The Analgesic Dipyrone Affects Pregnancy Outcomes and Endocrine-Sensitive Endpoints in Female and Male Offspring Rats.

Autor:	Passoni MT; Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paraná (UFPR), 81531-980 Curitiba, PR, Brazil., Krebs Ribeiro DC; Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paraná (UFPR), 81531-980 Curitiba, PR, Brazil., França de Almeida SC; Animal Endocrine and Reproductive Physiology Laboratory, Department of Physiology, Federal University of Paraná (UFPR), 81531-980 Curitiba, PR, Brazil., Furtado da Costa B; Animal Endocrine and Reproductive Physiology Laboratory, Department of Physiology, Federal University of Paraná (UFPR), 81531-980 Curitiba, PR, Brazil., Grechi N; Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paraná (UFPR), 81531-980 Curitiba, PR, Brazil., Lima Tolouei SE; Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paraná (UFPR), 81531-980 Curitiba, PR, Brazil., Curi TZ; Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paraná (UFPR), 81531-980 Curitiba, PR, Brazil., Degraf Cavallin M; Reproductive Toxicology Laboratory, Department of Medicine, State University of Centro-Oeste, 85040-167 Guarapuava, PR, Brazil., Romano RM; Reproductive Toxicology Laboratory, Department of Medicine, State University of Centro-Oeste, 85040-167 Guarapuava, PR, Brazil., Romano MA; Reproductive Toxicology Laboratory, Department of Medicine, State University of Centro-Oeste, 85040-167 Guarapuava, PR, Brazil., Spercoski KM; Department of Biosciences, Federal University of Paraná (UFPR), 85950-000 Palotina, PR, Brazil., Carvalho Dos Santos A; Histopathology Laboratory, Department of Health Sciences, Federal University of Grande Dourados (UFGD), 79804-970 Dourados, MS, Brazil., Carvalho Souza RI; Histopathology Laboratory, Department of Health Sciences, Federal University of Grande Dourados (UFGD), 79804-970 Dourados, MS, Brazil., Dalsenter PR; Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paraná (UFPR), 81531-980 Curitiba, PR, Brazil., Martino-Andrade AJ; Reproductive Toxicology Laboratory, Department of Pharmacology, Federal University of Paraná (UFPR), 81531-980 Curitiba, PR, Brazil.; Animal Endocrine and Reproductive Physiology Laboratory, Department of Physiology, Federal University of Paraná (UFPR), 81531-980 Curitiba, PR, Brazil.
Jazyk:	angličtina
Zdroj:	Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2022 Apr 26; Vol. 187 (1), pp. 80-92.
DOI:	10.1093/toxsci/kfac016
Abstrakt:	Dipyrone is an analgesic and antipyretic drug commonly used in many countries. Although generally not recommended during pregnancy, it is known that many women use dipyrone during the gestational period. In this study, we investigated the endocrine and reproductive effects of dipyrone in female and male offspring rats exposed in utero from gestational days 10-21. Pregnant rats were treated with dipyrone at 25, 75, and 225 mg/kg/day via oral gavage. Developmental landmarks-anogenital index (AGI), number of nipples, vaginal opening, first estrus, and preputial separation-were evaluated in the offspring. Reproductive parameters, including estrous cycle regularity, daily sperm production, weight and histopathology of reproductive organs, steroid hormone levels, and gene expression of selected markers of reproductive function were assessed at adulthood. At the highest dose, dipyrone induced a significant increase in postimplantation losses/fetal death and delayed parturition in dams. Offspring exposed in utero to the highest dose also exhibited significant changes in some early life markers of endocrine disruption, in particular increased AGI in females, indicating a proandrogenic effect, and increased rate of retained nipples in males, indicating an antiandrogenic response. No changes were observed in markers of puberty onset or reproductive parameters at adulthood. These results suggest that exposure to therapeutically relevant doses of dipyrone may induce mild endocrine disruptive effects that can be detected in late pregnancy and early life. Such effects may be relevant considering dipyrone use by pregnant women and the possibility of coexposures with other endocrine disruptors. (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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