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1.
Int J Mol Sci ; 22(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34445384

RESUMO

Diabetes is a predictor of nonalcoholic fatty liver disease (NAFLD). There are data suggesting that Tribulus terrestris (TT) saponins act as antidiabetic agents and protect against NAFLD. The effect of saponins may be increased by fermentable fibers such as inulin. The aim of the present study was to investigate the influence of TT saponins and TT saponins plus inulin on the plasma lipid profile and liver fatty acids of rats with induced diabetes mellitus type 2 (T2DM). The study was performed on 36 male Sprague-Dawley rats divided into two main groups: control and diabetic. Animals of the diabetic (DM) group were fed a high-fat diet and injected with streptozotocin (low doses). Animals of the control group (nDM) were on a regular diet and were injected with buffer. After the injections, the animals were split into subgroups: three non-diabetic (nDM): (i) control (c-C); (ii) saponin-treated rats (C-Sap); (iii) rats treated with saponins + inulin (C-Sap + IN), and three diabetic subgroups (DM): (iv) control (c-DM); (v) saponin-treated rats (DM-Sap); (vi) rats treated with saponins + inulin (DM-Sap + IN). Liver fatty acids were extracted and analyzed by gas chromatography, and plasma glucose and lipids were measured. The study showed significant changes in liver morphology, liver fatty acids, plasma lipid profile, and plasma glucose. In summary, supplementation with TT saponins or saponins with inulin for one month decreased the level of steatosis in rats with induced type 2 diabetes. Moreover, there were favorable effects on the plasma lipid profile in the rats. However, additional supplementation with inulin had a negative effect on liver morphology (with a microvesicular type of steatosis) in the non-diabetes group. Moreover, supplementation with inulin had a negative effect on plasma glucose in both diabetic and non-diabetic rats. These data show that a diet enriched with fermentable fibers reveals different effects in different organisms, and not all sources and forms of fiber are beneficial to health.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fígado Gorduroso/prevenção & controle , Inulina/administração & dosagem , Saponinas/administração & dosagem , Tribulus/química , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos/análise , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/metabolismo , Inulina/farmacologia , Fígado/química , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Saponinas/farmacologia , Estreptozocina , Resultado do Tratamento
2.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445399

RESUMO

Iron oxide nanoparticles and single domain antibodies from camelids (VHHs) have been increasingly recognized for their potential uses for medical diagnosis and treatment. However, there have been relatively few detailed characterizations of their pharmacokinetics (PK). The aim of this study was to develop imaging methods and pharmacokinetic models to aid the future development of a novel family of brain MRI molecular contrast agents. An efficient near-infrared (NIR) imaging method was established to monitor VHH and VHH conjugated nanoparticle kinetics in mice using a hybrid approach: kinetics in blood were assessed by direct sampling, and kinetics in kidney, liver, and brain were assessed by serial in vivo NIR imaging. These studies were performed under "basal" circumstances in which the VHH constructs and VHH-conjugated nanoparticles do not substantially interact with targets nor cross the blood brain barrier. Using this approach, we constructed a five-compartment PK model that fits the data well for single VHHs, engineered VHH trimers, and iron oxide nanoparticles conjugated to VHH trimers. The establishment of the feasibility of these methods lays a foundation for future PK studies of candidate brain MRI molecular contrast agents.


Assuntos
Camelídeos Americanos/imunologia , Rim/química , Fígado/química , Nanopartículas Magnéticas de Óxido de Ferro/química , Anticorpos de Domínio Único/administração & dosagem , Administração Intravenosa , Animais , Química Encefálica , Feminino , Fluorometria , Humanos , Camundongos , Modelos Teóricos , Tamanho da Partícula , Anticorpos de Domínio Único/sangue , Anticorpos de Domínio Único/química
3.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34210022

RESUMO

Food additive amorphous silicon dioxide (SiO2) particles are manufactured by two different methods-precipitated and fumed procedures-which can induce different physicochemical properties and biological fates. In this study, precipitated and fumed SiO2 particles were characterized in terms of constituent particle size, hydrodynamic diameter, zeta potential, surface area, and solubility. Their fates in intestinal cells, intestinal barriers, and tissues after oral administration in rats were determined by optimizing Triton X-114-based cloud point extraction (CPE). The results demonstrate that the constituent particle sizes of precipitated and fumed SiO2 particles were similar, but their aggregate states differed from biofluid types, which also affect dissolution properties. Significantly higher cellular uptake, intestinal transport amount, and tissue accumulation of precipitated SiO2 than of fumed SiO2 was found. The intracellular fates of both types of particles in intestinal cells were primarily particle forms, but slowly decomposed into ions during intestinal transport and after distribution in the liver, and completely dissolved in the bloodstream and kidneys. These findings will provide crucial information for understanding and predicting the potential toxicity of food additive SiO2 after oral intake.


