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1.
Braz. j. biol ; 84: e256916, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1355874

RESUMO

Abstract Crotalaria (Fabaceae) occurs abundantly in tropical and subtropical regions and has about 600 known species. These plants are widely used in agriculture, mainly as cover plants and green manures, in addition to their use in the management of phytonematodes. A striking feature of these species is the production of pyrrolizidine alkaloids (PAs), secondary allelochemicals involved in plant defense against herbivores. In Crotalaria species, monocrotaline is the predominant PA, which has many biological activities reported, including cytotoxicity, tumorigenicity, hepatotoxicity and neurotoxicity, with a wide range of ecological interactions. Thus, studies have sought to elucidate the effects of this compound to promote an increase in flora and fauna (mainly insects and nematodes) associated with agroecosystems, favoring the natural biological control. This review summarizes information about the monocrotaline, showing such effects in these environments, both above and below ground, and their potential use in pest management programs.


Resumo Crotalaria (Linnaeus, 1753) (Fabaceae) ocorre abundantemente em regiões tropicais e subtropicais e tem cerca de 600 espécies conhecidas. Estas plantas são amplamente utilizadas na agricultura, principalmente como cobertura e adubos verdes, além da sua utilização no manejo de fitonematoides. Uma característica marcante destas espécies é a produção de alcalóides pirrolizidinicos (APs), aleloquímicos secundários envolvidos na defesa das plantas contra os herbívoros. Nas espécies de Crotalaria, a monocrotalina é a AP predominante, que tem muitas atividades biológicas relatadas, incluindo citotoxicidade, tumorigenicidade, hepatotoxicidade e neurotoxicidade, além de uma vasta gama de interações ecológicas. Assim, estudos têm procurado elucidar os efeitos desse composto para promover um incremento na flora e fauna (principalmente insetos e nematoides) associados aos agroecossistemas, favorecendo o controle biológico natural. Esta revisão compila informações sobre a monocrotalina, mostrando tais efeitos nesses ambientes, tanto acima como abaixo do solo e a sua potencial utilização em programas de manejo de pragas.


Assuntos
Animais , Artrópodes , Alcaloides de Pirrolizidina , Crotalaria , Fabaceae , Monocrotalina/toxicidade
2.
Braz. j. biol ; 84: e251289, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1355889

RESUMO

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.


Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.


Assuntos
Animais , Coelhos , Dano ao DNA , Antineoplásicos , Testes para Micronúcleos , Relação Dose-Resposta a Droga , Eritrócitos , Cloridrato de Venlafaxina/toxicidade
3.
Sci Rep ; 13(1): 1824, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36725877

RESUMO

Water quality index (WQI) of Narora channel and health of endemic fish Bagarius bagarius and plant Eichhornia crassipes, district Bulandshahar, Uttar Pradesh, India were studied. Among the physicochemical properties of water, pH, D.O, Cr, Fe, Ni, and Cd were above the recommended standards. These factors lead to high WQI (4124.83), indicating poor quality and not suitable for drinking and domestic usage. In fish tissues, the highest metal load was reported in the liver (58.29) and the lowest in the kidney (33.73). Heavy metals also cause a lowering of condition indices. As expected, decreased serum protein (- 63.41%) and liver glycogen (- 79.10%) were recorded in the exposed fish. However, blood glucose (47.22%) and serum glycogen (74.69%) showed elevation. In the plant, roots (21.50) contained the highest, and leaves (16.87) had the lowest heavy metal load. Bioaccumulation factor (BAF) > 1, indicates hyperaccumulation of all metals. E. crassipes roots showed the highest translocation factor (TF) > 1 for Ni (1.57) and Zn (1.30). The high mobility factor (MF) reflected the suitability of E. crassipes for phytoextraction of Mn, Cd, Zn, Fe, Ni, and Cu. Moreover, Bagarius sp. consumption could not pose any non-cancer risk. Although, lower cancer risk can be expected from Ni and Cr.


