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  • 机译 纳米结构在即兴口服药物中的作用
    摘要:The most preferable mode of drugs administration is via the oral route but physiological barriers such as pH, enzymatic degradation etc. limit the absolute use of this route. Herein lies the importance of nanotechnology having a wide range of applications in the field of nano-medicine, particularly in drug delivery systems. The exclusive properties particularly small size and high surface area (which can be modified as required), exhibited by these nanoparticlesrender these structures more suitable for the purpose of drug delivery. Various nanostructures, like liposomes, dendrimers, mesoporous silica nanoparticles, etc. have been designed for the said purpose. These nanostructures have several advantages over traditional administration of medicine. Apart from overcoming the pharmacokinetic and pharmacodynamics limitations of many potential therapeutic molecules, they may also be useful for advanced drug delivery purposes like targeted drug delivery, controlled release, enhanced permeability and retention (EPR) effect. In this review, we attempt to describe an up-to-date knowledge on various strategically devised nanostructures to overcome the problems related to oral drug administration.
  • 机译 一流的GADD45β/ M​​KK7抑制剂和临床候选药物DTP3的临床前毒理学和安全药理学
    摘要:Keywords: NF-κB, GADD45β, Multiple myeloma, Cancer, Pharmacology

    Abstract

    Aberrant NF-κB activity drives oncogenesis and cell survival in multiple myeloma (MM) and many other cancers. However, despite an aggressive effort by the pharmaceutical industry over the past 30 years, no specific IκBα kinase (IKK)β/NF-κB inhibitor has been clinically approved, due to the multiple dose-limiting toxicities of conventional NF-κB-targeting drugs. To overcome this barrier to therapeutic NF-κB inhibition, we developed the first-in-class growth arrest and DNA-damage-inducible (GADD45)β/mitogen-activated protein kinase kinase (MKK)7 inhibitor, DTP3, which targets an essential, cancer-selective cell-survival module downstream of the NF-κB pathway. As a result, DTP3 specifically kills MM cells, ex vivo and in vivo, ablating MM xenografts in mice, with no apparent adverse effects, nor evident toxicity to healthy cells. Here, we report the results from the preclinical regulatory pharmacodynamic (PD), safety pharmacology, pharmacokinetic (PK), and toxicology programmes of DTP3, leading to the approval for clinical trials in oncology. These results demonstrate that DTP3 combines on-target-selective pharmacology, therapeutic anticancer efficacy, favourable drug-like properties, long plasma half-life and good bioavailability, with no target-organs of toxicity and no adverse effects preclusive of its clinical development in oncology, upon daily repeat-dose administration in both rodent and non-rodent species. Our study underscores the clinical potential of DTP3 as a conceptually novel candidate therapeutic selectively blocking NF-κB survival signalling in MM and potentially other NF-κB-driven cancers.
  • 机译 抗氧化剂在急性阿米替林中毒中的作用
    摘要:ObjectiveTo study the effect of Antioxidants supplementation in reducing oxidative stress induced in acute amitriptyline poisoning cases.
  • 机译 消炎痛对大鼠肾脏,小肠和肝脏中碳水化合物代谢酶,刷状缘膜和氧化应激的比较作用
    摘要:Indomethacin (IndoM) has prominent anti-inflammatory and analgesic-antipyretic properties. However, high incidence and severity of side-effects on the structure and functions of the kidney, liver and intestine limits its clinical use. The present study tested the hypothesis that IndoM causes multi-organ toxicity by inducing oxidative stress that alters the structure of various cellular membranes, metabolism and hence functions. The effect of IndoM was determined on the enzymes of carbohydrate metabolism, brush border membrane (BBM) and oxidative stress in the rat kideny, liver and intestine to understand the mechanism of IndoM induced toxicity. Adult male Wister rats were given IndoM (20 mg/kg) intra-peritoneally in sodium bicarbonate twice a day for 3 d. The body weights of the rats were recorded before and after experimental procedure. IndoM administration significantly increased blood urea nitrogen, serum creatinine, cholesterol and alkaline phosphatase but inorganic phosphate indicating IndoM induced renal, hepatic and intestinal toxicity. Activity of lactate dehydrogenase along with glucose-6- and fructose-1, 6-bis phosphatase, glucose-6-phosphate dehydrogenase and NADP-malic enzyme increased but malate dehydrogenase decreased in all tissues. Lipid peroxidation (LPO) significantly increased whereas the antioxidant enzymes decreased in all rat tissues studied. The results indicate that IndoM administration caused severe damage to kidney, liver and intestine by icreasing LPO, suppressing antioxidant enzymes and inhibiting oxidative metablolism. The energy dependence was shifted to anaerobic glycolysis due to mitochondrial damage supported by increased gluconeogenesis to provide more glucose to meet energy requirements.
  • 机译 在动物模型中造影剂诱发的肾病:血液和组织样品中新型生物标志物的评估
    摘要:Abbreviations: ADMA, asymmetric dimethylarginine; AVMA, American Veterinary Medical Association; AKI, acute kidney injury; ANOVA, analysis of variance; ARRIVE, animal research: reporting of in vivo experiments; BNMN, Bi-nucleated cells with micronuclei; CBPI, cytokinesis block proliferation index; CIN, contrast-induced nephropathy; CKD, chronic kidney disease; CM, contrast medium; ESI, electrospray ionization; GFR, glomerular filtration rate; KIM-1, kidney injury molecule-1; LC–MS, liquid chromatography mass spectrometry; MN, micronuclei; NO, nitric oxide; NGAL, meutrophil gelatinase–associated lipocalin; OECD, Organisation for Economic Co-operation and Development; RBF, renal blood flow; ROS, reactive oxygen species; SCR, serum creatinine; SD, standard deviation; SDMA, symmetric dimethylarginine; TPT, touch preparation techniqueKeywords: Asymmetric dimethylarginine, Contrast media, Kidney, Models, Animal, Iopromide, Nephropathy, Nephrotoxicity, Symmetric dimethylarginine

