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INTRODUCTION: Epidemiological evidence suggests an association between CS and offspring metabolic syndrome (MetS), but whether a causal relationship exists is unknown. METHODS: In this study, timed-mated Wistar rat dams were randomly assigned to cesarean section (CS), vaginal delivery (VD), and surrogate groups. The offspring from both CS and VD groups were reared by surrogate dams until weaning, and weaned male offspring from both groups were randomly assigned to receive normal diet (ND) or high-fat/high-fructose diet (HFF) ad libitum for 39 weeks. RESULTS: By the end of study, CS-ND offspring gained 17.8% more weight than VD-ND offspring, while CS-HFF offspring gained 36.4% more weight than VD-HFF offspring. Compared with VD-ND offspring, CS-ND offspring tended to have increased triglycerides (0.27 mmol/l, 95% CI, 0.05 to 0.50), total cholesterol (0.30 mmol/l, -0.08 to 0.68), and fasting plasma glucose (FPG) (0.30 mmol/l, -0.01 to 0.60); more pronounced differences were observed between CS-HFF and VD-HFF offspring in these indicators (triglyceride, 0.66 mmol/l, 0.35 to 0.97; total cholesterol, 0.46 mmol/l, 0.13 to 0.79; and FPG, 0.55 mmol/l, 0.13 to 0.98). CONCLUSIONS: CS offspring were more prone to adverse metabolic profile and HFF might exacerbate this condition, indicating the association between CS and MetS is likely to be causal. IMPACT: Whether the observed associations between CS and MetS in non-randomized human studies are causally relevant remains undetermined. Compared with vaginally born offspring rats, CS born offspring gained more body weight and tended to have compromised lipid profiles and abnormal insulin sensitivity, suggesting a causal relationship between CS and MetS that may be further amplified by a high-fat/high-fructose diet. Due to the high prevalence of CS births globally, greater clinical consideration must be given to the potential adverse effects of CS, and whether these risks should be made known to patients in clinical practice merits evaluation.
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Glucemia , Cesárea , Síndrome Metabólico , Ratas Wistar , Animales , Síndrome Metabólico/etiología , Femenino , Masculino , Embarazo , Ratas , Glucemia/metabolismo , Dieta Alta en Grasa/efectos adversos , Triglicéridos/sangre , Colesterol/sangre , Fructosa/efectos adversos , Fructosa/administración & dosificaciónRESUMEN
Numerous studies in recent years have questioned the safety of oral exposure to titanium dioxide nanoparticles (TiO2 NPs). TiO2 NPs are not only likely to accumulate in the gastrointestinal tract, but they are also found to penetrate the body circulation and reach distant organs. The liver, which is considered to be a target organ for nanoparticles, is of particular concern. TiO2 NPs accumulate in the liver and cause oxidative stress and inflammatory reactions, resulting in pathological damage. The impact of TiO2 NPs on liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was studied using a meta-analysis. According to the findings, TiO2 NPs exposure can cause an elevation in AST and ALT levels in the blood. Furthermore, TiO2 NPs are eliminated mostly through feces, and their lengthy residence in the gut exposes them to microbiota. The gut microbiota is also dysbiotic due to titanium dioxide's antibacterial capabilities. This further leads to changes in the amount of microbiota metabolites, which can reach the liver with blood circulation and trigger hepatotoxicity through the gut-liver axis. This review examines the gut-liver axis to assess the effects of gut microbiota dysbiosis on the liver to provide suggestions for assessing the gut-hepatotoxicity of TiO2 NPs.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Microbioma Gastrointestinal , Nanopartículas del Metal , Nanopartículas , Humanos , Nanopartículas/toxicidad , Titanio/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Nanopartículas del Metal/toxicidadRESUMEN
The association between short-term ambient air pollution (AAP) exposure and blood lipids is inconsistent across populations. This study aimed to investigate the modifying effects of fasting blood glucose (FBG) levels on the associations between short-term AAP exposure and blood lipids in 110,637 male participants from Beijing, China. The results showed that FBG modified the association between short-term AAP exposure and blood lipids, especially low-density lipoprotein cholesterol (LDL-C). In the hyperglycemia group, a 10-µg/m3 increase in particles with diameters ≤ 2.5 µm (PM2.5), particles with diameters ≤ 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), or a 1-mg/m3 increase in carbon monoxide (CO) was associated with a 0.454%, 0.305%, 1.507%, 0.872%, or 3.961% increase in LDL-C, respectively. In the nonhyperglycemic group, short-term increases in air pollutants were even associated with small decreases in LDL-C. The findings demonstrate that lipids in hyperglycemic individuals are more vulnerable to short-term AAP exposure than those in normal populations.
