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1.
BioTech (Basel) ; 12(4)2023 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-37873882

RESUMO

Oocyte developmental competence is the ability of a mature oocyte to be fertilized and subsequently support embryonic development. Such competence is gained during folliculogenesis and is facilitated by the bidirectional communication into a compacted cumulus-oocyte complex (COC). Human tissue inhibitor of metalloproteinases-1 (TIMP1) participates in biological processes, including cell growth, differentiation, and apoptosis. This study aimed to evaluate the influence of TIMP1 as a growth factor on the in vitro maturation (IVM) culture of bovine COCs to improve oocyte developmental competence. All TIMP1 treatments (50, 100, and 150 ng/mL) favored the COCs' compaction structure (p < 0.05). TIMP1 at 150 ng/mL produced more oocytes in metaphase II compared to the other treatments (p < 0.05). The 150 ng/mL TIMP1 generated oocytes with the most (p < 0.05) cortical granules below the plasma membrane (pattern I). In a parthenogenesis assay, oocyte IVM in 50 ng/mL of TIMP1 produced the most blastocyst compared to the other treatments (p < 0.05). The Principal Component Analysis (PCA) showed that 50 ng/mL of TIMP1 was the best condition to develop oocyte competence because it was associated with the COC compact and cortical granule pattern I. TIMP1 influences the development of oocyte competence when added to the IVM culture medium of COCs.

2.
Nanomaterials (Basel) ; 12(9)2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35564174

RESUMO

Carbon nanotubes (CNTs) have been proposed as nanovehicles for drug or antigen delivery since they can be functionalized with different biomolecules. For this purpose, different types of molecules have been chemically bonded to CNTs; however, this method has low efficiency and generates solvent waste. Candida antarctica lipase is an enzyme that, in an organic solvent, can bind a carboxylic to a hydroxyl group by esterase activity. The objective of this work was to functionalize purified CNTs with insulin as a protein model using an immobilized lipase of Candida antarctica to develop a sustainable functionalization method with high protein attachment. The functionalized CNTs were characterized by scanning electron microscope (SEM), Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzymatic functionalization of insulin on the surface of the CNTs was found to have an efficiency of 21%, which is higher in conversion and greener than previously reported by the diimide-activated amidation method. These results suggest that enzymatic esterification is a convenient and efficient method for CNT functionalization with proteins. Moreover, this functionalization method can be used to enhance the cellular-specific release of proteins by lysosomal esterases.

3.
Plants (Basel) ; 10(10)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34685883

RESUMO

Rhus trilobata (RHTR) is a medicinal plant with cytotoxic activity in different cancer cell lines. However, the active compounds in this plant against ovarian cancer are unknown. In this study, we aimed to evaluate the antineoplastic activity of RHTR and identify its active metabolites against ovarian cancer. The aqueous extract (AE) and an active fraction (AF02) purified on C18-cartridges/ethyl acetate decreased the viability of SKOV-3 cells at 50 and 38 µg/mL, respectively, compared with CHO-K1 (>50 µg/mL) in MTT assays and generated changes in the cell morphology with apoptosis induction in Hemacolor® and TUNEL assays (p ≤ 0.05, ANOVA). The metabolite profile of AF02 showed a higher abundance of flavonoid and lipid compounds compared with AE by UPLC-MSE. Gallic acid and myricetin were the most active compounds in RHTR against SKOV-3 cells at 50 and 166 µg/mL, respectively (p ≤ 0.05, ANOVA). Antineoplastic studies in Nu/Nu female mice with subcutaneous SKOV-3 cells xenotransplant revealed that 200 mg/kg/i.p. of AE and AF02 inhibited ovarian tumor lesions from 37.6% to 49% after 28 days (p ≤ 0.05, ANOVA). In conclusion, RHTR has antineoplastic activity against ovarian cancer through a cytostatic effect related to gallic acid and myricetin. Therefore, RHTR could be a complementary treatment for this pathology.