    Abstract

    Identification of novel biomarkers of contrast-induced nephropathy (CIN) that may more accurately detect renal function changes; reflect kidney damage; assist monitoring; and elucidate pathophysiology attract considerable scientific attention nowadays. To evaluate novel biomarkers of nephrotoxicity in blood/tissue samples of a CIN model, 10 New Zealand white rabbits were divided into group 1 (n = 5; iopromide) and group 2 (n = 5; control). Blood was drawn at 0 h (immediately), 24 h and 48 h after contrast medium (CM) administration. Animals were euthanized at 48 h and kidneys were removed. Serum creatinine (sCr)/symmetric-asymmetric dimethylarginine (SDMA-ADMA) levels were measured. CM genotoxic/cytotoxic effect was investigated 48 h post-CM exposure using micronucleus assay in lymphocytes. Cytological examination was conducted using touch preparation technique (TPT). All animals in group 1 developed CIN: mean sCr levels increased by 68.2% within 48 h. Significant SDMA-ADMA level elevation was observed at 0 h and 24 h with insignificant drop at 48 h in group 1, remaining normal in group 2 at all time-points. Significant increase in bi-nucleated cells with micronuclei and micronuclei frequency was detected in group 1. Cytokinesis block proliferation index was reduced insignificantly in group 1. TPT revealed degenerative lesions/inflammation, cell degeneration, abnormal uterine tubular casts and rubella in kidneys of all animals in group 1. Group 2 presented normal cells.
  • 机译 木棉花提取物可改善乙醇和中度脂肪饮食引起的肝脂肪变性
    摘要:Keywords: Alcohol consumption, Hepatosteatosis, B. ceiba flowers extract