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Titanium dioxide often enters the respiratory tract in the form of nano-dust in occupational sites. Metabolomics may be a promising method for studying the toxicology of nano titanium dioxide. The intention of this study was to explore the possible impact of titanium dioxide nanoparticles (TiO2 NPs) on the metabolomics signatures of human normal bronchial epithelial (BEAS-2B) cells and to search for investigate the role of reactive oxygen species (ROS). In this study, BEAS-2B cells were treated by TiO2 NPs (0, 25, 50 and 100 µg/mL) for 48 h. The metabolites extracted from BEAS-2B cells were determined by untargeted metabolomics technique, and the differential metabolites and metabolic pathways were discovered by using multivariate analysis. Intracellular ROS was detected by DCFH-DA probe and flow cytometry method. Machine learning was used to explore the relationship between ROS and metabolomics changes. Totally, seventy-six differential metabolites and the steroid biosynthesis pathway of BEAS-2B cells were observed after treatment of TiO2 NPs. Lipid and lipid-like metabolites were the most significant classes among the metabolite products induced by TiO2 NPs. TiO2 NPs resulted in a dose-dependent increase in intracellular ROS levels, and correlated with most of the differential metabolites. In conclusion, TiO2 NPs increased the level of the oxidative stress, which could contribute to the altered signature represented by lipid metabolism in BEAS-2B cells.
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Nanopartículas del Metal , Nanopartículas , Humanos , Lípidos , Metabolómica , Nanopartículas del Metal/toxicidad , Nanopartículas/toxicidad , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Titanio/toxicidadRESUMEN
PURPOSE: The contribution of household cooking salt to population iodine status is decreasing in China, the applicability of the coverage rate of iodized salt (IS), proportion of adequately iodized salt (AIS), and salt iodine concentration (SIC) of household cooking salt used for iodine status assessment of residents requires further investigation. METHODS: Through the IDD control project, 16,445 children and 4848 pregnant women were recruited from Tianjin, China and the relationship between the coverage rate of IS, proportion of AIS, SIC, and population iodine status was analyzed. Additionally, through the thyroid health survey project, 856 children with IS or noniodized salt were recruited. The effects of different household cooking salts on individual iodine status and thyroid health were analyzed. RESULTS: After adjusting for confounding factors, no relationship was found between the coverage rate of IS, proportion of AIS, SIC of household cooking salt, and iodine status of children and pregnant women (all P > 0.05). No differences in levels of thyroid function and structural indicators were found in children with different household cooking salts (all P > 0.05). Additionally, no relationship was found between noniodized salt exposure and goiter, overt hyperthyroidism, overt hypothyroidism, thyroid nodules, antibody single positivity, or subclinical hypothyroidism (all P > 0.05). CONCLUSION: Iodine in household cooking salt no longer plays a crucial role in iodine status in Tianjin, China. Other indicators must be identified as beneficial supplements for precise iodine status evaluation not only in Tianjin but also in other large cities in China.
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Hipotiroidismo , Yodo , Niño , China/epidemiología , Culinaria , Femenino , Humanos , Yodo/análisis , Estado Nutricional , Embarazo , Sales (Química) , Cloruro de Sodio Dietético/análisisRESUMEN
Concerns are growing over time on the adverse health effects of air pollution. However, the association between ambient air pollution and blood sex hormones in men is poorly understood. We included 72,917 men aged 20-55 years from February 2014 to December 2019 in Beijing, China in this study. Blood testosterone, follicle stimulating hormone, luteinizing hormone, estradiol, and prolactin levels of each participant were measured. We collected exposure data of daily ambient levels of particulate matter ≤10 µm (PM10) and ≤2.5 µm (PM2.5), nitrogen dioxide, sulfur dioxide (SO2), carbon monoxide, and ozone. Generalized linear mixed models were used to analyze the potential association between ambient air pollution exposure and blood sex hormone levels. The results showed that both immediate and short-term cumulative PM2.5, PM10, and SO2 exposure was related to altered serum sex hormone levels in men, especially testosterone. An increase of 10 µg/m3 in PM2.5 and PM10 in the current day was related to a 1.6% (95% confidence interval [CI]: 0.9%-2.3%) and 1.1% (95% CI: 0.5%-1.6%) decrease in testosterone, respectively, and a decreasing tendency of accumulated effects persisted within lag 0-30 days. The present study demonstrated that it is important to control ambient air pollution exposure to reduce effects on the reproductive health of men.