Assuntos
Intestinos/química , Dióxido de Silício/administração & dosagem , Dióxido de Silício/síntese química , Administração Oral , Animais , Análise Química do Sangue , Células CACO-2 , Linhagem Celular Tumoral , Precipitação Química , Feminino , Humanos , Intestinos/citologia , Rim/química , Fígado/química , Nanopartículas , Octoxinol/química , Tamanho da Partícula , Ratos , Dióxido de Silício/química , Dióxido de Silício/farmacocinética , Solubilidade
4.
Ecotoxicol Environ Saf ; 222: 112483, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34237640

RESUMO

Municipal wastewater treatment plant (WWTP) effluents are significant sources of organic and inorganic pollutants to aquatic ecosystems. Several studies have shown that the health of aquatic organisms can be adversely impacted following exposure to these complex chemical mixtures. The objective of this study was to examine the effects of in situ exposure in the St. Lawrence River (QC, Canada) of juvenile yellow perch (Perca flavescens) to a major WWTP effluent. Perch were caged at a reference site in the St. Lawrence River and downstream of a WWTP effluent-influenced site for one, three, and six weeks. Fish kept in controlled laboratory setting were also examined at the beginning of the experiment to evaluate the potential effect of caging on fish. Liver metabolites and gill oxidative stress biomarkers as well as body condition of perch were investigated at four time points (zero, one, three, and six weeks). Nitrogen (δ15N) and carbon (δ13C) stable isotopes as well as tissue concentrations of halogenated flame retardants and trace metals were also analyzed. Results indicated that body condition of perch caged in the effluent increased after three and six weeks of exposure compared to that of reference fish. Perch caged at the WWTP effluent-influenced site also had higher muscle δ13C and slightly depleted muscle δ15N after three and six weeks of exposure, suggesting differences in sewage-derived nutrient assimilation between sites. Concentrations of Σ34 polybrominated diphenyl ether (PBDE) were 2-fold greater in perch exposed downstream of the WWTP compared to those caged at the reference site. Metal concentrations in kidney of perch after three weeks of exposure were significantly lower at the effluent-influenced site. Kidney concentrations of Cd, Cu, Se, As, Zn and Fe were, however, higher after six weeks of exposure, supporting that metal accumulation is time- and element-specific. The metabolomes of perch from the effluent-influenced and reference sites were similar, but were distinct from the laboratory control fish, suggesting a caging effect on fish. Seven liver metabolites (glucose, malate, fumarate, glutamate, creatinine, histamine, and oxypurinol) were significantly more abundant in perch from cages than in the laboratory control perch. The combination of metabolomics and physiological variables provides a powerful tool to improve our understanding of the mechanisms of action of complex environmental pollutant mixtures in wild fish.


Assuntos
Percas , Poluentes Químicos da Água , Animais , Ecossistema , Fígado/química , Rios , Águas Residuárias , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
5.
Forensic Sci Int ; 325: 110896, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34243037

RESUMO

Fatal starvation is rarely seen in developed countries; when it occurs, it may be associated with medicolegal problems. Forensic pathologists are required to determine leading causes of death and provide opinions on the influence of starvation, especially in cases of suspected child abuse. Recently, starvation-induced steatosis was suggested to be regulated by lipophagy. Here, we report an extremely rare case of death by malnutrition of a 10-year-old boy, who was fed only infant formula throughout his life. The deceased presented with severe hepatic steatosis, probably related to prolonged malnutrition. Fatty liver changes, with deposition of small lipid droplets deposited in the peripheral lobules. High levels of P62 protein (overexpression of which indicates an autophagy impairment) were seen around the central vein region, whereas light-chain-3 (LC3) protein (an indicator of lipophagy activation) was unremarkable. Thus, in our case, impaired lipophagy influenced starvation-induced steatosis. To our knowledge, this article is the first to evaluate the application of lipophagy in forensic investigations as an objective diagnostic criterion.