    Abstract

    Chronic excessive alcohol consumption could induce serious liver injury. In this study, therapeutic effect of aqueous methanol extract of Bombax ceiba L. flowers (BCE) (Family: Bombacaceae) was investigated against hepatic steatosis. This study included seven groups, and the research period was eight weeks. The first group served as control. The six remaining groups were divided into two categories, three groups in each. The first category was fed fat diet. The second category was fed fat diet and orally administrated ethanol, which was given in graduate doses from 2 g/kg/d to 6 g/kg/d. Then, one group from each category was orally treated with the standard drug fluvastatin (2 mg/Kg/d). Another group was orally treated with BCE (200 mg/kg/d). The third group left untreated. The results revealed that BCE significantly decrease both the body and liver weight. The treatment with BCE extract also ameliorates the effect of alcohol induced increase of liver enzyme activities. In addition, the extract was significantly increased hepatic liver antioxidants and decreased malondialdehyde (MDA) level. Also, serum lipid profiles: triglycerides (TG), total cholesterol (TC) and low density lipoprotein (LDL) were significantly decreased after BCE treatment. Histopathological study showed fatty changes induced by alcohol which were improved by BCE treatment. These data suggest that the BCE has anti-inflammatory, anti-oxidant and anti-steatosis potential properties against alcohol induced liver damage. This may be due to the presence of flavonoids and other phenol compounds.
  • 机译 SGM-101的毒性和药代动力学特征,SGM-101是一种用于患者肿瘤荧光成像的荧光抗CEA嵌合抗体
    摘要:Abbreviations: FGS, fluorescence guided surgery; NIR, near infra-red; ICG, indocyanine green; CEA, carcinoembryonic antigen; mAb, monoclonal antibody; GLP, Good Laboratory Practices; PK, pharmacokinetics; AUC, Area Under the Curve; MTD, maximum tolerated dose; MRT, Mean Residence Time; NOAEL, no observable adverse effect level (NOAEL); TMDD, target-mediated drug dispositionKeywords: Carcinoembryonic antigen, Cancer, Fluorescence guided surgery, Near-infrared fluorochrome, Toxicity, Pharmacokinetics

    Abstract

    The real-time improvement of the intraoperative discrimination between different tissue types (particularly between tumor and adjacent normal tissue) using intraoperative imaging represents a considerable advance for oncology surgeons. However, the development of imaging agents is much slower than that of drug therapies, although surgery represents one of the few curative treatments for many solid tumors. SGM-101 is a recently described, innovative antibody conjugate in which the near-infrared fluorochrome BM-104 is covalently linked to a chimeric monoclonal antibody against carcinoembryonic antigen (CEA). SGM-101 was developed with the goal of providing oncology surgeons with an intraoperative imaging tool that allows the visualization of CEA-overexpressing tumors. This antigen is overexpressed in a wide range of human carcinomas, such as colorectal, gastric, pancreatic, non-small cell lung and breast carcinomas. Here we characterized SGM-101 safety prior to its clinical testing for real-time cancer mapping by oncology surgeons. Safety pharmacology and toxicology studies were performed after intravenous injection of SGM-101 in Wistar rats and in Beagle dogs. SGM-101 metabolism and pharmacokinetics were analyzed in rats and mice. Finally, the potential toxicity of the BM-104 dye and SGM-101 cross-reactivity were assessed in a panel of 42 human tissues. Our pre-clinical toxicology, pharmacology and pharmacokinetic results demonstrated the absence of significant adverse effects of both SGM-101 and BM-104 at doses well above the anticipated maximal human exposure. Taken together, the results of the pharmacology, pharmacokinetic and toxicology studies support the development of SGM-101 as a potentially useful and safe tumor-specific imaging tool that might improve the complete tumor resection rate.
  • 机译 姜(Roscoe)通过抗氧化剂,稳定膜和组织再生的潜力缓解了CCl4诱导的肝脏组织病理学和生化异常
    摘要:Keywords: CCl4, Zingiber officinale, Liver injury, Histopathology, Female Wistar rats

