Dichloroacetate‐induced developmental toxicity and production of reactive oxygen species in zebrafish embryos

Abstract

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.

Long-term dietary exposure to low concentration of dichloroacetic acid promoted longevity and attenuated cellular and functional declines in aged Drosophila melanogaster

“…Earlier reports have shown that DCA causes developmental and reproductive adversities in exposed organisms (rat and zebrafish) wherein very high concentrations of DCA (~400-4,000 mg/kg) were used (Hassoun et al 2005;Linder et al 1997;Smith et al 1992). However, none of the tested DCA concentrations were found to induce developmental and reproductive adversities in exposed Drosophila as evidenced by nonapparent change in the emergence pattern and reproductive performance of exposed flies.…”

Developmental toxicity screening in zebrafish

“…These included TCDD (Henry et al, 1997;Belair et al, 2001;Dong et al, 2002Dong et al, , 2004Teraoka et al, 2002Teraoka et al, , 2003Prasch et al, 2003;Antkiewicz et al, 2005;Carney et al, 2006;Ton et al, 2006), benzene and toluene (Mizell et al, 1996;Mizell and Romig, 1997), dichlorvos (Sisman, 2010), and BPA (Duan et al, 2008). Interestingly, PFOS and dichloroacetate exposures at earlier time points (in embryos \ 80 hpf) caused pericardial edema and brachycardia, but resulted in the opposite effect of tachychardia (increased heart rate) if exposures began after 80 hpf (Hassoun et al, 2005;Shi et al, 2008;Huang et al, 2010). Other heart malformations and decreased heart size have been reported to be caused by TCDD (Mizell and Romig, 1997;Antkiewicz et al, 2005;Carney et al, 2006;Mehta et al, 2008), 3,3 0 ,4,4 0 ,5-pentachlorobiphenyl (PCB126) (Grimes et al, 2008), benzene and toluene (Mizell et al, 1996;Mizell and Romig, 1997), and aristolochic acid (Huang et al, 2007) (Table 5).…”

Modulation by ellagic acid of DCA-induced developmental toxicity in the zebrafish (Danio rerio)

“…DCA administration to rats resulted in significant production of lipid peroxidation and DNA damage in hepatic tissues, and those effects were considered to play a possible role in the compound's hepatotoxic and hepatocarcinogenic effects [17,18]. The developmental toxic effects of DCA have been recently described in zebrafish embryos [19]. Those studies have also demonstrated an association between the developmental toxic effects in the DCA-exposed embryos and the overproduction of ROS in the same embryos [19].…”

“…The developmental toxic effects of DCA have been recently described in zebrafish embryos [19]. Those studies have also demonstrated an association between the developmental toxic effects in the DCA-exposed embryos and the overproduction of ROS in the same embryos [19].…”