RESUMEN

The widespread environmental contamination resulting from the misuse of tetracycline antibiotics (TCs) has garnered significant attention and study by scholars. Photocatalytic technology is one of the environmentally friendly advanced oxidation processes (AOPs) that can effectively solve the problem of residue of TCs in the water environment. This study involved the synthesis of the heterogeneous magnetic photocatalytic material of CoFe2O4/NaBiO3 via the solvothermal method, and it was characterized using different characterization techniques. Then, the photocatalytic system under visible light (Vis) was coupled with peroxymonosulfate (PMS) to explore the performance and mechanism of degradation of tetracycline hydrochloride (TCH) in the wastewater. The characterization results revealed that CoFe2O4/NaBiO3 effectively alleviated the agglomeration phenomenon of CoFe2O4 particles, increased the specific surface area, effectively narrowed the band gap, expanded the visible light absorption spectrum, and inhibited recombination of photogenerated electron-hole pairs. In the Vis+CoFe2O4/NaBiO3+PMS system, CoFe2O4/NaBiO3 effectively activated PMS to produce hydroxyl radicals (·OH) and sulfate radicals (SO4-). Under the conditions of a TCH concentration of 10 mg/L-1, a catalyst concentration of 1 g/L-1 and a PMS concentration of 100 mg/L-1, the degradation efficiency of TCH reached 94% after 100 min illumination. The degradation of TCH was enhanced with the increase in the CoFe2O4/NaBiO3 and PMS dosage. The solution pH and organic matter had a significant impact on TCH degradation. Notably, the TCH degradation efficiency decreased inversely with increasing values of these parameters. The quenching experiments indicated that the free radicals contributing to the Vis+CoFe2O4/NaBiO3+PMS system were ·OH followed by SO4-, hole (h+), and the superoxide radical (O2-). The main mechanism of PMS was based on the cycle of Co3+ and Co2+, as well as Fe3+ and Fe2+. The cyclic tests and characterization by XRD and FT-IR revealed that CoFe2O4/NaBiO3 had good degradation stability. The experimental findings can serve as a reference for the complete removal of antibiotics from wastewater.

Asunto(s)

Cobalto , Compuestos Férricos , Sulfatos , Tetraciclina , Contaminantes Químicos del Agua , Tetraciclina/química , Cobalto/química , Catálisis , Sulfatos/química , Compuestos Férricos/química , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Aguas Residuales/química , Luz , Oxidación-Reducción , Antibacterianos/química , Fotólisis , Peróxidos , Compuestos de Sodio

RESUMEN

The primary purpose of present study was to explore the effects of arsenic exposure on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear transcription factor-κB (NF-κB) signaling pathway in the hippocampus of offspring mice at different developmental stages. Sodium arsenite (NaAsO2) at doses of 0, 15, 30 or 60 mg/L administered to female mice and their pups. The nuclear translocation levels of NF-κB were assessed by EMSA. Real-time RT-PCR was used to measure Akt, NF-κB and PI3K mRNA levels. Protein expressions of PI3K, p-Akt, inhibitor kappa B kinase (IKK), p-NF-κB, protein kinase A (PKA), inhibitor kappa B (IκB), and cAMP response element-binding protein (CREB) were measured by Western blot. Results disclosed that exposure to 60 mg/L NaAsO2 could suppress NF-κB levels of nuclear translocation of postnatal day (PND) 20 and PND 40 mice. Arsenic downregulated the transcriptional and translational levels of PI3K, Akt and NF-κB. Additionally, protein expressions of p-IKK, p-IκB, PKA and p-CREB also reduced. Taken together, results of present study indicated that arsenic could downregulate the PI3K/Akt/NF-κB signaling pathway, particularly on PND 40, which might be involved in the cognitive impairments.

Asunto(s)

Arsénico , Hipocampo , FN-kappa B , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Femenino , Transducción de Señal/efectos de los fármacos , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Ratones , Arsénico/toxicidad , Fosfatidilinositol 3-Quinasas/metabolismo , Arsenitos/toxicidad , Compuestos de Sodio/toxicidad , Embarazo , Masculino , Efectos Tardíos de la Exposición Prenatal/inducido químicamente

RESUMEN

Arsenic (As) is a highly toxic metal and one of the main factors in cancer development through oxidative stress and production of reactive oxygen species. Prior research has demonstrated melatonin's potential as a free radical scavenger. Raf kinase inhibitory protein (RKIP) is an important regulator of intracellular signaling pathways that has been linked to various types of cancer. The aim of this research was to explore the influence of melatonin's antioxidant properties on the expression of the protein RKIP and the antioxidant status of liver tissue in rats that were exposed to arsenic. Thirty two male Wistar rats were divided into four groups of eight, including control, melatonin-treated (20 mg/Kg of melatonin), sodium arsenite-treated (5.5 mg/Kg of sodium arsenite), and melatonin + sodium arsenite-treated groups (combination) for 4 weeks. The expression level of protein RKIP was measured by Western blot, and malondialdehyde (MDA) content of the liver as well as the activities of antioxidant enzymes were measured. The data analyzed using one-way ANOVA (significance level of p < 0.05) and GraphPad Prism (9) software. Sodium arsenite treatment led to a significant decrease in RKIP protein expression and antioxidant enzyme activity, and an increase in liver MDA levels (p < 0.001). Conversely, melatonin treatment in the combination group resulted in a significant increase in RKIP protein expression and antioxidant enzyme activity and a decrease in liver MDA levels (p < 0.05). These findings suggest that melatonin can attenuate oxidative damage caused by arsenic in liver cells by enhancing RKIP protein expression and antioxidant enzyme activity.

