severe Acute Radiation Syndrome

Yamaguchi

Suzuki

Funaba

et al. 2020

Preprint

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Background:It has been reported that the high-dosage administration of domestically approved pharmaceutical drugs, especially granulocyte colony-stimulating factor (G-CSF) and romiplostim (RP), is a rapid and appropriate medical treatment for preventing severe acute radiation syndrome (ARS) of victims exposed to lethal total-body irradiation (TBI). However, it remains unclear whether or not the clinical dosage administration of these drugs can ameliorate TBI-induced ARS and related high mortality in order to find various drug treatment options and less toxic optimum protocol depending on the situation surrounding the radiological accidents.Methods:We assessed the clinical dosageadministration in combination with G-CSF and RP as intraperitoneal injection in C57BL/6J mice exposed to more than 7-Gy lethal dose of X-ray TBI for the survival studyevaluated by the log-rank test. Bone marrow and splenic cellswere collected on the 21st day, when1 week have passed from last administration, to detect the level of cell apoptosis, intracellular reactive oxygen species (ROS), and nuclear factor erythroid 2-related factor 2 (Nrf2)-related anti-oxidative gene expressions, and enzyme-linked immune sorbent assayusing serawas performed for cell senescence and inflammationstatusanalyzed with one-way ANOVA and Tukey-Kramer or Bonferroni/Dunn multiple comparison tests.Results: The combined once-daily administration of 10 μg/kg G-CSF for 4 times and 10 μg/kgRP once a week for 3 times improve the 30-day survival rate of lethal TBI mice compared with untreated TBI mice, accompanied by a gradual increase in the body weight and hematopoietic cell numbers. The radio-mitigative effect is probably attributed to the scavenging of ROS and the reduction in cell apoptosis. These changes were associated with the upregulation of Nrf2 and its downstream anti-oxidative targets in TBI mice. Furthermore, this combination modulated TBI-induced cell senescence and inflammation markers. Conclusions:This study suggested that the clinical dosage administration in combination with G-CSF and RP may also have radio-mitigative effects on mice exposed to lethal TBI and may be a potent therapeutic agent for mitigating radiation-induced severe ARS.

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“…Hematopoietic stresses are well known to mobilize hematopoietic stem cells from the bone marrow to the spleen, which induces extramedullary hematopoiesis [ 19 ]. Bykov et al also reported that lignin-derived polyphenolic composition with ammonium molybdate improved the 30-day survival rate and increased the formation of endogenous splenic colony-forming units, indicating that the radio-mitigative effects are mediated by the enhancement of extramedullary hematopoiesis in the spleen [ 29 ]. It is therefore possible that the administration of combination #4 also enhanced the hematopoietic function in the spleen instead of the damaged bone marrow of mice exposed to lethal TBI.…”

Section: Discussionmentioning

confidence: 99%

Mitigative efficacy of the clinical dosage administration of granulocyte colony-stimulating factor and romiplostim in mice with severe acute radiation syndrome

et al. 2020

View full text Add to dashboard Cite

Background: It has been reported that the high-dosage administration of domestically approved pharmaceutical drugs, especially granulocyte colony-stimulating factor (G-CSF) and romiplostim (RP), is a rapid and appropriate medical treatment for preventing severe acute radiation syndrome (ARS) of victims exposed to lethal total-body irradiation (TBI). However, it remains unclear whether or not the clinical dosage administration of these drugs can ameliorate TBI-induced ARS and related high mortality in order to find various drug treatment options and less toxic optimum protocol depending on the situation surrounding the radiological accidents. Methods: We assessed the clinical dosage administration in combination with G-CSF and RP as intraperitoneal injection in C57BL/6 J mice exposed to more than 7-Gy lethal dose of X-ray TBI for the survival study evaluated by the log-rank test. Bone marrow and splenic cells were collected on the 21st day, when 1 week has passed from last administration, to detect the level of cell apoptosis, intracellular reactive oxygen species (ROS), and nuclear factor erythroid 2-related factor 2 (Nrf2)-related anti-oxidative gene expressions, and enzyme-linked immune sorbent assay using sera was performed for cell senescence and inflammation status analyzed with one-way ANOVA and Tukey-Kramer or Bonferroni/Dunn multiple comparison tests. Results: The combined once-daily administration of 10 μg/kg G-CSF for 4 times and 10 μg/kg RP once a week for 3 times improve the 30-day survival rate of lethal TBI mice compared with untreated TBI mice, accompanied by a gradual increase in the body weight and hematopoietic cell numbers. The radio-mitigative effect is probably attributed to the scavenging of ROS and the reduction in cell apoptosis. These changes were associated with the upregulation of Nrf2 and its downstream anti-oxidative targets in TBI mice. Furthermore, this combination modulated TBI-induced cell senescence an d inflammation markers. Conclusions: This study suggested that the clinical dosage administration in combination with G-CSF and RP may also have radio-mitigative effects on mice exposed to lethal TBI and may be a potent therapeutic agent for mitigating radiation-induced severe ARS.

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Radioprotective and radiomitigative effects of BP-C2, a novel lignin-derived polyphenolic composition with ammonium molybdate, in two mouse strains exposed to total body irradiation

Abstract: BP-C2 mitigates radiation-induced damage in mid-lethal range of radiation doses. Effects are mediated by enhancement of extramedullar hematopoiesis in the spleen and a protective effect on the intestinal epithelium.

Cited by 23 publications

References 41 publications

Protective Effect of JXT Ethanol Extract on Radiation‐Induced Hematopoietic Alteration and Oxidative Stress in the Liver

Protective Effect of JXT Ethanol Extract on Radiation‐Induced Hematopoietic Alteration and Oxidative Stress in the Liver

Mitigative Efficacy of the Clinical Dosage Administration of Granulocyte Colony-stimulating Factor and Romiplostim in Mice With Severe Acute Radiation Syndrome

Mitigative efficacy of the clinical dosage administration of granulocyte colony-stimulating factor and romiplostim in mice with severe acute radiation syndrome

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