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1.
Toxicol Lett ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33609686

RESUMO

Neonicotinoids, which act as agonists of the nicotinic acetylcholine receptors of insects, are widely used pesticides worldwide. Although epidemiological studies revealed that the detection amounts of neonicotinoids in urine are higher in the elderly population than other age-groups, there is no available information regarding the risks of neonicotinoids to older mammals. This study was aimed to investigate aging-related differences in the behavioral effects of the neonicotinoid pesticide clothianidin (CLO). We acutely administered a sub-NOAEL level (5 mg/kg) of CLO to adult (12-week-old) and aging (90-week-old) mice and conducted four behavioral tests focusing on the emotional behavior. In addition, we measured the concentrations of CLO and its metabolites in blood, brain and urine. There were age-related changes in most parameters in all behavioral tests, and CLO significantly decreased the locomotor activity in the open field test and elevated plus-maze test in the aging group, but not in the adult group. The concentrations of most CLO and its metabolites were significantly higher in the blood and brain and were slightly lower in the urine in the aging group compared to the adult group. These findings should contribute to our understanding of age-related differences in the adverse effects of neonicotinoids in mammals.

2.
J Vet Med Sci ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33518607

RESUMO

Recently, it has been reported that neonicotinoid pesticides (NNs) are transferred from mother to child and are assumed to affect the next generation, but the behavioral effects of NN exposure at different developmental stages have not been investigated. We exposed mice to no-observed-adverse-effect level (NOAEL) doses of clothianidin (CLO) during the fetal and lactational period, and then evaluated the neurobehavioral effects in juvenile and adult mice. Significant increases in anxiety-like behavior and locomotor activity were observed in juveniles and adults, respectively, and neuronal activity and neurogenesis in the hippocampal dentate gyrus were affected in both stages. These results suggest that fetal and lactational exposure to CLO may inhibit neurogenesis and cause different behavioral abnormalities at different developmental stages.

3.
J Vet Med Sci ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563863

RESUMO

Recently, developmental exposure to clothianidin (CLO) has been shown to cause reproductive toxicity in male mice, but the effects in female mice remain to be clarified. Pregnant C57BL/6N mice were given a no-observed-adverse-effect-level (NOAEL) dose of CLO until weaning. We then examined ovaries of 3- or 10-week-old female offspring. In the CLO-administered group, morphological changes, a decrease in the immunoreactivity of the antioxidant enzyme glutathione peroxidase 4 (GPx4), and activation of genes in the steroid hormone biosynthesis pathway were observed in 3-week-old mice, and decreases of GPx4 immunoreactivity, 17OH-progesterone and corticosterone levels were observed in 10-week-old mice, along with high rates of infanticide and severe neglect, providing new evidence that developmental exposure to CLO affects juvenile and adult mice differently.

4.
J Vet Med Sci ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33487623

RESUMO

Hepatic steatosis is known to precede a continuum of events that lead to hepatic metabolic dysfunction, inflammation and carcinogenesis. Recently, studies have linked xenobiotic exposures to hepatic steatogenesis and its associated metabolic disorders; however, the underlying mechanisms remain elusive. This study aimed to elucidate the mechanistic role of imidacloprid in the prevalence of high fat diet (HFD)-induced liver steatosis, using a C57BL/6J mice model. Mice (3 weeks old) were fed with HFD and treated with 0.6 mg/kg bw/day (one-tenth of the NOAEL) of imidacloprid through water or diet, for 24 weeks. In a controlled group, mice were fed with only HFD. At the end of the study, imidacloprid treatment significantly potentiated HFD-induced body weight gain in mice. Also, imidacloprid increased the liver weights of mice, with complimentary reductions in mesenteric and gonadal white adipose tissue weights. Histopathological analysis of liver revealed a drastic steatosis in imidacloprid treated mice. Following a real-time qPCR analysis, imidacloprid upregulated transcriptions of hepatic fatty acid biosynthesis-related transcription factors and genes. Imidacloprid also induced hepatic expression of the gene encoding pregnane X receptor; but had no significant effect on hepatic expressions of liver X receptor and aryl hydrocarbon receptor. The imidacloprid treatment further enhanced serum alanine aminotransferase levels but downregulated hepatic antioxidant mRNA expressions. Ultimately, this study suggested an imidacloprid-potentiation effects on prevalence of HFD-induced liver steatosis via transcriptional modulations of the hepatic FA biosynthesis pathway.

