Zearalenone induced embryo and neurotoxicity in zebrafish model (Danio rerio): Role of oxidative stress revealed by a multi biomarker study Sellamani Muthulakshmi a , Kannan Maharajan a , Hamid R. Habibi b , Krishna Kadirvelu a , Mudili Venkataramana a, * a DRDO-BU Center for Life Sciences, Bharathiar University Campus, Coimbatore, 641046, India b Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta, T2N 1N4, Canada highlights graphical abstract  The effect of ZEA on zebrafish during early embryonic development was studied.  Dosages higher than 550 mg/L ZEA exposure resulted in developmental defects.  ZEA induced oxidative stress, DNA damage and apoptosis was reported.  ZEA could alter histopathology and inhibits AChE activity in zebrafish embryos. article info Article history: Received 21 November 2017 Received in revised form 25 January 2018 Accepted 27 January 2018 Handling Editor: David volz Keywords: Zearalenone Oxidative stress Antioxidant enzymes Apoptosis Histology Zebrafish embryos abstract In the present study, we evaluated the zearalenone induced adverse effects in zebrafish embryos using various endpoints like embryo toxicity, heart rate, oxidative stress indicators (reactive oxygen species (ROS), lipid peroxidation (LPO), Nitric oxide (NO)), antioxidant responses (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase enzyme (GST) and reduced glutathione (GSH), metabolic biomarkers (lactate dehydrogenase (LDH) and Nitric oxide (NO)), neuro- toxicity (acetylcholinesterase (AChE)), genotoxicity (comet assay and acridine orange staining (AO)) and histological analysis. In this study, four concentrations 350, 550, 750 and 950 mg/L of ZEA were chosen based on LC10 and LC50 values of the previous report. The results shows that ZEA induces developmental defects like pericardial edema, hyperemia, yolk sac edema, spine curvature and reduction in heart rate from above 550 mg/L exposure and the severity was increased with concentration and time dependent manner. Significant induction in oxidative stress indices (ROS, LPO and NO), reduction in antioxidant defence system (SOD, CAT, GPx, GST and GSH) and changes in metabolic biomarkers (LDH and AP) were observed at higher ZEA exposed concentration. Neurotoxic effects of ZEA were observed with significant inhibition of AChE activity at higher exposure groups (750 and 950 mg/L). Moreover, we also noticed DNA damage, apoptosis and histological changes in the higher ZEA treatments at 96 h post fertilization (hpf) embryos. Hence, in the present study we concluded that oxidative stress is the main culprit in ZEA induced developmental, genotoxicity and neurotoxicity in zebrafish embryos. © 2018 Elsevier Ltd. All rights reserved. * Corresponding author. Toxicology and Immunology Division, DRDO-BU-Centre for Life sciences, Bharathiar University Campus, Coimbatore, 641046, Tamil Nadu, India. E-mail address: ramana.micro@gmail.com (M. Venkataramana). Contents lists available at ScienceDirect Chemosphere journal homepage: www.elsevier.com/locate/chemosphere https://doi.org/10.1016/j.chemosphere.2018.01.141 0045-6535/© 2018 Elsevier Ltd. All rights reserved. Chemosphere 198 (2018) 111e121