Asunto(s)

Antioxidantes , Enfermedad Hepática Inducida por Sustancias y Drogas , Hígado , Melatonina , Proteínas de Unión a Fosfatidiletanolamina , Animales , Masculino , Ratas , Antioxidantes/farmacología , Antioxidantes/metabolismo , Arsénico/toxicidad , Arsenitos/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Hígado/metabolismo , Hígado/efectos de los fármacos , Malondialdehído/metabolismo , Melatonina/farmacología , Estrés Oxidativo/efectos de los fármacos , Proteínas de Unión a Fosfatidiletanolamina/metabolismo , Ratas Wistar , Compuestos de Sodio/toxicidad

RESUMEN

Bromodomain and WD-repeat domain-containing protein 3 (BRWD3) exhibits high expression in lung adenocarcinoma (LUAD) tissues and cells; however, its function in arsenic-induced toxicological responses remains unclear. This study aimed to investigate BRWD3 expression in response to arsenic-induced conditions and its impact on the proliferation and apoptosis of LUAD cell line SPC-A1 upon BRWD3 knockdown. The results revealed a decrease in BRWD3 expression in SPC-A1 cells treated with sodium arsenite (NaAsO2), but not sodium arsenite's metabolites. BRWD3 knockdown suppressed cell proliferation and induced apoptosis in SPC-A1 cells. Western blot analysis revealed that BRWD3 knockdown resulted in the upregulation of p53, phospho-p53-Ser392, and its downstream factors including MDM2, Bak, and Bax. Additionally, we observed the downregulation of p65, phospho-p65-Ser276, phospho-p65-Ser536, and its downstream factors, including IκBα, BIRC3, XIAP and CIAP1. Moreover, polymerase chain reaction analysis showed that BRWD3 knockdown also resulted in the downregulation of proliferation-related genes and upregulation of apoptosis-related genes. In conclusion, BRWD3 mediated proliferation and apoptosis via the p53 and p65 pathways in response to arsenic exposure, suggesting potential implications for LUAD treatment through BRWD3 downregulation by arsenic.

Asunto(s)

Adenocarcinoma del Pulmón , Apoptosis , Proliferación Celular , Regulación hacia Abajo , Neoplasias Pulmonares , Proteína p53 Supresora de Tumor , Humanos , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Línea Celular Tumoral , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Regulación hacia Abajo/efectos de los fármacos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Arsénico/toxicidad , Compuestos de Sodio/toxicidad , Arsenitos/toxicidad , Transducción de Señal/efectos de los fármacos , Factor de Transcripción ReIA/metabolismo , Factor de Transcripción ReIA/genética

RESUMEN

Arsenic is a metalloid found in the environment that causes toxic effects in different organs, mainly the liver. This study aimed to investigate the protective effects of epicatechin (EC), a natural flavonol, on glucose intolerance (GI) and liver toxicity caused by sodium arsenite (SA) in mice. Our findings showed that SA exposure led to the development of GI. Liver tissue damage and decreased pancreatic Langerhans islet size were also observed in this study. Mice exposed to SA exhibited hepatic oxidative damage, indicated by reduced antioxidant markers (such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione), along with elevated levels of thiobarbituric acid reactive substances. SA administration elevated the serum activities of liver enzymes alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Furthermore, notable increases in the levels of inflammatory and apoptotic markers (Toll-like receptor 4, nuclear factor-kappa B, tumor necrosis factor-α, nitric oxide, B-cell lymphoma-2, and cysteine aspartate-specific protease-3) were observed in the liver. Treatment of SA-exposed mice with EC considerably reversed these biochemical and histological changes. This study demonstrated the beneficial effects of EC in ameliorating SA-induced hyperglycemia and hepatotoxicity due to its ability to enhance the antioxidant system by modulating inflammation and apoptosis.

Asunto(s)

Arsenitos , Catequina , Enfermedad Hepática Inducida por Sustancias y Drogas , Intolerancia a la Glucosa , Hígado , Compuestos de Sodio , Animales , Arsenitos/toxicidad , Compuestos de Sodio/toxicidad , Ratones , Intolerancia a la Glucosa/inducido químicamente , Intolerancia a la Glucosa/tratamiento farmacológico , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Masculino , Catequina/farmacología , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/metabolismo , Alanina Transaminasa/sangre , Alanina Transaminasa/metabolismo , Apoptosis/efectos de los fármacos