5.
Sci Rep ; 11(1): 1063, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441793

RESUMO

The tick Rhipicephalus microplus is a harmful parasite of cattle that causes considerable economic losses to the cattle breeding industry. Although R. microplus saliva (Rm-saliva) contains several immunosuppressants, any association between Rm-saliva and the expression of immunoinhibitory molecules, such as programmed death (PD)-1 and PD-ligand 1 (PD-L1), has not been described. In this study, flow cytometric analyses revealed that Rm-saliva upregulated PD-1 expression in T cells and PD-L1 expression in CD14+ and CD11c+ cells in cattle. Additionally, Rm-saliva decreased CD69 expression in T cells and Th1 cytokine production from peripheral blood mononuclear cells. Furthermore, PD-L1 blockade increased IFN-γ production in the presence of Rm-saliva, suggesting that Rm-saliva suppresses Th1 responses via the PD-1/PD-L1 pathway. To reveal the upregulation mechanism of PD-1/PD-L1 by Rm-saliva, we analyzed the function of prostaglandin E2 (PGE2), which is known as an inducer of PD-L1 expression, in Rm-saliva. We found that Rm-saliva contained a high concentration of PGE2, and PGE2 treatment induced PD-L1 expression in CD14+ cells in vitro. Immunohistochemical analyses revealed that PGE2 and PD-L1 expression was upregulated in tick-attached skin in cattle. These data suggest that PGE2 in Rm-saliva has the potential to induce the expression of immunoinhibitory molecules in host immune cells.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33477475

RESUMO

Lead (Pb) is a metal toxicant of great public health concern. The present study investigated the applicability of the rat incisor in Pb exposure screening. The levels of lead in teeth (Pb-T) in the crown and root of incisors in laboratory Pb-exposed Sprague Dawley rats were quantified using inductively coupled plasma mass spectrometry (ICP-MS). The crown accumulated much Pb-T than the root of the Sprague Dawley rat incisor. The levels of lead in blood (Pb-B) were positively correlated with the Pb-T in the crown and root incisors of the Sprague Dawley rats. As an application of the Pb-T crown results in experimental rats, we subsequently analyzed the Pb-T in the crown incisors of Pb-exposed wild rats (Rattus rattus) sampled from residential sites within varying distances from an abandoned lead-zinc mine. The Pb-T accumulation in the crown of incisors of R. rattus rats decreased with increased distance away from the Pb-Zn mine. Furthermore, the Pb-T was strongly correlated (r = 0.85) with the Pb levels in the blood. Laser ablation ICP-MS Pb-T mappings revealed a homogenous distribution of Pb in the incisor with an increased intensity of Pb-T localized in the tip of the incisor crown bearing an enamel surface in both Sprague Dawley and R. rattus rats. These findings suggest that Pb-T in the crown incisor may be reflective of the rat's environmental habitat, thus a possible indicator of Pb exposure.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32979584

