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1.
J Environ Sci (China) ; 124: 835-845, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36182187

RESUMEN

Ambient particulate matter (PM) can cause adverse health effects via their ability to produce Reactive Oxygen Species (ROS). Water-Soluble Organic Compounds (WSOCs), a complex mixture of organic compounds which usually coexist with Transition Metals (TMs) in PM, have been found to contribute to ROS formation. However, the interaction between WSOCs and TMs and its effect on ROS generation are still unknown. In this study, we examined the ROS concentrations of V, Zn, Suwannee River Fulvic Acid (SRFA), Suwannee River Humic Acid (SRHA) and the mixtures of V/Zn and SRFA/SRHA by using a cell-free 2',7'-Dichlorodihydrofluorescein (DCFH) assay. The results showed that V or Zn synergistically promoted ROS generated by SRFA, but had an antagonistic effect on ROS generated by SRHA. Fluorescence quenching experiments indicated that V and Zn were more prone to form stable complexes with aromatic humic acid-like component (C1) and fulvic acid-like component (C3) in SRFA and SRHA. Results suggested that the underlying mechanism involving the fulvic acid-like component in SRFA more tending to complex with TMs to facilitate ROS generation through π electron transfer. Our work showed that the complexing ability and complexing stability of atmospheric PM organics with metals could significantly affect ROS generation. It is recommended that the research deploying multiple analytical methods to quantify the impact of PM components on public health and environment is needed in the future.


Asunto(s)
Sustancias Húmicas , Agua , Sustancias Húmicas/análisis , Compuestos Orgánicos , Material Particulado/química , Especies Reactivas de Oxígeno/química
2.
Ecotoxicol Environ Saf ; 246: 114181, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36252517

RESUMEN

To investigate the effect of estrogen deficiency on the small intestinal mucosal barrier induced by fluoride (F), F exposure models of ovariectomy (OVX) rats (surgically removed ovaries) and non-OVX rats (normal condition) were established by adding sodium fluoride (NaF) (0, 25, 50, and 100 mg/L, calculated by F ion) in drinking water for 90 days. The intestinal mucosal histomorphology, mucosal barrier function, and protein expression levels of tight junctions (TJs), adhesion junctions (AJs), and desmosomes were evaluated in the duodenum, jejunum, and ileum. Hematoxylin-eosin (HE) staining and 5-Bromo-2-deoxyUridine (BrdU) measurement showed that excessive F-induced damage to intestinal epithelial cells and inhibited the proliferation of intestinal epithelial cells, eventually decreasing the number of goblet cells and decreasing glycoprotein secretion, as indicated by Alcian blue and periodic acid-Schiff (AB-PAS) and periodic acid-Schiff (PAS) staining. Further immunofluorescence analysis demonstrated that excessive F decreased the protein expression levels of occludin, zonula occludens-1 (ZO-1), E-cadherin, and desmoplakin (P < 0.05, P < 0.01) and enhanced the expression of claudin-2 (P < 0.01), suggesting that cell-to-cell junctions were disrupted. Collectively, F exposure impaired the small intestinal mucosal barrier by inducing damage to intestinal epithelial cells and inhibiting intestinal epithelial cell proliferation. Disorders in the junctional complex protein expression blocked the synergy between intercellular communication and aggravated mucosal injury. In particular, estrogen deficiency exacerbated F-induced enterotoxicity, which provides new explanations for the development and severity of intestinal disease in postmenopausal women with high-F areas.


Asunto(s)
Fluoruros , Mucosa Intestinal , Ratas , Femenino , Animales , Fluoruros/metabolismo , Ácido Peryódico/metabolismo , Ácido Peryódico/farmacología , Mucosa Intestinal/metabolismo , Duodeno , Estrógenos/metabolismo
3.
Ecotoxicol Environ Saf ; 216: 112200, 2021 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-33862434

RESUMEN

Molybdenum is a trace element with extremely uneven distribution in the environment. It constitutes the active sites of molybdenum enzymes that can catalyze redox reactions in almost all organisms. In this study, a mouse model with a low molybdenum diet was established to investigate the differential protein expressions in the thymus and the mechanism of molybdenum regulating thymocyte development. Results showed that the thymus evidently atrophied, and the weight and organ index of the thymus substantially decreased under the condition of low molybdenum (P < 0.01). A total of 274 differentially expressed proteins (DEPs) were screened through isobaric tag for relative and absolute quantification; amongst them, ribosomal proteins (38) were the most abundant. Bioinformatics analysis revealed that DEPs were mainly involved in protein metabolism (18%), nucleus (15%) and nucleic acid binding activity (17%), corresponding to biological process, cellular component and molecular function, respectively. Moreover, DEPs induced by low molybdenum were enriched in 94 pathways, of which typical maps including ribosome, oxidative phosphorylation and systemic lupus erythematosus. Flow cytometry analysis indicated the prominent imbalances of CD4+ and CD8+ cell ratios (P < 0.05, P < 0.01), suggesting the disordered development of T cell subsets. Overall, low molybdenum resulted in thymus atrophy by interfering with ribosomal protein expression and protein metabolism. This study provides a data platform for revealing the linkage between molybdenum and thymus-dependent immunity.

