Exposição ao fungicida mancozebe resulta em alterações no equilíbrio redox de peixes adultos e em desenvolvimento embrionário

Abstract

Agrochemicals have been widely used in the control of pests in agricultural activity, however, they can be harmful to the environment. Oxidative stress which is characterized by an imbalance between pro-oxidants and antioxidants has been identified as one of the main mechanisms of toxicity induced by pesticides. Considering that aquatic organisms are dependent on the redox equilibrium for cellular homeostasis, imbalance in such process may result in neurotoxicity, or even compromise the embryonic development of organisms. The manzozeb (Mz), a manganese/zinc-containing dithiocarbamate multi-site fungicide of the dithiocarbamate class has been used in several crops for over 50 years due to its low acute toxicity and environmental persistence. Though, this compound has already been shown to be toxic to aquatic biota. However, there are few studies on the mechanisms of neurotoxicity and the potential induction of embryotoxicity of this compound. The common carp (Cyprinus carpio) and zebrafish (Danio rerio) have been highlighted as experimental models relevant to several fields of research, among them environmental toxicology. In the present study, our aim in chapter I was to investigate potential mechanisms of toxic action and adaptive responses related to oxidative stress in carps exposed to Mz. In chapter II, we sought to elucidate the toxic effects of Mz on the embryonic development of zebrafish and the use of a classical antioxidant, such as N-acetylcysteine, in order to verify the role of redox imbalance in Mz-induced embryotoxicity. The results obtained in Chapter I demonstrated a significant increase in the concentration of manganese in the blood and brain of carps exposed to Mz. We also observed significant changes in the activity of important antioxidant enzymes and the activation of the transcription factor Nrf2, the master regulator of the antioxidant response in organisms, indicating the potential neurotoxic effect of this fungicide in fish. In Chapter II, zebrafish exposure to Mz compromised the survival of treated embryos, induced DNA damage, cell death, morphological abnormalities and alterations in sensorimotor responses. In parallel, we observed significant changes in antioxidant defenses. In contrast, pre-treatment with N-acetylcysteine was able to block Mz-induced toxic effects in all analyzed parameters, reinforcing the hypothesis of the involvement of oxidative stress in embryotoxicity induced by Mz, and also contributing to the elucidation of the important role of redox balance in the normal development of zebrafish embryos. The data presented here are the first report on the activation of Nrf2 in fish exposed to Mz, as well as the deleterious effect of Mz on the normal embryogenesis of zebrafish. In addition, it is possible to emphasize the importance of these studies for the understanding of stress within the aquatic toxicology area.