Gestational Arsenic Trioxide Exposure Acts as a Developing Neuroendocrine-Disruptor by Downregulating Nrf2/PPARγ and Upregulating Caspase-3/NF-ĸB/Cox2/BAX/iNOS/ROS

Ahmed, R G; El-Gareib, A.W.

doi:10.1177/1559325819858266

Cited by 10 publications

(4 citation statements)

References 96 publications

(126 reference statements)

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“…Furthermore, a recent study in rats revealed the possible role of Nrf2 signaling in the neuroendocrine disruption caused by arsenic trioxide. Namely, gestational exposure to arsenic trioxide initiated hypothyroidism/thyrotoxicity in both dams and fetuses indicating fetal thyroid-cerebrum axis disruption partly relying on the suppression of Nrf2 mRNA expression and PPARγ as revealed in the fetal cerebrum in both maternal treated groups [ 101 ].…”

Section: Determining Toxic Elements Role In Nrf2 Signalingmentioning

confidence: 99%

The Role of Toxic Metals and Metalloids in Nrf2 Signaling

et al. 2021

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Nuclear factor erythroid 2-related factor 2 (Nrf2), an emerging regulator of cellular resistance to oxidants, serves as one of the key defensive factors against a range of pathological processes such as oxidative damage, carcinogenesis, as well as various harmful chemicals, including metals. An increase in human exposure to toxic metals via air, food, and water has been recently observed, which is mainly due to anthropogenic activities. The relationship between environmental exposure to heavy metals, particularly cadmium (Cd), lead (Pb), mercury (Hg), and nickel (Ni), as well as metaloid arsenic (As), and transition metal chromium (Cr), and the development of various human diseases has been extensively investigated. Their ability to induce reactive oxygen species (ROS) production through direct and indirect actions and cause oxidative stress has been documented in various organs. Taking into account that Nrf2 signaling represents an important pathway in maintaining antioxidant balance, recent research indicates that it can play a dual role depending on the specific biological context. On one side, Nrf2 represents a potential crucial protective mechanism in metal-induced toxicity, but on the other hand, it can also be a trigger of metal-induced carcinogenesis under conditions of prolonged exposure and continuous activation. Thus, this review aims to summarize the state-of-the-art knowledge regarding the functional interrelation between the toxic metals and Nrf2 signaling.

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Section: Determining Toxic Elements Role In Nrf2 Signalingmentioning

confidence: 99%

The Role of Toxic Metals and Metalloids in Nrf2 Signaling

et al. 2021

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“…For each virgin female, we determined the estrus cycle phase by daily examination of a vaginal smear. Two proestrus females were mated with one male in a separate cage for one or two consecutive days (Ahmed & El-Gareib, 2019;Ahmed, El-Gareib, & Shaker, 2018;Ahmed, Walaa, & Asmaa, 2018). On the morning after mating, vaginal smears were examined.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

Maternal LiCl exposure disrupts thyroid–cerebral axis in neonatal albino rats

Mohammed

Ahmed

2021

Intl J of Devlp Neuroscience

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This work aimed to elucidate whether maternal lithium chloride (LiCl) exposure disturbs the thyroid-cerebral axis in neonatal albino rats. 50 mg of LiCl/ kg b.wt. is orally given for pregnant Wistar rats from gestational day (GD) 1 to lactation day (LD) 28. The maternal administration of LiCl induced follicular dilatation and degeneration, hyperplasia, lumen obliteration and colloid vacuolation in the maternal and neonatal thyroid gland at postnatal days (PNDs) 14, 21 and 28. Neuronal degeneration (spongiform), gliosis, nuclear pyknosis, perivascular oedema, and meningeal hyperaemia were observed in the neonatal cerebral cortex of the maternal LiCl-treated group at examined PNDs. This disturbance appears to depend on intensification in the neonatal cerebral malondialdehyde (MDA), nitric oxide (NO), and hydrogen peroxide (H 2 O 2 ) levels, and attenuation in the glutathione (GSH), total thiol (t-SH), catalase (CAT), and superoxide dismutase (SOD) levels. In the neonatal cerebrum, the fold change in the relative mRNA expression of deiodinases (DII and DIII) increased significantly at PNDs 21 and 14, respectively, in the maternal LiCltreated group. These data suggest that maternal LiCl may perturb the thyroidcerebrum axis generating neonatal neurodevelopmental disorder.

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“…The abortion, mortality and gain in maternal and neonatal body weight were followed during the experimental period. Dams and neonates anesthetized by mild diethyl ether (Ahmed, 2011(Ahmed, , 2019a(Ahmed, , 2019bAhmed & El-Gareib, 2019) were killed on the examined PNDs (14, 21 and 28).…”

Section: Experimental Strategymentioning

confidence: 99%

Maternal lithium chloride exposure alters the neuroendocrine‐cytokine axis in neonatal albino rats

Mohammed

Ahmed

2020

Intl J of Devlp Neuroscience

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The aim of this work was to clarify whether maternal lithium chloride (LiCl) exposure disrupts the neonatal neuroendocrine‐cytokine axis. Pregnant Wistar rats were orally administrated 50 mg LiCl/kg b.wt. from gestational day (GD) 1 to postpartum day 28. Maternal administration of LiCl induced a hypothyroid state in both dams and their neonates compared to the control dams and neonates at lactation days (LDs) 14, 21 and 28, where the levels of serum free triiodothyronine (FT3) and free thyroxin (FT4) were decreased and the level of serum thyrotropin (TSH) level was increased. A noticeable depression in maternal body weight gain, neonatal body weight and neonatal serum growth hormone (GH) was observed on all examined postnatal days (PNDs; 14, 21 and 28). A single abortion case was recorded at GD 17, and three dead neonates were noted at birth in the LiCl‐treated group. Maternal administration of LiCl disturbed the levels of neonatal serum tumor necrosis factor‐alpha (TNF‐α), transforming growth factor‐beta (TGF‐β), interleukin‐1 beta (IL‐1β), interferon‐gamma (INF‐γ), leptin, adiponectin and resistin at all tested PNDs compared to the control group. This administration produced a stimulatory action on the level of neonatal cerebral serotonin (5‐HT) at PND 14 and on the level of neonatal cerebral norepinephrine (NE) at PNDs 21 and 28. However, this administration produced an inhibitory action on the level of neonatal cerebral dopamine (DA) at all examined PNDs and on the level of neonatal cerebral NE at PND 14 and the level of neonatal cerebral 5‐HT at PNDs 21 and 28 compared to the corresponding control group. Thus, maternal LiCl exposure‐induced hypothyroidism disrupts the neonatal neuroendocrine‐cytokine system, which delay cerebral development.

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Gestational Arsenic Trioxide Exposure Acts as a Developing Neuroendocrine-Disruptor by Downregulating Nrf2/PPARγ and Upregulating Caspase-3/NF-ĸB/Cox2/BAX/iNOS/ROS

Cited by 10 publications

References 96 publications

The Role of Toxic Metals and Metalloids in Nrf2 Signaling

The Role of Toxic Metals and Metalloids in Nrf2 Signaling

Maternal LiCl exposure disrupts thyroid–cerebral axis in neonatal albino rats

Maternal lithium chloride exposure alters the neuroendocrine‐cytokine axis in neonatal albino rats

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