4.
BMC Complement Med Ther ; 20(1): 110, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32276584

RESUMO

BACKGROUND: Ovarian cancer is the leading cause of mortality among malignant gynecological tumors. Surgical resection and chemotherapy with intravenous platinum/taxanes drugs are the treatments of choice, with little effectiveness in later stages and severe toxicological effects. Therefore, this study aimed to evaluate the antineoplastic activity of gallic acid (GA) and myricetin (Myr) administrated peritumorally in Nu/Nu mice xenotransplanted with SKOV-3 cells. METHODS: Biological activity of GA and MYR was evaluated in SKOV-3 and OVCAR-3 cells (ovarian adenocarcinomas) by confocal/transmission electron microscopy, PI-flow cytometry, H2-DCF-DA stain, MTT, and Annexin V/PI assays. Molecular targets of compounds were determined with ACD/I-Labs and SEA. Antineoplastic activity was performed in SKOV-3 cells subcutaneously xenotransplanted into female Nu/Nu mice treated peritumorally with 50 mg/kg of each compound (2 alternate days/week) for 28 days. Controls used were paclitaxel (5 mg/kg) and 20 µL of vehicle (0.5% DMSO in 1X PBS). Tumor lesions, organs and sera were evaluated with NMR, USG, histopathological, and paraclinical studies. RESULTS: In vitro studies showed a decrease of cell viability with GA and Myr in SKOV-3 (50 and 166 µg/mL) and OVCAR-3 (43 and 94 µg/mL) cells respectively, as well as morphological changes, cell cycle arrest, and apoptosis induction due to ROS generation (p ≤ 0.05, ANOVA). In silico studies suggest that GA and MYR could interact with carbonic anhydrase IX and PI3K, respectively. In vivo studies revealed inhibitory effects on tumor lesions development with GA and MYR up to 50% (p ≤ 0.05, ANOVA), with decreased vascularity, necrotic/fibrotic areas, neoplastic stroma retraction and apoptosis. However, toxicological effects were observed with GA treatment, such as leukocyte infiltrate and hepatic parenchyma loss, hypertransaminasemia (ALT: 150.7 ± 25.60 U/L), and hypoazotemia (urea: 33.4 ± 7.4 mg/dL), due to the development of chronic hepatitis (p ≤ 0.05, ANOVA). CONCLUSION: GA and Myr (50 mg/kg) administered by peritumoral route, inhibit ovarian tumor lesions development in rodents with some toxicological effects. Additional studies will be necessary to find the appropriate therapeutic dose for GA. Therefore, GA and Myr could be considered as a starting point for the development of novel anticancer agents.


Assuntos
Antineoplásicos/farmacologia , Flavonoides/farmacologia , Ácido Gálico/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos
5.
Sci Total Environ ; 684: 621-628, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31158625

RESUMO

Arsenic (As) and fluoride (F) are two common groundwater toxicants. The toxicity of As is closely related to As metabolism, and several biological and environmental factors have been associated with As modification. However, limited information about the effect of F exposure on the modification of the As metabolism profile has been described. The aim of this study was to assess the interaction effect of AsF coexposure on the As metabolism profile in an adult population environmentally exposed to low-moderate As levels. A cross-sectional study was conducted in 236 adults from three Mexican communities. F and As concentrations were quantified in water samples. The concentrations of urinary F and As species [inorganic arsenic (iAs), monomethylated arsenic (MAs) and dimethylated arsenic (DMAs)] were also determined and used as exposure biomarkers. As species percentages and methylation indices were estimated to evaluate the As methylation profile. Our results showed a relationship between the water and urine concentrations of both contaminants and, a significant correlation between the As and F concentrations in water and urine samples. A statistically significant interaction of F and As exposure on the increase in MAs% (ß = 0.16, p = 0.018) and the decrease in DMAs% (ß = -0.3, p = 0.034), PMI (ß = -0.07, p = 0.052) and SMI (ß = -0.13, p = 0.097) was observed. These findings indicate that drinking water is the main source of AsF coexposure and suggest that F exposure decreases As methylation capacity. However, additional large and prospective studies are required to confirm our findings, and to elucidate the involved mechanisms of interaction and their implications in adverse health effects.


Assuntos
Arsênio/metabolismo , Arsenicais/metabolismo , Exposição Ambiental/efeitos adversos , Fluoretos/efeitos adversos , Poluentes Químicos da Água/efeitos adversos , Adulto , Biomarcadores/análise , Estudos Transversais , Feminino , Água Subterrânea/química , Humanos , Masculino , Pessoa de Meia-Idade , Poluentes Químicos da Água/metabolismo
6.
Environ Res ; 169: 220-228, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30471530