Assuntos
Transtornos da Nutrição Infantil/etiologia , Fórmulas Infantis/efeitos adversos , Inanição , Autofagia , Criança , Transtornos da Nutrição Infantil/complicações , Desidratação/complicações , Evolução Fatal , Fígado Gorduroso/patologia , Glicogênio/análise , Humanos , Lactente , Fígado/química , Fígado/patologia , Masculino , Proteínas de Ligação a RNA/sangue
6.
Forensic Sci Int ; 325: 110893, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34273605

RESUMO

Toxicology investigation on human's buried dead bodies is a rare and challenging task in the forensic field. As requested by the Judicial Authority, this work aimed to verify testimonial evidence that emerged during a criminal investigation involving multiple murder cases. The statements indicated an improper medical administration of one or more alleged drugs (propofol, morphine, diazepam, and midazolam) which presumably caused the deaths. Since the supposed crimes took place several years before, the task of the present work was to obtain results to support the charges. The analyses involved 18 biological samples taken from four exhumed bodies, three of which were female and one male, each buried in a different date and mode. Each sample was treated with specific purification and extraction techniques (LLE - SPE) after the addition of the deuterated analogs of the searched analytes (propofol-d17, morphine-d3, diazepam-d5, midazolam-d4) as internal standards. Afterwards, the extracts were subjected to qualitative analysis by gas chromatography-mass spectrometry-Electron Impact (GC/MS - EI), both in full scan and SIM mode. Propofol, morphine, and diazepam were identified in the corpses. It supports testimonials that were administered just before the deaths occurred.


Assuntos
Diazepam/análise , Homicídio , Midazolam/análise , Morfina/análise , Propofol/análise , Idoso , Idoso de 80 Anos ou mais , Cadáver , Diazepam/envenenamento , Exumação , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Rim/química , Fígado/química , Masculino , Midazolam/envenenamento , Morfina/envenenamento , Propofol/envenenamento , Bexiga Urinária/química
7.
ACS Appl Mater Interfaces ; 13(24): 28899-28907, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34106688

RESUMO

Salbutamol (SAL), a ß-2 adrenoreceptor agonist, is an unpopular addition to livestock and poultry, causing several side effects to human health. Thus, it is very important to develop a simple and rapid analytical method to screen SAL in the field of food safety. Here, we present an immunochromatographic assay (ICA) method for sensitively detecting SAL with polydopamine-decorated iridium oxide nanoparticles (IrO2@PDA NPs) as a signal tag. The IrO2@PDA with excellent hydrophilicity, biocompatibility, and stability was synthesized by oxidating self-polymerization of dopamine hydrochloride (DAH) on the surface of IrO2 NPs and used to label monoclonal antibodies (mAbs) through simple physical adsorption. Compared with IrO2 NPs, the IrO2@PDA also possessed superior optical properties and higher affinity with mAbs. With the proposed method, the limit of detection for SAL was 0.002 ng/mL, which was improved at least 24-fold and 180-fold compared with the IrO2 NPs-based ICA and conventional gold nanoparticles-based ICA, respectively. Furthermore, the SAL residuals in pork, pork liver, and beef were successfully detected by the developed biosensor and the recoveries ranged from 85.56% to 115.56%. Briefly, this work indicated that the powerful IrO2@PDA-based ICA can significantly improve detection sensitivity and has huge potential for accurate and sensitive detection of harmful small molecules analytes in food safety fields.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/análise , Albuterol/análise , Técnicas Biossensoriais/métodos , Contaminação de Alimentos/análise , Nanopartículas Metálicas/química , Agonistas de Receptores Adrenérgicos beta 2/imunologia , Albuterol/imunologia , Animais , Anticorpos Imobilizados/imunologia , Anticorpos Monoclonais/imunologia , Bovinos , Cromatografia de Afinidade , Ouro/química , Indóis/química , Irídio/química , Limite de Detecção , Fígado/química , Polímeros/química , Carne de Porco/análise , Carne Vermelha/análise , Suínos
8.
Int J Biol Macromol ; 184: 349-357, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34119542

