ATO disrupts developing neuroendocrine-disruptor

What is it about?

Ahmed, R.G., A.W. El-Gareib, 2019. Gestational arsenic trioxide exposure acts as a developing neuroendocrine-disruptor by downregulating Nrf2/PPARγ and upregulating Caspase-3/NF-ĸB/Cox2/BAX/iNOS/ROS. Dose-Response: An International Journal, 1-12. DOI: 10.1177/1559325819858266. The goal of this investigation was to evaluate the effects of gestational administrations of arsenic trioxide (ATO; As2O3) on fetal neuroendocrine development (the thyroid-cerebrum axis). Pregnant Wistar rats were orally administered ATO (5 or 10 mg/kg mg/kg) from gestation day (GD) 1 to 20.

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Why is it important?

Both doses of ATO diminished free thyroxine (FT4) and free triiodothyronine (FT3) levels and augmented thyrotropin (TSH) level in both dams and fetuses at GD 20. Also, the maternofetal hypothyroidism in both groups caused a dose-dependent reduction in the fetal serum growth hormone (GH), insulin growth factor-I (IGF-I), and IGF-II levels at embryonic day (ED) 20. These disorders perturbed the maternofetal body weight, fetal brain weight, and survival of pregnant and their fetuses. In addition, destructive degeneration, vacuolation, hyperplasia, and oedema were observed in the fetal thyroid and cerebrum of both ATO groups at ED 20. These disruptions appear to depend on intensification in the values of lipid peroxidation (LPO), NO, and H2O2, suppression of mRNA expression of Nrf2 and PPARγ, and activation of mRNA expression of caspase-3, NF-κB, Cox2, BAX, and iNOS in the fetal cerebrum. These data suggest that gestational ATO may disturb thyroid-cerebrum axis generating fetal neurodevelopmental toxicity.

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