RESUMO

Exposure to inorganic fluoride (F) has been implicated in cardiovascular and kidney dysfunction mainly in adult populations. However, limited epidemiological information from susceptible populations, such as children, is available. In this study we evaluated the relationship of F exposure with some vascular and kidney injury biomarkers in children. A cross-sectional study was conducted in 374 Mexican schoolchildren. Dental fluorosis and F concentrations in the water and urine were evaluated. The glomerular filtration rate (eGFR) and the urinary concentrations of kidney injury molecule 1 (KIM-1) and cystatin-C (uCys-C) were examined to assess kidney injury. The carotid intima media thickness (cIMT) and serum concentrations of vascular adhesion molecule 1 (VCAM-1), intracellular adhesion molecule 1 (ICAM-1), endothelin 1(ET-1) and cystatin-C (sCys-C) were measured to assess vascular alterations. High proportions of children exposed to F were observed (79.7% above 1.2 ppm F in urine) even in the low water F exposure regions, which suggested additional sources of F exposure. In robust multiple linear regression models, urinary F was positively associated with eGFR (ß = 1.3, p = 0.015), uCys-C (ß = -8.5, p = 0.043), VCAM-1 (ß = 111.1, p = 0.019), ICAM-1 (ß = 57, p = 0.032) and cIMT (ß = 0.01, p = 0.032). An inverse association was observed with uCys-C (ß = -8.5, p = 0.043) and sCys-C (ß = -9.6, p = 0.021), and no significant associations with ET-1 (ß = 0.069, p = 0.074) and KIM-1 (ß = 29.1, p = 0.212) were found. Our findings revealed inconclusive results regarding F exposure and kidney injury. However, these results suggest that F exposure is related to early vascular alterations, which may increase the susceptibility of cardiovascular diseases in adult life.


Assuntos
Injúria Renal Aguda/metabolismo , Fluoretos/toxicidade , Adulto , Biomarcadores/metabolismo , Espessura Intima-Media Carotídea , Criança , Estudos Transversais , Humanos , Rim , México
7.
Environ Int ; 123: 292-300, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30553202

RESUMO

BACKGROUND: Exposure to inorganic arsenic (iAs) via drinking water is a serious global health threat. Various factors influence susceptibility to iAs-associated health outcomes, including differences in iAs metabolism. Previous studies have shown that obesity is associated with iAs metabolism. It has been hypothesized that this association can be explained by confounding from nutritional factors involved in one-carbon metabolism, such as folate or other B vitamins, whose intake may differ across BMI categories and is known be associated with iAs metabolism. However, no studies have explored whether this association is confounded by nutritional factors. METHODS: We investigated the relationship between body mass index (BMI) and the distribution of urinary arsenic species in a cross-sectional cohort of 1166 adults living in Chihuahua, Mexico from 2008 to 2013. Nutrient intake related to one-carbon metabolism, including folate, vitamin B2, and vitamin B12, was assessed using a food frequency questionnaire developed for Mexican populations. Multivariable linear regression was used to estimate the association between BMI and the distribution of urinary arsenic metabolites. Effect modification by drinking water iAs level and sex was also examined. RESULTS: After adjusting for potential confounders, including age, educational attainment, smoking, alcohol consumption, seafood consumption, water iAs, and sex, BMI was negatively associated with the proportion of urinary inorganic arsenic (%U-iAs) and urinary monomethylated arsenic (%U-MMAs) and positively associated with urinary dimethylated arsenic (%U-DMAs). This relationship was not influenced by additional adjustment for folate, vitamin B2, or vitamin B12 intake. Additionally, there was significant effect modification by both drinking water iAs level and sex. CONCLUSIONS: This study provides further evidence for an association between BMI and arsenic metabolism. However, contrary to previous hypotheses, these results suggest that this association is not confounded by the intake of micronutrients involved in one-carbon metabolism.


Assuntos
Arsênio/urina , Índice de Massa Corporal , Carbono/metabolismo , Nutrientes/metabolismo , Adulto , Arsênio/análise , Estudos de Coortes , Estudos Transversais , Exposição Ambiental , Feminino , Humanos , Masculino , México , Estado Nutricional , Fumar
8.
Toxicol Appl Pharmacol ; 352: 97-106, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29800643

