Dichloroacetate-induced developmental toxicity and production of reactive oxygen species in zebrafish embryos.
Dichloroacetate (DCA) is one of the toxic by products that are formed during the chlorine disinfection process of drinking water. In this study, the developmental toxicity of DCA has been determined in zebrafish (Danio rerio) embryos. Embryos were exposed to different concentrations (4, 8, 16, and 32 mM) of the compound at the 4 h postfertilization (hpf) stage of development, and were observed for different developmental toxic effects at 8, 24, 32, 55, 80, and 144 hpf. Exposure of embryos to 8-32 mM of DCA resulted in significant increases in the heart rate and blood flow of the 55 and 80 hpf embryos that turned into significant decreases at the 144 hpf time point. At 144 hpf, malformations of mouth structure, notochord bending, yolk sac edema and behavioral effects including perturbed swimming and feeding behaviors were also observed. DCA was also found to produce time- and concentration-dependent increases in embryonic levels of superoxide anion (O2*-) and nitric oxide (NO), at various stages of development. The results of the study suggest that DCA-induced developmental toxic effects in zebrafish embryos are associated with production of reactive oxygen species in those embryos.
Hassoun
Ezdihar
E
Department of Pharmacology, College of Pharmacy, The University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606, USA. ehassou@utnet.utoledo.edu
Kariya
Chirag
C
Williams
Frederick E
FE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001775:Blood Circulation / Q000187:drug effects; D019465:Craniofacial Abnormalities / Q000139:chemically induced; D003999:Dichloroacetic Acid / Q000633:toxicity*; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D010063:Ovum / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D015027:Zebrafish / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism*
D017382:Reactive Oxygen Species; D013481:Superoxides; D009569:Nitric Oxide; D003999:Dichloroacetic Acid