Assuntos
Eichhornia , Metais Pesados , Poluentes Químicos da Água , Biomarcadores Ambientais , Eichhornia/química , Cádmio , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Metais Pesados/toxicidade , Metais Pesados/análise , Plantas , Medição de Risco , Monitoramento Ambiental
4.
FASEB J ; 37(3): e22792, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36723904

RESUMO

Cistanche tubulosa (Schrenk) Wight, named Guan hua Rou Cong-Rong in Chinese, is a traditional plant with liver, kidney, and intestine protective effects. Echinacoside (ECH) is its active constituent and has been found to have various biological effects, including antioxidative stress and anti-inflammatory effects. Liver injury caused by acetaminophen or CCL4 has been proven to benefit from ECH; however, the effects of ECH against alcoholic liver disease (ALD) remain unclear. This study was used to estimate the effect of echinacoside on nuclear factor erythroid 2-related factor 2 (Nrf2), which ameliorates ALD by inhibiting oxidative stress and cell apoptosis through affecting Nrf2.A mouse model of ALD was established with ethanol using hematoxylin and eosin (HE) staining, oiled staining, and biochemical indices. Alpha Mouse Liver 12 (AML-12) cells were induced with ethanol in vitro and analyzed using western blotting, flow cytometry, and biochemical assays. In the animal model of ALD, ECH dramatically reduced liver damage, as proven by the downregulation of aspartate aminotransferase (AST) and HE staining. In vitro, ECH distinctly reduced the damage caused by ethanol through the decreased expression of cleaved caspase-3 measured by western blotting. ECH significantly increased the activity of Nrf2 in vivo and in vitro. Nrf2 knockout may diminish the influence of ECH on ALD. Meanwhile, ECH also increased the expression of haem oxygenase-1 (HO-1) and glutamate-cysteine ligase catalytic subunit (GCLC), while it inhibited levels of oxidative stress and cell apoptosis. Our findings suggest that ECH protects against ethanol-induced liver injuries by alleviating oxidative stress and cell apoptosis by increasing the activity of Nrf2. Therefore, ECH is promising for the treatment of ALD.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Cistanche , Camundongos , Animais , Cistanche/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Fígado/metabolismo , Estresse Oxidativo , Etanol/toxicidade
5.
Yakugaku Zasshi ; 143(2): 133-138, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-36724927

RESUMO

Neurodevelopment is one of the most complex events in human growth and is very sensitive to disruption. Various genetic factors are the main causes of neuronal dysfunction; however, recent epidemiological studies have also revealed relationships between environmental factors and the onset of neurodevelopmental disorders. Humans are regularly exposed to a wide range of environmental factors, among which fine particles have attracted recent interest. In this regards, the development of products containing nanomaterials has expanded substantially in a wide variety of fields including medicine, food, and cosmetics. As the size of the particles in these nanomaterials decreases, their reactivity at the tissue interface and their tissue penetration increases. In addition, the reduction of particle size could alter kinetics and lead to unexpected biological effects compared with those seen with conventional materials. Thus, we need to identify potential sources of unpredictable adverse effects of nanomaterials on neurodevelopment to ensure their safe use. From this perspective, nano-safety science research has been conducted through the collection of toxicity information on nanoparticles based on their physicochemical properties and kinetics via the association analysis of physicochemical properties, kinetics, and toxicity. The results of this nano-safety science research were then used in nano-safety design research to develop safer forms of nanomaterials. In this paper, we introduce findings that demonstrate that nanomaterials translocate into the brain and describe the effects on cranial nerves.


