Polypharmacy to Mitigate Acute and Delayed Radiation Syndromes

Area of Science:

• Radiation biology
• Toxicology
• Pharmacology

Background:

• Acute Radiation Syndrome (ARS) and Delayed Effects of Acute Radiation Exposure (DEARE) pose significant health risks.
• Current monotherapies lack efficacy in mitigating both ARS and DEARE.
• WAG/RijCmcr rats are used to model radiation-induced gastrointestinal (GI), hematopoietic (H-ARS), lung, and kidney toxicities.

Purpose of the Study:

• To develop and evaluate a polypharmacy approach for mitigating lethal ARS and DEARE.
• To enhance survival rates and organ function following acute radiation exposure.

Main Methods:

• A combination of three hematopoietic growth factors (PEG-hG-CSF, PEG-mGM-CSF, PEG-hIL-11) was tested for H-ARS mitigation.
• This triple combination (TC) was further combined with enrofloxacin, saline, and lisinopril to address GI-ARS and DEARE.
• Survival, blood cell recovery, and lung/kidney function were assessed in rats after total body irradiation (TBI) or partial body irradiation (PBI).

Main Results:

• The triple combination (TC) of hematopoietic growth factors improved 30-day survival from ~25% to >60% after 7.5 Gy TBI.
• The comprehensive polypharmacy (TC + enrofloxacin, saline, lisinopril) significantly improved survival from GI-ARS, H-ARS, and DEARE after 7.5 Gy TBI or 13 Gy PBI.
• Circulating blood cell recovery and lung/kidney function were notably improved by the TC + lisinopril combination.

Conclusions:

• An efficacious polypharmacy has been demonstrated to mitigate radiation-induced ARS and DEARE in a rat model.
• This multi-drug approach offers a promising strategy for enhancing survival and reducing long-term organ damage after radiation exposure.
• Further research may explore the translation of this polypharmacy for clinical application in radiation countermeasures.