4.
Toxicol Ind Health ; 35(1): 43-52, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30463494

RESUMEN

This study was designed to investigate the effects of excessive fluoride on spleen toxicity. Twenty-four healthy female rats were randomly divided into two groups, each of 12 rats. Each group of female rats was given a control diet and either F- = 0 mg/L or an excessive F- = 150 mg/L in the drinking water for 120 days. The histomorphological and ultrastructural changes in their splenic tissues were observed under light and transmission electron microscopes. DNA damage and splenocyte apoptosis were examined using the micronucleus (MN) assay, single-cell gel electrophoresis (SCGE), and flow cytometry. The expression levels of cytokines, including interleukin (IL)-1ß, IL-2, IL-6, and tumor necrosis factor (TNF)-α, were determined through immunohistochemistry and Western-blot analysis. Results demonstrated that the histomorphological characteristics and ultrastructure of the splenic tissues were affected by excessive fluoride. Nuclear dying, nuclear membrane dissolution, mitochondrial vacuolation, and endoplasmic reticulum dilation were observed. SCGE and MN assays showed that the nuclear DNA of splenocytes was damaged by fluoride treatment, and splenocyte apoptosis was exacerbated in the fluoride group. With damage to the splenocyte structure and DNA, the protein expression levels of IL-1ß, IL-2, IL-6, and TNF-α were significantly downregulated by exposure to fluoride. Excessive fluoride ingestion caused splenic pathological damage and abnormal cytokine expression in female rats.


Asunto(s)
Citocinas/metabolismo , Fluoruros/toxicidad , Bazo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Femenino , Citometría de Flujo , Fluoruros/administración & dosificación , Interleucina-1beta/metabolismo , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Pruebas de Micronúcleos , Microscopía Electrónica de Transmisión , Ratas , Ratas Wistar , Bazo/metabolismo , Bazo/patología , Bazo/ultraestructura , Factor de Necrosis Tumoral alfa/metabolismo
5.
Ecotoxicol Environ Saf ; 138: 1-8, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27987418

RESUMEN

Tributyltin (TBT) is a toxic compound released into aquatic ecosystems through antifouling paints. This study was designed to examine the effects of TBT on antioxidant ability and immune responses of zebrafish (Danio rerio). Three hundred sixty healthy zebrafish were randomly grouped into four groups and exposed to different doses of TBT (0, 1, 10 and 100ngL-1). At the end of 8 weeks, the fish were sampled, and antioxidant capability, immune parameters and immune-related genes were assessed. The results showed that with an increase in TBT dose, the concentration of malonaldehyde in the liver was significantly increased (p<0.05), whereas the activities of total superoxide dismutase, catalase and glutathione peroxidase were significantly decreased (p<0.05) compared to the control. The activity and expression of lysozyme and the content of immunoglobulin M were significantly decreased compared to those of the fish exposed to 0ngL-1 TBT (p<0.05). However, the expression of the HSP70, HSP90, tumor necrosis factor-α(TNF-α), interleukins (IL-1ß, IL-6), and nuclear factor-kappa B p65 (NF-κ B p65) genes were all enhanced with an increase in TBT dose. The results indicated that TBT induced oxidative stress and had immunotoxic effects on zebrafish.


Asunto(s)
Desinfectantes/toxicidad , Inmunidad/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Compuestos de Trialquiltina/toxicidad , Contaminantes Químicos del Agua/toxicidad , Pez Cebra , Animales , Antioxidantes/metabolismo , Catalasa/metabolismo , Citocinas/metabolismo , Glutatión Peroxidasa/metabolismo , Proteínas de Choque Térmico/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Malondialdehído/metabolismo , Muramidasa/metabolismo , Distribución Aleatoria , Superóxido Dismutasa/metabolismo , Compuestos de Trialquiltina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Pez Cebra/inmunología , Pez Cebra/metabolismo
6.
Toxicol Ind Health ; 32(9): 1598-606, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25691499

RESUMEN

To evaluate the effects of dietary high molybdenum (HMo) and low copper (LCu) concentrations on reproductive toxicity of male mice, 80 mice were divided into 4 groups of 20. These groups were fed with the following: (1) normal control (NC) diet (NC group); (2) NC and HMo diets (HMo group); (3) LCu diet (LCu group); and (4) HMo and LCu diets (HMoLCu group). On the 50th and 100th day, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) were analyzed to determine oxidative stress states. Morphological changes in testicular tissue were evaluated with hematoxylin and eosin staining and ultrastructural changes were monitored by transmission electron microscopy. The results showed that administration of HMo, LCu, and HMoLCu not only decreased sperm density and motility but also increased the rate of teratosperm occurrence. A significant increase in MDA content and a decrease in SOD, GSH-Px, and T-AOC contents were observed in LCu, HMo, and HMoLCu groups. Testicular tissues and cells of mice were damaged by HMo and the damages were more serious in the case of Cu deficiency. Exposure to HMo adversely affected the reproductive system of male mice, and dietary LCu plays key roles in HMo-induced reproductive toxicity.