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Contaminantes Atmosféricos , Contaminación del Aire , Ozono , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , China , Exposición a Riesgos Ambientales/análisis , Humanos , Masculino , Dióxido de Nitrógeno/análisis , Ozono/análisis , Material Particulado/análisis , Dióxido de Azufre/análisis , TestosteronaRESUMEN
BACKGROUND: The application of titanium dioxide nanoparticles (TiO2 NPs) as food additives poses a risk of oral exposure that may lead to adverse health effects. Even though the substantial evidence supported liver as the target organ of TiO2 NPs via oral exposure, the mechanism of liver toxicity remains largely unknown. Since the liver is a key organ for lipid metabolism, this study focused on the landscape of lipidomic metabolites in gut-liver axis of Sprague Dawley (SD) rats exposed to TiO2 NPs at 0, 2, 10, 50 mg/kg body weight per day for 90 days. RESULTS: TiO2 NPs (50 mg/kg) caused slight hepatotoxicity and changed lipidomic signatures of main organs or systems in the gut-liver axis including liver, serum and gut. The cluster profile from the above biological samples all pointed to the same key metabolic pathway and metabolites, which was glycerophospholipid metabolism and Phosphatidylcholines (PCs), respectively. In addition, absolute quantitative lipidomics verified the changes of three PCs concentrations, including PC (16:0/20:1), PC (18:0/18:0) and PC (18:2/20:2) in the serum samples after treatment of TiO2 NPs (50 mg/kg). The contents of malondialdehyde (MDA) in serum and liver increased significantly, which were positively correlated with most differential lipophilic metabolites. CONCLUSIONS: The gut was presumed to be the original site of oxidative stress and disorder of lipid metabolism, which resulted in hepatotoxicity through the gut-liver axis. Lipid peroxidation may be the initial step of lipid metabolism disorder induced by TiO2 NPs. Most nanomaterials (NMs) have oxidation induction and antibacterial properties, so the toxic pathway revealed in the present study may be primary and universal.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Nanopartículas , Animales , Lipidómica , Nanopartículas/toxicidad , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Titanio/toxicidadRESUMEN
OBJECTIVES: Exposure to high altitude can affect human health, including the development of adverse cardiovascular effects. This study aimed to investigate alterations in cardiac morphology and function in high-altitude workers and to identify risk factors associated with cardiac abnormalities. METHODS: A retrospective cohort study was conducted with 286 Qinghai-Tibetan Railroad maintenance workers. Participant data were collected from company personnel records. Data on echocardiography and diagnosis of cardiac abnormalities were extracted from participants' medical records. Time-to-event analysis was used to investigate the risk of cardiac abnormalities among participants with different baseline characteristics and identify risk factors associated with cardiac abnormalities that developed as a result of working at high altitude. RESULTS: A total of 173 participants had developed cardiac abnormalities during the follow-up period. The most common cardiac abnormality was right atrial enlargement, followed by left ventricular diastolic dysfunction and tricuspid regurgitation. Among participants with cardiac abnormalities, the median follow-up time was 17 months. Compared with participants who were younger than 20 years and working at altitude <4000 m, participants older at employment and working at extremely high altitude were more likely to develop cardiac abnormalities. Nearly 40% of the participants who worked at altitude <4000 m remained without cardiac abnormalities during the follow-up period. CONCLUSIONS: Over 60% of participants developed cardiac abnormalities after working at high altitude, predominantly right heart enlargement and left ventricular diastolic dysfunction. Age at employment and workplace altitude were significant risk factors for cardiac abnormalities. Enhanced regular physical examinations are recommended for high-altitude workers.