RESUMO

Neonicotinoid insecticides are used for agricultural and non-agricultural purposes worldwide. Pets are directly exposed to neonicotinoids in veterinary products and through environmental contamination. Cytochrome P450 (CYP) is among the most significant xenobiotic metabolizing enzymes that oxidizes several chemicals, including neonicotinoids. However, CYP activities and metabolite compositions of neonicotinoid metabolites are unknown in most domesticated pet species. Our objectives were to reveal the differences in metabolites of neonicotinoids (imidacloprid, clothianidin, and acetamiprid) and CYP activities among common pet species (cats and dogs), humans, and rats. The results indicated that the CYP-mediated neonicotinoid metabolism was different depending on species and each neonicotinoid. Among these four species, the kinetics of imidacloprid metabolism indicated that rats have the highest rate of oxidation of imidacloprid to 4OH-imidacloprid, while the greatest enzyme kinetics of imidacloprid metabolism to 5OH-imidacloprid were found in rats and humans. Clothianidin was rapidly metabolized to 1-methyl-3-nitroguanidine and dm-clothianidin in rats, but cats and humans showed the lowest formation of dm-clothianidin. CYP activities in metabolism of acetamiprid to dm-acetamiprid and N-acetyl-acetamiprid were determined to be significantly higher in humans compared to other species. However, further studies should be targeted at identifying the differences in hepatic metabolism of neonicotinoids in these species using recombinant CYP enzymes.

8.
Chemosphere ; 262: 127788, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33182082

RESUMO

Lead (Pb) interferes with various bodily functions. Although high blood Pb (Pb-B) levels in residents from Kabwe, Zambia have been reported, the accumulation pattern of other metals remains unknown. The study was designed to determine the Pb-B, blood cadmium (Cd-B), and zinc (Zn-B) values of 504 representative samples from Kabwe, as well as the potential associated adverse health effects. The Pb-B level ranged from 0.79 to 154.75 µg/dL and generally increased in areas near the mine. A significant elevation of Cd-B was observed in two areas (0.37 ± 0.26 and 0.32 ± 0.30 µg/L) where the two highest mean Pb-B levels were recorded. By contrast, the Zn-B values did not differ greatly with respect to area. Some blood biochemical parameters relating to hepatic and renal functions were out of the normal range in approximately 20-50% of studied adult participants. The δ-aminolevulinic acid dehydratase (δ-ALAD) activity was significantly inhibited in the two areas contaminated by Pb and Cd. A significant negative relationship was observed between metal levels and clinical parameters, e.g., between Pb-B and δ-ALAD for all the age categories and between Cd-B and the estimated glomerular filtration rate for all the age categories except 0-4 years. The elevated Cd-B in areas near the mine relative to the other areas suggested the potential adverse health effects of Cd and/or the interaction of Pb and Cd. A significant association of metal levels with clinical parameters also indicated the effects of metal exposure on hematopoietic, hepatic, and renal systems.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/análise , Metais/análise , Adulto , Cádmio/análise , Coleta de Dados , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Exposição Ambiental/estatística & dados numéricos , Monitoramento Ambiental/métodos , Taxa de Filtração Glomerular , Humanos , Fígado/química , Registros , Valores de Referência , Adulto Jovem , Zâmbia , Zinco
9.
Chemosphere ; 264(Pt 1): 128368, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33007566

RESUMO

Mass Nile crocodile (Crocodylus niloticus) deaths in Africa's premier conservation area, the Kruger National Park (KNP), prompted numerous studies to determine possible causes of the sudden die-offs. The majority highlighted the involvement of the anthropocene to crocodile mass mortalities. One of the potential causative agents was identified as legacy compounds such as organochlorine pesticides (OCPs) present in the various aquatic ecosystems of the KNP. Thus, this study aimed to quantify OCP levels in wild crocodiles from the aquatic systems associated with the KNP. As part of a larger study, muscle tissue samples were collected from tails of 12 wild crocodiles. Results indicated that eight of the 19 OCPs analysed for were quantifiable. These included DDTs (2130-167968 ng/g lw), chlordanes (BD - 7583 ng/g lw) and cyclodeines (BD - 872 ng/g lw). Measured concentrations indicated spatial- and sex-related differences in accumulation patterns. DDT and its metabolites, paricularly p,p'-DDE accumulated to the highest concentrations of the OCP groups. Levels of the different groups of OCPs were the highest recorded in recent history from any crocodilian tissue. The different measured OCP residues were between 2.5 and 120 times higher than levels reported in literature, depending on the compound. These results are of ecotoxicological significance and have several management implications. In view of individuals being sampled from a conservation area it emphasizes the fact that pollutants know no boundaries and that premier conservation areas such as the world renowned KNP may be some of the most contaminated areas of the world.