Assuntos
Nanopartículas , Nanoestruturas , Humanos , Nanopartículas/efeitos adversos , Nanoestruturas/toxicidade , Tamanho da Partícula , Medição de Risco , Diferenciação Celular
6.
Yakugaku Zasshi ; 143(2): 159-170, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-36724929

RESUMO

We investigated the cytotoxicity on a mast cell line (C57 cells) of water-soluble extracts of coarse (>3 µm, PM>3) and fine (0.05-3 µm, PM0.05-3) atmospheric particulates collected from April 2016 to March 2019 in Fukuoka, Japan. We examined the direct cytotoxicity with punched-out membrane filter fragments of PM>3 and PM0.05-3 collected from April 2019 to March 2021, without extraction of the components. Also, cell proliferation and degranulation assays were conducted under conditions which caused no cytotoxicity with water-soluble extracts of PM>3 from FY2016 and PM>3 direct samples from FY2019. The findings revealed the significant direct cytotoxicity of many PM>3 and all PM0.05-3 samples, with higher cytotoxicity for PM0.05-3 (FY2019-2020). These results were different from the cytotoxicity effects of water-soluble extracts of PM>3 and PM0.05-3 samples (FY2016) in previous studies. In addition, inhibition of cell proliferation and induction of degranulation were significantly induced in a few PM>3 samples, showing a correlation with the suspended particulate matter (SPM) concentrations. This method using punched-out membrane filters is convenient and useful for assessing the direct effects of atmospheric particles on a small scale.


Assuntos
Poluentes Atmosféricos , Material Particulado , Material Particulado/toxicidade , Material Particulado/análise , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Tamanho da Partícula , Linhagem Celular , Água
7.
Biol Pharm Bull ; 46(2): 359-363, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36724966

RESUMO

Amyloid ß (Aß) plays a key role in the pathology of Alzheimer's disease (AD) and is toxic owing to its ability to aggregate into oligomers and fibrils. Aß has high aggregative ability and potent toxicity due to the "toxic turn" at positions 22 and 23. Furthermore, APP knock-in mice producing E22P-Aß with the toxic turn exhibited AD-related phenotypes such as cognitive impairment, Aß plaque accumulation, and tau hyperphosphorylation. In these mice, it is suggested that the activation of neuroinflammation and dysregulation of hypoxia-inducible factor (HIF) expression in the hippocampus contribute to the pathogenesis of AD-related phenotype. However, it remains unclear which cells are responsible for the dysregulation of HIF expression and the neuroinflammation which was induced by E22P-Aß with the toxic turn. Here, we investigated the effects of chronic treatment with E22P-Aß42 and lipopolysaccharides (LPS) on the inflammatory response in BV-2 microglia. Chronic treatment with E22P-Aß42 and LPS increased nitric oxide production and the expression of interleukin-6 (IL-6), whereas it reduced the expression of HIF-1α and HIF-3α in BV-2 microglia. The reduction of HIF-1α caused by E22P-Aß42 and LPS was milder than that caused by LPS. Furthermore, chronic treatment with E22P-Aß42 and LPS increased the nuclear translocation of nuclear factor-kappaB (NF-κB). E22P-Aß42 could enhance the inflammatory response of microglia with abnormal HIF signaling and contribute to the progression of AD pathology.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Camundongos , Animais , Peptídeos beta-Amiloides/metabolismo , Microglia , Lipopolissacarídeos/toxicidade , Doenças Neuroinflamatórias , Doença de Alzheimer/metabolismo , Hipóxia
8.
Biol Pharm Bull ; 46(2): 320-333, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36724960