RESUMEN

In this study, a microcosm experiment was conducted to investigate the effects of Na2S2O8 preoxidation combined with biostimulation on petroleum-contaminated soil remediation. The response of microbial community during this process was explored using BIOLOG ECO microplate carbon utilization method and 16 s rDNA high-throughput sequencing. The results showed that use of 10 mg/g Na2S2O8 removed 19.8 % of the petroleum hydrocarbons, reduced soil biotoxicity and did not affect soil microbial activity compared to other concentrations. Therefore, sodium persulfate of ca. 10 mg/g was used to oxidize petroleum in soil before the biostimulation experiment with organic and inorganic fertilizers. Our finding showed that the content of total petroleum hydrocarbons (TPHs) in soil was reduced by 43.3 % in inorganic fertilizer treatment after 60 days. The results of BIOLOG ECO microplate carbon utilization analysis and 16 S rDNA high-throughput sequencing further confirmed that biostimulation quickly restored the microbial activities in oxidant treated soil. The main marker bacteria in chemical oxidation combined with biostimulation remediation were Arthrobacter and Paenarthrobacter, and their relative abundances were both significantly negatively correlated with the content of petroleum hydrocarbons in soil.

Asunto(s)

Biodegradación Ambiental , Oxidación-Reducción , Petróleo , Microbiología del Suelo , Contaminantes del Suelo , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Fertilizantes/análisis , Sulfatos , Hidrocarburos , Compuestos de Sodio/toxicidad , Suelo/química , Arthrobacter , Restauración y Remediación Ambiental/métodos , Bacterias/efectos de los fármacos , Bacterias/genética

RESUMEN

Environmental heavy metals pollution have seriously threatened the health of human beings. An increasing number of researches have demonstrated that environmental heavy metals can influence the telomere length of Peripheral Blood Mononuclear Cells (PBMCs), which implicate biological aging as well as predicts diseases. Our previous study has shown that methylmercury (MeHg)-induced telomere shortening in rat brain tissue was associated with urinary melatonin metabolite 6-sulfatoxymelatonin (aMT6s) levels. Here, we aimed to further elucidate the impact of 4 typical heavy metals (As, Hg, Cd and Pb) on telomere length of PBMCs and their association with urinary aMT6s in rats. In this study, eighty-eight male Sprague-Dawley rats were randomized grouped into eleven groups. Among them, forty 3-month-old (young) and forty 12-month-old (middle-aged) rats were divided into young or middle-aged control groups as well as typical heavy metals exposed groups, respectively. Eight 24-month-old rats (old) was divided into aging control group. The results showed that MeHg exposure in young rats while sodium arsenite (iAs), MeHg, cadmium chloride (CdCl2), lead acetate (PbAc) exposure in middle-aged rats for 3 months significantly reduced the levels of and urinary aMT6s, as well as telomere length of PBMCs. In addition, they also induced abnormalities in serum oxidative stress (SOD, MDA and GPx) and inflammatory (IL-1ß, IL-6 and TNF-α) indicators. Notably, there was a significant positive correlation between declined level of urinary aMT6s and the shortening of telomere length in PBMCs in rats exposed to 4 typical heavy metals. These results suggested that 4 typical heavy metals exposure could accelerate the reduction of telomere length of PBMCs partially by inducing oxidative stress and inflammatory in rats, while ageing may be an important synergistic factor. Urinary aMT6s detection may be a alternative method to reflect telomere toxic effects induced by heavy metal exposure.

Asunto(s)

Leucocitos Mononucleares , Metales Pesados , Ratas Sprague-Dawley , Acortamiento del Telómero , Animales , Masculino , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Ratas , Metales Pesados/toxicidad , Metales Pesados/orina , Acortamiento del Telómero/efectos de los fármacos , Compuestos de Metilmercurio/toxicidad , Melatonina/orina , Melatonina/análogos & derivados , Estrés Oxidativo/efectos de los fármacos , Arsenitos/toxicidad , Cadmio/toxicidad , Cadmio/orina , Contaminantes Ambientales/toxicidad , Plomo/toxicidad , Plomo/sangre , Mercurio/toxicidad , Mercurio/orina , Compuestos de Sodio

RESUMEN

Arsenic, a poisonous metalloid element, is linked to liver diseases, but the exactmechanisms for this process are not yet to be completely elucidated. Toll like receptor 4 (TLR4), acting as a pathogenic pattern recognition receptor, plays a pivotal role in various inflammatory diseases via the myeloid differentiation factor 88 (MyD88) pathway. This study aims to investigate the involvement of the TLR4-MyD88 signaling pathway in liver injury induced by prolonged exposure to sodium arsenite (NaAsO2) in Sprague-Dawley rats. Our research findings demonstratethe activation of TLR4-MyD88 signaling pathway in long-term NaAsO2-exposed rat liver tissues, leading to a significant release of inflammatory factors, which suggests its potential involvement in the pathogenesis of NaAsO2-induced liver injury. We further administered lipopolysaccharide (LPS), a natural ligand of TLR4, and TAK-242, a specific inhibitor of TLR4, to rats in order to validate the specific involvement of the TLR4-MyD88 signaling pathway in NaAsO2-induced liver injury. The results showed that, 1 mg/kg.bw LPS treatment significantly activated TLR4-MyD88 signalling pathway and its mediated pro-inflammatory factors, leading to up-regulation of activation indicators in hepatic stellate cells (HSCs) as well as increased secretion levels of extracellular matrix (ECM) in the liver, and ultimately induced liver fibrosis and dysfunction in rats. Relevantly, subsequent administration of 0.5 mg/kg.bw TAK-242 significantly attenuated the expression levels of TLR4 and its associated proteins, mitigated collagen deposition, and partially improved liver fibrosis and dysfunction caused by NaAsO2 in rats. Our study fully confirms the pivotal role of the TLR4-MyD88 signaling in promoting liver injury induced by NaAsO2, thereby providing a novel molecular target for preventing and treating patients with arsenic poisoning-related liver injury.