RESUMO

IFITM3 is interferon-induced transmembrane 3, which plays an extremely key role in anti-proliferation, anti-virus and anti-tumor diseases. In this study, the yak (Bos grunniens) IFITM3 (BgIFITM3) gene contained a 5'-untranslated region (UTR) (25 bp), a coding region (441 bp), and a 3'-UTR (115 bp). The expression of BgIFITM3 gene in liver was significantly higher than that in heart, spleen, lung and kidney (P < 0.01). BgIFITM3 protein was localized on the yak hepatocyte plasma membrane, and its expression was significantly different between 1 day and 15 months of age (P < 0.05). Moreover, the prokaryotic expression vector of BgIFITM3 protein was constructed and expressed successfully, with a molecular weight of 19.5 kDa. The activities of yak hepatocyte were significantly inhibited after treating with BgIFITM3 protein (10 and 20 µg/mL) (P < 0.01). The expression levels of ERBB-2, IRS-1, PI3KR-1, AKT-1 and MAPK-3 were significantly lower after treating with 20 µg/mL BgIFITM3 protein (P < 0.05). Besides, the activities of HepG2 cells were significantly inhibited after treating with BgIFITM3 protein (1, 10 and 20 µg/mL) (P < 0.05). While, the cloning ability and migration ability of HepG2 cells were significantly inhibited after treating with 10 µg/mL BgIFITM3 protein (P < 0.05). Finally, the mitochondria of HepG2 cells was concentrated, cristae widened, and the double film density of mitochondria was increased after treating with 10 µg/mL BgIFITM3 protein. After 10 µg/mL BgIFITM3 protein treating, the expression levels of VDAC-2, VDAC-3 and p53 genes were significantly increased, but the expression level of GPX-4 gene was significantly decreased (P < 0.01). Taken together, the BgIFITM3 protein could inhibit the proliferations of yak hepatocyte and HepG2 cells by regulating the PI3K/Akt pathway or ferroptosis-related genes, respectively. These results benefit for further study of the function of BgIFITM3 protein.


Assuntos
Clonagem Molecular/métodos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Regiões 3' não Traduzidas , Regiões 5' não Traduzidas , Animais , Bovinos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Rim/química , Fígado/química , Pulmão/química , Células MCF-7 , Proteínas de Membrana/farmacologia , Peso Molecular , Miocárdio/química , Baço/química , Distribuição Tecidual
9.
Analyst ; 146(14): 4480-4486, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34160503

RESUMO

Exploring the metabolic disturbance of fipronil and its derivatives in aquatic organisms may provide a more comprehensive understanding of the impact of fipronil on the ecological environment. In this work, internal extractive electrospray ionization mass spectrometry (iEESI-MS) was used to directly analyze metabolites in the liver tissue of zebrafish exposed to fipronil and its three derivatives. Partial least squares-discriminant analysis (PLS-DA) revealed that 32 signals were considered as differential signals in zebrafish after the exposure treatment of fipronil and its derivatives, including phosphatidylcholines (PCs), lysophosphatidylcholines (LPCs), phosphatidylethanolamines (PEs), fatty acids and so on. The pathway analysis result showed that both fipronil and its derivatives have a significant impact on the glycerophospholipid metabolism of zebrafish. Besides, the intensities of PC signals in the liver samples of each group showed such a trend: mixed fiprole exposed group > fipronil sulfone exposed group ≈ fipronil sulfide exposed group > fipronil exposed group > fipronil desulfinyl exposed group > control group, indicating that mixed exposure of fipronil and its derivatives exhibited more significant metabolic disturbance in zebrafish. Taken together, iEESI-MS is applied to environmental toxicology and investigating the metabolic disturbance induced by fipronil and its derivatives in aquatic organisms, providing a new analytical method for this field.


Assuntos
Inseticidas , Peixe-Zebra , Animais , Inseticidas/análise , Fígado/química , Espectrometria de Massas por Ionização por Electrospray
10.
Environ Sci Technol ; 55(13): 8691-8699, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34100289

RESUMO

Nontarget screening studies have recently revealed the accumulation of typically unmonitored organohalogen compounds (OHCs) in various marine animals, but information for terrestrial food chains is still lacking. This study investigated the accumulation profiles of known and unknown OHCs in the liver of representative wild bird specimens from Osaka, Japan using nontarget analysis based on two-dimensional gas chromatography-time-of-flight mass spectrometry. A large number of unmonitored OHCs were identified, including anthropogenic contaminants and marine halogenated natural products (HNPs), and their accumulation profiles were considered to be influenced by terrestrial and brackish water-based diets. Anthropogenic OHCs were highly accumulated in terrestrial predator species (peregrine falcon, hawks, and black kite), and some unmonitored highly chlorinated contaminants reached the levels of microgram per gram lipid in the liver, i.e., C10-/C15-based chlordane related compounds (CHLs) and their epoxides, dichlorodiphenyldichloroethylene (DDE) homologues, and polychlorinated terphenyls (PCTs). In contrast, HNPs were accumulated at higher levels in piscivorous birds (gray heron and common cormorant). Considering the enrichment of the unmonitored C10-/C15-based CHLs, PCTs, and DDE homologues relative to structurally similar persistent organic pollutants (POPs) in high trophic-level species such as raptors, further studies are needed to elucidate their environmental levels, behavior in terrestrial food chains, and ecotoxicological impacts.