    Abstract

    The world-wide increasing incidence of liver injury has attracted scientific interest in the exploration of better treatment or adjuvant treatment therapies. This study investigated the effects of methanol extract of Zingiber officinale (Roscoe) rhizome (MEZOR) in a Wistar rat model of carbon tetrachloride (CCl4)-induced liver injury. The study recruited thirty female Wistar rats that received graded doses of MEZOR (determined by its LD50) by oral gavage through an oral canula, for 4 consecutive weeks following 1 week oral administration of CCl4 (0.7 ml/kg in olive oil; 1:1, v/v) while livolin forte® (5.2 mg/kg p.o.) was used as a standard. CCl4 induced deleterious hepatic effects as revealed by the liver function biomarkers (AST, ALT, ALP and total protein), antioxidant indicators (GSH and CAT) and histopathological effects, demonstrated by H & E, Gordon and Sweet, Masson’s trichrome, PAS staining techniques as well as by quantificational analyses of the liver micrographs, using image–J. MEZOR treatment was associated with a dose-dependent and significant mitigation of the aforementioned parameters (p < 0.05). This study concluded that MEZOR is a potential therapeutic choice in the adjuvant treatment of subjects with chemically-induced liver injury.
  • 机译 穿心莲标准化的第一种真叶乙醇提取物的急性口服毒性评价
    摘要:Keywords: Andrographis paniculata, Standardized first true leaf, Acute oral toxicity

