N -acetylcysteine inhibits Mancozeb-induced impairments to the normal development of zebrafish embryos

Toxic effects of a mancozeb-containing commercial formulation at environmental relevant concentrations on zebrafish embryonic development

“…Altogether, the data points to the disturbed notochord differentiation and morphogenesis as the potential reason for the developmental effects caused by the exposure to this MZ formulation. Additionally, during zebrafish embryo development, the heart is the first functioning organ, and previous studies have shown affected physiological cardiac parameters after short exposure to MZ (Costa- Silva et al 2018b), similar to what was observed in the present study. However, the MZ-induced cardiac changes during early zebrafish development are still poorly characterised and deserves further elucidation.…”

“…While to the authors' knowledge, responses to dark/light and aversive stimulus following exposure of zebrafish's early life stages to MZ have not been described in the literature, similar effects were observed in other animals (Harrison Brody et al 2013;Zizza et al 2017). Nevertheless, the dysregulation of dopaminemediated neurotransmission, which was responsible for changing the embryonic response to touch stimuli following a short MZ exposure (Costa-Silva et al 2018b), could be a possible hypothesis for the observed behavioural phenotype. Dopamine plays critical roles in early neuronal development (Iversen and Iversen 2007) being involved in the regulation of circadian rhythm and aversive behaviours (Korshunov et al 2017;Pignatelli and Bonci 2015).…”

“…Previous studies have reported that a variety of compounds can affect the hatching of the embryo by interfering with the biosynthesis and release of the hatching enzyme (Osterauer and Kohler 2008;Zhou et al 2009) and its distribution (Hagenmaier 1974;Rosenthal and Alderdice 1976), as well as by diminishing the embryo activity (Papiya and Kanamadi 2000), culminating in the inability to emerge from the chorion, which could be a possible explanation for the results obtained. Moreover, MZ has been reported to interfere with the development of Astyanax jacuhiensis by causing several malformations (cardiac and yolk sac oedema, tail, spinal curvature, and severely twisted notochord) (Goldoni and da Silva 2012;Santos et al 2009) and interfering with the normal development of zebrafish by causing notochord defects (Costa- Silva et al 2018b) similar to what was observed with other EBDC fungicides (Cao et al 2019a, b;Lulla et al 2016;van Boxtel et al 2010). In the present study, exposure to the highest concentration of this MZ formulation resulted in an increased number of malformations at 96 hpf and a reduction in body length, an increased yolk sac area, and a decreased eye area.…”

“…While not measured in this study, changes to the dopamine content and AChE activity have been previously associated with the exposure of zebrafish embryos to developmental neurotoxicants (Eddins et al 2010;Liu et al 2016;Wu et al 2016), thereby validating the neurotoxic profile of this MZ formulation at high concentrations. However, while further research is necessary to determine the induced effects on neurotransmitter levels, the proposed dysregulation of the dopamine neurotransmission following MZ exposure was previously associated with cell death processes (Costa- Silva et al 2018b). ROS play a central role in several cell-signalling pathways, as well as in the regulation of main apoptosis-related pathways mediated by mitochondria (Redza-Dutordoir and Averill-Bates 2016).…”

“…Briefly, the transparency of the embryonic stages, the high fecundity, cost-effectiveness, small size, and rapid developmental period make them a valuable tool for the evaluation of pesticide toxicity (Glaberman et al 2017). Recent toxicological evidence has shown that exposure to MZ impairs the normal development of zebrafish embryos (Costa- Silva et al 2018b;Tilton et al 2006), pointing to the key role of redox homeostasis during early development (Costa-Silva et al 2018b). Notwithstanding, the reported effects were only observed at higher than environmental relevant concentrations (above 1 μM~500 μg L −1 ) and at relatively short exposure periods (< 96 h).…”