Asunto(s)
Cobre/deficiencia , Enfermedades Carenciales/fisiopatología , Dieta/efectos adversos , Intoxicación por Metales Pesados , Infertilidad Masculina/etiología , Molibdeno/envenenamiento , Intoxicación/fisiopatología , Testículo/ultraestructura , Animales , Animales no Consanguíneos , Enfermedades Carenciales/etiología , Enfermedades Carenciales/metabolismo , Enfermedades Carenciales/patología , Peroxidación de Lípido , Masculino , Metales Pesados/metabolismo , Ratones , Microscopía Electrónica de Transmisión , Estrés Oxidativo , Oxidorreductasas/sangre , Oxidorreductasas/metabolismo , Intoxicación/etiología , Intoxicación/metabolismo , Intoxicación/patología , Motilidad Espermática , Espermatogénesis , Espermatozoides/enzimología , Espermatozoides/metabolismo , Espermatozoides/ultraestructura , Teratozoospermia/etiología , Testículo/enzimología , Testículo/metabolismo , Aumento de Peso
7.
Korean J Parasitol ; 53(6): 675-82, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26797433

RESUMEN

The effects of diclazuril on the bursa of Fabricius (BF) structure and secretory IgA (SIgA) expression in chickens infected with Eimeria tenella were examined. The morphology of the BF was observed by hematoxylin and eosin staining, while ultrastructural changes were monitored by transmission electron microscopy. E. tenella infection caused the BF cell volumes to decrease, irregularly arranged, as well as, enlargement of the intercellular space. Diclazuril treatment alleviated the physical signs of damages associated with E. tenella infection. The SIgA expression in BF was analyzed by immunohistochemistry technique. The SIgA expression increased significantly by 350.4% (P<0.01) after E. tenella infection compared to the normal control group. With the treatment of diclazuril, the SIgA was relatively fewer in the cortex, and the expression level was significantly decreased by 46.7% (P<0.01) compared with the infected and untreated group. In conclusion, E. tenella infection in chickens induced obvious harmful changes in BF morphological structure and stimulated the expression of SIgA in the BF. Diclazuril treatment effectively alleviated the morphological changes. This result demonstrates a method to develop an immunological strategy in coccidiosis control.


Asunto(s)
Bolsa de Fabricio/parasitología , Coccidiosis/veterinaria , Coccidiostáticos/efectos adversos , Eimeria tenella/fisiología , Inmunoglobulina A Secretora/genética , Nitrilos/efectos adversos , Enfermedades de las Aves de Corral/tratamiento farmacológico , Triazinas/efectos adversos , Animales , Bolsa de Fabricio/anatomía & histología , Pollos , Coccidiosis/tratamiento farmacológico , Coccidiosis/metabolismo , Coccidiosis/parasitología , Coccidiostáticos/administración & dosificación , Femenino , Inmunoglobulina A Secretora/metabolismo , Masculino , Nitrilos/administración & dosificación , Enfermedades de las Aves de Corral/genética , Enfermedades de las Aves de Corral/metabolismo , Enfermedades de las Aves de Corral/parasitología , Triazinas/administración & dosificación
8.
Parasitol Res ; 113(11): 4057-64, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25154426

RESUMEN

Secretory immunoglobulin A (SIgA), as a vital actor involving in the mucosal immunity, plays a key role in defending a variety of pathogenic infections, such as bacteria, viruses and parasites. Eimeria tenella is an obligate intracellular apicomplexan parasite contacting with the digestive tract mucosa and specially parasitizes chicken caecum, causing a severe form of coccidiosis. Coccidiosis is currently mainly controlled using chemotherapeutic agents. Diclazuril, a classic coccidiostat, was used widely in the poultry industry. Because of the rising problem of drug resistance, it is therefore crucial to understand the pattern of the SIgA expression in the action of diclazuril against E. tenella. In this study, the intestinal morphology in the caecum was analyzed by haematoxylin-eosin (HE) staining, and the SIgA expression was examined by immunohistochemical technique. At the same time, the duodenum, jejunum and ileum tissues have also been evaluated. HE staining results showed that E. tenella infection caused severe damage characterized by structural disorder, haemorrhage, inflammatory cell infiltration, serous and fibrinous exudation in chicken caecum and invisible damage in the duodenum, jejunum and ileum. With the treatment of diclazuril, the damage in the caecum was alleviated obviously. Immunohistochemical analysis demonstrated that the SIgA level in the infected group was increased in the duodenum (p < 0.05), jejunum and ileum, respectively, but decreased (p < 0.01) in the caecum, compared with the control group. Interestingly, the SIgA level was decreased in the duodenum (p < 0.05), jejunum and ileum but increased (p < 0.05) in the caecum in the infected/diclazuril group in comparison to the infected group. The results showed that diclazuril effectively alleviated the damage in the caecum induced by E. tenella and provided a cure for coccidiosis by improving the immune function in chickens.