RESUMO

Fluoride (F) is a toxicant widely distributed in the environment. Experimental studies have shown kidney toxicity from F exposure. However, co-exposure to arsenic (As) has not been considered, and epidemiological information remains limited. We evaluated the association between F exposure and urinary kidney injury biomarkers and assessed As co-exposure interactions. A cross-sectional study was conducted in 239 adults (18-77 years old) from three communities in Chihuahua, Mexico. Exposure to F was assessed in urine and drinking water, and As in urine samples. We evaluated the urinary concentrations of albumin (ALB), cystatin-C (Cys-C), kidney injury molecule 1 (KIM-1), clusterin (CLU), osteopontin (OPN), and trefoil factor 3 (TFF-3). The estimated glomerular filtration rate (eGFR) was calculated using serum creatinine (Creat) levels. We observed a positive correlation between water and urine F concentrations (ρ = 0.7419, p < 0.0001), with median values of 1.5 mg/L and 2 µg/mL, respectively, suggesting that drinking water was the main source of F exposure. The geometric mean of urinary As was 18.55 ng/mL, approximately 39% of the urine samples had As concentrations above the human biomonitoring value (15 ng/mL). Multiple linear regression models demonstrated a positive association between urinary F and ALB (ß = 0.56, p < 0.001), Cys-C (ß = 0.022, p = 0.001), KIM-1 (ß = 0.048, p = 0.008), OPN (ß = 0.38, p = 0.041), and eGFR (ß = 0.49, p = 0.03); however, CLU (ß = 0.07, p = 0.100) and TFF-3 (ß = 1.14, p = 0.115) did not show significant associations. No interaction with As exposure was observed. In conclusion, F exposure was related to the urinary excretion of early kidney injury biomarkers, supporting the hypothesis of the nephrotoxic role of F exposure.


Assuntos
Arsênio/efeitos adversos , Exposição Ambiental/efeitos adversos , Fluoretos/efeitos adversos , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Poluentes Químicos da Água/efeitos adversos , Adolescente , Adulto , Idoso , Albuminúria/induzido quimicamente , Albuminúria/diagnóstico , Albuminúria/urina , Arsênio/urina , Biomarcadores/urina , Clusterina/urina , Estudos Transversais , Cistatina C/urina , Monitoramento Ambiental/métodos , Feminino , Fluoretos/urina , Taxa de Filtração Glomerular/efeitos dos fármacos , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Rim/metabolismo , Rim/fisiopatologia , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Nefropatias/urina , Masculino , México , Pessoa de Meia-Idade , Osteopontina/urina , Valor Preditivo dos Testes , Medição de Risco , Fator Trefoil-3/urina , Poluentes Químicos da Água/urina , Adulto Jovem
9.
Artigo em Inglês | MEDLINE | ID: mdl-28475152

RESUMO

In areas lacking potable water treatment, drinking contaminated water may represent a public health threat. In addition to enteropathogenic bacteria and parasites, fecal contamination in water environments is associated with the transmission of enteric viruses and other causal agents of infectious disease. Rotavirus and norovirus are the main enteric viral agents responsible for diarrheic outbreaks. The aim of the present study was to detect seasonal variation of rotavirus and norovirus in the surface water at Bassaseachic Falls National Park during 2013. Rivers and streams within and nearby this park were sampled once in each season during 2013. Viral concentration was carried out by a handmade filtration equipment, using a commercial electropositive membrane coupled with the virus absortion elution technique (VIRADEL©). Detection of rotavirus and norovirus was performed by SYBR Green reverse transcription-real time polymerase chain reaction (SYBR GREEN© RT-qPCR) analyses. Norovirus genogroup II was detected in samples collected in June and October 2013. In the case of rotavirus, genogroup A was detected in March and June. The presence of rotavirus and norovirus was related to viral acute diarrhea in children less than five years of age, who were inhabiting the sampled areas. This may indicates that the contaminated water was potentially a risk factor for regional diarrheic outbreaks.


Assuntos
Norovirus/isolamento & purificação , Parques Recreativos , Rios/virologia , Rotavirus/isolamento & purificação , Criança , Pré-Escolar , Surtos de Doenças , Feminino , Genótipo , Humanos , Lactente , México/epidemiologia , Norovirus/genética , Prevalência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rotavirus/genética
10.
Environ Health Perspect ; 124(1): 104-11, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26068977