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Altitud , Cardiopatías/epidemiología , Exposición Profesional/efectos adversos , Adulto , China , Estudios de Cohortes , Ecocardiografía , Femenino , Cardiopatías/diagnóstico por imagen , Cardiopatías/etiología , Humanos , Masculino , Vías Férreas , Estudios Retrospectivos , TibetRESUMEN
Titanium dioxide nanoparticles (TiO2 NPs) were usually consumed with a high content of sugar, and children were identified as having the highest exposures due to sweet food preferences. Research on the combined effect of ingested TiO2 NPs and glucose has great significance, particularly in young people. We examined young Sprague-Dawley rats administered TiO2 NPs (0, 2, 10 and 50 mg/kg) orally with and without glucose (1.8 g/kg) for 90 days. Blood glucose homeostasis was assessed by monitoring blood glucose and detecting glycoproteins. Glucose tolerance was also evaluated by the oral glucose tolerance test. The levels of blood glucose-related hormones such as insulin, C-peptide and glucagon were measured. We found that subchronic co-exposure of TiO2 NPs and glucose caused slight imbalance of blood glucose homeostasis in vivo. Mild and temporary hypoglycemia, impaired glucose tolerance and changes of glucose-regulating hormones were shown in the exposure groups. The combined effect of TiO2 NPs and glucose was more apparent than that of TiO2 NPs alone, which may be due to the effects of excess glucose and the interactions between TiO2 NPs and glucose. The antagonistic effect of TiO2 NPs with glucose did exist in the level of glycosylated hemoglobin in female rats. Gender differences were apparent in these effects induced by TiO2 NPs and glucose. Female rats seemed to be more susceptible for blood glucose disorders. Co-exposure of TiO2 NPs and excessive glucose could induce gender-dependent imbalance of blood glucose homeostasis in rats. It may be the reason that these consumers face greater health risks glycosylated hemoglobin.
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Glucemia/efectos de los fármacos , Colorantes de Alimentos/toxicidad , Homeostasis/efectos de los fármacos , Nanopartículas/toxicidad , Titanio/toxicidad , Administración Oral , Animales , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Modelos Animales , Ratas , Ratas Sprague-Dawley , Factores SexualesRESUMEN
OBJECTIVE: To explore the effect of combined oral exposure of titanium dioxide nanoparticles(TiO_2 NPs) and glucose on blood glucose homeostasis in young SD rats. METHODS: Eighty 4-week-old young SD rats were randomly divided into 8 groups(10 rats in each group, half male and half female). The rats were exposed to TiO_2 NPs through intragastric administration at 0, 2, 10 and 50 mg/kg with or without 1. 8 g/kg glucose daily for 30 days. Blood glucose was monitored weekly during the experiment. Oral glucose tolerance test(OGTT) was carried out after subacute exposure(30 days), and the biomarkers related to blood glucose homeostasis were detected, including the contents of glycosylated serum protein(GSP), glycosylated hemoglobin(HbA1 c), insulin, C-peptide and glucagon. At the same time, the pancreatic pathology of rats was observed. RESULTS: TiO_2 NPs were anatase crystals, closely spherical shape, with an average particle size of(24±5)nm. Exposure of TiO_2 NPs alone had little effect on blood glucose homeostasis. Blood glucose decreased on the 16 th exposure day at dose of 10 mg/kg TiO_2 NPs, and postprandial blood glucose(2 h) decreased after 30 days of TiO_2 NPs exposure at doses of 2 and 50 mg/kg in male rats(P<0. 05). The combined effect of oral exposure of TiO_2 NPs and glucose on blood glucose homeostasis was more obvious than that of TiO_2 NPs alone. Blood glucose decreased on the 9 th exposure day at dose of 10 mg/kg TiO_2 NPs+glucose in female rats, and postprandial blood glucose(2 h) decreased at dose of 2 and 50 mg/kg TiO_2 NPs+glucose after 30 days of exposure in male rats(P<0. 05). Blood glucose decreased on the 9 th day after 10 mg/kg TiO_2 NPs+glucose exposure in female rats. The glycosylated serum protein decreased and postprandial blood glucose(30 and 60 min) as well as the area under curve of OGTT increased in male rats after 30 days of exposure(P<0. 05). The changes of blood glucose-regulating hormones were only found after the combined exposure of 10 mg/kg TiO_2 NPs+glucose for 30 days, including the decrease of insulin in female rats, as well as the decrease of insulin and the increase of glucagon in male rats(P<0. 05). The interaction analysis showed that TiO_2 NPs and glucose had significant synergistic effect on postprandial blood glucose(60 min) in male rats(P<0. 05). No abnormality was found in the pathological observation of pancreas in rats of experimental groups. CONCLUSION: Subacute combined oral exposure of TiO_2 NPs and glucose could affect the blood glucose homeostasis of young SD rats, resultsing in temporary hypoglycemia and impaired glucose tolerance, as well as adaptive changes of blood glucose-regulating hormones. The male rats were more sensitive. Compared with the exposure of TiO_2 NPs alone, the combined exposure of TiO_2 NPs and glucose induced more significant effects. Significant synergistic effect between them occurred on postprandial blood glucose.
