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


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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    ABSTRACT: Ionizing radiation technology was suggested as an alternative method to disinfection processes, such as chlorine, UV, and ozone. Although many studies have demonstrated the effectiveness of irradiation technology for microbial disinfection, there has been a lack of information on comparison studies of disinfection techniques and a regrowth of each treatment. In the present study, an ionizing radiation was investigated to inactivate microorganisms and to determine the critical dose to prevent the regrowth. As a result, it was observed that the disinfection efficiency using ionizing radiation was not affected by the seasonal changes of wastewater characteristics, such as temperature and turbidity. In terms of bacterial regrowth after disinfection, the ionizing radiation showed a significant resistance of regrowth, whereas, on-site UV treatment is influenced by the suspended solid, temperature, or precipitation. The electric power consumption was also compared for the economic feasibility of each technique at a given value of disinfection efficiency of 90% (1-log), showing 0.12, 36.80, and 96.53Wh/(L/day) for ionizing radiation, ozone, and UV, respectively. The ionizing radiation requires two or three orders of magnitude lower power consumption than UV and ozone. Consequently, ionizing radiation can be applied as an effective and economical alternative technique to other conventional disinfection processes. Copyright © 2015 Elsevier B.V. All rights reserved.
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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.
    No preview · Article · Sep 2012
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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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    ABSTRACT: Dichloroacetonitrile (DCAN) is one of the disinfection by-products of chlorination of drinking water. Limited mechanistic studies exist on the developmental toxicity of haloacetonitriles (HANs). The present study was designed to investigate the potential adverse effects of maternal exposure to DCAN on mouse fetal brain. Based on initial dose-response experiment, DCAN (14 mg/kg/day) was administered orally to pregnant mice at gestation day (GD) 6, till GD 15. Maternal exposure to DCAN resulted in redox imbalance in fetal cortex and cerebellum, characterized by significant decrease in reduced glutathione (GSH), and elevation of malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. Further, DCAN induced apoptosis indicated by significant enhancement of DNA fragmentation and active caspase-3 level in fetal cortex and cerebellum. Neuronal degeneration was indicated by positive cupric silver staining. 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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