10.
Environ Int ; 144: 106081, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32889485

RESUMO

Food can be health-giving. A global transition towards plant-based diets may equally help curb carbon emissions, slow land-system change and conserve finite resources. Yet, projected benefits of such 'planetary health' diets imperfectly capture the environmental or societal health outcomes tied to food production. Here, we examine pesticide-related hazards of fruit and vegetable consumption, and list proven management alternatives per commodity, geography and chemical compound. Across countries, pesticide use in these alleged healthful foods is extensive with up to 97% food items containing residues and up to 42% posing dietary risks to consumers. Multiple residues are present in 70-92% of US- and China-grown stone fruit while 58% US cauliflower is tainted with neonicotinoid insecticides. Science-based alternatives and decision-support frameworks can help food producers reduce risks and potential harm by deliberately abstaining from pesticide use. As such, opportunities abound to advance 'win-win' diets that simultaneously nurture human health and conserve global biodiversity.

11.
Vet Anim Sci ; 9: 100095, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32734105

RESUMO

Vitamin K epoxide reductase (VKOR) is a target enzyme for anticoagulants, such as warfarin, that are used as medicines or rodenticides. Assessing VKOR activity is required to ensure the proper usage of these drugs. Dithiothreitol (DTT) is a typical disulfide reductant that is used as a substrate for in vitro VKOR assays. However, DTT is considered problematic because of its side effects. Tris(3-hydroxypropyl)phosphine (THP) has been found to be a reliable alternative to DTT, as shown by kinetic analyses of the VKOR with them. THP showed significantly lower V max and Km values than those of DTT; however, there was no significant difference in their V max/Km and IC50 for warfarin.

12.
Aquat Toxicol ; 227: 105607, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32861022

RESUMO

The ubiquitous contamination of environmental lead (Pb) remains a worldwide threat. Improper Pb mine waste disposal from an abandoned lead-zinc mine has recently unearthed widespread Pb poisoning in children in Kabwe Zambia. Although the adverse effects of Pb on human health have begun to receive attention, the ecotoxicological effects on aquatic vertebrates still need further investigation. In addition, there is paucity in the knowledge on the behavioural and molecular subcellular responses in larval zebrafish exposed to Pb within the range of environmental relevant concentration (average 3 µg/L with maximum of 94 µg/L) on aquatic organisms such as zebrafish. The adverse effects of environmentally relevant levels of Pb on larval zebrafish was evaluated by measuring swimming behaviour under alternating dark and light conditions. Larval zebrafish acutely exposed to environmentally relevant Pb exhibited neuro-behavioural alteration including enhanced hyperactivity under light conditions evidenced by increased distanced covered and speed compared to the control. The alteration of entire behavioral profiles was further associated with the disturbed expression patterns of mRNA level of key genes associated with antioxidant (HO-1, Ucp-2 and CoxI), proapoptotic gene (TP53), and antiapoptotic gene (Bcl-2). To our knowledge, this is the first report on the effects of environmentally relevant Pb levels from Kabwe, Zambia and their adverse neurobehavioural effects and subcellular molecular oxidative responses in larval zebrafish acutely exposed within a 30 min period. The current results would be beneficial in our understanding of the effects of low Pb levels acutely discharged into an aquatic environment and the life of aquatic organisms.