Asunto(s)
Coccidiosis/veterinaria , Eimeria tenella , Inmunoglobulina A Secretora/inmunología , Intestinos/patología , Nitrilos/farmacología , Enfermedades de las Aves de Corral/patología , Triazinas/farmacología , Animales , Ciego/parasitología , Ciego/patología , Pollos/inmunología , Pollos/parasitología , Coccidiosis/patología , Coccidiostáticos/farmacología , Eimeria tenella/efectos de los fármacos , Inmunidad Mucosa , Intestinos/parasitología , Masculino , Enfermedades de las Aves de Corral/parasitología , Distribución Aleatoria
9.
Huan Jing Ke Xue ; 45(7): 3881-3892, 2024 Jul 08.
Artículo en Zh | MEDLINE | ID: mdl-39022936

RESUMEN

The spatio-temporal variation characteristics and potential sources of carbonaceous aerosols in the Guanzhong Plain during the Spring Festival in 2023 were analyzed using inverse distance weighting spatial interpolation (IDW), secondary organic carbon (SOC) estimation, and potential source contribution factor analysis (PSCF), with the OC and EC in the PM2.5 of five cities: Xi'an, Baoji, Xianyang, Weinan, and Tongchuan as the research objects. The results showed that in terms of time distribution, ρ(OC) was as follows: after the Spring Festival [(18.6 ±11.0) µg·m-3] > during the Spring Festival [(16.2 ±15.1) µg·m-3] > before the Spring Festival [(10.0 ±8.3) µg·m-3], and ρ(EC) was as follows: after the Spring Festival [(2.2 ±1.2) µg·m-3] > during the Spring Festival [(1.7 ±1.5) µg·m-3] > before the Spring Festival [(1.4 ±1.1) µg·m-3], which indicated that OC and EC concentrations were the most severe after the Spring Festival. In terms of spatial distribution, ρ(OC) was as follows: Xianyang [(21.4 ±17.3) µg·m-3] > Baoji [(15.8 ±12.8) µg·m-3] > Xi'an [(13.6 ±11.3) µg·m-3] > Weinan [(11.6 ±9.1) µg·m-3] > Tongchuan [(10.0 ±8.3) µg·m-3], and ρ(EC) was as follows: Xianyang [(2.1 ±1.4) µg·m-3] > Weinan [(1.8 ±1.4) µg·m-3] > Xi'an [(1.8 ±1.2) µg·m-3] > Tongchuan [(1.6 ±1.4) µg·m-3] > Baoji [(1.2 ±0.9) µg·m-3]. Overall, Xianyang had the most severe PM2.5 and carbon aerosol pollution, whereas Tongchuan had the least pollution. IDW results showed that the high-value center of OC and EC concentration [ρ(OC) > 27.3 µg·m-3, ρ(EC) > 2.9 µg·m-3] was in the middle of the plain, the low-value center of OC and EC concentration [ρ(OC) <7.0 µg·m-3, ρ(EC) < 1.0 µg·m-3] was in the northern plain, and the distribution of OC was higher in the west and lower in the east, whereas the distribution of EC was higher in the east and lower in the west. The proportion of SOC in OC was as follows: after the Spring Festival (51.7%) > during the Spring Festival (41.1%) > before the Spring Festival (36.8%). The SOC/OC values of each city and the contribution rate of SOC of each city to the Guanzhong Plain indicated that Tongchuan, Baoji, and Xianyang were greatly affected by the secondary conversion of organic carbon. The correlation of OC and EC before, during, and after the Spring Festival (r = 0.85, r = 0.98, and r = 0.94, respectively) indicated a high degree of homology between them. Carbonaceous aerosols had a certain correlation with humidity and wind speed before and during the Spring Festival but had a weak correlation with meteorological factors after the Spring Festival. Carbonaceous aerosols generally were strongly correlated with CO and NO2, and the correlation was strongest after the Spring Festival, whereas the correlation with SO2 was strongest during the Spring Festival. The potential source areas of carbonaceous aerosols in the five cities were mainly concentrated in the local and surrounding areas of southern Gansu, northern Shaanxi, and southern Shaanxi. They were also affected by long-distance transportation from the northwest before the Spring Festival.

10.
Biol Trace Elem Res ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38995434

RESUMEN

The integrity of colonic gland cells is a prerequisite for normal colonic function and maintenance. To evaluate the underlying injury mechanisms in colonic gland cells induced by excessive fluoride (F), forty-eight female Kunming mice were randomly allocated into four groups and treated with different concentrations of NaF (0, 25, 50, and 100 mg F-/L) for 70 days. As a result, the integrity of the colonic mucosa and the cell layer was seriously damaged after F treatment, as manifested by atrophy of the colonic glands, colonic cell surface collapse, breakage of microvilli, and mitochondrial vacuolization. Alcian blue and periodic acid Schiff staining revealed that F decreased the number of goblet cells and glycoprotein secretion. Furthermore, F increased the protein expression of TLR4, NF-κB, and ERK1/2 and decreased IL-6, interfered with NF-κB signaling, following induced colonic gland cells inflammation. The accumulation of F inhibited proliferation via the JAK/STAT signaling pathway, as characterized by decreased mRNA and protein expression of JAK, STAT3, STAT5, PCNA, and Ki67 in colon tissue. Additionally, the expression of CDK4 was up-regulated by increased F concentration. In conclusion, excessive F triggered colonic inflammation and inhibited colonic gland cell proliferation via regulation of the NF-κB and JAK/STAT signaling pathways, leading to histopathology and barrier damage in the colon. The results explain the damaging effect of the F-induced inflammatory response on the colon from the perspective of cell proliferation and provide a new idea for explaining the potential mechanism of F-induced intestinal damage.