Assuntos
Poluentes Ambientais , Hidrocarbonetos Clorados , Bifenilos Policlorados , Aves Predatórias , Animais , Aves , Monitoramento Ambiental , Poluentes Ambientais/análise , Japão , Fígado/química
11.
Exp Parasitol ; 226-227: 108123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34144040

RESUMO

The failures in the treatment of leishmaniasis is an increasing problem around the world, especially related to resistance. Thus, we describe the synthesis and in vivo anti-Leishmania activity of alkylphosphocholine and alkyltriazoles; besides, their likely action mechanisms stem from some eventual inhibition of parasite enzymes using computational tools. These compounds were tested in an in vivo hamster model infected with Leishmania Leishmania infantum chagasi. Fifty days after parasite inoculation, the two compounds 12-azidedodecylphosphocholine (3) and 3-(1-(12-fluorododecyl)-1H-1,2,3-triazol-1-yl)propano-1-ol (9), were separately administered once a day as oral suspensions (25 and 12.5 mg/kg/day, respectively) during ten days, and their efficacy was compared to the reference compound pentavalent antimonial Glucantime (GLU). Compound 3 significantly reduced the number of parasites in the spleen (4.93 × 102 amastigotes/g) and liver (4.52 × 103 amastigotes/g). Compound 9 reduced the number of amastigotes in the spleen to 1.30 × 104 and 1.36 × 103 amastigotes/g in the liver. GLU was the most effective overall treatment (7.50 × 101 and 2.28 × 102 amastigotes/g in the spleen and liver, respectively). The high activity levels of these compounds in vivo may stem from their high in vitro leishmanicidal activity and lipophilicity. The in silico absorption, distribution, metabolism, and excretion studies also showed some anti-Leishmania potential. Compound 9 had more lipophilic characteristics than those of compound 3. In silico studies of the nine enzymes of compounds 3 and 9 showed significant evidence of interactions with nicotimidase and tyrosine aminotransferase, demonstrating possible inhibition enzymes present in L. (L.) infantum chagasi. These compounds could be a promising template for developing a new class of leishmanicidal agents, by oral route, and deserve further investigation to explore different therapeutic regimens.


Assuntos
Antiprotozoários/farmacologia , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Fosforilcolina/farmacologia , Triazóis/farmacologia , Administração Oral , Animais , Antiprotozoários/administração & dosagem , Antiprotozoários/uso terapêutico , Cricetinae , DNA Complementar/biossíntese , Feminino , Fígado/química , Mesocricetus , Simulação de Acoplamento Molecular , Fosforilcolina/administração & dosagem , Fosforilcolina/química , Fosforilcolina/uso terapêutico , RNA/isolamento & purificação , Baço/química , Triazóis/administração & dosagem , Triazóis/química , Triazóis/uso terapêutico
12.
Mar Pollut Bull ; 170: 112610, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34146858

RESUMO

Telomeres protect the coding sequence of chromosome ends and Telomere Length (TL) has been proposed as a biomarker of cellular aging, cumulative stress exposure and life-span in humans. With the aim to propose new biomarkers, a q-PCR protocol was adapted for the measurement of TL in the European flounder Platichthys flesus. The protocol was then applied in 2-year-old flounders from the Seine Estuary. The absolute TL in the flounder is 54 ± 13 kbp per genome (mean ± standard error). Considering relative or absolute TL, no correlation was observed with DNA damage and any of the measured contaminant concentrations (trace elements, metabolites of polycyclic aromatic hydrocarbons, polychlorobiphenyls, organochlorinated pesticides, polybrominated diphenyl ethers, perfluoroalkyl substances). Because sampling was limited, further investigations are required to state a possible impact of chemical pollution on flatfish telomeres. This is motivated by correlations observed with organochlorinated compounds when decreasing statistical significance (p ≤ 0.10).


