Modulation of serum concentrations and hepatic metabolism of 17β-estradiol and testosterone by amitraz in rats
| Autor: | Chen-Ping Chou, Shui-Yuan Lu, Tzuu-Huei Ueng |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Toluidines medicine.drug_class Ovariectomy Health Toxicology and Mutagenesis Estrone Endocrine Disruptors Biology Hydroxylation Toxicology Gas Chromatography-Mass Spectrometry Rats Sprague-Dawley chemistry.chemical_compound Tandem Mass Spectrometry Internal medicine medicine Animals Cytochrome P-450 CYP3A Testosterone Androstenedione Pesticides Chromatography High Pressure Liquid Amitraz Dose-Response Relationship Drug Estradiol General Medicine Androgen Rats Endocrinology Liver chemistry Estrogen Ovariectomized rat Female Injections Intraperitoneal Drug metabolism |
| Zdroj: | Archives of Toxicology. 82:729-737 |
| ISSN: | 1432-0738 0340-5761 |
| DOI: | 10.1007/s00204-008-0288-8 |
| Popis: | The present study has investigated the ability of amitraz, a widely used formamidine pesticide, to modulate serum concentrations and liver microsomal metabolism of 17beta-estradiol (E2) and testosterone in rats. Amitraz was administered intraperitoneally to male rats for 4 days and to intact female rats or ovariectomized (OVX) and 0.5 mg/kg E2-supplemented female rats for 7 days. E2 and metabolites were analyzed by gas chromatography-electron capture detection and testosterone and metabolites were analyzed by high-pressure liquid chromatography. In OVX and E2-supplemented females, 50 mg/kg amitraz caused an 85% decrease of serum E2 concentration and a marked increase of 2-OH-E2 concentration. Amitraz at 25 and 50 mg/kg produced 9.0-fold or greater increases of serum testosterone and 2beta-OH-testosterone levels in males. Amitraz at 25 mg/kg resulted in no or minimal increases of liver microsomal formation of E2 or testosterone metabolites. Amitraz at 50 mg/kg produced 1.4- to 3.6-fold increases of 2-OH-E2; estrone; 2beta-, 6beta-, and 16alpha-OH-testosterone; and androstenedione formation in males and intact females. Amitraz at 50 mg/kg preferentially increased intact female 16beta-OH-testosterone production by 8.6-fold. In OVX females, E2 supplement alone or cotreatment with E2 and 50 mg/kg amitraz produced 1.3- to several-fold increases of 2- and 4-OH-E2 formation and 2beta- and 16alpha-OH-testosterone production. The cotreatment increased 6beta- and 16beta-OH-testosterone formation by 1.8- and 1.6-fold, respectively. The present findings show that amitraz induces hepatic E2 and testosterone metabolism in male and female rats, decreases serum E2 concentration in OVX and E2-supplemented females, but increases serum testosterone in males. |
| Databáze: | OpenAIRE |
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