RESUMO

BACKGROUND: Exposure to arsenic (As) concentrations in drinking water > 150 µg/L has been associated with risk of diabetes and cardiovascular disease, but little is known about the effects of lower exposures. OBJECTIVE: This study aimed to examine whether moderate As exposure, or indicators of individual As metabolism at these levels of exposure, are associated with cardiometabolic risk. METHODS: We analyzed cross-sectional associations between arsenic exposure and multiple markers of cardiometabolic risk using drinking-water As measurements and urinary As species data obtained from 1,160 adults in Chihuahua, Mexico, who were recruited in 2008-2013. Fasting blood glucose and lipid levels, the results of an oral glucose tolerance test, and blood pressure were used to characterize cardiometabolic risk. Multivariable logistic, multinomial, and linear regression were used to assess associations between cardiometabolic outcomes and water As or the sum of inorganic and methylated As species in urine. RESULTS: After multivariable adjustment, concentrations in the second quartile of water As (25.5 to < 47.9 µg/L) and concentrations of total speciated urinary As (< 55.8 µg/L) below the median were significantly associated with elevated triglycerides, high total cholesterol, and diabetes. However, moderate water and urinary As levels were also positively associated with HDL cholesterol. Associations between arsenic exposure and both dysglycemia and triglyceridemia were higher among individuals with higher proportions of dimethylarsenic in urine. CONCLUSIONS: Moderate exposure to As may increase cardiometabolic risk, particularly in individuals with high proportions of urinary dimethylarsenic. In this cohort, As exposure was associated with several markers of increased cardiometabolic risk (diabetes, triglyceridemia, and cholesterolemia), but exposure was also associated with higher rather than lower HDL cholesterol. CITATION: Mendez MA, González-Horta C, Sánchez-Ramírez B, Ballinas-Casarrubias L, Hernández Cerón R, Viniegra Morales D, Baeza Terrazas FA, Ishida MC, Gutiérrez-Torres DS, Saunders RJ, Drobná Z, Fry RC, Buse JB, Loomis D, García-Vargas GG, Del Razo LM, Stýblo M. 2016. Chronic exposure to arsenic and markers of cardiometabolic risk: a cross-sectional study in Chihuahua, Mexico. Environ Health Perspect 124:104-111; http://dx.doi.org/10.1289/ehp.1408742.


Assuntos
Arsênio/toxicidade , Doenças Cardiovasculares/sangue , Diabetes Mellitus/sangue , Adulto , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , México , Pessoa de Meia-Idade , Poluentes Químicos da Água/toxicidade
11.
Biomed Res Int ; 2015: 175025, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26339590

RESUMO

Inorganic arsenic (iAs) exposure induces a decrease in glucose type 4 transporter (GLUT4) expression on the adipocyte membrane, which may be related to premature births and low birth weight infants in women exposed to iAs at reproductive age. The aim of this study was to analyze the effect of sodium arsenite (NaAsO2) exposure on GLUT1, GLUT3, and GLUT4 protein expression and on placental morphology. Female Balb/c mice (n = 15) were exposed to 0, 12, and 20 ppm of NaAsO2 in drinking water from 8th to 18th day of gestation. Morphological changes and GLUT1, GLUT3, and GLUT4 expression were evaluated in placentas by immunohistochemical and image analysis and correlated with iAs and arsenical species concentration, which were quantified by atomic absorption spectroscopy. NaAsO2 exposure induced a significant decrease in fetal and placental weight (P < 0.01) and increases in infarctions and vascular congestion. Whereas GLUT1 expression was unchanged in placentas from exposed group, GLUT3 expression was found increased. In contrast, GLUT4 expression was significantly lower (P < 0.05) in placentas from females exposed to 12 ppm. The decrease in placental GLUT4 expression might affect the provision of adequate fetal nutrition and explain the low fetal weight observed in the exposed groups.


Assuntos
Arsenitos/toxicidade , Transportador de Glucose Tipo 1/biossíntese , Transportador de Glucose Tipo 2/biossíntese , Transportador de Glucose Tipo 4/biossíntese , Compostos de Sódio/toxicidade , Adipócitos/efeitos dos fármacos , Adipócitos/patologia , Animais , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Glucose/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 2/genética , Transportador de Glucose Tipo 4/genética , Humanos , Recém-Nascido de Baixo Peso/metabolismo , Camundongos , Placenta/efeitos dos fármacos , Placenta/metabolismo , Placenta/patologia , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/genética , Nascimento Prematuro/patologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/patologia , Espectrofotometria Atômica
12.
Biomed Res Int ; 2015: 796456, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26075262

RESUMO

Carbon nanotubes (CNTs) are used as carriers in medicine due to their ability to be functionalized with chemical substances. However, cytotoxicity analysis is required prior to use for in vivo models. The aim of this study was to evaluate the cytotoxic effect of CNTs functionalized with a 46 kDa surface protein from Entamoeba histolytica (P46-CNTs) on J774A macrophages. With this purpose, CNTs were synthesized by spray pyrolysis and purified (P-CNTs) using sonication for 48 h. A 46 kDa protein, with a 4.6-5.4 pI range, was isolated from E. histolytica HM1:IMSS strain trophozoites using an OFFGEL system. The P-CNTs were functionalized with the purified 46 kDa protein, classified according to their degree of functionalization, and characterized by Raman and Infrared spectroscopy. In vitro cytotoxicity was evaluated by MTT, apoptosis, and morphological assays. The results demonstrated that P46-CNTs exhibited cytotoxicity dependent upon the functionalized grade. Contrary to what was expected, P46-CNTs with a high grade of functionalization were more toxic to J774 macrophages than P46-CNTs with a low grade of functionalization, than P-CNTs, and had a similar level of toxicity as UP-CNT. This suggests that the nature of the functionalized protein plays a key role in the cytotoxicity of these nanoparticles.