Assuntos
Poluentes Ambientais , Linguado , Poluentes Químicos da Água , Animais , Monitoramento Biológico , Biomarcadores , Pré-Escolar , Monitoramento Ambiental , Linguado/genética , Humanos , Fígado/química , Reação em Cadeia da Polimerase , Telômero/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
13.
FASEB J ; 35(8): e21745, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34191346

RESUMO

Studies are needed to identify useful biomarkers to assess the severity and prognosis of COVID-19 disease, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus. Here, we examine the levels of various plasma species of the SARS-CoV-2 host receptor, the angiotensin-converting enzyme 2 (ACE2), in patients at different phases of the infection. Human plasma ACE2 species were characterized by immunoprecipitation and western blotting employing antibodies against the ectodomain and the C-terminal domain, using a recombinant human ACE2 protein as control. In addition, changes in the cleaved and full-length ACE2 species were also examined in serum samples derived from humanized K18-hACE2 mice challenged with a lethal dose of SARS-CoV-2. ACE2 immunoreactivity was present in human plasma as several molecular mass species that probably comprise truncated (70 and 75 kDa) and full-length forms (95, 100, 130, and 170 kDa). COVID-19 patients in the acute phase of infection (n = 46) had significantly decreased levels of ACE2 full-length species, while a truncated 70-kDa form was marginally higher compared with non-disease controls (n = 26). Levels of ACE2 full-length species were in the normal range in patients after a recovery period with an interval of 58-70 days (n = 29), while the 70-kDa species decreased. Levels of the truncated ACE2 species served to discriminate between individuals infected by SARS-CoV-2 and those infected with influenza A virus (n = 17). In conclusion, specific plasma ACE2 species are altered in patients with COVID-19 and these changes normalize during the recovery phase. Alterations in ACE2 species following SARS-CoV-2 infection warrant further investigation regarding their potential usefulness as biomarkers for the disease process and to asses efficacy during vaccination.


Assuntos
Enzima de Conversão de Angiotensina 2/sangue , COVID-19/sangue , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Enzima de Conversão de Angiotensina 2/líquido cefalorraquidiano , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/urina , Biomarcadores/sangue , Química Encefálica , Colo/química , Feminino , Humanos , Fígado/química , Masculino , Pessoa de Meia-Idade , Saliva/química
14.
J Forensic Sci ; 66(5): 2024-2028, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34117775

RESUMO

Autopsy findings in intravenous drug addicts are quite variable and may involve a number of organ systems. Reports of the macroscopic identification at autopsy of components of tablets that have been crushed and injected are, however, exceedingly rare. The case of 34-year-old man who died of zolpidem toxicity on a background of pulmonary hypertension attributed to intravenous injections of crushed tablets is described. A very unusual finding was very fine white stippling on the cut surfaces of both the liver and spleen which was shown on energy-dispersive x-ray spectroscopy (EDS) to be titanium dioxide most likely from the coating of the zolpidem tablets. This case is significant in demonstrating titanium dioxide accumulation within organs at both macroscopic and microscopic levels, with confirmation of exposure by EDS analysis. The clinical significance of exposure to such high levels of titanium dioxide is unclear.


Assuntos
Fígado/patologia , Baço/patologia , Titânio/análise , Adulto , Usuários de Drogas , Humanos , Hipertensão Pulmonar/complicações , Fígado/química , Masculino , Medicamentos Indutores do Sono/envenenamento , Espectrometria por Raios X , Baço/química , Abuso de Substâncias por Via Intravenosa , Comprimidos , Zolpidem/envenenamento
15.
Artigo em Inglês | MEDLINE | ID: mdl-34072519

RESUMO

This study aimed to determine toxic element concentrations in aquatic environments, including water and sediment, and in the Hampala macrolepidota fish, and to evaluate chromosome abnormalities, serum liver enzyme changes and liver histopathological alterations in H. macrolepidota from the Nam Kok River near the Sepon gold-copper mine, Lao People's Democratic Republic, as compared with a control area without mining activity. The results revealed significant differences (p < 0.05) in As, Ba, Cu, Fe, Mn, Ni, Se and Zn in water, in all of the studied potentially toxic elements in sediment, and in As, Ba, Cd, Cr, Cu, Mn, Ni, Se, and Zn in the fish between the study and control areas. A chromosome assessment demonstrated 6 types of chromosome abnormalities, among which centric gap had the highest total number of chromosome abnormalities. Percentage of chromosome abnormalities, percentage of cells with chromosome abnormalities and serum liver enzymes in H. macrolepidota were significantly different (p < 0.05) between the two studied areas and were higher in the contaminated fish than in the control fish. The observation of liver histopathological changes revealed cellular degeneration, such as nuclear damage, abnormal cytoplasmic mitochondria and the disintegration of rough endoplasmic reticulum. The results indicate that the contamination of potentially toxic elements in the Nam Kok River near the Sepon gold-copper mine area negatively affected chromosomes, serum liver enzymes and liver cell structures in H. macrolepidota.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Animais , Cobre/análise , Cobre/toxicidade , Análise Citogenética , Monitoramento Ambiental , Ouro , Laos , Fígado/química , Metais Pesados/análise , Rios , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
16.
Environ Sci Technol ; 55(12): 8180-8190, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34096267

