Uterotrophic and in vitro screening for (anti)estrogenic activity of dipyrone

Passoni, Marcella Tapias; Palu, Gabriele; Grechi, Nicole; Amaral, Bruna Andreotti da Silva; Gomes, Caroline de Barros; Rülker, Claudia; Ravenzwaay, Bennard van; Martino‐Andrade, Anderson Joel

doi:10.1016/j.toxlet.2021.09.004

Cited by 2 publications

(1 citation statement)

References 42 publications

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“…This study found that BPAF markedly up-regulated the mRNA relative levels of some target genes related to ERα and GPER1-mediated estrogenic signaling pathways in the hypothalamus, ovary, uterus, liver, and kidney and BPAF at 20 mg/kg bw/day markedly increased uterine weight and uterine coefficient of nude mice with SK-BR-3 xenograft tumor. The uterine weight gain of mice is an important index to judge the estrogenic activity of compounds [ 28 , 29 ]. The results indicated that BPAF affected the development of uterus by exerting its estrogenic activity in nude mice with SK-BR-3 tumor.…”

Section: Discussionmentioning

confidence: 99%

Bisphenol AF Promoted the Growth of Uterus and Activated Estrogen Signaling Related Targets in Various Tissues of Nude Mice with SK-BR-3 Xenograft Tumor

Tang

Lei

et al. 2022

IJERPH

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Environmental estrogens can promote the growth, migration, and invasion of breast cancer. However, few studies evaluate adverse health impacts of environmental estrogens on other organs of breast cancer patients. Therefore, the present study investigated the effects of environmental estrogen bisphenol AF (BPAF) on the main organs of female Balb/cA nude mice with SK-BR-3 xenograft tumor by detecting the organ development and gene expression of targets associated with G protein-coupled estrogen receptor 1 (GPER1)-mediated phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways in hypothalamus, ovary, uterus, liver, and kidney. The results showed that BPAF at 20 mg/kg bw/day markedly increased the uterine weight and the uterine coefficient of nude mice compared to SK-BR-3 bearing tumor control, indicating that BPAF promoted the growth of uterus due to its estrogenic activity. Additionally, BPAF significantly up-regulated the mRNA relative expression of most targets related to nuclear estrogen receptor alpha (ERα) and GPER1-mediated signaling pathways in the hypothalamus, followed by the ovary and uterus, and the least in the liver and kidney, indicating that BPAF activated different estrogen activity related targets in different tissues. In addition, BPAF markedly up-regulated the mRNA expression of GPER1 in all tested tissues, and the molecular docking showed that BPAF could dock into GPER1. Because gene change is an early event of toxicity response, these findings suggested that BPAF might aggravate the condition of breast cancer patients through exerting its estrogenic activity via the GPER1 pathway in various organs.

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Section: Discussionmentioning

confidence: 99%

Bisphenol AF Promoted the Growth of Uterus and Activated Estrogen Signaling Related Targets in Various Tissues of Nude Mice with SK-BR-3 Xenograft Tumor

Tang

Lei

et al. 2022

IJERPH

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

Passoni

Ribeiro

Almeida

et al. 2022

Toxicological Sciences

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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 post-implantation 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 co-exposures with other endocrine disruptors.

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Uterotrophic and in vitro screening for (anti)estrogenic activity of dipyrone

Cited by 2 publications

References 42 publications

Bisphenol AF Promoted the Growth of Uterus and Activated Estrogen Signaling Related Targets in Various Tissues of Nude Mice with SK-BR-3 Xenograft Tumor

Bisphenol AF Promoted the Growth of Uterus and Activated Estrogen Signaling Related Targets in Various Tissues of Nude Mice with SK-BR-3 Xenograft Tumor

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

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