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by dementia. The most characteristic pathological changes in AD brain include extracellular amyloid-ß (Aß) accumulation and neuronal loss. Particularly, cholinergic neurons in the nucleus basalis of Meynert are some of the first neuronal groups to degenerate; accumulating evidence suggests that Aß oligomers are the primary form of neurotoxicity. Bacopa monniera is a traditional Indian memory enhancer whose extract has shown neuroprotective and Aß-reducing effects. In this study, we explored the low molecular weight compounds from B. monniera extracts with an affinity to Aß aggregates, including its oligomers, using Aß oligomer-conjugated beads and identified plantainoside B. Plantainoside B exhibited evident neuroprotective effects by preventing Aß attachment on the cell surface of human induced pluripotent stem cell (hiPSC)-derived cholinergic neurons. Moreover, it attenuated memory impairment in mice that received intrahippocampal Aß injections. Furthermore, radioisotope experiments revealed that plantainoside B has affinity to Aß aggregates including its oligomers and brain tissue from a mouse model of Aß pathology. In addition, plantainoside B could delay the Aß aggregation rate. Accordingly, plantainoside B may exert neuroprotective effects by binding to Aß oligomers, thus interrupting the binding of Aß oligomers to the cell surface. This suggests its potential application as a theranostics in AD, simultaneously diagnostic and therapeutic drugs.


Assuntos
Doença de Alzheimer , Bacopa , Células-Tronco Pluripotentes Induzidas , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Camundongos , Humanos , Animais , Bacopa/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Células-Tronco Pluripotentes Induzidas/metabolismo , Peptídeos beta-Amiloides/toxicidade , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/tratamento farmacológico , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico
9.
J Toxicol Sci ; 48(2): 57-64, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36725021

RESUMO

In non-clinical animal studies for drug discovery, histopathological evaluation is the most powerful tool to assess testicular toxicity. However, histological analysis is extremely invasive; many experimental animals are needed to evaluate changes in the pathology and anatomy of the testes over time. As an alternative, small animal magnetic resonance imaging (MRI) offers a non-invasive methodology to examine testicular toxicity without radiation. The present study demonstrated the suitability of a new, ready-to-use compact MRI platform using a high-field permanent magnet to assist with the evaluation of testicular toxicity. To validate the utility of the MRI platform, male mice were treated with busulfan (40 mg/kg, intraperitoneal injection). Twenty-eight days after treatment, both testes in busulfan-treated and control mice (n = 6/group) were non-invasively scanned in situ by MRI at 1 tesla. On a T1-weighted 3D gradient-echo MRI sequences (voxel size: 0.23 × 0.23 × 0.50 mm), the total testicular volume in busulfan-treated mice was significantly smaller than in controls. On T1-weighted images, the signal intensity of the testes was significantly higher in busulfan-treated mice than in controls. The mice were sacrificed, and the testes were isolated for histopathological analysis. The weight of the testes in busulfan-treated mice significantly decreased, similar to the results of the non-invasive analysis. Additionally, periodic acid-Schiff stain-positive effusions were observed in the interstitium of the busulfan-treated mouse testes, potentially explaining T1 shortening due to a high concentration of glycoproteinaceous content. The present data demonstrated a rapid evaluation of testicular toxicity in vivo by compact MRI.


Assuntos
Espermatogênese , Testículo , Masculino , Camundongos , Animais , Testículo/diagnóstico por imagem , Bussulfano/toxicidade , Injeções Intraperitoneais , Imageamento por Ressonância Magnética
10.
J Toxicol Sci ; 48(2): 65-73, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36725022

RESUMO

Lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, induces various biological reactions in vivo. Our previous study suggested that LPS administration disrupts respiratory chain complex activities, enhances reactive oxygen species production, especially in the liver mitochondria, and sensitizes mitochondrial permeability transition (MPT) pore opening in rats. However, it is unknown whether LPS-induced MPT pore opening in rats is similarly observed in mice and whether the mechanism is the same. LPS administration to mice increased not only cyclosporin A-sensitive swelling (MPT pore opening) susceptibility, but also induced cyclosporin A-insensitive basal swelling, unlike in rats. In addition, respiratory activity observed after adding ADP was significantly decreased. Based on these results, we further investigated the role of adenine nucleotide translocase (ANT). Carboxyatractyloside (CATR; an ANT inhibitor) treatment decreased respiratory activity after ADP was added in vehicle-treated mitochondria similarly to LPS administration. Additionally, CATR treatment increased MPT pore opening susceptibility in LPS-treated mitochondria compared to that of vehicle-treated mitochondria. Our study shows that ANT maintained a c-state conformation upon LPS administration, which increased MPT pore opening susceptibility in mice. These results suggest that LPS enhances MPT pore opening susceptibility across species, but the mechanism may differ between rat and mouse.