Assuntos
Apoptose/efeitos dos fármacos , Entamoeba histolytica/química , Macrófagos/metabolismo , Nanotubos de Carbono/efeitos adversos , Proteínas de Protozoários/toxicidade , Animais , Linhagem Celular , Macrófagos/patologia , Camundongos , Nanotubos de Carbono/química , Proteínas de Protozoários/química , Proteínas de Protozoários/farmacologia
13.
Biomed Res Int ; 2015: 898467, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26090455

RESUMO

During amoebic liver abscess (ALA) formation in susceptible animals, immune response is regulated by prostaglandin E2 (PGE2) dependent mechanisms. The aim of this study was to analyze the effect of misoprostol (MPL), a PGE1 analogue, on ALA formation in BALB/c mice. Male mice from BALB/c strain were intrahepatically infected with 7.5 × 10(5) trophozoites of E. histolytica strain HM1:IMSS and treated with 10(-4) M of MPL daily until sacrifice at 2, 4, and 7 days postinfection (p.i.). ALA formation was evaluated at 2, 4, and 7 days postinfection; trophozoite morphology was analyzed using immunohistochemistry and image analysis. Results showed an increase in frequency of ALA formation in infected and MPL-treated mice only at 2 days p.i. (P = 0.03). A significant diminution in the size of trophozoites was detected in abscesses from mice independently of MPL treatment (from 5.8 ± 1.1 µm at 2 days p.i. to 2.7 ± 1.9 µm at 7 days p.i.) compared with trophozoites dimensions observed in susceptible hamsters (9.6 ± 2.7 µm) (P < 0.01). These results suggest that MPL treatment may modify the adequate control of inflammatory process to allow the persistence of trophozoites in the liver; however, natural resistance mechanisms cannot be discarded.


Assuntos
Abscesso Hepático Amebiano/tratamento farmacológico , Misoprostol/administração & dosagem , Trofozoítos/patologia , Alprostadil/administração & dosagem , Alprostadil/metabolismo , Animais , Cricetinae , Dinoprostona/metabolismo , Modelos Animais de Doenças , Entamoeba histolytica/efeitos dos fármacos , Entamoeba histolytica/imunologia , Entamoeba histolytica/patogenicidade , Abscesso Hepático Amebiano/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Trofozoítos/efeitos dos fármacos
14.
Int J Environ Res Public Health ; 12(5): 4587-601, 2015 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-25918912

RESUMO

Inorganic arsenic (iAs) and fluoride (F-) are naturally occurring drinking water contaminants. However, co-exposure to these contaminants and its effects on human health are understudied. The goal of this study was examined exposures to iAs and F- in Chihuahua, Mexico, where exposure to iAs in drinking water has been associated with adverse health effects. All 1119 eligible Chihuahua residents (>18 years) provided a sample of drinking water and spot urine samples. iAs and F- concentrations in water samples ranged from 0.1 to 419.8 µg As/L and from 0.05 to 11.8 mg F-/L. Urinary arsenic (U-tAs) and urinary F- (U-F-) levels ranged from 0.5 to 467.9 ng As/mL and from 0.1 to 14.4 µg F-/mL. A strong positive correlation was found between iAs and F- concentrations in drinking water (rs = 0.741). Similarly, U-tAs levels correlated positively with U-F- concentrations (rs = 0.633). These results show that Chihuahua residents exposed to high iAs concentrations in drinking water are also exposed to high levels of F-, raising questions about possible contribution of F- exposure to the adverse effects that have so far been attributed only to iAs exposure. Thus, investigation of possible interactions between iAs and F- exposures and its related health risks deserves immediate attention.


