期刊
TOXICOLOGY LETTERS
卷 352, 期 -, 页码 1-8出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2021.09.004
关键词
Metamizole; Analgesics; Uterotrophic assay; Yeast estrogen screening; Endocrine disruptors; Reproductive toxicology
类别
资金
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) [001]
Through in vivo and in vitro studies, it was found that dipyrone and its metabolites do not exhibit estrogenic or antiestrogenic activity in rats and yeast cells.
Dipyrone is a commonly used analgesic in many countries and there is limited data on its possible endocrine disrupting effects. We performed a screening for in vivo and in vitro anti(estrogenic) activity of dipyrone. For the in vivo uterotrophic assay, immature female rats (22-days-old) were treated daily by oral gavage for three days with different doses of dipyrone alone (50, 100, 200 mg/kg/ day) and associated with three ethynylestradiol (EE) doses (1, 3 and 10 mg/kg/day), which were based on a dose-response curve experiment. The uterine weight was used as a biomarker for estrogenicity. In a parallel in vitro approach, we used a yeast-based transcriptional activation reporter gene assay (Yeast Estrogen Screening - YES) for assessment of estrogenic agonistic and antagonistic effects of dipyrone and its main metabolites 4-methylaminoantipyrine (MAA) and 4-aminoantipyrine (AA). In the uterotrophic assay, animals that received EE at 1, 3 and 10 mg/kg/day showed an increase in relative uterine weight compared with vehicle-only rats (canola oil). Dipyrone did not increase uterine weight at any dose tested (50, 100 and 200 mg/kg/day) in relation to vehicle control, indicating absence of estrogenic activity. Furthermore, co-administration of dipyrone (50 and 200 mg/ kg/day) and EE (1, 3 or 10 mg/kg/day) was unable to block EE estrogenic action in comparison to the groups treated with EE alone, indicating absence of antiestrogenic activity. In the YES assay dipyrone and its metabolites did not demonstrate estrogen agonistic or antagonistic properties in the yeast cells. These results suggest that dipyrone and its metabolites do not produce (anti)estrogenic effects in vivo or in vitro. (C) 2021 Elsevier B.V. All rights reserved.
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