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Glucemia , Nanopartículas , Animales , Femenino , Glucosa , Homeostasis , Masculino , Ratas , Ratas Sprague-Dawley , TitanioRESUMEN
BACKGROUND: Due to its excellent physicochemical properties and wide applications in consumer goods, titanium dioxide nanoparticles (TiO2 NPs) have been increasingly exposed to the environment and the public. However, the health effects of oral exposure of TiO2 NPs are still controversial. This study aimed to illustrate the hepatotoxicity induced by TiO2 NPs and the underlying mechanisms. Rats were administered with TiO2 NPs (29 nm) orally at exposure doses of 0, 2, 10, 50 mg/kg daily for 90 days. Changes in the gut microbiota and hepatic metabolomics were analyzed to explore the role of the gut-liver axis in the hepatotoxicity induced by TiO2 NPs. RESULTS: TiO2 NPs caused slight hepatotoxicity, including clear mitochondrial swelling, after subchronic oral exposure at 50 mg/kg. Liver metabolomics analysis showed that 29 metabolites and two metabolic pathways changed significantly in exposed rats. Glutamate, glutamine, and glutathione were the key metabolites leading the generation of energy-related metabolic disorders and imbalance of oxidation/antioxidation. 16S rDNA sequencing analysis showed that the diversity of gut microbiota in rats increased in a dose-dependent manner. The abundance of Lactobacillus_reuteri increased and the abundance of Romboutsia decreased significantly in feces of TiO2 NPs-exposed rats, leading to changes of metabolic function of gut microbiota. Lipopolysaccharides (LPS) produced by gut microbiota increased significantly, which may be a key factor in the subsequent liver effects. CONCLUSIONS: TiO2 NPs could induce slight hepatotoxicity at dose of 50 mg/kg after long-term oral exposure. The indirect pathway of the gut-liver axis, linking liver metabolism and gut microbiota, played an important role in the underlying mechanisms.
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Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Microbioma Gastrointestinal/efectos de los fármacos , Hígado/efectos de los fármacos , Redes y Vías Metabólicas/efectos de los fármacos , Nanopartículas/toxicidad , Titanio/toxicidad , Administración Oral , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Enfermedad Hepática Inducida por Sustancias y Drogas/microbiología , Relación Dosis-Respuesta a Droga , Hígado/inmunología , Hígado/metabolismo , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula , Ratas , Ratas Sprague-Dawley , Propiedades de SuperficieRESUMEN
Existing literature pointed out that the liver may be the target organ of toxicity induced by titanium dioxide nanoparticles (TiO2 NPs) via oral exposure. Gender differences in health effects widely exist and relevant toxicological research is important for safety assessment. To explore the gender susceptibility of TiO2 NP-induced hepatic toxicity and the underlying mechanism, we examined female and male Sprague-Dawley rats administrated with TiO2 NPs orally at doses of 0, 2, 10 and 50 mg/kg body weight per day for 90 days. The serum biochemical indicators and liver pathological observation were used to assess hepatic toxicity. We found significant hepatic toxicity could be induced by subchronic oral exposure to TiO2 NPs, which was more obvious and severe in female rats. No accumulation of TiO2 NPs in the liver was observed, indicating that hepatic toxicity may not be caused through direct pathways. Oxidized glutathione, lipid peroxidation products increased significantly and reduced glutathione decreased significantly in the liver of rats in repeated TiO2 NP-exposed groups. Hematological parameters of white blood cells and inflammatory cytokines in serum including interleukin 1α, interleukin 4 and tumor necrosis factor also increased significantly. Indirect pathways through initiating oxidative stress and inflammatory responses were suggested as the possible mechanism of the hepatic toxicity in this experiment. The higher sensitivity to redox homeostasis imbalance and inflammation of female rats may be the main reason for gender differences. Our research suggested that gender should be a susceptible factor for identifying and monitoring long-term oral toxicity of TiO2 NPs.
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Hígado/efectos de los fármacos , Nanopartículas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Caracteres Sexuales , Titanio/toxicidad , Administración Oral , Animales , Biomarcadores/metabolismo , Citocinas/sangre , Relación Dosis-Respuesta a Droga , Femenino , Hígado/inmunología , Hígado/metabolismo , Hígado/patología , Masculino , Ratas Sprague-Dawley , Propiedades de SuperficieRESUMEN
Titanium dioxide nanoparticles (TiO2 NPs) have already been used as food additive in various products and are usually consumed with a considerable amount of sugar. Oral consumption of TiO2 NPs poses concerning health risks; however, research on the combined effect of ingested TiO2 NPs and glucose is limited. We examined young Sprague-Dawley rats administrated TiO2 NPs orally at doses of 0, 2, 10 and 50 mg/kg body weight per day with and without 1.8 g/kg body weight glucose for 30 and 90 days. Heart rate, systolic and diastolic blood pressure, blood biochemical parameters and histopathology of cardiac tissues was assessed to quantify cardiovascular damage. The results showed that oral exposure to TiO2 NPs and high doses of glucose both could induce cardiovascular injuries. The toxic effects were dose-, time- and gender-dependent. The interaction effects between oral-exposed TiO2 NPs and glucose existed and revealed to be antagonism in most of the biological parameters. However, toxic effects of the high-dose glucose seemed to be more severe than TiO2 NPs and the interaction of TiO2 NPs with glucose. These results suggest that it may be more important to control the sugar intake than TiO2 NPs for protecting the health of TiO2 NP consumers.