Asunto(s)

Arsenitos , Enfermedad Hepática Inducida por Sustancias y Drogas , Hígado , Factor 88 de Diferenciación Mieloide , Transducción de Señal , Compuestos de Sodio , Receptor Toll-Like 4 , Animales , Masculino , Ratas , Arsenitos/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Lipopolisacáridos , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/patología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Factor 88 de Diferenciación Mieloide/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Compuestos de Sodio/toxicidad , Sulfonamidas/farmacología , Receptor Toll-Like 4/metabolismo

RESUMEN

Efficient dewatering of sewage sludge is an energy- and carbon-saving procedure for sludge treatment in wastewater treatment facilities. The ultrasound-coupled divalent iron ion activated persulfate process can effectively promote sludge dewatering and improve organic substance content. Under the action of ultrasound (US 50 w/L), divalent iron ions (Fe2+) 200 mg/g (TS), and persulfate (PDS) 200 mg/g (TS) for 60 min, the capillary suction time (CST) was reduced by 79.74%, and the moisture content of the dewatered sludge cake reached 56.51 wt%. The organic carbon content of treated sludge was also four times higher than the original sludge and types were richer in short-chain volatile species in US/Fe2+/PDS. Moreover, the correlation analysis found that the relationship of between CST and SV30, Zeta and lactate dehydrogenase (LDH) were positive correlation, and the relationship of SCOD and TC were positively correlated with the PN (SB-EPS). Mechanistic studies showed that the US/Fe2+/PDS system could produce oxygen activators by US coupling Fe2+ to strengthen the effect of activated PDS strongly, while the sulfate radicals (SO4·-) radical was a dominant role. The cracking mechanism is divided into two pathways effectively degraded the macromolecule EPS into a small-molecule acid and further reduced the water-holding interfacial affinity as follow: (1) the radical path dominated by hydroxyl radicals (·OH), SO4·-, and superoxide radical (O2·-); (2) the non-radicals dominated by monoclinic oxygen (1O2). Afterwards, the electrostatic force and interfacial free energy were reduced, resulting in enhanced self-flocculation and mobility to enhanced dewaterability. These findings demonstrated the US/Fe2+/PDS system had significant advantages in sludge cracking and provided theoretical support for its practical application.

Asunto(s)

Hierro , Aguas del Alcantarillado , Compuestos de Sodio , Sulfatos , Eliminación de Residuos Líquidos , Aguas Residuales , Sulfatos/química , Aguas del Alcantarillado/química , Eliminación de Residuos Líquidos/métodos , Hierro/química , Compuestos de Sodio/química , Aguas Residuales/química

RESUMEN

The model of RNA stability has undergone a transformative shift with the revelation of a cytoplasmic capping activity that means a subset of transcripts are recapped autonomously of their nuclear counterparts. The present study demonstrates nucleo-cytoplasmic shuttling of the mRNA-capping enzyme (CE, also known as RNA guanylyltransferase and 5'-phosphatase; RNGTT), traditionally acknowledged for its nuclear localization and functions, elucidating its contribution to cytoplasmic capping activities. A unique nuclear export sequence in CE mediates XPO1-dependent nuclear export of CE. Notably, during sodium arsenite-induced oxidative stress, cytoplasmic CE (cCE) congregates within stress granules (SGs). Through an integrated approach involving molecular docking and subsequent co-immunoprecipitation, we identify eIF3b, a constituent of SGs, as an interactive associate of CE, implying that it has a potential role in guiding cCE to SGs. We measured the cap status of specific mRNA transcripts from U2OS cells that were non-stressed, stressed and recovered from stress, which indicated that cCE-target transcripts lost their caps during stress but remarkably regained cap stability during the recovery phase. This comprehensive study thus uncovers a novel facet of cytoplasmic CE, which facilitates cellular recovery from stress by maintaining cap homeostasis of target mRNAs.

Asunto(s)

Citoplasma , Homeostasis , ARN Mensajero , Gránulos de Estrés , Humanos , ARN Mensajero/metabolismo , ARN Mensajero/genética , Gránulos de Estrés/metabolismo , Citoplasma/metabolismo , Caperuzas de ARN/metabolismo , Arsenitos/farmacología , Estrés Oxidativo , Transporte Activo de Núcleo Celular , ARN Nucleotidiltransferasas/metabolismo , ARN Nucleotidiltransferasas/genética , Compuestos de Sodio/farmacología , Proteína Exportina 1 , Carioferinas/metabolismo , Carioferinas/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Gránulos Citoplasmáticos/metabolismo , Estabilidad del ARN , Núcleo Celular/metabolismo , Línea Celular Tumoral , Nucleotidiltransferasas

