RADIOPROTECTIVE EFFICACY AND ACUTE TOXICITY OF 5-ANDROSTENEDIOL AFTER SUBCUTANEOUS OR ORAL ADMINISTRATION IN MICE

Autor:	Venita Miner, Catherine L. Wilhelmsen, Mark H. Whitnall, Thomas M. Seed, LuAnn McKinney, William E. Jackson
Rok vydání:	2002
Předmět:	Androstenediol medicine.medical_specialty Ratón Injections Subcutaneous Immunology Administration Oral Radiation-Protective Agents Toxicology Mice Route of administration chemistry.chemical_compound Oral administration Weight loss Internal medicine Animals Immunology and Allergy Medicine Pharmacology Mice Inbred C3H business.industry Body Weight Bilirubin Lipase General Medicine Alkaline Phosphatase Acute toxicity Endocrinology chemistry Toxicity Female Histopathology medicine.symptom business
Zdroj:	Immunopharmacology and Immunotoxicology. 24:595-626
ISSN:	1532-2513 0892-3973
DOI:	10.1081/iph-120016038
Popis:	We previously showed that one subcutaneous (sc) injection of 5-androstene-3beta,17beta-diol (AED) stimulated the innate immune system in mice and prevented mortality due to hemopoietic suppression after whole-body ionizing irradiation with gamma rays. In the present study, we tested whether there was any significant toxicity in mice that might hinder development of this steroid for human use. There were no indications of toxicity in chemical analyses of serum after sc doses as high as 4000 mg/kg. At this dose, 2 of 54 mice died when given AED alone. When 4800 mg/kg was given orally, no deaths resulted. The only adverse findings attributed to AED administration were 1) a moderate elevation of granulocytes in abdominal organs and fat after sc injections of 320 mg/kg; and 2) occasional wasting of skin over the injection site in female B6D2F1 but not male C3H/HeN mice. Significant weight loss (6%) was observed after sc injections of 320 mg/kg but not 160 or 80 mg/kg. When male C3H/HeN mice were injected sc with AED at doses of 0-200 mg/kg 24 h before whole body gamma-irradiation (9 Gy), a significant improvement in survival was observed at doses as low as 5 mg/kg. Oral administration of AED produced significant survival enhancement at a dose of 1600 mg/kg. We conclude that the radioprotective efficacy of AED is accompanied by low toxicity.
Databáze:	OpenAIRE
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