Assuntos
Lipopolissacarídeos , Poro de Transição de Permeabilidade Mitocondrial , Ratos , Camundongos , Animais , Lipopolissacarídeos/toxicidade , Ciclosporina/farmacologia , Mitocôndrias Hepáticas/metabolismo , Translocases Mitocondriais de ADP e ATP , Fígado/metabolismo , Cálcio/metabolismo , Permeabilidade
11.
J Toxicol Sci ; 48(2): 75-86, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36725023

RESUMO

Quaternary ammonium compounds, including benzalkonium chloride (BAC) and cetylpyridinium chloride (CPC), are widely used as disinfectants. Increased use of inhalable products containing BAC or CPC has raised concerns for lung toxicity. This study sought to elucidate the microstructure of plasma membrane damage caused by BAC and CPC and the subsequent mechanism by which the damage is mediated, as assessed using two human pulmonary epithelial cell lines (A549 and BEAS-2B). Scanning electron microscopic observation showed that exposure to BAC or CPC for 3 hr reduced the length and density of microvilli on the plasma membrane in A549 cells. Analysis of cell cycle distribution following plasma membrane damage revealed that BAC and CPC promote G0/G1 cell cycle arrest in both cell lines. The protein levels of Cdc6, an essential regulator of DNA replication during G1/S transition, are decreased significantly and dose dependently by BAC or CPC exposure. CPC and BAC decreased the Cdc6 levels that had been increased by a PI3K agonist in A549 cells, and levels of phosphorylated AKT were reduced in response to BAC or CPC. Conversely, exposure to equivalent concentrations of pyridinium chloride (lacking a hydrocarbon tail) induce no changes. These results suggest that plasma membrane damage triggered by BAC or CPC causes Cdc6-dependent G0/G1 cell cycle arrest in pulmonary cells. These effects are attributable to the long alkyl chains of BAC and CPC. The reduction of Cdc6 following plasma membrane damage may be caused, at least in part, by diminished signaling via the PI3K/AKT pathway.


Assuntos
Compostos de Benzalcônio , Cetilpiridínio , Humanos , Compostos de Benzalcônio/toxicidade , Cetilpiridínio/toxicidade , Cetilpiridínio/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pulmão , Células Epiteliais , Pontos de Checagem do Ciclo Celular , Membrana Celular , Proteínas Nucleares/metabolismo , Proteínas Nucleares/farmacologia , Proteínas de Ciclo Celular/metabolismo
12.
J Toxicol Sci ; 48(2): 87-97, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36725024

RESUMO

Mammalian cells generate ATP through mitochondrial respiration and glycolysis. Mitochondria not only play a key role in cell energy metabolism but also in cell cycle regulation. As a neurotoxic pollutant, benzo(a)pyrene (BaP) can trigger neuronal oxidative damage and apoptosis. However, the features of BaP-induced energy metabolism disturbance in SH-SY5Y cells has rarely been addressed. This study aimed to measure oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) as indications of respiratory activities and glycolytic. SH-SY5Y cells were treated with BaP to establish a cytotoxicity model, and butylated hydroxy anisole (BHA) was used to alleviate the damages induced by BaP. Using the Seahorse Extracellular Flux analyzer (XFp), we found that BaP significantly reduced basal respiration, ATP-linked OCR in SH-SY5Y cells with dose- and time-dependent. BHA supplementation recovered the mitochondrial respiration, synchronously attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers, then rescued BaP-induced cell apoptosis. But long-term exposure to BaP or exposure to a high dosage of BaP could decrease OCR associated with maximal respiratory, spare capacity, and glycolysis metabolism. At the same time, the damage to cells is also more severe with the rate of apoptosis and mitochondrial membrane potential (ΔΨm) loss rising sharply, which were not entirely reversed by BHA. This study provides energy metabolism-related, indicative biomarkers of cytotoxicity induced by BaP, which might provide information for early prevention and intervention.