Assuntos
Arsênio/urina , Água Potável/análise , Fluoretos/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Água Subterrânea/análise , Humanos , Masculino , México , Pessoa de Meia-Idade , Fosfatos , Adulto Jovem
15.
Toxicol Sci ; 144(2): 338-46, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25577196

RESUMO

Chronic exposure to inorganic arsenic (iAs) has been linked to an increased risk of diabetes, yet the specific disease phenotype and underlying mechanisms are poorly understood. In the present study we set out to identify iAs exposure-associated metabolites with altered abundance in nondiabetic and diabetic individuals in an effort to understand the relationship between exposure, metabolomic response, and disease status. A nested study design was used to profile metabolomic shifts in urine and plasma collected from 90 diabetic and 86 nondiabetic individuals matched for varying iAs concentrations in drinking water, body mass index, age, and sex. Diabetes diagnosis was based on measures of fasting plasma glucose and 2-h blood glucose. Multivariable models were used to identify metabolites with altered abundance associated with iAs exposure among diabetic and nondiabetic individuals. A total of 132 metabolites were identified to shift in urine or plasma in response to iAs exposure characterized by the sum of iAs metabolites in urine (U-tAs). Although many metabolites were altered in both diabetic and nondiabetic 35 subjects, diabetic individuals displayed a unique response to iAs exposure with 59 altered metabolites including those that play a role in tricarboxylic acid cycle and amino acid metabolism. Taken together, these data highlight the broad impact of iAs exposure on the human metabolome, and demonstrate some specificity of the metabolomic response between diabetic and nondiabetic individuals. These data may provide novel insights into the mechanisms and phenotype of diabetes associated with iAs exposure.


Assuntos
Arsênio/toxicidade , Diabetes Mellitus/epidemiologia , Metabolômica , Adolescente , Adulto , Idoso , Diabetes Mellitus/sangue , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/urina , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
16.
Environ Health Perspect ; 122(10): 1088-94, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25000461

RESUMO

BACKGROUND: A growing number of studies link chronic exposure to inorganic arsenic (iAs) with the risk of diabetes. Many of these studies assessed iAs exposure by measuring arsenic (As) species in urine. However, this approach has been criticized because of uncertainties associated with renal function and urine dilution in diabetic individuals. OBJECTIVES: Our goal was to examine associations between the prevalence of diabetes and concentrations of As species in exfoliated urothelial cells (EUC) as an alternative to the measures of As in urine. METHODS: We measured concentrations of trivalent and pentavalent iAs methyl-As (MAs) and dimethyl-As (DMAs) species in EUC from 374 residents of Chihuahua, Mexico, who were exposed to iAs in drinking water. We used fasting plasma glucose, glucose tolerance tests, and self-reported diabetes diagnoses or medication to identify diabetic participants. Associations between As species in EUC and diabetes were estimated using logistic and linear regression, adjusting for age, sex, and body mass index. RESULTS: Interquartile-range increases in trivalent, but not pentavalent, As species in EUC were positively and significantly associated with diabetes, with ORs of 1.57 (95% CI: 1.19, 2.07) for iAsIII, 1.63 (1.24, 2.15) for MAsIII, and 1.31 (0.96, 1.84) for DMAsIII. DMAs/MAs and DMAs/iAs ratios were negatively associated with diabetes (OR = 0.62; 95% CI: 0.47, 0.83 and OR = 0.72; 95% CI: 0.55, 0.96, respectively). CONCLUSIONS: Our data suggest that uncertainties associated with measures of As species in urine may be avoided by using As species in EUC as markers of iAs exposure and metabolism. Our results provide additional support to previous findings suggesting that trivalent As species may be responsible for associations between diabetes and chronic iAs exposure.


Assuntos
Arsênio/urina , Diabetes Mellitus/epidemiologia , Exposição Ambiental/estatística & dados numéricos , Urotélio/metabolismo , Poluentes Químicos da Água/urina , Adulto , Arsênio/análise , Arsênio/metabolismo , Intoxicação por Arsênico , Arsenicais/análise , Arsenicais/metabolismo , Arsenicais/urina , Biomarcadores/metabolismo , Glicemia/análise , Diabetes Mellitus/induzido quimicamente , Exposição Ambiental/efeitos adversos , Células Epiteliais/química , Células Epiteliais/metabolismo , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Urotélio/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo , Abastecimento de Água/análise , Abastecimento de Água/estatística & dados numéricos
17.
Chem Res Toxicol ; 25(1): 216-24, 2012 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-22136492

