title: Dichloroacetonitrile induces oxidative stress and developmental apoptotic imbalance in mouse fetal brain.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Esmat
authors.forename: Asser I
authors.initials: AI
authors.lastname: Ghoneim
authors.forename: Ebtehal
authors.initials: E
authors.lastname: El-Demerdash
authors.forename: Amani E
authors.initials: AE
authors.lastname: Khalifa
authors.forename: Ashraf B
authors.initials: AB
authors.lastname: Abdel-Naim
mesh_terms: D000097:Acetonitriles / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D053938:DNA Fragmentation; D060766:Drinking Water / Q000009:adverse effects; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011247:Pregnancy; D011897:Random Allocation; D014874:Water Pollutants, Chemical / Q000494:pharmacology
chemical_list: D000097:Acetonitriles; D060766:Drinking Water; D014874:Water Pollutants, Chemical; C051716:dichloroacetonitrile