Assuntos
Chumbo/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Humanos , Larva/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Testes de Toxicidade Aguda
13.
Mar Pollut Bull ; 157: 111309, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32658675

RESUMO

Tsitsikamma and Sheffield Beach are two relatively pristine sites along the South African east coast representing warm temperate and subtropical biogeographic rocky shore intertidal ecosystems, respectively. Stable isotopes (δ15N and δ13C), metals and organochlorine pesticides (OCPs) were measured in 38 intertidal components to study biomagnification or biodilution of metals and OCPs in these marine food webs. Comparison of the four species common to both sites revealed that the highest Al, Fe and OCP concentrations were measured in intertidal organisms from Sheffield Beach and was attributed to diffuse input into the nearshore marine environment sources via estuaries and groundwater. All other metals were higher in intertidal organisms from Tsitsikamma and were attributed to the metal-rich phytoplankton blooms during upwelling events. There was no correlation between metal and OCP accumulation and dietary source (δ13C) or trophic level (δ15N). The application of trophic magnification factors (TMFs) using a relatively short benthic food chain indicated biomagnification for As, Cd, Cu, Se and Zn and biodilution of OCPs at both sites. Since these food chains represent only a small portion of the intertidal ecosystems we found limited evidence of biomagnification or biodilution of metals and OCPs across species. This was attributed to different dietary sources in the same food web and similar trophic levels being occupied by the same species in different food chains. We found that food web composition rather than temperature-based biogeographical distribution influenced trophic transfer of metals and OCPs.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água/análise , Ecossistema , Monitoramento Ambiental , Peixes , Cadeia Alimentar , África do Sul
14.
Environ Sci Technol ; 54(22): 14474-14481, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-32490671

RESUMO

We investigated the potential effects of different land use and other environmental factors on animals living in a contaminated environment. The study site in Kabwe, Zambia, is currently undergoing urban expansion, while lead contamination from former mining activities is still prevalent. We focused on a habitat generalist lizards (Trachylepis wahlbergii). The livers, lungs, blood, and stomach contents of 224 lizards were analyzed for their lead, zinc, cadmium, copper, nickel, and arsenic concentrations. Habitat types were categorized based on vegetation data obtained from satellite images. Multiple regression analysis revealed that land use categories of habitats and three other factors significantly affected lead concentrations in the lizards. Further investigation suggested that the lead concentrations in lizards living in bare fields were higher than expected based on the distance from the contaminant source, while those in lizards living in green fields were lower than expected. In addition, the lead concentration of lungs was higher than that of the liver in 19% of the lizards, implying direct exposure to lead via dust inhalation besides digestive exposure. Since vegetation reduces the production of dust from surface soil, it is plausible that dust from the mine is one of the contamination sources and that vegetation can reduce exposure to this.

15.
Environ Res ; 188: 109759, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32554272

RESUMO

BACKGROUND: Lead (Pb) is a well-known toxic heavy metal which can have serious public health hazards. As of today, there is no safe threshold for Pb exposure, especially for children. Lead exposure has been associated with adverse health outcomes involving epigenetic mechanisms, such as aberrant DNA methylation. The objective of the present study was to elucidate the associations between blood lead levels (BLLs) and gene-specific promoter DNA methylation status in environmental Pb-exposed children from Kabwe, Zambia. METHODS: A cross-sectional study was conducted using 2 to 10-year-old children from high Pb exposed area (N = 102) and low Pb exposed area (N = 38). We measured BLLs using a LeadCare II analyzer and investigated the methylation status of the ALAD and p16 gene promoters by methylation-specific PCR. RESULTS: The mean BLLs were 23.7 µg/dL and 7.9 µg/dL in high Pb exposed and low Pb exposed children, respectively. Pb exposure was correlated with increased methylation of the ALAD and p16 genes. The promoter methylation rates of ALAD and p16 in high Pb exposed children were 84.3% and 67.7%, and 42.1% and 44.7% in low Pb exposed children, respectively. Significantly increased methylation was found in both genes in high Pb exposed children compared with low Pb exposed children (p < 0.05). Children with methylated ALAD and p16 genes showed an increased risk of Pb poisoning (odd ratio >1) compared to the unmethylated status. CONCLUSIONS: This study for the first time tries to correlate promoter methylation status of the ALAD and p16 genes in environmental Pb-exposed children from Kabwe, Zambia as a representative. The result suggests that Pb exposure increases aberrations in ALAD and p16 gene methylation, which may be involved in the mechanism of Pb toxicity.