RESUMEN

The prostate gland is one of the main sites of hyperplasia and cancer in elderly men. Numerous factors have been demonstrated to disrupt prostate homeostasis, including exposure to environmental pollutants. Arsenic is a metalloid found ubiquitously in soil, air, and water, which favors human poisoning through the involuntary intake of contaminated drinking water and food and has harmful effects by increasing the oxidative stress response. This study aimed to investigate the effects of prolonged exposure to arsenic at environmentally relevant concentrations on the prostate biology of adult Wistar rats. Thirty 80-day-old male rats were divided into three experimental groups. Rats from the control group received filtered water, whereas animals from the arsenic groups ingested 1 mg L-1 and 10 mg L-1 of arsenic, in the form of sodium arsenite, daily. The arsenic solutions were provided ad libitum in the drinking water for eight weeks. Our results showed that 1 mg L-1 and 10 mg L-1 of arsenic made the prostate susceptible to evolving benign and premalignant histopathological changes. While the ingestion of 1 mg L-1 of arsenic reduced SOD activity only, 10 mg L-1 diminished SOD and CAT activity in the prostate tissue, culminating in high MDA production. These doses, however, did not affect the intraprostatic levels of DHT and estradiol. In conclusion, exposure to arsenic at environmentally relevant concentrations through drinking water induces histological and oxidative stress-related changes in the prostate of adult rats, strengthening the between arsenic exposure and prostate disorders.

Asunto(s)

Estrés Oxidativo , Próstata , Ratas Wistar , Animales , Masculino , Estrés Oxidativo/efectos de los fármacos , Próstata/efectos de los fármacos , Próstata/patología , Próstata/metabolismo , Superóxido Dismutasa/metabolismo , Arsénico/toxicidad , Contaminantes Ambientales/toxicidad , Arsenitos/toxicidad , Catalasa/metabolismo , Compuestos de Sodio/toxicidad , Ratas , Malondialdehído/metabolismo , Estradiol/sangre

RESUMEN

Arsenic (As) is globally detected in drinking water and food products at levels repeatedly surpassing regulatory thresholds. Several neurological and mental health risks linked to arsenic exposure are proposed; however, the nature of these effects and their association with the chemical forms of arsenic are not fully understood. Gaining a clear understanding of the etiologies and characteristics of these effects is crucial, particularly in association with developmental exposures where the nervous system is most vulnerable. In this study, we investigated the effects of early developmental exposure (6- to 120-h postfertilization [hpf]) of larval zebrafish to environmentally relevant concentrations of arsenic species-trivalent/pentavalent, inorganic/organic forms-on developmental, behavioral, and molecular endpoints to determine their effect on stress response and their potential association with stress-related disorders. At 120 hpf, the developing larvae were assessed for a battery of endpoints including survival, developmental malformities, background activity, and behavioral responses to acute visual and acoustic stimuli. Pooled larval samples were analyzed for alterations in the transcript levels of genes associated with developmental neurotoxicity and stress-related disorders. Developmental exposures at target concentrations did not significantly alter survival, overall development, or background activity, and had minor effects on developmental morphology. Sodium arsenate and monomethylarsonic acid exaggerated the behavioral responses of larval zebrafish, whereas sodium arsenite depressed them. Sodium arsenate induced significant effects on molecular biomarkers. This study highlights the effects of developmental exposure to arsenicals on the behavioral stress response, the role chemical formulation plays in exerting toxicological effects, and the possible association with stress-related disorders.

Asunto(s)

Conducta Animal , Larva , Pez Cebra , Animales , Larva/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Compuestos de Sodio/toxicidad , Contaminantes Químicos del Agua/toxicidad , Arsenitos/toxicidad , Estrés Fisiológico/efectos de los fármacos , Arsénico/toxicidad , Arseniatos/toxicidad

RESUMEN

OBJECTIVE: Long-term exposure to arsenic has been linked to several illnesses, including hypertension, diabetes, hepatic and renal diseases and cardiovascular malfunction. The aim of the current investigation was to determine whether zingerone (ZN) could shield rats against the hepatotoxicity that sodium arsenite (SA) causes. METHODS: The following five groups of thirty-five male Sprague Dawley rats were created: I) Control; received normal saline, II) ZN; received ZN, III) SA; received SA, IV) SA + ZN 25; received 10 mg/kg body weight SA + 25 mg/kg body weight ZN, and V) SA + ZN 50; received 10 mg/kg body weight SA + 50 mg/kg body weight ZN. The experiment lasted 14 days, and the rats were sacrificed on the 15th day. While oxidative stress parameters were studied by spectrophotometric method, apoptosis, inflammation and endoplasmic reticulum stress parameters were measured by RT-PCR method. RESULTS: The SA disrupted the histological architecture and integrity of the liver and enhanced oxidative damage by lowering antioxidant enzyme activity, such as those of glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) level and increasing malondialdehyde (MDA) level in the liver tissue. Additionally, SA increased the mRNA transcript levels of Bcl2 associated x (Bax), caspases (-3, -6, -9), apoptotic protease-activating factor 1 (Apaf-1), p53, tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), c-Jun NH2-terminal kinase (JNK), mitogen-activated protein kinase 14 (MAPK14), MAPK15, receptor for advanced glycation endproducts (RAGE) and nod-like receptor family pyrin domain-containing 3 (NLRP3) in the liver tissue. Also produced endoplasmic reticulum stress by raising the mRNA transcript levels of activating transcription factor 6 (ATF-6), protein kinase RNA-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and glucose-regulated protein 78 (GRP-78). These factors together led to inflammation, apoptosis, and endoplasmic reticulum stress. On the other hand, liver tissue treated with ZN at doses of 25 and 50 mg/kg showed significant improvement in oxidative stress, inflammation, apoptosis and endoplasmic reticulum stress. CONCLUSIONS: Overall, the study's data suggest that administering ZN may be able to lessen the liver damage caused by SA toxicity.