    Abstract

    Andrographis paniculata is widely used in traditional herbal medicines for the treatment of common cold, fever and diarrhea, in many regions of Scandinavia and Asia, including Thailand. The pharmacological activities of A. paniculata are mainly attributed to active diterpenoids including 14-deoxyandrographolide, which is uniquely high in first true leaf ethanolic extract (FTLEE) of A. paniculata. In this study, the acute toxicity of the standardized FTLEE of A. paniculata was examined according to the OECD test guideline No. 420. Mice were divided into four groups of each sex and orally received the standardized FTLEE of A. paniculata (0, 300, 2000, or 5000 mg/kg BW). Post-treatment, body weight, signs of toxicity, and/or mortality were observed for 14 days. At Day 15, animals were euthanized, internal organs were observed grossly, and blood samples collected were subjected to hematology and clinical biochemistry analyses. The results showed that all treated animals survived and no apparent adverse effects were observed during the duration of the study. Gross necropsy observation revealed no lesion in any organ of all the standardized FTLEE-treated mice. Although significant alterations in BUN, lymphocytes, neutrophils, hematocrit and hemoglobin were observed, these alterations were not treatment-related toxic effects. Therefore, we concluded that a single oral administration of the standardized FTLEE of A. paniculata with an upper fixed dose of 5000 mg/kg BW has no significant acute toxicological effects.
  • 机译 低剂量和短期暴露于甲硫醇后大鼠中毒性研究的初步结果
    摘要:The present study was carried out to evaluate the hematotoxicity and respiratory toxicity of methyl mercaptan in Sprague-Dawley rats. A dynamic exposure methodology was adopted in this study following 7 days of exposure by repeated inhalation. The concentration of methyl mercaptan used in the exposure was 0.5 ppm and the exposure time was 6 h/day for 7 days. After exposure, the rats were sacrificed to collect lung tissue and blood samples. Routine blood and serum biochemistry were conducted. Morphological injury of lung tissue was detected by hematoxylin and eosin staining. Decreased food consumption and body weight gain in both sexes were noted in the exposure group compared with the control group. Several significant changes in hematological parameters were observed. The results showed that the blood urea nitrogen (UREA) levels and superoxide dismutase (SOD) values were significantly decreased in exposed male rats. Malondialdehyde (MDA) in lung tissue was significantly increased in both males and females in the exposed group. In the histopathological examination of lung tissue, terminal bronchiole constriction, alveolar congestion, and erythrocyte exudation were observed, suggesting that the lungs may be target organs after inhaling methyl mercaptan and workers exposed to this concentration may cause some pulmonary stimulation and injury.
  • 机译 未经处理的药用植物废水对小鼠心脏的Na + -K + -ATPase和Ca2 + -Mg2 + -ATPase活性的影响
    摘要:Cardiovascular diseases are major causes of non-communicable diseases (NCDs)-related throughout the world. Water pollution has been linked with the high global NCD burden but no report exists on the cardiotoxicity of untreated or poorly treated pharmaceutical effluent, despite its indiscriminate discharge into the aquatic environment in Nigeria, as in many other locations of the world. Thus, this study investigated the cardiotoxic effect of oral exposure to pharmaceutical effluent in mice. Thirty (30) male mice (Mus musculus) were randomly divided into 6 groups. Group A (control) received 0.2 ml distilled water, while groups B-F were treated with 0.2 ml 2.5%, 5.0%, 10.0%, 20.0% and 40% concentrations (v/v, effluent/distilled water) of the effluent respectively, for 28 days. Significant reductions (p<0.05) in heart weight and cardiac weight index were observed in the groups treated with 5%, 10%, 20% and 40% concentrations of the effluent, without significant change in body weight. Similarly, 28 day administration of the effluent showed significant decrease in cardiac Na+-K+-ATPase activity (p<0.05) at concentrations 10% and above, in a concentration dependent manner. However, there was insignificant decrease in cardiac Ca2+-Mg2+-ATPase activity of the exposed mice, when compared with the control group. This study provides novel information on the cardiotoxic effects of oral exposure to untreated pharmaceutical effluent, showing reduced Na+-K+-ATPase activity and decreseased myocardial atrophy. Therefore, drinking water contaminated with pharmaceutical effluent may promote the incidence of cardiovascular diseases. Further studies on the exact mechanistic routes of the induced cardiotoxicity are recommended.
  • 机译 甘露微乳剂(纳米颗粒)对溴苯致小鼠毒性的保肝作用
    摘要:Livergol (LG), which is the extract of Silybum marianum and commonly known as milk thistle possess hepatoprotective effect and have got licensed for sale in Iran and other countries. LG was evaluated for its capacity to counteract the toxic effects of bromobenzene (BB) on mouse liver. The bioactive component of this plant is known to reinforce naturally occurring liver function through antioxidant activity, the stimulation of bile production and regeneration by the liver organ, resulting in enhanced protection against toxicants, hepatitis, and cirrhosis. The major bioactive components of this product are the flavonolignan ssilibinin, silidianin, silicristin, and isosilibinin. Mice were treated for 10 days with daily gavage of microemulsions (MEs), into which 0–400 mg/kg LG was dispersed. 0.36 ml/kg BB was injected intraperitoneally (ip) to each animal on day 10, followed by sacrifice on day 11, and histological evaluation of hematoxylin-eosin (HE)‐stained liver tissue samples, afterwards followed by evaluation liver enzymes level, aminotransferase (AST), alanine aminotransaminase (ALT) and alkaline phosphatase (ALP) activities. Significant suppression of BB-mediated damage to liver tissue, and increased in AST, ALT, and ALP level was observed to occur dose-responsively with LG administration, suggesting a use for LG as a chemoprotectant for persons chronically exposed to industrial solvents.
  • 机译 尼日利亚汽车面板车间二手车中汽车油漆粉尘中镉,铬和镍的健康风险评估
    摘要:Keywords: Heavy metals, Cancer risk, Non-cancer risks, Paint dust, Imported automobiles, Auto-panel workshops

