Article

Neurological impairment in fetal mouse brain by drinking water disinfectant byproducts

Texas A&M University - Galveston, Galveston, Texas, United States
NeuroToxicology (Impact Factor: 3.38). 09/2005; 26(4):633-40. DOI: 10.1016/j.neuro.2004.11.001
Source: PubMed

ABSTRACT

Developmental exposure to environmental chemicals may have detrimental effects on embryonic brains that could play a major role in the etio-pathology of fetal and adult neurological diseases. The exact mechanism by which prenatal exposures to environmental agents, such as drinking water disinfectant byproducts (DBP), cause neurological impairment in fetus is not known. Our objective is to examine the impact of prenatal exposure to DBP on fetal brain development. Pregnant CD-1 mice, at the sixth day of gestation (GD-6), received a daily (GD-6-GD-18) oral dose of chloroacetonitrile (CAN, 25 ppm), a member of DBP. To assess fetal brain uptake of CAN, several animals were injected with a tracer dose of 2-[(14)C]-CAN (333 microCi/kg, i.v.), at GD-12 and processed for quantitative in situ micro whole-body autoradiography (QIMWBA) at 1 and 24 h after treatment. The remaining animals continued receiving CAN until GD-18 when fetal brains were processed for biochemical determination of oxidative stress (OS) or prepared for histological examinations. The results indicate a rapid placental transfer and fetal brain uptake of 2-[(14)C]-CAN/metabolites in cortical areas and hippocampus. In treated animals 3-fold decrease in glutathione (GSH), 1.3-fold increase in lipid peroxidation and 1.4-fold increase in DNA oxidation were detected as compared to control. DeOlmos cupric silver staining of fetal brains indicated significant increase in cortical neurodegeneration in treated animals. Immunohistochemical labeling (TUNEL) of apoptotic nuclei in the cortices and choroid plexuses were also increased in treated animals as compared to control. In conclusion, CAN crosses the placental and fetal blood-brain barriers and induces OS that triggered apoptotic neurodegenration in fetal brain. Future studies will examine the molecular mechanisms of these events and its impact on neural development of offspring.

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Available from: Sam Jacob, Jun 09, 2015
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    • "properties [9] [10] [11]. Neurological impairment and developmental toxicity were also reported [12] [13] [14]. The carcinogenicity and genotoxic properties were well discussed in the review by Richardson et al., showing that the level of DBPs (trihalomethanes, THMs), exposure routes (dermal/inhalation), and specific genotype (having the GSTT1-1 gene) were considered as important factors associated with bladder cancer [11]. "
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    • "Jacob et al. (1998) described rapid uptake and covalent interaction of HANs and/or their metabolites with DNA in mouse fetal brain. Whole-body autoradiography studies indicated a significant uptake and retention of chloroacetonitrile (CAN) and/or metabolites in the fetal brain areas: cerebral cortex, hippocampus and cerebellum (Ahmed et al., 2005a). In addition, in utero exposure to HANs induces oxidative stress, apoptosis and neurodegeneration in mouse fetal brain (Ahmed et al., 2005b; Esmat et al., 2012). "
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    ABSTRACT: Dibromoacetonitrile (DBAN) is a disinfection by-product of water chlorination. Epidemiological studies indicate that it might present a potential hazard to human health. The present study aimed to investigate the possible neurotoxicity of DBAN in rats and possible protection by taurine. Based on initial dose-response experiment, DBAN (60mg/kg) was administrated orally for 7 days. DBAN administration significantly impaired behavior of rats. Further, DBAN produced significant decrease of monoamines, γ-aminobutyric acid (GABA), glutamate contents, acetylcholinestrase (AChE) and aspartate aminotransferase (AST) activities, in rat brain. On the other hand, a significant increase in malondialdehyde (MDA), nitric oxide (NO) contents and lactic dehydrogenase (LDH) activity was observed. Co-administration of taurine (200mg/kg, i.p.) with DBAN mitigated most tested parameters. In conclusion, the present study indicates that DBAN has the propensity to cause significant oxidative damage in rat brain. However, taurine has a promising role in attenuating the obtained hazardous effects of DBAN.
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    • "Our results indicated that DCAN causes neuronal degeneration, as evidenced by positive silver staining . This is in line with the results ofAhmed et al. (2005a)who reported fetal neuronal degeneration by CAN. In conclusion , maternal exposure to DCAN adversely affects mouse fetal brain as evidenced by induction of oxidative stress, apoptotic imbalance and neurodegeneration. "
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