Asunto(s)

Arsenitos , Enfermedad Hepática Inducida por Sustancias y Drogas , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Ratas Sprague-Dawley , Transducción de Señal , Compuestos de Sodio , Factor de Necrosis Tumoral alfa , Animales , Masculino , Transducción de Señal/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Arsenitos/toxicidad , Compuestos de Sodio/toxicidad , Ratas , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Caspasa 3/metabolismo , Caspasa 3/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo , Proteína X Asociada a bcl-2/genética , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Chaperón BiP del Retículo Endoplásmico , Endorribonucleasas , Complejos Multienzimáticos , Proteínas Serina-Treonina Quinasas

RESUMEN

Arsenite is an important heavy metal. Some Chinese traditional medicines contain significant amounts of arsenite. The aim of this study was to investigate subacute exposure of arsenite on activities of cytochrome P450 enzymes and pharmacokinetic behaviors of drugs in rats. Midazolam, tolbutamide, metoprolol, omeprazole, caffeine, and chlorzoxazone, the probe substrates for cytochrome P450 (CYP) s3A, 2C6, 2D, 2C11, 1A, and 2E, were selected as probe drugs for the pharmacokinetic study. Significant decreases in areas under the curves of probe substrates were observed in rats after consecutive 30-day exposure to As at 12 mg/kg. Microsomal incubation study showed that the subacute exposure to arsenite resulted in little change in effects on the activities of P450 enzymes examined. However, everted gut sac study demonstrated that such exposure induced significant decreases in intestinal absorption of these drugs by both passive diffusion and carrier-mediated transport. In addition, in vivo study showed that the arsenite exposure decreased the rate of peristaltic propulsion. The decreases in intestinal permeability of the probe drugs and peristaltic propulsion rate most likely resulted in the observed decreases in the internal exposure of the probe drugs. Exposure to arsenite may lead to the reduction of the efficiencies of pharmaceutical agents coadministered resulting from the observed drug-drug interactions. SIGNIFICANCE STATEMENT: Exposure to arsenite may lead to the reduction of the efficiencies of pharmaceutical agents coadministered resulting from the observed drug-drug interactions. The present study, we found that P450 enzyme probe drug exposure was reduced in arsenic-exposed animals (areas under the curve) and the intestinal absorption of the drug was reduced in the animals. Subacute arsenic exposure tends to cause damage to intestinal function, which leads to reduced drug absorption.

Asunto(s)

Arsenitos , Sistema Enzimático del Citocromo P-450 , Interacciones Farmacológicas , Ratas Sprague-Dawley , Animales , Arsenitos/toxicidad , Arsenitos/farmacocinética , Masculino , Ratas , Sistema Enzimático del Citocromo P-450/metabolismo , Absorción Intestinal/efectos de los fármacos , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Omeprazol/farmacología , Omeprazol/farmacocinética , Midazolam/farmacocinética , Cafeína/farmacocinética , Clorzoxazona/farmacocinética , Metoprolol/farmacocinética , Metoprolol/farmacología , Tolbutamida/farmacocinética , Compuestos de Sodio/toxicidad , Compuestos de Sodio/farmacocinética

RESUMEN

Zinc finger MYND-type containing 15 (ZMYND15) has been documented to play important roles in spermatogenesis, and mutants contribute to recessive azoospermia, severe oligozoospermia, non-obstructive azoospermia, teratozoospermia, even male infertility. ZMYND10 is involved in sperm motility. Whether environmental pollutants impair male fertility via regulating the expression of ZMYND15 and ZMYND10 has not been studied. Arsenic exposure results in poor sperm quality and male infertility. In order to investigate whether arsenic-induced male reproductive toxicity is related to the expression of ZMYND15, ZMYND10 and their target genes, we established a male rat model of sodium arsenite exposure-induced reproductive injury, measured sperm quality, serum hormone levels, mRNA and protein expressions of intratesticular ZMYND15 and ZMYND10 as well as their target genes. The results showed that, in addition to the increased mRNA expression of Tnp1, sodium arsenite exposure reduced sperm quality, serum hormone levels, and mRNA and protein expression of intratesticular ZMYND15 and ZMYND10 and their target genes in male rats compared with the control group (p < .05). Therefore, our study first showed that the environmental pollutant arsenic impairs sperm quality in male rats by reducing the expression of ZMYND10 and ZMYND15 and their regulatory genes, which provides a possible diagnostic marker for environmental pollutants-induced male infertility.