Assuntos
Benzo(a)pireno , Neuroblastoma , Animais , Humanos , Benzo(a)pireno/toxicidade , Neuroblastoma/metabolismo , Glicólise , Mitocôndrias/metabolismo , Respiração , Trifosfato de Adenosina/metabolismo , Mamíferos/metabolismo
13.
Zhongguo Zhong Yao Za Zhi ; 48(1): 193-201, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36725271

RESUMO

Alcoholic liver disease(ALD), with its increasing morbidity and mortality, has seriously and extensively affected the health of people worldwide. Methyl ferulic acid(MFA) has been proven to significantly inhibit alcohol-induced lipid production in L02 cells through the AMP-activated protein kinase(AMPK) pathway, but its in-depth mechanism remains unclear. This study aimed to further clarify the mechanism of MFA in improving lipid accumulation in L02 cells through the microRNA-378b(miR-378b)-mediated calcium/calmodulin-dependent protein kinase kinase 2(CaMKK2)-AMPK signaling pathway based on existing researches. L02 cells were induced by 100 mmol·L~(-1) ethanol for 48 h to establish the model of ALD in vitro, and 100, 50, and 25 µmol·L~(-1) concentration of MFA was treated. MiR-378b plasmids(containing the overexpression plasmid-miR-378b mimics, silence plasmid-miR-378b inhibitor, and their respective negative control-miR-378b NCs) were transfected into L02 cells by electroporation to up-regulate or down-regulate the levels of miR-378b in L02 cells. The levels of total cholesterol(TC) and triglyceride(TG) in cells were detected by commercial diagnostic kits and automatic biochemical analyzers. The expression levels of miR-378b in L02 cells were detected by real-time quantitative polymerase chain reaction(qRT-PCR). CaMKK2 mRNA levels were detected by PCR, and protein expressions of related factors involved in lipid synthesis, decomposition, and transport in lipid metabolism were detected by Western blot. The results displayed that ethanol significantly increased TG and TC levels in L02 cells, while MFA decreased TG and TC levels. Ethanol up-regulated the miR-378b level, while MFA effectively inhibited the miR-378b level. The overexpression of miR-378b led to lipid accumulation in ethanol-induced L02 cells, while the silence of miR-378b improved the lipid deposition induced by ethanol. MFA activated the CaMKK2-AMPK signaling pathway by lowering miR-378b, thus improving lipid synthesis, decomposition, and transport, which improved lipid deposition in L02 cells. This study shows that MFA improves lipid deposition in L02 cells by regulating the CaMKK2-AMPK pathway through miR-378b.


Assuntos
Fígado Gorduroso , MicroRNAs , Humanos , Etanol/toxicidade , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Triglicerídeos , MicroRNAs/genética , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/genética
14.
Sci Total Environ ; 865: 161307, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36596421