RESUMO

Surface waters often contain a variety of chemical contaminants potentially capable of producing adverse outcomes in both humans and wildlife due to impacts from industrial, urban, and agricultural activity. Here, we report the results of a zebrafish liver (ZFL) cell-based lipidomics approach to assess the potential ecotoxicological effects of complex contaminant mixtures using water collected from eight impacted streams across the United States mainland and Puerto Rico. We initially characterized the ZFL lipidome using high resolution mass spectrometry, resulting in the annotation of 508 lipid species covering 27 classes. We then identified lipid changes induced by all streamwater samples (nonspecific stress indicators) as well as those unique to water samples taken from specific streams. Subcellular impacts were classified based on organelle-specific lipid changes, including increased lipid saturation (endoplasmic reticulum stress), elevated bis(monoacylglycero)phosphate (lysosomal overload), decreased ubiquinone (mitochondrial dysfunction), and elevated ether lipids (peroxisomal stress). Finally, we demonstrate how these results can uniquely inform environmental monitoring and risk assessments of surface waters.


Assuntos
Rios , Poluentes Químicos da Água , Animais , Misturas Complexas , Humanos , Lipidômica , Fígado/química , Porto Rico , Estados Unidos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
17.
Gene ; 794: 145752, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34082065

RESUMO

Intron retention (IR) is an important regulatory mechanism that affects gene expression and protein functions. Using klotho mice at the pre-symptomatic state, we discovered that retained-introns accumulated in several organs including the liver and that among these retained introns in the liver a subset was recovered to the normal state by a Japanese traditional herbal medicine. This is the first report of IR recovery by a medicine. IR-recovered genes fell into two categories: those involved in liver-specific metabolism and in splicing. Metabolome analysis of the liver showed that the klotho mice were under starvation stress. In addition, our differentially expressed gene analysis showed that liver metabolism was actually recovered by the herbal medicine at the transcriptional level. By analogy with the widespread accumulation of intron-retained pre-mRNAs induced by heat shock stress, we propose a model in which retained-introns in klotho mice were induced by an aging stress and in which this medicine-related IR recovery is indicative of the actual recovery of liver-specific metabolic function to the healthy state. Accumulation of retained-introns was also observed at the pre-symptomatic state of aging in wild-type mice and may be an excellent marker for this state in general.


Assuntos
Envelhecimento/genética , Perfilação da Expressão Gênica/métodos , Marcadores Genéticos/efeitos dos fármacos , Glucuronidase/genética , Fígado/química , Compostos Fitoquímicos/administração & dosagem , Envelhecimento/efeitos dos fármacos , Processamento Alternativo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Resposta ao Choque Térmico , Íntrons , Japão , Fígado/efeitos dos fármacos , Medicina Tradicional , Metabolômica , Camundongos , Modelos Animais , Compostos Fitoquímicos/farmacologia , Precursores de RNA/genética , Análise de Sequência de RNA
18.
Ecotoxicol Environ Saf ; 219: 112311, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33993092

RESUMO

Given the opposing responses reported for bisphenol A (BPA) in terms of induction of obesogenic effects and impaired lipid metabolism, the increasing use of bisphenol F (BPF), and the relatively low information available regarding the effects of bisphenol A bis(3-chloro-2- hydroxypropyl) ether (BADGE·2HCl) in aquatic organisms, this work aims to use the zebrafish liver cell line (ZFL) as an alternative model to characterize the toxicity and the lipid metabolism disruptive potential of the selected compounds in fish. All three bisphenols increased intracellular levels of dihydroceramides and ether-triacylglycerides (ether-TGs), suggestive of inhibited cell growth. However, while BPA and BADGE·2HCl caused an increase of saturated and lower unsaturated TGs, BPF caused oxidative stress and the decrease of TGs containing polyunsaturated fatty acids (PUFAs). Analysis by qPCR highlighted the up-regulation of the lipogenic genes scd and elovl6 by BPA and BPF in line with an increase of lipids containing saturated and monounsaturated FA and a decrease of lipids containing PUFAs. This study shows that BPA, BPF and BADGE·2HCl target lipid homeostasis in ZFL cells through different mechanisms, and highlights the higher lipotoxicity of BADGE·2HCl compared to BPA and BPF.