    Abstract

    Nigeria’s economic problems which inhibited local production has resulted in massive importation of used automobiles. Most of these automobiles need some repairs and reworking, having outlived their lifespan in the manufacturer’s country. This study centers on the human carcinogenic and non-carcinogenic health risk assessment of cadmium, chromium and nickel exposures from reworking of imported used vehicles. Scraped car paint dusts from 56 Japanese made cars were collected from 8 different panel beating (body works) workshops (A–H) in Southeastern Nigeria. They were homogenized, mixed, divided into fine particles, filtered and digested by standard method. The filtrates were assayed for cadmium, chromium and nickel with atomic absorption spectrophotometry (AAS, 200A), workshops F and D have the highest concentration (mg/kg) of Cd (3.58 ± 0.02) and (3.36 ± 0.04) and higher than levels in workshops A, B, C, E, G and H. Chromium (mg/kg) in workshops F and G were (2.87 ± 0.04) and (2.95 ± 0.06) and higher than the other workshops. Nickel in workshop A (3.84 ± 0.04) is close to other workshop values. The highest hazard quotients for adults were cadmium in workshops B (1.37E-01), D (1.69E-01), E (1.79E-01) (inhalation), chromium [workshops G (5.45E-02), F (5.29E-02) and C (5.24E-02) inhalation]. Nickel -workshop A (5.9E-03) for children (inhalation). HQ in children through ingestion is cadmium (3.72E-04) workshop F and ingestion- 3.21E-01(workshop F) while nickel is 1.06E-02 (workshop A).The highest cancer risks were in exponents -4,-7 and -8 (adult) and -3, -6 and -9 (children) for workshops A–H through inhalation, ingestion and dermal contact, exposures to scrap car paint dust may be of significant public health importance in Nigeria as it can add to body burden of some carcinogenic heavy metals.
  • 机译 IL-6和NFE2L2:N. Sativa,P。Ginseng和C. Sempervirens在AFB-1诱导的肝细胞癌中的保护作用
    摘要:Keywords: HCC, NFE2L2, N. Sativa, P. Ginseng, C. Sempervirens, IL-6

    Abstract

    In this study, we investigated possible hepato-protective effects of N. Sativa, P. Ginseng, and C. Sempervirens in Aflatoxin B1 (AFB-1) induced hepatocellular carcinoma rat model.Fifty-four male albino rats were randomly assigned to experimental groups. Alcoholic extracts of aforementioned herbs were administered orally for 28 days at different doses. IL-6, hs-CRP, MDA, SOD and NFE2L2 were determined using ELISA. Histopathological changes in treated groups were examined.Herbal treatment significantly reduced IL-6, hs-CRP, and MDA (P < 0.001) whereas it significantly increased SOD (p < 0.001). C. Sempervirens 600 and N. Sativa 1000 increased NFE2L2 level compared to P. Ginseng 500 group (P value<0.01). Histopathological evaluation of treated groups showed different grades of healing of the liver.This study confirms a beneficial hepatoprotective effect for aforementioned herbal extracts orally administered in rat model of AFB1 induced HCC. This effect is putatively mediated via modulation of inflammatory cytokines as well as amelioration of oxidative stress.
  • 机译 危地马拉成年人黄曲霉毒素-白蛋白加合物水平与玉米饼消费之间的关联
    摘要:Aflatoxin B1 (AFB1) is a known human hepatocarcinogen and a recent study reported elevated AFB1 levels, measured by serum albumin biomarkers, among Guatemalan adults. While AFB1 can contaminate a variety of foodstuffs, including maize, Guatemala’s main dietary staple, the relationship of maize intake to serum AFB1-albumin adducts levels in Guatemala has not been previously examined. As a result, a cross-sectional study was conducted among 461 Guatemalan adults living in five geographically distinct departments of the country. Participants provided a serum sample and completed a semi-quantitative food frequency questionnaire and a sociodemographic questionnaire. Multiple linear regression analysis was used to estimate the least square means (LSQ) and 95% confidence intervals (95% CI) of log-transformed AFB1-albumin adducts by quintiles of maize consumption in crude and adjusted models. Additionally, analyses of tortilla consumption and levels of maize processing were conducted. The median maize intake was 344.3 g per day [Interquartile Range (IQR): 252.2, 500.8], and the median serum AFB1-albumin adduct level was 8.4 pg/mg albumin (IQR: 3.8, 22.3). In adjusted analyses, there was no association between overall maize consumption and serum AFB1-albumin levels. However, there was a statistically significant association between tortilla consumption and AFB1-albumin levels (ptrend = 0.01). The LSM of AFB1-albumin was higher in the highest quintile of tortilla consumption compared to the lowest quintile [LSM:9.03 95%CI: 7.03,11.70 vs 6.23, 95%CI: 4.95,8.17, respectively]. These findings indicate that tortilla may be an important source of AFB1 exposure in the Guatemalan population. Therefore, efforts to control or mitigate AFB1 levels in contaminated maize used for tortillas may reduce overall exposure in this population.
  • 机译 恒河流域鱼类鱼类的生物蓄积和重金属污染的潜在来源:可能的人类健康风险评估
    摘要:Keywords: Heavy metal, Fish, Bioaccumulation, Human health, Risk assessment, THQ