11.
Parasitol Res ; 112(4): 1771-80, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23417098

RESUMEN

Screening the anticoccidial drug targets is very important for developing novel drugs and revealing the molecular basis of drug resistance in coccidia. Due to high effectivity and safety, diclazuril was used widely in the poultry industry. To assess the roles of the serine/threonine protein phosphatase type 5 of second-generation merozoites in Eimeria tenella (EtPP5) in the anticoccidial activity of diclazuril against chicken coccidiosis, EtPP5 was cloned using reverse transcriptase polymerase chain reaction and rapid amplification of cDNA ends. Ultrastructural changes in second-generation merozoites and mRNA expression level of EtPP5 were monitored by transmission electron microscopy (TEM) and quantitative real-time PCR, respectively. The results showed that the full length of the cloned EtPP5 cDNA (2,495 bp) encompassed a 1,647-bp open reading frame encoding a polypeptide of 548 residues with an estimated molecular mass of 60.82 kDa and a theoretical isoelectric point of 5.89. Molecular analysis of EtPP5 reveals the presence of a C-terminal phosphatase domain and an extended N-terminal tetratricopeptide repeat motif, a typical feature of protein phosphatases. The cDNA sequence has been submitted to the GenBank database with accession number JX987508. EtPP5 shared 89% homology with the published sequence of a PP5 ortholog of Toxoplasma gondii at the amino acid level (GenBank XP_002364442.1). TEM observed that diclazuril induced ultrastructural changes in second-generation merozoites. Quantitative real-time PCR analysis showed that compared with the control group, the level of EtPP5 mRNA expression was significantly downregulated by 51.4% by diclazuril treatment. The high similarity of EtPP5 to previously described PP5 of other organisms, as well as its downregulated expression and connection with apoptosis in the second-generation merozoites induced by diclazuril, suggests that it could act an important role in understanding the signaling mechanism underlining the diclazuril-induced merozoites apoptosis.


Asunto(s)
Apoptosis , Coccidiosis/tratamiento farmacológico , Coccidiostáticos/farmacología , Eimeria tenella/enzimología , Nitrilos/farmacología , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fosfoproteínas Fosfatasas/genética , Fosfoproteínas Fosfatasas/metabolismo , Triazinas/farmacología , Secuencias de Aminoácidos , Animales , Pollos , Clonación Molecular , Coccidiosis/parasitología , Coccidiostáticos/uso terapéutico , ADN Protozoario/química , ADN Protozoario/genética , Eimeria tenella/efectos de los fármacos , Eimeria tenella/genética , Eimeria tenella/ultraestructura , Perfilación de la Expresión Génica , Punto Isoeléctrico , Masculino , Microscopía Electrónica de Transmisión , Datos de Secuencia Molecular , Peso Molecular , Nitrilos/uso terapéutico , Proteínas Nucleares/química , Sistemas de Lectura Abierta , Fosfoproteínas Fosfatasas/química , Estructura Terciaria de Proteína , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Triazinas/uso terapéutico
12.
Biol Trace Elem Res ; 201(9): 4497-4507, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36538210

RESUMEN

To investigate fluoride (F)-induced intestine barrier damage and the role of estrogen deficiency in this progress, a rat model of estrogen deficiency was established through bilateral surgical removal of ovaries. The F exposure model was then continued by adding sodium fluoride (0, 25, 50, and 100 mg/L, calculated on a fluorine ion basis) to drinking water for 90 days. Afterward, intestinal mucosal structure, barrier function, and inflammatory cytokines were evaluated. The results showed that excessive F decreased the developmental parameters (crypt depth) of the cecum and rectum and inhibited the proliferation capacity of the intestinal epithelia, which are more obvious in the state of estrogen deficiency. The distribution of goblet cells and glycoproteins in the intestinal mucosa decreased with the increase in F concentration, and estrogen deficiency led to a further decline, especially in the rectum. Using the immunofluorescence method, the study showed that excessive F caused interleukin-17A (IL-17A) significantly decrease in the cecum and increase in the rectum. Meanwhile, F treatment remarkably upregulated the expression of intestinal IL-1ß, IL-23, and IL-22, while the level of IL-6 was downregulated. In addition, estrogen deficiency increased IL-1ß, IL-6, IL-23, and IL-22, but decreased IL-17A expression in the cecum and rectum. Collectively, F exposure damaged intestinal morphological structure, inhibited epithelial cell proliferation and mucus barrier function, and resulted in the disturbance of T helper (Th) 17 cell-related cytokines expression. Estrogen deficiency may further aggravate F-induced damage to the cecum and rectum.