Assuntos
Intoxicação por Chumbo , Chumbo , Criança , Pré-Escolar , Estudos Transversais , Metilação de DNA , Genes p16 , Humanos , Chumbo/toxicidade , Intoxicação por Chumbo/epidemiologia , Intoxicação por Chumbo/genética , Sintase do Porfobilinogênio/genética , Zâmbia
16.
J Vet Med Sci ; 82(8): 1118-1123, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32554936

RESUMO

Birds of a number of species have died as a result of lead (Pb) poisoning, including many Steller's sea eagles (Haliaeetus pelagicus) and white-tailed sea eagles (Haliaeetus albicilla) in Hokkaido, the northernmost island of Japan. To address this issue, the use of any type of Pb ammunition for hunting of large animals was prohibited in Hokkaido in 2004. However, Pb poisoning is still being reported in this area, and there are few regulations regarding the use of Pb ammunition in other parts of Japan, where it has been reported that eagles and water birds have been exposed to Pb. This study was performed to accurately determine the current level of Pb exposure of birds found dead in the field or dead in the wild bird centers in Japan (June 2015-May 2018) and to identify the sources of Pb. Pb exposure was found to still be occurring in raptors and water birds in various parts of Japan. Twenty-six point five % and 5.9% of the recorded deaths of Steller's sea eagles and white-tailed sea eagles, respectively, were found to have been poisoned by Pb. In addition, Pb isotope ratio analysis showed that both Pb rifle bullets and Pb shot pellets cause Pb exposure in birds, and these endangered eagles are also exposed to Pb in Hokkaido due to the illegal use of Pb ammunition. Changing to Pb-free ammunition, such as copper (Cu) rifle bullets, steel shot pellets, or bismuth shot pellets, will be essential for the conservation of avian species in Japan.

17.
J Vet Med Sci ; 82(7): 978-982, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32435004

RESUMO

The knowledge of cytochrome P450 (CYP) expression involved in chemical exposure are necessary in clinical applications for the medication and prediction of adverse effects. The aim of this study was to evaluate the mRNA expression of CYP1-CYP3 families in cats exposed to BDE-209 for one year. All selected CYP isoforms showed no significant difference in mRNA expressions between control and exposure groups, however, CYP3A12 and CYP3A131 revealed tend to be two times higher in the exposure group compared to control group. The present results indicate that the chronic exposure of BDE209 could not alter CYP expression in the liver of cats. This result considered caused by the deficiency of CYP2B subfamily which is major metabolism enzyme of polybrominated diphenyl ethers (PBDEs) in cat.

18.
Curr Biol ; 30(4): 723-728.e3, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32008901

RESUMO

Plastic debris is ubiquitous and increasing in the marine environment [1]. A wide range of marine organisms ingest plastic, and its impacts are of growing concern [2]. Seabirds are particularly susceptible to plastic pollution because of high rates of ingestion [3]. Because marine plastics contain an array of hazardous compounds, the chemical impacts of ingestion are concerning. Several studies on wild seabirds suggested accumulation of plastic-derived chemicals in seabird tissues [4-7]. However, to date, the evidence has all been indirect [4-7], and it is unclear whether plastic debris is the source of these pollutants. To obtain direct evidence for the transfer and accumulation of plastic additives in the tissues of seabirds, we conducted an in vivo plastic feeding experiment. Environmentally relevant exposure of plastics compounded with one flame retardant and four ultraviolet stabilizers to streaked shearwater (Calonectris leucomelas) chicks in semi-field conditions resulted in the accumulation of the additives in liver and adipose fat of 91 to 120,000 times the rate from the natural diet. Additional monitoring of six seabird species detected these chemical additives only in those species with high plastic ingestion rates, suggesting that plastic debris can be a major pathway of chemical pollutants into seabirds. These findings provide direct evidence of seabird exposure to plastic additives and emphasize the role of marine debris ingestion as a source of chemical pollution in marine organisms.

