Molecular Specificity of 5-Androstenediol as a Systemic Radioprotectant in Mice

Autor:	Thomas M. Seed, James Benjack, William E. Jackson, Marvin L. Lewbart, Charles A. Dowding, Vilmar Villa, Mark H. Whitnall, Venita Miner
Rok vydání:	2005
Předmět:	Androstenediol Male medicine.medical_specialty Neutrophils medicine.medical_treatment Immunology Dehydroepiandrosterone Alpha (ethology) Radiation-Protective Agents Toxicology Steroid Leukocyte Count Mice chemistry.chemical_compound Fluasterone In vivo Internal medicine medicine Animals Immunology and Allergy Testosterone Pharmacology Mice Inbred C3H Chemistry General Medicine Sex hormone receptor Mice Inbred C57BL Endocrinology Gamma Rays Mice Inbred DBA Female
Zdroj:	Immunopharmacology and Immunotoxicology. 27:15-32
ISSN:	1532-2513 0892-3973
Popis:	We compared in vivo radioprotective efficacy of 5-androstenediol (5-AED) to that of ten other steroids: 17alpha-androstenediol, dehydroepiandrosterone, 5-androstenetriol (AET), 4-androstenedione (AND), testosterone, estradiol, fluasterone, 16alpha-bromoepiandrosterone, 16alpha-fluoro-androst-5-en-17alpha-ol (alpha-fluorohydrin, AFH), and 16alpha-fluoro-androst-5-en-17beta-ol (beta-fluorohydrin). Steroids were administered 24 or 48 hr before, or 1 hr after, whole-body gamma-irradiation. Two days after irradiation at 3 Gy, blood elements were counted. In addition, after irradiation at 9-12.5 Gy, survival was recorded for 30 days. The results showed radioprotective efficacy was specific for 5-AED. One other steroid, AFH, demonstrated appreciable survival effects but was less efficacious than 5-AED. AND and AET produced slight enhancement of survival in some experiments. This is the first demonstration that the prophylactic window for survival enhancement by 1 subcutaneous (s.c.) injection of 5-AED is as long as 48 hr in mice. Moreover, the results indicate that 1 s.c. injection of 5-AED 1 hr after irradiation is much less effective than 1 injection 24-48 hr before irradiation. Comparing the molecular features of steroids with radioprotective efficacy leads to the following conclusions: 1) these effects are due to interaction with specific receptors, since s.c. injection of extremely similar molecules with the same physicochemical properties as 5-AED were not radioprotective; 2) the 17-hydroxyl group is essential; 3) this group must be in the beta configuration in the absence of nearby side groups; 4) a halogen atom at 16 changes the 17-hydroxyl specificity to alpha; 5) the 3beta-hydroxyl group is not essential; 6) addition of a 7beta-hydroxyl group is deleterious; and 7) the effects are not due to activation of sex steroid receptors.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::70250127b824c96417ebcd256a97fb8a https://doi.org/10.1081/iph-51289 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.