Asunto(s)
Citocinas , Fluoruros , Animales , Ratas , Ciego/metabolismo , Citocinas/metabolismo , Estrógenos/farmacología , Fluoruros/toxicidad , Interleucina-17/metabolismo , Interleucina-23 , Interleucina-6 , Mucosa Intestinal/metabolismo , Recto/metabolismo
13.
Environ Pollut ; 336: 122407, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37597730

RESUMEN

Osteosclerosis and osteoporosis are the two main clinical manifestations of skeletal fluorosis. However, the reasons for the different clinical manifestations are unclear. In this study, we established the fluoride (F) -exposed ovariectomized (OVX) and non-OVX rat models to assess the potential role of ovarian function loss in osteosclerosis and osteoporosis. Micro-CT scanning showed that excessive F significantly induced a high bone mass in non-OVX rats. In contrast, a low bone mass manifestation was presented in OVX F-exposed rats. Also, a prominent feature of increasing trabecular connectivity, collagen area, growth plate thickness, and reduced trabecular space was found by histopathological morphology in non-OVX F-exposed rats; an opposite result was observed in OVX F-exposed. These alterations indicated ovariectomy was a vital factor leading to osteosclerosis or osteoporosis in skeletal fluorosis. Furthermore, levels of bone alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase (TRAP) increased, combined with the increasing osteoclasts number, showing a sign of high bone turnover in both OVX and non-OVX F-exposed rats. Mechanistically, oophorectomy considerably activated the RANKL/RANK/OPG signaling pathway. Meanwhile, it was discovered that upregulated NF-κB positively facilitated the accumulation of nuclear factor of activated T-cells 1 (NFATC1), significantly promoting osteoclast differentiation. To sum up, this study greatly enriched the causes of clinical skeletal fluorosis and provided a new perspective for studying the pathogenesis of skeletal fluorosis.

14.
Biol Trace Elem Res ; 201(9): 4389-4399, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36595130

RESUMEN

To investigate the effects of molybdenum (Mo) on apoptosis of lymphocytes and changes of peripheral blood in sheep, a total of 20 5-month-old healthy female sheep were randomly divided into five groups of 4 and orally administered with water containing Na2MoO4·2H2O (0, 5, 10, 20, and 50 mg/kg BW/day) for 28 days. Jugular vein blood was taken on the 0th, 7th, 14th, 21st, and 28th day of Mo treatment, respectively. On the 28th day, the spleen and thymus were removed for observing histopathology and apoptosis-related DNA damage by hematoxylin and eosin (HE) staining and TdT­mediated dUTP Nick-End Labeling (TUNEL) staining, respectively. The blood routine indexes were determined by an automatic blood analyzer. Further, the apoptosis of lymphocytes and changes in mitochondrial membrane potential (MMP) of peripheral blood were analyzed by flow cytometry. Results showed that excessive Mo induced apoptosis-related DNA damage in the splenocytes and thymocytes and significantly increased the apoptosis indexes of the splenocytes and thymocytes (P < 0.01). Furthermore, the treatment with excessive Mo significantly decreased the MMP (P < 0.01) and promoted apoptosis in peripheral blood lymphocytes (P < 0.01). And the number of WBC, Lymph, Gran, and RBC and the indexes of HGB and HCT were also significantly decreased (P < 0.05 or P < 0.01), while RDW was significantly increased by excessive Mo (P < 0.05 or P < 0.01). In conclusion, excessive Mo-induced DNA damage and apoptosis of the lymphocytes changed the RBC-related indexes of the peripheral blood in sheep.


Asunto(s)
Molibdeno , Timocitos , Animales , Femenino , Apoptosis , Linfocitos , Molibdeno/farmacología , Ovinos , Bazo , Timo
15.
Mol Biochem Parasitol ; 255: 111575, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37302489

RESUMEN

Diclazuril is a classic anticoccidial drug. The key molecules of diclazuril in anticoccidial action allows target screening for the development of anticoccidial drugs. Cyclin-dependent kinases (CDK) are prominent target proteins in apicomplexan parasites. In this study, a diclazuril anticoccidiosis animal model was established, and the transcription and translation levels of the CDK-related kinase 2 of Eimeria tenella (EtCRK2) were detected. mRNA and protein expression levels of EtCRK2 decreased in the infected/diclazuril group compared with those in the infected/control group. In addition, immunofluorescence analysis showed that EtCRK2 was localised in the cytoplasm of the merozoites. The fluorescence intensity of EtCRK2 in the infected/diclazuril group was significantly weaker than that in the infected/control group. The anticoccidial drug diclazuril against E.tenella affects the expression pattern of EtCRK2 molecule, and EtCRK2 is a potential target for new drug development.


