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Mancozeb exposure results in manganese accumulation and Nrf2-related antioxidant responses in the brain of common carp Cyprinus carpio

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Abstract

Manganese (Mn)-containing dithiocarbamates such as Mancozeb (MZ) have been shown to induce oxidative stress-related toxicity in rodents and humans. However, little is known about the neurotoxic effects induced by MZ in fish. In this study, carp (Cyprinus carpio) were exposed to non-lethal waterborne concentrations of MZ, and oxidative stress parameters as well as metal accumulation in fish brains were evaluated. The experimental groups were as follows: control, MZ 5 mg/L, and MZ 10 mg/L. Fish were exposed for 7 days, and then brain was removed and prepared for subsequent analysis of antioxidant enzymes, reactive oxygen species (ROS), and expression of Nrf2 and phosphoNrf2. In parallel, manganese (Mn) levels were evaluated in blood and brain tissues. Mn levels were significantly increased in blood and brain of MZ-exposed carps. In addition, a concentration-dependent increase (p < 0.05) in ROS levels was observed in parallel to increments (p < 0.05) in the activity of major antioxidant enzymes, such as GPx, GR, and GST. On the other hand, significant decreases (p < 0.05) in CAT and SOD activities were observed. The expression of total and phosphorylated forms of Nrf2 was significantly (p < 0.05) upregulated in the brain of carps exposed to Mz when compared to the control, indicating an activation of the Nrf2 antioxidant pathway. Our study showed for the first time the activation of the Nrf2/ARE pathway and bioaccumulation of Mn induced by MZ exposure in fish species, highlighting important mechanisms of action and its toxicological impacts to aquatic organisms.

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Funding

The authors received financial support from the Brazilian agencies CNPq (310861/2014-4) and FAPERGS (16/2551-0000499-4).

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Authors and Affiliations

  1. Campus São Gabriel, Universidade Federal do Pampa, Campus São Gabriel, São Gabriel, RS, 97300-000, Brazil

    Dennis Guilherme Costa-Silva, Andressa Rubim Lopes, Illana Kemmerich Martins, Luana Paganotto Leandro, Mauro Eugênio Medina Nunes, Nelson Rodrigues de Carvalho, Nathane Rosa Rodrigues, Giulianna Echeveria Macedo, Ana Paula Saidelles, Cassiana Aguiar, Thais Posser & Jeferson Luis Franco

  2. Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil

    Morgana Doneda & Erico Marlon Moraes Flores

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  1. Dennis Guilherme Costa-Silva
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  2. Andressa Rubim Lopes
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Correspondence to Jeferson Luis Franco.

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Animal experimentation in this study fully adhered to the National Institute of Health Guide for Care and Use of Laboratory and the protocols were approved by the Ethics Commission on Animal Use of the Federal University of Pampa under process number 043/2013.

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Costa-Silva, D.G., Lopes, A.R., Martins, I.K. et al. Mancozeb exposure results in manganese accumulation and Nrf2-related antioxidant responses in the brain of common carp Cyprinus carpio. Environ Sci Pollut Res 25, 15529–15540 (2018). https://doi.org/10.1007/s11356-018-1724-9

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