RESUMO

Research utilizing the model soil nematode Caenorhabditis elegans has revealed that agriculturally relevant nanoparticles (NP), such as zinc oxide NP (ZnONP), cause toxicity at low concentrations and disrupt molecular pathways of pathogen resistance. However, in most nanotoxicity assessments, model organisms are exposed to a single stressor but in nature organisms are affected by multiple sources of stress, including infections, which might exacerbate or mitigate negative effects of NP exposure. Thus, to expand our understanding of the environmental consequences of released NP, this project examined the synergistic/antagonistic effects of ZnONP on C. elegans infected with a common pathogen, Klebsiella pneumoniae. Individual exposures of C. elegans to ZnONP, zinc sulfate (Zn2+ ions) or K. pneumoniae significantly decreased nematode reproduction compared to controls. To assess the combined stress of ZnONP and K. pneumoniae, C. elegans were exposed to equitoxic EC30 concentrations of ZnONP (or Zn ions) and K. pneumoniae. After the combined exposure there was no decrease in reproduction. This complete elimination of reproductive toxicity was unexpected because exposures were conducted at EC30 Zn concentrations and reproductive toxicity due to Zn should have occurred. Amelioration of the pathogen effects by Zn are partially explained by the Zn impact on the K. pneumoniae biofilm. Quantitative assessments showed that external biofilm production and estimated colony forming units (CFU) of K. pneumoniae within the nematodes were significantly decreased. Taken together, our results suggest that during the combined exposure of C. elegans to both stressors Zn in ionic or particulate form inhibits K. pneumoniae ability to colonize nematode's intestine through decreasing pathogen biofilm formation. This highlights the unpredictable nature of combined stressor effects, calling into question the utility of exposures in simplified laboratory media.


Assuntos
Nanopartículas , Óxido de Zinco , Animais , Caenorhabditis elegans , Óxido de Zinco/farmacologia , Klebsiella pneumoniae , Solo , Nanopartículas/toxicidade , Íons/metabolismo
16.
Curr Opin Pulm Med ; 29(2): 65-75, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36695765

RESUMO

PURPOSE OF REVIEW: There is a considerable burden of silica-associated lung diseases in the developing world. This review summarizes the epidemiology of these diseases, especially silicosis and silico-tuberculosis, mitigative efforts and treatment, especially in the context of developing countries. RECENT FINDINGS: In 2017, the highest incidence of silicosis was in China, India and Brazil among the developing countries. The prevalence of silicosis amongst exposed workers may vary from 4 to 55%; there is a risk of underestimation because of the 'healthy worker effect'. The permissible exposure limit for respirable silica adopted by governments in developing countries remains higher than the proposed 0.025 mg/m3. Silica exposure in informal or unorganized industries is challenging, as it falls outside statutory controls. Recent efforts on regulation and compensation by various governments in developing countries are encouraging but need proper implementation on the ground. Biomarkers such as club cell protein 16 and imaging methods such as computed tomography may offer earlier and easier detection of silicosis. Advanced silicosis remains incurable; novel treatments such as antifibrotics agents may be potentially effective. SUMMARY: Silica-associated lung diseases are prevalent in developing countries. Efforts directed at preventing or minimizing exposure to respirable crystalline silica are required for mitigation.


Assuntos
Exposição Ocupacional , Silicose , Humanos , Dióxido de Silício/toxicidade , Países em Desenvolvimento , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/prevenção & controle , Silicose/epidemiologia , Incidência
17.
Environ Health Perspect ; 131(1): 17004, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36695591