    Abstract

    This paper assesses the potential human health risks posed by five heavy metals (Zn, Pb, Cu, Cd, and Cr) found in seven most consumable fish species (Cirrhinus mrigala, Cirrhinus reba, Catla catla, Lebio rohita, Crossocheilus latius, Clupisoma garua, and Mystus tengara) collected from local markets of Varanasi, Allahabad, Mirzapur, and Kanpur of Uttar Pradesh, India. The Cu concentration was found at Varanasi (4.58 mg/l), Allahabad (2.54 mg/l), and Mirzapur (2.54 mg/l). Pb was recorded 0.54, 0.62, 0.85, and 0.24 mg/l at Kanpur, Allahabad, Mirzapur, and Varanasi, respectively. The Cd concentration was recorded 0.54, 0.68, 0.78, and 0.85 mg/l at Kanpur, Allahabad, Mirzapur, and Varanasi, respectively. The Cr, Cd, and Pb concentrations in the river water were observed over the prescribed safe limits at all sampling sites, while Cu concentration was higher than the standards at all sites except Kanpur. However, Zn was observed under the permissible limits (15 mg/l) at all sampling sites. In case of fish tissues, WHO reported the concentration of Pb, Cd, and Cr higher than the prescribed safe limits. The results determined that the highest heavy metals accumulation was found settled in the liver of all selected fish species. Zn ranked the highest quantity, which was found in fish tissues with the concentration of 32.41 ± 2.55 μg/g in the gill of C. catla and 4.77 ± 0.34 μg/g in the gill C. Reba. The metals followed the magnitude order of Zn > Pb > Cu > Cd > Cr in selected fish tissues.
  • 机译 多壁碳纳米管暴露后,与人微血管内皮细胞共培养的人小气道上皮细胞中的差异基因调控
    摘要:Concurrent with rising production of carbon-based engineered nanomaterials is a potential increase in respiratory and cardiovascular diseases due to exposure to nanomaterials in the workplace atmosphere. While single-cell models of pulmonary exposure are often used to determine the potential toxicity of nanomaterials in vitro, previous studies have shown that coculture cell models better represent the cellular response and crosstalk that occurs in vivo. This study identified differential gene regulation in human small airway epithelial cells (SAECs) grown either in monoculture or in coculture with human microvascular endothelial cells following exposure of the SAECs to multiwalled carbon nanotubes (MWCNTs). SAEC genes that either changed their regulation direction from upregulated in monoculture to downregulated in coculture (or vice versa) or had a more than a two-fold changed in the same regulation direction were identified. Genes that changed regulation direction were most often involved in the processes of cellular growth and proliferation and cellular immune response and inflammation. Genes that had a more than a two-fold change in regulation in the same direction were most often involved in the inflammatory response. The direction and fold-change of this differential gene regulation suggests that toxicity testing in monoculture may exaggerate cellular responses to MWCNTs, and coculture of cells may provide a more in-depth assessment of toxicological responses.
  • 机译 南非西北省冬季和夏季生姜中黄曲霉毒素的比较研究
    摘要:The presence of mycotoxins in staple food can have adverse effect that result in ill health and associated socio-economic losses. Mycotoxins are naturally occurring toxins produced by certain fungi and can be found in staple food plants such as ginger. Ginger is a renowned medicinal plant that is extensively used for cooking and healing. However, this medicinal plant is with little information about its possible mycotoxins contamination. This study determined the occurrence and prevalence of Aflatoxin B1, B2, G1 and G2 and Ochratoxin A contamination in raw ginger sold around Mahikeng, North West Province, South Africa. Samples were collected purposively from various retailers over winter and summer. The analytical procedure optimized was based on immunoaffinity column cleanup (IAC), followed by High performance liquid chromatography with fluorescence (HPLC-FLC) detection. ELISA was also used for mycotoxin screening. On HPLC, the limits of detection and quantification for the four Aflatoxins were 3.9 × 10−7-1.4 × 10 -3 and 1.3 × 10-6 - 4.7 × 10-3 for samples collected in winter, and 3.7 × 10−7- 1.4 × 10-3, LOQ 1.2 × 10-6 – 4.6 × 10-3 for the summer samples. The average recoveries at three spiking levels ranged from 62 to 91% for the summer samples and 70–93% for those collected in winter. A linearity was observed for the analytes whose correlation coefficients were within the range of 0.9995 and 1.000 for the winter samples and 0.9995 and 1.000 for those collected in summer. The results showed that the contamination levels, especially for samples collected in summer were greater than the legally permissible limits. The t-test analysis shows that the mean and standard deviation of the four types of Aflatoxins considered were higher in summer than in winter. The findings of the study indicated that ginger, as for all agricultural commodities, are prone to mycotoxin contamination.
  • 机译 洋地黄的甲醇叶提取物馏分对雄性Wistar大鼠生殖的安全性影响
    摘要:Keywords: Reproductive toxicity, Serum testosterone, Sperm parameters, Testes