Asunto(s)
Coccidiosis , Eimeria tenella , Animales , Eimeria tenella/genética , Merozoítos , Nitrilos/farmacología , Triazinas/farmacología , Pollos/parasitología , Coccidiosis/tratamiento farmacológico , Coccidiosis/veterinaria , Coccidiosis/parasitología
16.
Parasitol Res ; 111(4): 1447-55, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22752697

RESUMEN

The receptor for activated C kinase (RACK) cDNA of second-generation merozoites of Eimeria tenella was cloned using reverse transcriptase polymerase chain reaction and rapid amplification of cDNA ends, compared with other species, and then successfully expressed using the pET-28a vector in Escherichia coli BL21 (DE3) (EtRACK). Nucleotide sequence analysis revealed that the full length of the cloned cDNA (1,264 bp) encompassed a 957-bp open reading frame encoding a polypeptide of 318 residues with an estimated molecular mass of 34.94 kDa and a theoretical isoelectric point of 5.97. Molecular analysis of EtRACK reveals the presence of seven WD40 repeat motifs. EtRACK localizes to the cytoplasm and nucleus in second-generation merozoites of E. tenella. The cDNA sequence has been submitted to the GenBank Database with accession number JQ292804. EtRACK shared 98% homology with the published sequence of a RACK protein from Toxoplasma gondii at the amino acid level (GenBank XP_002370996.1). Recombinant protein expression was induced using 1 mM of isopropyl ß-D-1-thiogalactopyranoside in vitro at 30 °C. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed that the 39.79-kDa fusion protein existed in unsolvable form. Quantitative real-time PCR analysis showed that compared with the control group, the level of EtRACK mRNA expression in the treatment group was downregulated by 81.3% by diclazuril treatment. The high similarity of EtRACK to previously described RACKs of other organisms, as well as its downregulated expression in second-generation merozoites induced by diclazuril, suggests that it could play a key role in the signaling event that precedes protein secretion and parasite invasion. Moreover, the downregulation of EtRACK mRNA expression also enriches studies on the mechanism of action of diclazuril on E. tenella.


Asunto(s)
Eimeria tenella/genética , Nitrilos/metabolismo , ARN Mensajero/biosíntesis , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Activación Transcripcional/efectos de los fármacos , Triazinas/metabolismo , Animales , Clonación Molecular , ADN Protozoario/química , ADN Protozoario/genética , Escherichia coli/genética , Expresión Génica , Perfilación de la Expresión Génica , Punto Isoeléctrico , Merozoítos , Datos de Secuencia Molecular , Peso Molecular , Sistemas de Lectura Abierta , Receptores de Cinasa C Activada , Receptores de Superficie Celular/química , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Toxoplasma/genética
17.
Toxicol Lett ; 362: 26-37, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35504524

RESUMEN

To investigate the role and molecular mechanism of estrogen deficiency in fluorine ion (F-)-induced renal fibrosis, the models of F- exposure in ovary removed rats were established by drinking water with different doses of F- (0, 25, 50 and 100 mg/L) for 90 days. Results of H&E staining and BrdU labeled experiment showed that F- induced renal pathomorphological damage and inhibited cell proliferation. Further, Masson staining showed that F- induced renal glomerular and tubulointerstitial fibrosis. Meanwhile, renal fibrosis was confirmed by detecting the expression levels of collagen I, collagen III, collagen IV and fibronectin using immunofluorescence. In the state of estrogen deficiency, F--induced renal damage and fibrosis were aggravated. Moreover, the molecular mechanism of F--induced renal fibrosis was evaluated, and the results showed that F- induced TGF-ß1/Smad signaling pathway further dysregulation after ovariectomy, which manifested as the further up-regulated expression of TGF-ß1, Smad2, p-Smad2, Smad3 and p-Smad3, and further down-regulated of Smad7. Accompanied by renal damage and renal fibrosis, renal function was also disturbed, especially in ovariectomized rats. This study indicated that estrogen deficiency aggravated F--induced renal fibrosis via the TGF-ß1/Smad signaling pathway, leading to more serious renal dysfunction.


Asunto(s)
Enfermedades Renales , Factor de Crecimiento Transformador beta1 , Animales , Estrógenos/toxicidad , Femenino , Fibrosis , Flúor/metabolismo , Enfermedades Renales/inducido químicamente , Ratas , Transducción de Señal , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo
18.
Environ Pollut ; 292(Pt B): 118381, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34673156

RESUMEN

Colon microenvironment and microbiota dysbiosis are closely related to various human metabolic diseases. In this study, a total of 72 healthy female mice were exposed to fluoride (F) (0, 25, 50 and 100 mg/L F-) in drinking water for 70 days. The effect of F on intestinal barrier and the diversity and composition in colon microbiota have been evaluated. Meanwhile, the relationship among F-induced colon microbiota alterations and antimicrobial peptides (AMPs) expression and short-chain fatty acids (SCFAs) level also been assessed. The results suggested that F decreased the goblet cells number and glycoprotein expression in colon. And further high-throughput 16S rRNA gene sequencing result demonstrated that F exposure induced the diversity and community composition of colonic microbiota significantly changes. Linear Discriminant Analysis Effect Size (LEfSe) analysis identified 11 predominantly characteristic taxa which may be the biomarker in response to F exposure. F-induced intestinal microbiota perturbations lead to the significantly decreased SCFAs levels in colon. Immunofluorescence results showed that F increased the protein expression of interleukin-17A (IL-17A) and IL-22 (P < 0.01) and disturbed the expression of interleukin-17 receptor A (IL-17RA) and IL-22R (P < 0.05 or P < 0.01). In addition, the increased expression of IL-17A and IL-22 cooperatively enhanced the mRNA expression of AMPs which response to F-induced microbiota perturbations. Collectively, destroyed microenvironment and disturbed AMPs are the primary reason of microbiota dysbiosis in colon after F exposure. Colonic homoeostasis imbalance would be helpful for finding the source of F-induced chronic systemic diseases.


