A new orally active, aminothiol radioprotector-free of nausea and hypotension side effects at its highest radioprotective doses

International Journal of Radiation Oncology, Biology, Physics
Cheryl M SorefWilliam E Fahl

Abstract

A new aminothiol, PrC-210, was tested for orally conferred radioprotection (rats, mice; 9.0 Gy whole-body, which was otherwise lethal to 100% of the animals) and presence of the debilitating side effects (nausea/vomiting, hypotension/fainting) that restrict use of the current aminothiol, amifostine (Ethyol, WR-2721). PrC-210 in water was administered to rats and mice at times before irradiation, and percent-survival was recorded for 60 days. Subcutaneous (SC) amifostine (positive control) or SC PrC-210 was administered to ferrets (Mustela putorius furo) and retching/emesis responses were recorded. Intraperitoneal amifostine (positive control) or PrC-210 was administered to arterial cannulated rats to score drug-induced hypotension. Oral PrC-210 conferred 100% survival in rat and mouse models against an otherwise 100% lethal whole-body radiation dose (9.0 Gy). Oral PrC-210, administered by gavage 30-90 min before irradiation, conferred a broad window of radioprotection. The comparison of PrC-210 and amifostine side effects was striking because there was no retching or emesis in 10 ferrets treated with PrC-210 and no induced hypotension in arterial cannulated rats treated with PrC-210. The tested PrC-210 doses were the ferret and...Continue Reading

References

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Citations

Jan 26, 2016·Medicinal Research Reviews·Mohammad Zahid KamranVibha Tandon
Feb 4, 2014·Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology·Cheryl M Soref, William E Fahl
Sep 27, 2014·Life Sciences in Space Research·Ann R Kennedy
Feb 2, 2013·International Journal of Radiation Biology·Richard R CoppWilliam E Fahl
Jun 19, 2012·Radiation Research·Daniel D PeeblesWilliam E Fahl
Apr 11, 2018·Journal of Dental Research·J J VargheseC E Ovitt
Jul 24, 2012·Lab Animal
Sep 19, 2019·Expert Opinion on Drug Safety·Vijay K Singh, Thomas M Seed
Nov 19, 2019·Radiation Research·William E FahlRichard B Halberg
Nov 2, 2019·Hematology/oncology Clinics of North America·Deborah E Citrin
Feb 12, 2021·The Journal of Biological Chemistry·Trisiani AffandiMary E Reyland
May 29, 2021·Cardiovascular Engineering and Technology·Saeideh Edalati, Safoura Khajeniazi
May 28, 2021·Frontiers in Oncology·Marike W van GisbergenLudwig J Dubois
Sep 3, 2021·Oxidative Medicine and Cellular Longevity·Xuejiao LiHongqi Tian

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