RESUMO

Glutathione S-transferases, including GST-T1 and GST-M1, are known to be involved in the phase II detoxification pathways for xenobiotics as well as in the metabolism of endogenous compounds. Polymorphisms in these genes have been linked to an increased susceptibility to carcinogenesis and associated with risk factors that predispose to certain inflammatory diseases. In addition, GST-T1 and GST-M1 null genotypes have been shown to be responsible for interindividual variations in the metabolism of arsenic, a known human carcinogen. To assess the specific GST genotypes in the Mexican population chronically exposed to arsenic, we have developed a multiplex High Resolution Melting PCR (HRM-PCR) analysis using a LightCycler480 instrument. This method is based on analysis of the PCR product melting curve that discriminates PCR products according to their lengths and base sequences. Three pairs of primers that specifically recognize GST-T1, GST-M1, and ß-globin, an internal control, to produce amplicons of different length were designed and combined with LightCycler480 High Resolution Melting Master Mix containing ResoLight, a completely saturating DNA dye. Data collected from melting curve analysis were evaluated using LightCycler480 software to determine specific melting temperatures of individual melting curves representing target genes. Using this newly developed multiplex HRM-PCR analysis, we evaluated GST-T1 and GST-M1 genotypes in 504 DNA samples isolated from the blood of individuals residing in Zimapan, Lagunera, and Chihuahua regions in Mexico. We found that the Zimapan and Lagunera populations have similar GST-T1 and GST-M1 genotype frequencies which differ from those of the Chihuahua population. In addition, 14 individuals have been identified as carriers of the double null genotype, i.e., null genotypes in both GST-T1 and GST-M1 genes. Although this procedure does not distinguish between biallelic (+/+) and monoallelic (+/-) genotypes, it can be used in an automated workflow as a simple, sensitive, and time and money saving procedure for rapid identification of the GST-T1 and GST-M1 positive or null genotypes.


Assuntos
Genótipo , Glutationa Transferase/genética , Reação em Cadeia da Polimerase Multiplex/métodos , Adulto , Idoso , DNA/genética , Feminino , Hepatócitos/enzimologia , Humanos , Masculino , México , Pessoa de Meia-Idade , Polimorfismo Genético , Globinas beta/genética
18.
Ginecol Obstet Mex ; 77(7): 323-8, 2009 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-19681362

RESUMO

BACKGROUND: Studies in the human term placenta have shown that muscarinic cholinergic receptors M1-M4 are located in the sincitiotrofoblasto in the basement membrane and in the brush border membrane of the villi. However, in both studies the methodology has not been implicated microscopy methods to reveal its location. OBJECTIVE: To determine the expression of muscarinic cholinergic receptors M1 and M2 in human term placenta. MATERIALS AND METHODS: We analyzed 20 samples of human placenta at term newborns. Muscarinic cholinergic receptors M1 and M2 were detected by immunohistochemistry and polyclonal antisera. The optical density of the signal for each muscarinic cholinergic receptor was analyzed with Image Pro Plus software. 30 readings were made by the placenta (n=600). The expression of muscarinic cholinergic receptors were analyzed using the Student t test. RESULTS: The expression of muscarinic cholinergic receptors M1 and M2 in human term placenta were found in the sincitiotrofoblasto of secondary and tertiary villi. The expression of muscarinic cholinergic receptors M1 and M2 in the population showed that the RCM M2 is expressed in a greater proportion than RCM M1 (p < 0.01). The expression of muscarinic cholinergic receptors M1 and M2 was lower in newborns with low weight for gestational age, although the difference was not significant (p > 0.05). CONCLUSIONS: The expression of muscarinic cholinergic receptors were identified in placental sincitiotrofoblasto predominantly M2 muscarinic cholinergic receptor. The values reported here represent a baseline that can be used to analyze the expression of muscarinic cholinergic receptors in the placenta of women with a history of environmental exposure to toxic substances.


Assuntos
Placenta/metabolismo , Receptores Muscarínicos/biossíntese , Adulto , Feminino , Humanos
19.
Chemosphere ; 55(10): 1421-7, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15081785

RESUMO

The increased use of organophosphorus insecticides in agriculture and their widespread existence in the environment poses a potential health hazard. To determine the relationship between exposure to pesticides and intrauterine growth retardation (IUGR), live newborns from singleton pregnancies, with (n = 79) and without (n = 292) IUGR were studied. During the gestational period the mothers were living in agricultural communities in the state of Chihuahua, Mexico. Exposure to agrochemical products was evaluated. A significant association between the history of positive exposure to pesticides (i.e. the women themselves or their newborns who showed acetylcholinesterase activity levels lower than 20%) and the presence of IUGR was found. The proportions of exposure in the cases were 18% and 8% in the control group; the adjusted OR (fat free mass, anti-cytomegalovirus antibodies and placental weight) was 2.33 (p = 0.04).


Assuntos
Exposição Ambiental , Retardo do Crescimento Fetal/induzido quimicamente , Inseticidas/toxicidade , Compostos Organofosforados , Acetilcolinesterase , Anticorpos/imunologia , Peso ao Nascer , Estudos de Casos e Controles , Citomegalovirus/imunologia , Feminino , Humanos , Recém-Nascido , México , Gravidez
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