RESUMO

BACKGROUND: Fine particulate matter (PM2.5) has been found to be detrimental to respiratory health of children, but few studies have examined the effects of prenatal PM2.5 oxidative potential (OP) on lung function in infants and preschool children. OBJECTIVES: We estimated the associations of personal exposure to PM2.5 and OP during pregnancy on offspring objective lung function parameters and compared the strengths of associations between both exposure metrics. METHODS: We used data from 356 mother-child pairs from the SEPAGES cohort. PM filters collected twice during a week were analyzed for OP, using the dithiothreitol (DTT) and the ascorbic acid (AA) assays, quantifying the exposure of each pregnant woman. Lung function was assessed with tidal breathing analysis (TBFVL) and nitrogen multiple-breath washout (N2MBW) test, performed at 6 wk, and airwave oscillometry (AOS) performed at 3 y. Associations of prenatal PM2.5 mass and OP with lung function parameters were estimated using multiple linear regressions. RESULTS: In neonates, an interquartile (IQR) increase in OPvDTT (0.89 nmol/min/m3) was associated with a decrease in functional residual capacity (FRC) measured by N2MBW [ß=-2.26mL; 95% confidence interval (CI): -4.68, 0.15]. Associations with PM2.5 showed similar patterns in comparison with OPvDTT but of smaller magnitude. Lung clearance index (LCI) and TBFVL parameters did not show any clear association with the exposures considered. At 3 y, increased frequency-dependent resistance of the lungs (Rrs7-19) from AOS tended to be associated with higher OPvDTT (ß=0.09 hPa×s/L; 95% CI: -0.06, 0.24) and OPvAA (IQR=1.14 nmol/min/m3; ß=0.12 hPa×s/L; 95% CI: -0.04, 0.27) but not with PM2.5 (IQR=6.9 µg/m3; ß=0.02 hPa×s/L; 95% CI: -0.13, 0.16). Results for FRC and Rrs7-19 remained similar in OP models adjusted on PM2.5. DISCUSSION: Prenatal exposure to OPvDTT was associated with several offspring lung function parameters over time, all related to lung volumes. https://doi.org/10.1289/EHP11155.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Efeitos Tardios da Exposição Pré-Natal , Recém-Nascido , Feminino , Gravidez , Humanos , Lactente , Pré-Escolar , Estudos Prospectivos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Exposição Ambiental/análise , Material Particulado/toxicidade , Material Particulado/análise , Pulmão , Estresse Oxidativo , Poluição do Ar/efeitos adversos , Poluição do Ar/análise
19.
Chemosphere ; 316: 137717, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36610512

RESUMO

The applicability of herbicidal ionic liquids (HILs) as an alternative form of herbicides is currently evaluated. Yet, the available research is lacking information on the behaviour of herbicidal ionic liquids upon addition to the environment, i.e., if cations and anions act as separate moieties or remain an ionic salt. Hence, we tested degradation of five HILs with the glyphosate anion, their bioavailability in soil, toxicity towards microorganisms, impact on the biodiversity and the abundance of phnJ and soxA genes. The cations were proven to be slightly or moderately toxic. The properties of cations determined the properties of the whole formulation, which might suggest that cations and anion act as the independent mixture of ions. The mineralisation efficiencies were in the range of 15-53%; however, in the case of cations (except non-toxic choline), only 13-20% were bioavailable for degradation. The hydrophobic cations were proven to be highly sorbed, while the anion was readily available for microbial degradation regardless of its counterion. The approach to enrich test samples with isolated microorganisms specialised in glyphosate degradation resulted in higher degradation efficiencies, yet not high enough to mitigate the negative impact of cations. In addition, increased activity of enzymes participating in glyphosate degradation was observed. In the view of obtained results, the use of cationic surfactants in HILs structure is not recommended, as sorption was shown to be determining factor in HILs degradation efficiency. Moreover, obtained results indicate that corresponding ions in HILs might act as separate moieties in the environment.


Assuntos
Herbicidas , Líquidos Iônicos , Ânions/química , Cátions/química , Herbicidas/toxicidade , Herbicidas/química , Líquidos Iônicos/toxicidade , Líquidos Iônicos/química , Microbiologia do Solo
20.
Can J Physiol Pharmacol ; 101(2): 74-79, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36621961

RESUMO

This study investigated the effect of buprenorphine (BUP) on the livers of pups exposed to this drug during the fetal stage. BUP decreased the activities of serum liver enzymes in exposed animals versus the controls. BUP (0.5 mg/kg) decreased malondialdehyde levels and increased the glutathione levels in the liver of animals versus other groups. The superoxide dismutase activity was elevated in the BUP 0.5 mg/kg group versus the control group. BUP (1 mg/kg) induced histopathological changes in the livers of pups. In conclusion, BUP may induce hepatotoxicity in pups exposed to this drug during the fetal stage.


Assuntos
Buprenorfina , Doença Hepática Induzida por Substâncias e Drogas , Ratos , Gravidez , Animais , Feminino , Buprenorfina/toxicidade , Feto , Glutationa , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Analgésicos Opioides
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