Mitigation of total body irradiation-induced mortality and hematopoietic injury of mice by a thrombopoietin mimetic (JNJ-26366821).
Mitigation of total body irradiation-induced mortality and hematopoietic injury of mice by a thrombopoietin mimetic (JNJ-26366821).
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DOI：
10.1038/s41598-022-07426-7
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发表时间：
2022-03-03
影响因子：
4.6
通讯作者：
Ghosh SP
中科院分区：
文献类型：
--
作者：
Kumar VP;Holmes-Hampton GP;Biswas S;Stone S;Sharma NK;Hritzo B;Guilfoyle M;Eichenbaum G;Guha C;Ghosh SP
近年来，核攻击的威胁有所增加，凸显了开发额外疗法来治疗急性辐射综合症（ARS）受害者的好处。在这项工作中，我们评估了聚乙二醇化血小板生成素模拟肽 JNJ-26366821 对暴露于致死剂量全身辐射 (TBI) 的小鼠中与 ARS 相关的死亡率和造血作用的影响。 JNJ-26366821 可有效缓解暴露于钴 60 伽马射线源 TBI 的 CD2F1 和 C57BL/6 小鼠中与 ARS 相关的死亡率和血小板减少症。与盐水对照治疗相比，在 TBI 后 4、8、12 或 24 小时（LD70 剂量）单次施用 0.3 至 1 mg/kg 的剂量可将生存率提高 30-90%。在为期 30 天的研究结束时，与施用盐水的动物相比，施用 JNJ-26366821 的动物观察到骨髓集落形成单位和巨核细胞显着增加。此外，在 JNJ-26366821 治疗的动物中观察到 FLT3-L 水平恢复增强。对 JNJ-26366821 和盐水治疗组的生存概率分析显示，剂量减少因子为 1.113，并且照射后长达 6 个月的生存时间显着增加。这些结果支持在 TBI 后 4 至 24 小时内施用 JNJ-26366821 作为治疗急性 TBI 暴露的医疗对策，以防发生放射性/核事件。
The threat of a nuclear attack has increased in recent years highlighting the benefit of developing additional therapies for the treatment of victims suffering from Acute Radiation Syndrome (ARS). In this work, we evaluated the impact of a PEGylated thrombopoietin mimetic peptide, JNJ-26366821, on the mortality and hematopoietic effects associated with ARS in mice exposed to lethal doses of total body irradiation (TBI). JNJ-26366821 was efficacious as a mitigator of mortality and thrombocytopenia associated with ARS in both CD2F1 and C57BL/6 mice exposed to TBI from a cobalt-60 gamma-ray source. Single administration of doses ranging from 0.3 to 1 mg/kg, given 4, 8, 12 or 24 h post-TBI (LD70 dose) increased survival by 30–90% as compared to saline control treatment. At the conclusion of the 30-day study, significant increases in bone marrow colony forming units and megakaryocytes were observed in animals administered JNJ-26366821 compared to those administered saline. In addition, enhanced recovery of FLT3-L levels was observed in JNJ-26366821-treated animals. Probit analysis of survival in the JNJ-26366821- and saline-treated cohorts revealed a dose reduction factor of 1.113 and significant increases in survival for up to 6 months following irradiation. These results support the potential use of JNJ-26366821 as a medical countermeasure for treatment of acute TBI exposure in case of a radiological/nuclear event when administered from 4 to 24 h post-TBI.
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影响因子：
3.4
作者：
Satyamitra, Merriline;Lombardini, Eric;Srinivasan, Venkataraman
通讯作者：
Srinivasan, Venkataraman
影响因子：
2
作者：
Ghosh SP;Kulkarni S;Perkins MW;Hieber K;Pessu RL;Gambles K;Maniar M;Kao TC;Seed TM;Kumar KS
通讯作者：
Kumar KS
影响因子：
2.6
作者：
Bunin, Deborah I.;Bakke, James;Chang, Polly Y.
通讯作者：
Chang, Polly Y.
DOI：
10.1016/s0360-3016(98)00477-5
发表时间：
1999-03-01
影响因子：
7
作者：
Mouthon, MA;van der Meeren, A;Wagemaker, G
通讯作者：
Wagemaker, G
影响因子：
3.4
作者：
Kulkarni, Shilpa;Ghosh, Sanchita P.;Kumar, K. Sree
通讯作者：
Kumar, K. Sree