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Sistema Cardiovascular/efectos de los fármacos , Aditivos Alimentarios/toxicidad , Glucosa/toxicidad , Nanopartículas/toxicidad , Titanio/toxicidad , Administración Oral , Animales , Presión Sanguínea/efectos de los fármacos , Sistema Cardiovascular/crecimiento & desarrollo , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/patología , Relación Dosis-Respuesta a Droga , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Tamaño de la Partícula , Ratas Sprague-Dawley , Propiedades de SuperficieRESUMEN
As food additives, titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various products that are usually simultaneously consumed with a high content of sugar, thus necessitating research on the effect of TiO2 NPs on glucose homeostasis. We conducted an animal study to explore the effect of orally administrated TiO2 NPs on glucose absorption and metabolism in rats at 0, 2, 10 and 50 mg kg-1 body weight day-1 for 30 and 90 days. The results showed that oral exposure to TiO2 NPs caused a slight and temporary hypoglycemic effect in rats at 30 days post-exposure but recovered at 90 days post-exposure. Decreased levels of intestinal glucose absorption and increased levels of hepatic glucose metabolism may be responsible for the hypoglycemic effect. Remodeling of the villi in the small intestine that decreased the surface area available for glucose absorption and increased levels of hepatic glucose uptake, utilization and storage related to hepatocellular injury are supposed to be the mechanisms. Our results demonstrated that dietary intake of TiO2 NPs as food additives could affect the absorption and metabolism of glucose.
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Glucemia/efectos de los fármacos , Aditivos Alimentarios/toxicidad , Hipoglucemia/inducido químicamente , Titanio/toxicidad , Administración Oral , Animales , Biomarcadores/sangre , Glucemia/metabolismo , Relación Dosis-Respuesta a Droga , Aditivos Alimentarios/administración & dosificación , Homeostasis , Hipoglucemia/sangre , Absorción Intestinal/efectos de los fármacos , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Intestino Delgado/ultraestructura , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratas Sprague-Dawley , Factores de Tiempo , Titanio/administración & dosificaciónRESUMEN
Titanium dioxide nanoparticles (TiO2 NPs) have a broad application prospect in replace with TiO2 used as a food additive, especially used in sweets. Understanding the interaction of TiO2 NPs with sugar is meaningful for health promotion. We used a young animal model to study the toxicological effect of orally administrated TiO2 NPs at doses of 0, 2, 10 and 50 mg/kg per day with or without daily consumption of 1.8 g/kg glucose for 30 days and 90 days. The results showed that oral exposure to TiO2 NPs and TiO2 NPs+glucose both induced liver, kidney, and heart injuries as well as changes in the count of white and red blood cells in a dose, time and gender-dependent manner. The toxicological interactions between orally-administrated TiO2 NPs and glucose were evident, but differed among target organs. These results suggest that it is necessary to limit dietary co-exposure to TiO2 NPs and sugar. FROM THE CLINICAL EDITOR: Nanotechnology has gained entrance in the food industry, with the presence of nanoparticles now in many food items. Despite this increasing trend, the potential toxic effects of these nanoparticles to human remain unknown. In this article, the authors studied titanium dioxide nanoparticles (TiO2 NPs), which are commonly used as food additive, together with glucose. The findings of possible adverse effects on liver, kidney, and heart might point to a rethink of using glucose and TiO2 NPs combination.
