Tebuconazole alters morphological, behavioral and neurochemical parameters in larvae and adult zebrafish (Danio rerio)

Altenhofen, Stefani; Nabinger, Débora Dreher; Wiprich, Melissa Talita; Pereira, Talita Carneiro Brandão; Bogo, Maurı́cio Reis; Bonan, Carla Denise

doi:10.1016/j.chemosphere.2017.04.029

Cited by 103 publications

(38 citation statements)

References 59 publications

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“…Memory consolidation prepares animals to defend themselves from dangerous situations, such as predation risk (Oliveira et al, 2017), via an aversive memory (Gerlai, 2016). In the memory process, several distinct mechanisms can be affected by different chemical compounds (Altenhofen et al, 2017a;Woodcock et al, 2018) and traumatic effects (Manuel et al, 2014). Studies in mammals (rats and humans) have demonstrated that negative emotions are regulated by the hippocampus (Goosens, 2012).…”

Section: Introductionmentioning

confidence: 99%

Pyriproxyfen Exposure Impairs Cognitive Parameters and Alters Cortisol Levels in Zebrafish

Gusso

Reolon

Gonzalez

et al. 2020

Front. Behav. Neurosci.

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Pyriproxyfen is one of the most used larvicides and insecticides; it acts as an analog of juvenile insect hormone (a growth regulator). It is highly toxic during all stages of mosquito development, suppresses metamorphosis, and interferes in insect reproduction and proliferation. Pyriproxyfen and its main metabolite have been shown to affect brain development in rodents. This compound is employed mainly to eliminate outbreaks of the genus Aedes, even in potable water. Despite the increasing number of toxicological studies about larvicides and insecticides-with an indication of continuous use-there have been few studies about the effects of pyriproxyfen in non-target species such as fish. This study evaluated the effects of pyriproxyfen on behavioral, cognitive, and endocrine parameters in zebrafish. We exposed adult zebrafish to different pyriproxyfen (Pestanal) concentrations (0.125, 0.675, and 1.75 mg/l) for 96 h. We analyzed behavioral parameters, memory, cortisol levels, and gene expression of glucocorticoid receptor (gr) and corticotrophin-releasing factor (crf) after pyriproxyfen exposure. This exposure did not alter locomotion (distance or mean speed), anxiety-like behavior (latency to enter to the top zone of the tank or time in the top zone of the tank), and social or aggressive behavior. However, there was impaired inhibitory avoidance memory at all tested pyriproxyfen concentrations. Cortisol levels were reduced in exposed groups when compared to control or vehicle. However, gr and crf gene expression in pyriproxyfen-treated animals were unaltered when compared to control or vehicle groups. Taken together, these findings indicate that pyriproxyfen may induce cognitive impairment and altered cortisol levels in zebrafish, a non-target species.

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Section: Introductionmentioning

confidence: 99%

Pyriproxyfen Exposure Impairs Cognitive Parameters and Alters Cortisol Levels in Zebrafish

Gusso

Reolon

Gonzalez

et al. 2020

Front. Behav. Neurosci.

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“…Toxicity of azole fungicides in embryo-larval zebrafish-Environmental Toxicology and Chemistry, 2019;38:1455-1466 did not alter behavior or morphology in larval zebrafish even up to 2000 µg/L exposure (Altenhofen et al 2017). However, tebuconazole has the potential to disrupt energy metabolism and the endocrine system in male zebrafish with 7-d exposure to 230 µg/L (Sancho et al 2010).…”

Section: Discussionmentioning

confidence: 98%

Comparative Lipid Peroxidation and Apoptosis in Embryo‐Larval Zebrafish Exposed to 3 Azole Fungicides, Tebuconazole, Propiconazole, and Myclobutanil, at Environmentally Relevant Concentrations

