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1.
Neurotoxicol Teratol ; 68: 66-71, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29807111

RESUMEN

Mancozeb (MZ), an organic-metal fungicide used predominantly on vegetables and fruits, has been linked to neurodegeneration and behavioral disruptions in a variety of organisms, including humans. Both γ-aminobutyric acid and dopamine neurons appear to be more vulnerable to MZ exposure than other neuronal populations. Based on these observations, we hypothesized that MZ may be differentially transported into these cells through their presynaptic neurotransmitter transporters. To test this, we pretreated Caenorhabditis elegans with transporter antagonists followed by exposure to various concentrations of MZ. Potential neuroprotection was monitored via green fluorescence associated with various neuron populations in transgenic worm strains. Neurodegeneration associated with subacute MZ treatment (30 min) was not altered by transporter antagonist pretreatment. On the other hand, pretreatment with a dopamine transporter antagonist (GBR12909) appeared to protect dopaminergic neurons from chronic (24 h) MZ treatment. These results are consistent with other reports that dopamine transporter levels or activity may modulate toxicity for neurotoxicants.


Asunto(s)
Maneb/toxicidad , Degeneración Nerviosa/prevención & control , Piperazinas/farmacología , Zineb/toxicidad , Animales , Animales Modificados Genéticamente , Caenorhabditis elegans , Clomipramina/farmacología , Inhibidores de Captación de Dopamina/farmacología , Fungicidas Industriales/toxicidad , Inhibidores de Recaptación de GABA/farmacología , Maneb/antagonistas & inhibidores , Fármacos Neuroprotectores/farmacología , Ácidos Nipecóticos/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Zineb/antagonistas & inhibidores
2.
Neurotoxicol Teratol ; 68: 1-12, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29665402

RESUMEN

Mancozeb (MZ), a manganese/zinc-containing ethylene-bis-dithiocarbamate (EBCD) fungicide has been claimed to present low acute toxicity and short environmental persistence, however, its effects on embryogenesis in non-target organisms is unclear. Here, we used zebrafish embryos (5 hpf) to assess the potential embryotoxic effects induced by MZ (up to 72 hpf) as well as the role of reactive oxygen species (ROS) in this process by pre-treatment with a classical antioxidant (N-acetylcysteine, NAC). Markers of reactive oxygen species production (ROS), glutathione (GSH) levels and glutathione S-transferase (GST) activity were measured along with genotoxicity (comet assay), cell death (Acridine Orange) and behavioral parameters (spontaneous movement, touch stimulation and swimming response), in order to determine potential mechanisms of embryotoxicity. According to results, MZ was able to induce morphological abnormalities such as body axis distortion, DNA damage, cell death, increased ROS generation and changes in behavioral endpoints during zebrafish development. All these toxic effects were inhibited by the pre-treatment with NAC indicating a key role of redox unbalance during MZ-induced embryotoxicity. At least in our knowledge, this is the first report on the deleterious effect of MZ to the normal embryogenesis of zebrafish. In addition, the importance of ROS generation during this pathophysiological condition was highlighted.


Asunto(s)
Acetilcisteína/farmacología , Embrión no Mamífero/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Maneb/toxicidad , Pez Cebra , Zineb/toxicidad , Animales , Conducta Animal/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Ensayo Cometa , Daño del ADN/efectos de los fármacos , Fungicidas Industriales/antagonistas & inhibidores , Fungicidas Industriales/toxicidad , Maneb/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Zineb/antagonistas & inhibidores
3.
Toxicol Ind Health ; 30(6): 561-9, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23024109

RESUMEN

Mancozeb is a fungicide belonging to the ethylene-bisdithiocarbamate group and is widely used in agriculture. The aim of this study was to examine the protective effect of quercetin (QRN) against oxidative stress induced by mancozeb in human erythrocytes. In order to verify this, 5 ml of venous blood was collected and the erythrocytes were separated and divided into equal parts. One part was incubated with different concentrations of mancozeb (0, 10, 30, 100 µM) for 4 h at 37°C. The other part was preincubated with QRN (40 and 80 µM) for 30 min, followed by mancozeb (0, 10, 30, 100 µM) incubation for 4 h. We found reduction in the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH) along with elevated levels of lipid peroxide (LPO) in erythrocytes incubated with 30 and 100 µm of mancozeb. Pre-incubation with QRN (80 µM) reversed oxidative stress induced by mancozeb (30 µM) and inhibited LPO induced at 100 µM by 64.36%. QRN also reduced the haemolytic effect on erythrocytes but could not prevent the induction of haemolysis by mancozeb. Therefore, these results suggest that QRN may play a role in preventing the oxidative stress induced by mancozeb in human erythrocytes.


Asunto(s)
Eritrocitos/efectos de los fármacos , Fungicidas Industriales/farmacología , Maneb/farmacología , Estrés Oxidativo/efectos de los fármacos , Quercetina/farmacología , Zineb/farmacología , Adulto , Catalasa/sangre , Relación Dosis-Respuesta a Droga , Eritrocitos/química , Femenino , Fungicidas Industriales/efectos adversos , Glutatión/sangre , Hemoglobinas/análisis , Humanos , Peróxidos Lipídicos/sangre , Masculino , Maneb/antagonistas & inhibidores , Superóxido Dismutasa/sangre , Zineb/antagonistas & inhibidores
4.
Mutat Res ; 298(3): 157-61, 1993 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7678149

RESUMEN

Vitamin C, when administered concurrently with a pesticide (endosulfan, phosphamidon or mancozeb), could significantly decrease the frequency of pesticide-induced clastogenic and mitosis-disruptive changes in the bone marrow cells of young Swiss albino mice. Of the three doses (10, 20 or 40 mg/kg b.wt./day) of the vitamin, the one which is double the human therapeutic dose (20 mg/kg b.wt./day) was most effective as an antimutagen to be followed by 40 mg and 10 mg. None of these doses of vitamin C showed any genotoxicity of their own for the parameters studied here.


Asunto(s)
Antimutagênicos/farmacología , Ácido Ascórbico/administración & dosificación , Aberraciones Cromosómicas , Mutagénesis/efectos de los fármacos , Animales , Células de la Médula Ósea , Endosulfano/antagonistas & inhibidores , Maneb/antagonistas & inhibidores , Ratones , Ratones Endogámicos , Mitosis/efectos de los fármacos , Fosfamidón/antagonistas & inhibidores , Zineb/antagonistas & inhibidores
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