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Administración Oral , Glucosa/metabolismo , Nanopartículas del Metal/administración & dosificación , Titanio/administración & dosificación , Animales , Carbohidratos/química , Relación Dosis-Respuesta a Droga , Humanos , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Nanopartículas del Metal/efectos adversos , Nanopartículas del Metal/química , Ratas , Titanio/efectos adversos , Titanio/químicaRESUMEN
OBJECTIVE: To compare the effect of TiO2 nanoparticles on antioxidant function and element content of liver and kidney tissues in young and adult rats. METHODS: Forty-eight SD male rats, half in 4-week (youth) old and half in 9-week (adult) old rats, were randomly divided into 8 groups, which were exposed to TiO2 nanoparticles [(75 ± 15) nm, anatase] through intragastric administration at 0, 10, 50 and 200 mg/kg body weight every day for 30 days. The liver and kidney tissues were collected for antioxidant function and element content analysis. RESULTS: 200 mg/kg TiO2 nanoparticles exposure significantly increased the liver total superoxide dismutase (T-SOD) activity and the kidney reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios in young rats, and significantly decreased the liver Mo, Co, Mn and P contents and the kidney Rb and Na contents in young rats. 200 mg/kg TiO2 nanoparticles exposure significantly increased GSH/GSSG ratios and Rb contents and decreased Na contents in the liver of adult rats. No significantly difference was found in antioxidant indexes and elements content in the kidney of adult rats between three experimental groups and control group. CONCLUSION: TiO2 nanoparticles can enhance the antioxidant capacity and decrease the elements content in rat liver and kidney tissues. The liver is the more sensitive target organ and the young animals are more susceptible to TiO2 nanoparticles toxicity by the oral routes.
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Antioxidantes/metabolismo , Riñón/metabolismo , Hígado/metabolismo , Nanopartículas , Titanio/farmacología , Administración Oral , Animales , Glutatión , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To explore the genotoxic effects of oral-exposed TiO2 nanoparticles on bone marrow cells in young rats. METHODS: Twenty-eight SD male young rats (4 weeks old) were randomly divided into 4 groups, which were exposed to TiO2 nanoparticles ((75 ± 15) nm, anatase) through intragastric administration at 0, 10, 50 and 200 mg/kg body weight (bw) every day for 30 days. The bone marrow cells were collected for micronuclei and γ-H2AX immunofluorescence analysis. RESULTS: The percentage of γ-H2AX foci-positive cells (37.4 ± 10.0)% in the 50 mg/kg bw dose group were significantly higher than that in the control group (19.8 ± 3.1)% (t value was -17.59, P < 0.01). No significantly difference was found in polychromatic erythrocyte/normochromatic erythrocyte (PCE/NCE) ratio and PCE micronucleus rate between three experimental groups and control group. CONCLUSION: TiO2 nanoparticles can increase the frequency of DNA double-strand breaks in bone marrow cells, but has no effect on micronucleus of bone marrow cells in young rats.
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Células de la Médula Ósea , Daño del ADN , Micronúcleos con Defecto Cromosómico , Nanopartículas , Titanio , Animales , Histonas , Masculino , RatasRESUMEN
Titanium dioxide nanoparticles (TiO2 NPs) have potential applications as food additives, but concerns persist about their safety. Children are identified as having the highest exposure and may face the greatest health risks. However, the toxicological sensitivity of TiO2 NPs in different ages is not clear. Here, a comparative toxicity study of TiO2 NPs in 3-week (youth) and 8-week (adult) old Sprague-Dawley rats is reported following oral exposure at doses of 0, 10, 50, 200 mg kg(-1) body weight per day for 30 days. The organ mass and histology, blood biochemistry and redox state, intestinal function, and biodistribution of NPs are characterized. The results show that TiO2 NPs induce different toxic effects on young and adult rats. The liver edema, heart injuries and non-allergic mast cell activation in stomach tissues are found in young rats. On the other hand, only slight injury in the liver and kidney and decreased intestinal permeability and molybdenum contents are found in adult rats. Furthermore, TiO2 NP exposure can provoke reductive stress (i.e., increased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios) in plasmas through enhancing the glucose and GSH levels in young rats or reducing the glutathione peroxidase (GSH-Px) acitivity and GSSG levels in adult rats. These results suggest that different ages may require different biomarkers for identifying and monitoring oral toxicity of nanoparticles.