Kumar

Awoyemi

Willis

et al. 2019

Enviro Toxic and Chemistry

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Azole fungicides have entered the aquatic environment through agricultural and residential runoff. In the present study, we compared the off‐target toxicity of tebuconazole, propiconazole, and myclobutanil using embryo‐larval zebrafish as a model. The aim of the present study was to investigate the relative toxicity of tebuconazole, propiconazole, and myclobutanil using multiple‐level endpoints such as behavioral endpoints and enzymatic and molecular biomarkers associated with their mode of action. Zebrafish embryos were exposed to azoles at environmentally relevant and high concentrations, 0.3, 1.0, and 1000 µg/L, starting at 5 h postfertilization (hpf) up to 48 hpf, as well as 5 d postfertilization (dpf). Relative mRNA expressions of cytochrome P450 family 51 lanosterol‐14α‐demethylase, glutathione S‐transferase, caspase 9, phosphoprotein p53, and BCL2‐associated X protein were measured to assess toxicity attributable to fungicides at the mRNA level, whereas caspase 3/7 (apoptosis) and 3,4‐methylenedioxyamphetamine (lipid peroxidation) levels were measured at the enzymatic level. Furthermore, mitochondrial dysfunction was measure through the Mito Stress test using the Seahorse XFe24 at 48 hpf. In addition, light to dark movement behavior was monitored at 5 dpf using Danio Vision® to understand adverse effects at the organismal level. There was no significant difference in the light to dark behavior with exposure to azoles compared to controls. The molecular biomarkers indicated that propiconazole and myclobutanil induced lipid peroxidation, oxidative stress, and potentially apoptosis at environmentally relevant concentrations (0.3 and 1 µg/L). The results from the mitochondrial respiration assay indicated a slight decrease in spare respiratory capacity with an acute exposure (48 hpf) to all 3 azoles at 1000 µg/L. Based on the present results, propiconazole and myclobutanil are acutely toxic compared to tebuconazole in aquatic organisms at environmentally relevant concentrations. Environ Toxicol Chem 2019;38:1455–1466. © 2019 SETAC

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“…The locomotor activity was recorded and analyzed during 5 min, following 1 min of acclimation, using Noldus Ethovision XT system (Wageningen, Netherlands). Total distance, mean speed, maximum acceleration, absolute turn angle and immobility time were considered the main parameters of locomotor activity ( Altenhofen et al, 2017 ; Nery et al, 2017 ). The experiments were performed in a temperature-controlled room (27 ± 2 °C) between 9:00 and 14:00 h.…”

Section: Methodsmentioning

confidence: 99%

“…At 7 dpf the larvae were individually placed in a Petri plate containing 200 μL of 3% methylcellulose with 0.1 g/L ethyl 3-aminobenzoate methanesulfonate (MS-222) solution and each larva was photographed using an inverted stereomicroscope (Nikon, Melville, NY, USA) connected to NIS-Elements Viewer software. Total length, head length, forebrain width, midbrain width and eyes distance were considered the main morphological parameters ( Altenhofen et al, 2017 ) and measured by investigators who were blind to the experimental groups using Image J software. The experiments were performed in a temperature-controlled room (27 ± 2 °C) between 13:00 and 15:00 h.…”

Section: Methodsmentioning

confidence: 99%

N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae

Benvenutti

Marcon

Reis

et al. 2018

PeerJ

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BackgroundParkinson’s disease (PD) is the second most common neurodegenerative disorder. In addition to its highly debilitating motor symptoms, non-motor symptoms may precede their motor counterparts by many years, which may characterize a prodromal phase of PD. A potential pharmacological strategy is to introduce neuroprotective agents at an earlier stage in order to prevent further neuronal death. N-acetylcysteine (NAC) has been used against paracetamol overdose hepatotoxicity by restoring hepatic concentrations of glutathione (GSH), and as a mucolytic in chronic obstructive pulmonary disease by reducing disulfide bonds in mucoproteins. It has been shown to be safe for humans at high doses. More recently, several studies have evidenced that NAC has a multifaceted mechanism of action, presenting indirect antioxidant effect by acting as a GSH precursor, besides its anti-inflammatory and neurotrophic effects. Moreover, NAC modulates glutamate release through activation of the cystine-glutamate antiporter in extra-synaptic astrocytes. Its therapeutic benefits have been demonstrated in clinical trials for several neuropsychiatric conditions but has not been tested in PD models yet.MethodsIn this study, we evaluated the potential of NAC to prevent the damage induced by 6-hydroxydopamine (6-OHDA) on motor, optomotor and morphological parameters in a PD model in larval zebrafish.ResultsNAC was able to prevent the motor deficits (total distance, mean speed, maximum acceleration, absolute turn angle and immobility time), optomotor response impairment and morphological alterations (total length and head length) caused by exposure to 6-OHDA, which reinforce and broaden the relevance of its neuroprotective effects.DiscussionNAC acts in different targets relevant to PD pathophysiology. Further studies and clinical trials are needed to assess this agent as a candidate for prevention and adjunctive treatment of PD.

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Tebuconazole alters morphological, behavioral and neurochemical parameters in larvae and adult zebrafish (Danio rerio)

Cited by 103 publications

References 59 publications

Pyriproxyfen Exposure Impairs Cognitive Parameters and Alters Cortisol Levels in Zebrafish

Pyriproxyfen Exposure Impairs Cognitive Parameters and Alters Cortisol Levels in Zebrafish

Comparative Lipid Peroxidation and Apoptosis in Embryo‐Larval Zebrafish Exposed to 3 Azole Fungicides, Tebuconazole, Propiconazole, and Myclobutanil, at Environmentally Relevant Concentrations

N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae

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