19.
Toxicol Lett ; 322: 32-38, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31923464

RESUMO

Neonicotinoids (NNs), a widely used class of systemic pesticides, are regarded as exhibiting selective toxicity in insects. However, NNs are suspected of exerting adverse effects on mammals as well, including humans. To date, only adult male animal models have been subjected to general toxicity studies of NNs; fetuses have yet to be considered in this context. Here, we focused on the NN clothianidin (CLO) for the first quantitative LC-MS/MS analysis of maternal-to-fetal transfer and residual property of once-daily (single or multiple days), orally administered CLO and its metabolites in mice. The results revealed the presence of CLO and its five metabolites at approximately the same respective blood levels in both dams and fetuses. In the dams, CLO showed a peak value 1 h after administration, after which levels rapidly decreased at 3 and 6 h. In the fetuses of each group, levels of CLO were almost the same as those observed in the corresponding dams. The present results clearly demonstrated rapid passage of CLO through the placental barrier. However, metabolite-dependent differences observed in blood pharmacokinetics and residual levels. This is the first quantitative demonstration of the presence of CLO and its metabolites in fetal mouse blood.


Assuntos
Sangue Fetal/metabolismo , Guanidinas/sangue , Inseticidas/sangue , Troca Materno-Fetal , Neonicotinoides/sangue , Tiazóis/sangue , Animais , Biotransformação , Feminino , Guanidinas/administração & dosagem , Guanidinas/farmacocinética , Guanidinas/toxicidade , Inseticidas/administração & dosagem , Inseticidas/farmacocinética , Inseticidas/toxicidade , Exposição Materna , Camundongos Endogâmicos ICR , Neonicotinoides/administração & dosagem , Neonicotinoides/farmacocinética , Neonicotinoides/toxicidade , Gravidez , Medição de Risco , Tiazóis/administração & dosagem , Tiazóis/farmacocinética , Tiazóis/toxicidade , Toxicocinética
20.
J Vet Med Sci ; 82(3): 350-359, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-31983702

RESUMO

Dinotefuran (DIN) belongs to the neonicotinoids (NNs), a class of globally applied pesticides originally developed to exhibit selective toxicity in insects. However, several reports have suggested that NNs also exert neurotoxic effects in mammals. We previously demonstrated neurobehavioral effects of DIN on mice under non-stressful conditions. For further toxicity assessments in the present study, we investigated the effects of DIN on mice exposed to stressful conditions. After subacutely administering a no-observed-effect-level (NOEL) dose of DIN and/or chronic unpredictable mild stress (CUMS) to mice, we conducted three behavioral tests (i.e., open field test [OFT], tail suspension test [TST] and forced swimming test [FST]). In addition, serotonin (5-HT) and tryptophan hydroxylase 2 (TPH2) of the dorsal raphe nuclei (DRN) and median raphe nuclei (MRN) and tyrosine hydroxylase (TH) of the ventral tegmental area and substantia nigra (SN) were evaluated immunohistochemically. A NOEL dose of DIN or CUMS alone increased of the total distance in OFT, decreased or increased the immobility time in TST or FST, respectively, and increased the positive intensity of 5-HT and TPH2 in the DRN/MRN, and TH in the SN. These changes were suppressed under the conditions of combined exposure to DIN and CUMS, though the blood corticosterone level was increased depending on the blood DIN values and the presence of CUMS. The present study suggests the multifaceted toxicity of the neurotoxin DIN.


Assuntos
Encéfalo/metabolismo , Guanidinas/toxicidade , Neonicotinoides/toxicidade , Nitrocompostos/toxicidade , Estresse Psicológico , Animais , Comportamento Animal/efeitos dos fármacos , Corticosterona/sangue , Emoções/fisiologia , Comportamento Exploratório/efeitos dos fármacos , Guanidinas/sangue , Elevação dos Membros Posteriores , Inseticidas/toxicidade , Masculino , Camundongos Endogâmicos C57BL , Neonicotinoides/sangue , Nitrocompostos/sangue , Serotonina/metabolismo , Natação , Triptofano Hidroxilase/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo
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