Asunto(s)
Disbiosis , Microbioma Gastrointestinal , Animales , Colon , Disbiosis/inducido químicamente , Femenino , Fluoruros , Ratones , Proteínas Citotóxicas Formadoras de Poros , ARN Ribosómico 16S/genética
19.
Biol Trace Elem Res ; 200(6): 2767-2776, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34392477

RESUMEN

Estrogen exerts essential role in liver metabolism, and its deficiency is frequently accompanied by a series of metabolic disorder diseases. To investigate the role of estrogen deficiency in fluorine ions (F-) induced liver injury, the ovariectomy (OVX) rat models were performed by surgically removing the ovaries, and the rats from OVX and non-OVX models were exposed to differential dose of F- (0, 25, 50 and 100 mg/L) in drinking water for 90 days. The liver morphological structure was evaluated by hematoxylin-eosin staining. Proliferation ability of hepatocytes was evaluated by 5-bromo-2-deoxyuridine (BrdU) assay. And distribution of lipid droplets in liver tissue was observed via oil red O staining. In addition, the liver function and lipid metabolism parameters in serum were detected by commercial kits. Results showed that F- induced hepatocytes morphological damage and inhibited the proliferation ability of hepatocytes; estrogen deficiency exacerbated these changes. The deposition of lipid droplets in the liver tissue was multiplicative with increased F- dose, especially after estrogen deficiency. In addition, F- exposure increased (P < 0.05 or P < 0.01) serum aminotransferase (ALT), aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transpeptidase (γ-GT) activities and total bilirubin (T-bil) level; meanwhile, serum triglyceride (TG) and cholesterol (TC) levels were also elevated (P < 0.05 or P < 0.01). F--induced liver function and lipid metabolism indexes were further increased (P < 0.05 or P < 0.01) in the state of estrogen deficiency. In conclusion, estrogen deficiency aggravated F--induced liver damage and lipid metabolism disorder.


Asunto(s)
Trastornos del Metabolismo de los Lípidos , Metabolismo de los Lípidos , Animales , Estrógenos/metabolismo , Femenino , Fluoruros/metabolismo , Trastornos del Metabolismo de los Lípidos/inducido químicamente , Trastornos del Metabolismo de los Lípidos/metabolismo , Hígado/metabolismo , Ratas , Ratas Sprague-Dawley , Transaminasas/metabolismo
20.
Vet Parasitol ; 296: 109477, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34087564

RESUMEN

An anticoccidial model of chicken infected with Eimeria tenella was established to investigate the effect of toltrazuril (Tol) combined with the Radix Sophorae Flavescentis (RSF) on coccidiosis. The anticoccidial index (ACI) was evaluated, and the cecal developmental parameters (i.e., villus height, [VH], crypt depth, [CD], and VH/CD) were determined. The distributions of glycoproteins and goblet cells in the cecal tissue were determined through the Periodic Acid-Schiff (PAS) and Alcian blue PAS staining methods, respectively. The mRNA expression levels of interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-10, and IL-17 of the cecal tissue were determined through quantitative real-time PCR. The moderate ACI was obtained using the combination of Tol and RSF. Compared with the normal control (NC) group, the infected control (IC) group showed remarkably lower VH and VH/CD at five and seven days postinfection. Compared with the IC group, the IC + RSF and IC + TolRSF groups showed remarkably higher VH and VH/CD at five and seven days postinfection. Compared with the NC group, the IC group contained fewer glycoproteins and goblet cells, but the Tol and RSF treatment promoted more glycoproteins and goblet cells at five and seven days postinfection. The mRNA expression levels of IL-1ß, IL-2, IL-4, IL-6, IL-10, and IL-17 in the IC group were upregulated (P < 0.01) compared with those in the NC group. The IC + RSF and IC + TolRSF groups had downregulated mRNA expression levels of IL-1ß, IL-6, and IL-17 cytokines (P < 0.01), and upregulated mRNA expression levels of IL-2 and IL-4 cytokines (P < 0.01) compared with the IC group. Results showed that the combination of Tol and RSF exerts anticoccidial effect by reducing inflammation and promoting intestinal mucosal immunity.


Asunto(s)
Inmunidad Mucosa , Extractos Vegetales , Ranunculaceae , Triazinas , Animales , Pollos , Coccidiosis/tratamiento farmacológico , Coccidiosis/veterinaria , Coccidiostáticos/farmacología , Coccidiostáticos/uso terapéutico , Eimeria tenella , Regulación de la Expresión Génica/efectos de los fármacos , Inmunidad Mucosa/efectos de los fármacos , Inflamación/veterinaria , Interleucinas/genética , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Enfermedades de las Aves de Corral/tratamiento farmacológico , Ranunculaceae/química , Triazinas/farmacología , Triazinas/uso terapéutico
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