    Abstract

    This study evaluates the reproductive toxicity of ethyl acetate and butanolic fractions from crude methanolic leaf extract of Ocimum gratissimum in male Wistar rats. Acute toxicity was assessed to determine the safety dose, Sub-chronic reproductive toxicity studies were carried out by administering daily 25, 100 and 400 mg/kg body weight doses of the fractions to respective group of animals and 1 ml of normal saline daily for the control group for 28 days. Blood, epididymis and testes were harvested for reproductive hormones, sperm parameters, and histopathologic analysis respectively. There was significant (P < 0.05) increase in serum levels of testosterone, body-weight gain, sperm count. There was also apparent increase in mean-testicular weight and preservation of testicular histology with increase spermatogenesis in both the ethyl acetate and butanolic fraction treated groups compared with control. Serum levels of luteinising hormone was however significantly (P < 0.05) decrease across the groups compared to control. These effects were more pronounced in the butanolic fraction group compared to the ethyl acetate treated group. Sperm motility was also significantly (P < 0.05) higher in the ethyl acetate treated group compared to control. Findings from this studies demonstrate that these fractions were non-toxic at the tested doses with regards to male reproduction but, rather, exhibited fertility enhancing effects which was better with the butanolic fraction. Our findings also shows that the ethyl acetate fraction may be safer than the butanolic fraction.
  • 机译 没食子酸对紫杉醇诱发的小鼠神经性疼痛的改善作用
    摘要:Keywords: Allodynia, Gallic acid, Hyperalgesia, Myeloperoxidase, Paclitaxel, Sciatic nerve

    Abstract

    The present study has been investigated the role of gallic acid (GA) in paclitaxel-induced neuropathic pain. The neuropathic pain was developed with paclitaxel (PT: 2 mg/kg, i.p.) administration in mice. GA (20 and 40 mg/kg) and pregabalin (PreG: 5 mg/kg) were administered intravenously for 10 consecutive days. The neuralgic sensations were investigated by assessing various pain tests like acetone drop, pinprick, plantar, tail flick, and tail pinch test. Mice pain behaviors were evaluated on 0, 4th, 8th, 12th and 16th days. The levels of sciatic nerve thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide anion, calcium, myeloperoxidase (MPO), and TNF-α were estimated. Treatment of GA and PreG attenuate PT induced thermal &mechanical hyperalgesia and allodynia symptoms along with the reduction of TBARS, total calcium, TNF-α, superoxide anion, and MPO activity levels; and decreased GSH level. Therefore, it has been concluded that GA has potential neuroprotective actions against PT induced neuropathic pain due to it's anti-oxidant, anti-inflammation and regulation of intracellular calcium ion concentration.

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