Asunto(s)

Arsenitos , Regulación hacia Abajo , Compuestos de Sodio , Espermatozoides , Masculino , Animales , Compuestos de Sodio/toxicidad , Arsenitos/toxicidad , Espermatozoides/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Contaminantes Ambientales/toxicidad , Testículo/efectos de los fármacos , Testículo/metabolismo , Infertilidad Masculina/inducido químicamente , Infertilidad Masculina/genética

RESUMEN

NaAsO2 is known as a harmful pollutant all over the world, and many chronic heart diseases can be attributed to its prolonged exposure in NaAsO2-contaminated water. Therefore, considering the anti-inflammatory and antioxidant effects of betaine (BET), in this study, our team investigated the cardioprotective effects of this phytochemical agent on sodium arsenite (NaAsO2)-induced cardiotoxicity. Forty male mice were randomly divided into 4 groups: (I) Control; (II) BET (500 mg/kg); (III) NaAsO2 (50 ppm); and (IV) NaAsO2 + BET. NaAsO2 was given to the animals for 8 weeks, but BET was given in the last two weeks. After decapitation, inflammatory factors and biochemical parameters were measured, and Western blot analyses were performed. BET decrease the activity level of alanine aspartate aminotransferase, creatine kinase MB, thiobarbituric acid reactive substances level, inflammatory factors (tumor necrosis factor-α) content, and nuclear factor kappa B expression. Furthermore, BET increased cardiac total thiol and activity levels of catalase, superoxide dismutase, and glutathione peroxidase and nuclear factor erythroid-2 expression. Hence, the administration of BET ameliorated the deleterious effects stemming from the imbalance of oxidative and antioxidant pathways and histopathological alterations observed in NaAsO2-intoxicated mice, thereby attenuating oxidative stress-induced damage and inflammation.

Asunto(s)

Antiinflamatorios , Antioxidantes , Arsenitos , Betaína , Cardiotoxicidad , Modelos Animales de Enfermedad , Cardiopatías , Mediadores de Inflamación , Estrés Oxidativo , Transducción de Señal , Compuestos de Sodio , Animales , Arsenitos/toxicidad , Compuestos de Sodio/toxicidad , Masculino , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Antiinflamatorios/farmacología , Ratones , Betaína/farmacología , Cardiopatías/prevención & control , Cardiopatías/inducido químicamente , Cardiopatías/patología , Cardiopatías/metabolismo , Mediadores de Inflamación/metabolismo , Transducción de Señal/efectos de los fármacos , Biomarcadores/metabolismo , Biomarcadores/sangre , Citoprotección , Miocardio/patología , Miocardio/metabolismo

RESUMEN

This study aimed to characterize the effects of arsenic exposure on the expression of microsomal epoxide hydrolase (mEH or EPHX1) and soluble epoxide hydrolase (sEH or EPHX2) in the liver and small intestine. C57BL/6 mice were exposed to sodium arsenite in drinking water at various doses for up to 28 days. Intestinal, but not hepatic, mEH mRNA and protein expression was induced by arsenic at 25 ppm, in both males and females, whereas hepatic mEH expression was induced by arsenic at 50 or 100 ppm. The induction of mEH was gene specific, as the arsenic exposure did not induce sEH expression in either tissue. Within the small intestine, mEH expression was induced only in the proximal, but not the distal segments. The induction of intestinal mEH was accompanied by increases in microsomal enzymatic activities toward a model mEH substrate, cis-stilbene oxide, and an epoxide-containing drug, oprozomib, in vitro, and by increases in the levels of PR-176, the main hydrolysis metabolite of oprozomib, in the proximal small intestine of oprozomib-treated mice. These findings suggest that intestinal mEH, playing a major role in converting xenobiotic epoxides to less reactive diols, but not sEH, preferring endogenous epoxides as substrates, is relevant to the adverse effects of arsenic exposure, and that further studies of the interactions between drinking water arsenic exposure and the disposition or possible adverse effects of epoxide-containing drugs and other xenobiotic compounds in the intestine are warranted. SIGNIFICANCE STATEMENT: Consumption of arsenic-contaminated water has been associated with increased risks of various adverse health effects, such as diabetes, in humans. The small intestinal epithelial cells are the main site of absorption of ingested arsenic, but they are not well characterized for arsenic exposure-related changes. This study identified gene expression changes in the small intestine that may be mechanistically linked to the adverse effects of arsenic exposure and possible interactions between arsenic ingestion and the pharmacokinetics of epoxide-containing drugs in vivo.

Asunto(s)

Agua Potable , Epóxido Hidrolasas , Intestino Delgado , Ratones Endogámicos C57BL , Animales , Epóxido Hidrolasas/metabolismo , Epóxido Hidrolasas/genética , Ratones , Masculino , Femenino , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/enzimología , Arsénico/toxicidad , Arsénico/metabolismo , Arsenitos/toxicidad , Arsenitos/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Microsomas/efectos de los fármacos , Microsomas/metabolismo , Microsomas/enzimología , Compuestos de Sodio/toxicidad