Asunto(s)
Factores de Edad , Nanopartículas del Metal/toxicidad , Titanio/toxicidad , Administración Oral , Animales , Relación Dosis-Respuesta a Droga , Nanopartículas del Metal/administración & dosificación , Ratas , Ratas Sprague-Dawley , Distribución Tisular , Titanio/administración & dosificaciónRESUMEN
OBJECTIVE: To compare the cytotoxicity and DNA strand breakage induced by multi-walled carbon nanotubes (MWCNTs) with different lengths and different surface modifications in human alveolar type II cells (A549 cells). METHODS: Two different lengths (5-15 µm, 350-700 nm) of MWCNTs and three different kinds of surface modified MWCNTs (COOH-MWCNTs, NH2-MWCNTs, and Tau-MWCNTs) were used in the experiments. The short MWCNTs were used as pristine MWCNTs to compare with the 3 surface modified MWCNTs. The cytotoxicity was determined by cell counting kit-8 (CCK-8) assay at the concentrations of 2, 8, and 32 mg/L at hours 12, 24, 36, and 48 respectively. Single cell gel electrophoresis (SCGE) assay was performed to evaluate DNA strand breakage in A549 cells after 24 h treatment of 8 mg/L of each tested material. RESULTS: Long multi-walled carbon nanotubes (Long-MWCNTs) and short multi-walled carbon nanotubes (Short-MWCNTs) showed a dose-dependent cytotoxicity within the exposure time 12-48 h. Especially, Long-MWCNTs showed greater cytotoxicity than Short-MWCNTs from 24 to 48 h at the same concentration. The relative cell viability of the 3 surface modified MWCNTs was higher than that of the pristine MWCNTs at h 12 at the concentration of 32 mg/L [COOH-MWCNTs (86.55±1.80)%, NH2-MWCNTs (84.67±1.32)%, Tau-MWCNTs (80.15±3.53)% and Pristine-MWCNTs (71.44±5.58)%], at h 24 at the concentration of 8 mg/L [COOH-MWCNTs (96.74±1.00)%, NH2-MWCNTs (96.74±3.35)%, Tau-MWCNTs (106.39±3.83)% and Pristine-MWCNTs (91.02±2.53)%], at h 24 at the concentration of 32 mg/L [COOH-MWCNTs (80.88±2.67)%, NH2-MWCNTs (82.90±3.25)%, Tau-MWCNTs (82.55±3.32)% and Pristine-MWCNTs (76.08±4.27)%] and at h 36 at the concentration of 8 mg/L [COOH-MWCNTs (96.87±1.05)%, NH2-MWCNTs (96.66±4.76)%, Tau-MWCNTs (100.23± 2.84)% and Pristine-MWCNTs (89.61±3.78)%], and the differences were statistically significant (P<0.05). Compared with the Pristine-MWCNTs, the relative cell viability of the 3 surface modified MWCNTs didn't demonstrate a statistically significant difference (P>0.05) at other observation time and exposure concentrations. The DNA strand breakage of the 3 surface modified MWCNTs: the Olive tail moment of COOH-MWCNTs was 1.56±0.22, the Olive tail moment of NH2-MWCNTs 2.25±1.62 and the Olive tail moment of Tau-MWCNTs 2.23±0.94; the tail DNA% of COOH-MWCNTs was (3.96± 0.60)%, the tail DNA% of NH2-MWCNTs (6.16±4.68)% and the tail DNA% of Tau-MWCNTs (6.05±2.31)%, which were lower than that of the pristine MWCNTs (P<0.05), whose Olive tail moment was 3.00±0.64 and tail DNA% (8.23±2.27)%. Moreover, the COOH-MWCNTs induced the lowest DNA damage among the three modified MWCNTs. CONCLUSION: Long-MWCNTs compared with Short-MWCNTs demonstrated a greater cytotoxicity and lower DNA strand breakage damage. The surface modifications of MWCNTs can reduce the cytotoxicity and DNA strand breakage in A549 cells.
Asunto(s)
Nanotubos de Carbono/toxicidad , Línea Celular Tumoral , Supervivencia Celular , Daño del ADN , Humanos , Nanotubos de Carbono/químicaRESUMEN
Respiration is considered to be the main occupational or environmental exposure pathway of titanium dioxide nanoparticles (TiO2 NPs), and the lung is considered to be the target organ of respiratory exposure; however, the mechanism of respiratory toxicity is not fully understood. In this study, the effect of TiO2 NPs on the expression profile of long non-coding RNA (lncRNA) in bronchial epithelial cells (BEAS-2B) was investigated to understand their potential toxic mechanism. BEAS-2B cells were treated with 100 µg/mL TiO2 NPs for 48 h, then RNA sequencing was performed to screen the differential lncRNAs compared with the control group, and the enrichment pathways of the differentially expressed lncRNAs were further analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG). The results identified a total of 45,769 lncRNAs, and 277 different lncRNAs were screened. KEGG pathway analysis showed that the targeted mRNAs of these different lncRNAs were enriched in the pyrimidine metabolism pathway. This work demonstrates that TiO2 NPs could alter the lncRNA expression profile in BEAS-2B cells, and epigenetics may play a role in the mechanism of respiratory toxicity induced by TiO2 NPs.