Assuntos
Compostos Benzidrílicos/toxicidade , Fenóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Compostos de Epóxi/análise , Éter , Éteres , Hepatócitos , Lipidômica , Fígado/química , Peixe-Zebra
19.
Int J Mol Sci ; 22(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946157

RESUMO

The metabolic ratios lactate/pyruvate and ß-hydroxybutyrate/acetoacetate are considered valuable tools to evaluate the in vivo redox cellular state by estimating the free NAD+/NADH in cytoplasm and mitochondria, respectively. The aim of the current study was to validate a gas-chromatography mass spectrometry method for simultaneous determination of the four metabolites in plasma and liver tissue. The procedure included an o-phenylenediamine microwave-assisted derivatization, followed by liquid-liquid extraction with ethyl acetate and silylation with bis(trimethylsilyl)trifluoroacetamide:trimethylchlorosilane 99:1. The calibration curves presented acceptable linearity, with a limit of quantification of 0.001 mM for pyruvate, ß-hydroxybutyrate and acetoacetate and of 0.01 mM for lactate. The intra-day and inter-day accuracy and precision were within the European Medicines Agency's Guideline specifications. No significant differences were observed in the slope coefficient of three-point standard metabolite-spiked curves in plasma or liver and water, and acceptable recoveries were obtained in the metabolite-spiked samples. Applicability of the method was tested in precision-cut liver rat slices and also in HepG2 cells incubated under different experimental conditions challenging the redox state. In conclusion, the validated method presented good sensitivity, specificity and reproducibility in the quantification of lactate/pyruvate and ß-hydroxybutyrate/acetate metabolites and may be useful in the evaluation of in vivo redox states.


Assuntos
Ácido 3-Hidroxibutírico/metabolismo , Acetoacetatos/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Lactatos/metabolismo , Piruvatos/metabolismo , Ácido 3-Hidroxibutírico/análise , Ácido 3-Hidroxibutírico/sangue , Acetoacetatos/análise , Acetoacetatos/sangue , Animais , Feminino , Cromatografia Gasosa-Espectrometria de Massas/métodos , Células Hep G2 , Humanos , Lactatos/análise , Lactatos/sangue , Limite de Detecção , Fígado/química , Fígado/metabolismo , Oxirredução , Piruvatos/análise , Piruvatos/sangue , Ratos Wistar
20.
J Nutr Biochem ; 95: 108762, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33965534

RESUMO

The physiological functions of the aryl hydrocarbon receptor (AHR) are only beginning to unfold. Studies in wildtype and AHR knockout (AHRKO) mice have recently disclosed that AHR activity is required for obesity and steatohepatitis to develop when mice are fed with a high-fat diet (HFD). In addition, a line of AHRKO mouse has been reported to accumulate retinoids in the liver. Whether these are universal manifestations across species related to AHR activity level is not known yet. Therefore, we here subjected wildtype and AHRKO male rats (on Sprague-Dawley background) to HFD feeding coupled with free access to 10% sucrose solution and water; controls received a standard diet and water. Although the HFD-fed rats consumed more energy throughout the 24-week feeding regimen, they did not get overweight. However, relative weights of the brown and epididymal adipose tissues were elevated in HFD-fed rats, while that of the liver was lower in AHRKO than wildtype rats. Moreover, the four groups exhibited diet- or genotype-dependent differences in biochemical variables, some of which suggested marked dissimilarities from AHRKO mice. Expression of pro- and anti-inflammatory genes was induced in livers of HFD-fed AHRKO rats, but histologically they did not differ from others. HFD reduced the hepatic concentrations of retinyl palmitate, 9-cis-4-oxo-13,14-dihydroretinoic acid and (suggestively) retinol, whereas AHR status had no effect. Hence, the background strain/line of AHRKO rat is resistant to diet-induced obesity, and AHR does not modulate this or liver retinoid concentrations. Yet, subtle AHR-dependent differences in energy balance-related factors exist despite similar weight development.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/farmacologia , Metabolismo Energético/efeitos dos fármacos , Fígado/química , Receptores de Hidrocarboneto Arílico/deficiência , Retinoides/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Deleção de Genes , Genótipo , Fígado/metabolismo , Fígado/patologia , Masculino , Tamanho do Órgão , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Hidrocarboneto Arílico/metabolismo , Retinoides/química
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