RESUMEN

Arsenic exposure is connected with lung toxicity and is related to lung fibrotic changes. Idiopathic pulmonary fibrosis (IPF) is characterized by extracellular matrix (ECM) deposition. Various genetic mechanisms and environmental factors induce or exacerbate pulmonary fibrosis. Collagen synthesis induced by sodium arsenite (NaAsO2) is closely associated with IPF. Fibroblasts tend to fine-tune their metabolic networks to support their synthetic requirements in response to environmental stimuli. Alterations in metabolism have an influential role in the pathogenesis of IPF. However, it is unclear how arsenic affects the metabolism in IPF. The urea cycle (UC) is needed for collagen formation, which provides adequate levels of proline (Pro) for biosynthesis of collagen. Carbamoyl phosphate synthetase 1 (CPS1) converts the ammonia to carbamoyl phosphate, which controls the first reaction of the UC. We show that, in arsenite-exposed mice, high amounts of ammonia in the lung microenvironment promotes the expression levels of CPS1 and the Pro metabolism. Reduction of ammonia and CPS1 ablation inhibit collagen synthesis and ameliorate IPF phenotypes induced by arsenite. This work takes advantage of multi-omics data to enhance understanding of the underlying pathogenic mechanisms, the key molecules and the complicated cellular responses to this pollutant, which provide a target for the prevention of pulmonary fibrosis caused by arsenic.

Asunto(s)

Amoníaco , Arsenitos , Carbamoil-Fosfato Sintasa (Amoniaco) , Colágeno , Ratones Endogámicos C57BL , Fibrosis Pulmonar , Urea , Animales , Arsenitos/toxicidad , Amoníaco/metabolismo , Colágeno/metabolismo , Ratones , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Carbamoil-Fosfato Sintasa (Amoniaco)/metabolismo , Urea/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Pulmón/efectos de los fármacos , Masculino , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar Idiopática/patología , Compuestos de Sodio

RESUMEN

Phthalate esters (PAEs) have become one of the most concerned emerging organic pollutants in the world, due to the toxicity to human health, and hard to remove it efficiently. In this study, the degradation performance of DBP and DEHP in the soil by water bath heating activated sodium persulfate (PS) method under different factors were studied, in which the degradation rate of DBP and DEHP were improved with the increasing of temperature, PS concentration and water/soil ratio, and higher diffusion efficiency treatments methods, due to the improved mass transfer from organic phase to aqueous media. However, the degradation rate of DEHP was much lower than that of DBP, because DEHP in the soil was more difficult to contact with SO4•- for reaction on soil surface, and the degradation rate of PAEs in soil was significantly lower than that in water. Redundancy analysis of degradation rate of DBP and DEHP in water demonstrated that the key factors that determine the degradation rate is time for DBP, and cosolvent dosage for DEHP, indicating that the solubility and diffusion rate of PAEs from soil to aqueous are predominance function. This study provides comprehensive scenes in PAEs degradation with persulfate oxidation activated by thermal in soil, reveal the difference of degradation between DBP and DEHP is structure-dependent. So that we provide fundamental understanding and theoretical operation for subsequent filed treatment of various structural emerging pollutants PAEs contaminated soil with thermal activated persulfate.

Asunto(s)

Oxidación-Reducción , Ácidos Ftálicos , Contaminantes del Suelo , Suelo , Sulfatos , Sulfatos/química , Ácidos Ftálicos/química , Contaminantes del Suelo/química , Suelo/química , Ésteres/química , Compuestos de Sodio/química , Calor

RESUMEN

The compound known as Sodium arsenite (NaAsO2), which is a prevalent type of inorganic arsenic found in the environment, has been strongly associated with liver fibrosis (LF), a key characteristic of nonalcoholic fatty liver disease (NAFLD), which has been demonstrated in our previous study. Our previous research has shown that exposure to NaAsO2 triggers the activation of hepatic stellate cells (HSCs), a crucial event in the development of LF. However, the molecular mechanism is still unknown. N6-methyladenosine (m6A) modification is the most crucial post-transcriptional modification in liver disease. Nevertheless, the precise function of m6A alteration in triggering HSCs and initiating LF caused by NaAsO2 remains unknown. Here, we found that NaAsO2 induced LF and HSCs activation through TGF-ß/Smad signaling, which could be reversed by TGF-ß1 knockdown. Furthermore, NaAsO2 treatment enhanced the m6A modification level both in vivo and in vitro. Significantly, NaAsO2 promoted the specific interaction of METTL14 and IGF2BP2 with TGF-ß1 and enhanced the TGF-ß1 mRNA stability. Notably, NaAsO2-induced TGF-ß/Smad pathway and HSC-t6 cells activation might be avoided by limiting METTL14/IGF2BP2-mediated m6A modification. Our findings showed that the NaAsO2-induced activation of HSCs and LF is made possible by the METTL14/IGF2BP2-mediated m6A methylation of TGF-ß1, which may open up new therapeutic options for LF brought on by environmental hazards.

Asunto(s)

Adenosina , Arsenitos , Células Estrelladas Hepáticas , Cirrosis Hepática , Compuestos de Sodio , Factor de Crecimiento Transformador beta1 , Arsenitos/toxicidad , Células Estrelladas Hepáticas/efectos de los fármacos , Compuestos de Sodio/toxicidad , Cirrosis Hepática/patología , Cirrosis Hepática/inducido químicamente , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Adenosina/análogos & derivados , Metiltransferasas/genética , Metiltransferasas/metabolismo , Masculino , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Transducción de Señal/efectos de los fármacos , Ratones , Humanos , Ratones Endogámicos C57BL