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  • 机译 灭活的非致病性肺炎链球菌对小鼠呼吸道合胞病毒感染引起的肺炎严重程度的影响
    摘要:Abbreviations: RSV, respiratory syncytial virus; S. pneumoniae, Streptococcus pneumoniae; TiO2, titanium dioxide; IFN, interferon; BALF, bronchoalveolar lavage fluids; ISP, inactivated S. pneumoniae; PFU, plaque-forming units; PBS, phosphate-buffered saline; CFU, colony-forming units; ELISA, enzyme-linked immunosorbent assayKeywords: RSV, Streptococcus pneumonia, Pneumonia, Infiltrated cells, Non-pathogenic pneumococcal particles

    Abstract

    The severity of pneumonia in respiratory syncytial virus (RSV) infection is strongly related to host immune response and external factors such as bacteria and environmental chemicals. We investigated the effect of inactivated Streptococcus pneumoniae (ISP) as non-pathogenic particles on the severity of pneumonia in RSV-infected mice. Mice were intranasally exposed to ISP before RSV infection. On day 5 post-infection, we examined tissues, virus titer, and infiltrated cells in the lungs. The ISP did not cause significant histopathological effects in the lungs of RSV infected mice, but reduced virus titer. It also reduced the ratio of lymphocyte infiltration into the lungs and consequently the ratio of macrophage increased. In addition, we found that ISP increased RANTES level in bronchoalveolar lavage fluid from RSV-infected mice on day 1 post-infection, but reduced type I interferon levels. Thus, ISP did not exacerbate pneumonia in RSV infection, rather, it might mildly reduce the severity. We characterize and discuss the inherent activity of ISP as non-pathogenic particles inducing the role of RANTES on the pneumonia in RSV infection.
  • 机译 芳香姜(Kaempferia galanga L.)提取物具有改善和保护作用,可作为功能性食品,其风味和营养价值均得到超越
    摘要:Abbreviations: KGR, Kaempferia galanga rhizome; EPMC, Ethyl p-methoxy cinnamate; ROS, Reactive oxygen species; TMS, TetramethylsilaneKeywords: Anti-nutritional composition, HPLC-PDA analysis, Medicinal spices, Zingiberaceae

    Abstract

    Aromatic ginger (Kaempferia galanga L) is native to India and believed to be originated in Burma. Despite substantial uses in a pickle and south-east Asian cuisines, aromatic ginger is chemically less studied than white and red ginger. Multi-directional investigations have been performed to evaluate chemical composition, nutritional values, ameliorative and protective potential of aromatic ginger (Kaempferia galanga) rhizome (KGR). Macro and micro components analysis confirmed that KGR contains protein, fiber, and high amount of essential minerals (potassium, phosphorous, and magnesium) along with appreciable amounts of iron, manganese, zinc, cobalt, and nickel. The anti-proliferative potential of KGR evaluated nine human cell lines. We have evaluated the anti-proliferative potential of hydrodistillate, extract, and key compound isolated from KGR on nine human cancer cell line and also reporting the safety to normal peritoneal macrophage cells. The current study demonstrates the anticancer potential of the KGR on MDA-MB-231 and WRL-68 cells. Very likely, results can be extrapolated to an animal or human system. Ethyl p-methoxy cinnamate (EPMC) was responsible for inhibiting the proliferation action which varied in a tested cell by intracellular reactive oxygen species (ROS) production. The present study demonstrates KGR as safe and high energy value medicinal spices with chemo-preventive action, without toxic phytochemicals, and tolerable other anti-nutritional factors.
  • 机译 糖皮质激素受体依赖性的cripto-1(单眼针头)诱导抑制斑马鱼尾鳍再生
    摘要:Abbreviations: AEC, apical epithelial cap; BDP, beclomethasone dipropionate; DMSO, dimethyl sulfoxide; dpa, days post-amputation; dpf, days post-fertilization; EB, embryoid body; ECM, extracellular matrix; EMT, epithelial-to-mesenchymal transition; ERK, extracellular signal-regulated kinase; eSC, embryonic stem cell; FGF, fibroblast growth factor; GC, glucocorticoid; GR, glucocorticoid receptor; hpa, hours post-amputation; hpf, hours post-fertilization; ISH, in situ hybridization; MIAME, Minimum Information About a Microarray Experiment; mLIF, murine leukemia inhibitory factor; MO, morpholino oligonucleotide; RA, retinoic acid; SEM, standard error of the mean; TGF-β, transforming growth factor beta; qRT-PCR, quantitative reverse transcription polymerase chain reaction; zf, zebrafishKeywords: Zebrafish, Epimorphic regeneration, Beclomethasone dipropionate, Glucocorticoids, Cripto-1, One-eyed pinhead

    Abstract

    We previously used a chemical genetics approach with the larval zebrafish to identify small molecule inhibitors of tissue regeneration. This led to the discovery that glucocorticoids (GC) block early stages of tissue regeneration by the inappropriate activation of the glucocorticoid receptor (GR). We performed a microarray analysis to identify the changes in gene expression associated with beclomethasone dipropionate (BDP) exposure during epimorphic fin regeneration. Oncofetal cripto-1 showed > eight-fold increased expression in BDP-treated regenerates. We hypothesized that the mis-expression of cripto-1 was essential for BDP to block regeneration. Expression of cripto-1 was not elevated in GR morphants in the presence of BDP indicating that cripto-1 induction was GR-dependent. Partial translational suppression of Cripto-1 in the presence of BDP restored tissue regeneration. Retinoic acid exposure prevented increased cripto-1 expression and permitted regeneration in the presence of BDP. We demonstrated that BDP exposure increased cripto-1 expression in mouse embryonic stem cells and that regulation of cripto-1 by GCs is conserved in mammals.
  • 机译 一些埃及水果中重金属残留物的暴露评估
    摘要:Keywords: Heavy metals, Apples, Grapes, Oranges, Estimated daily intake, Tolerable daily intake

    Abstract

    Heavy metals are considered a main public health hazards, they are known to accumulate in fruits, which are heavily consumed by humans because of their unique sweet taste and potential health benefits. Therefore, the aim of this study was to determine the possible contamination levels of cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb) and nickel (Ni) in some selected fruits obtained from four Egyptian governorates and to compare the contamination levels with those of the recommended permissible limits. Results revealed that Pb and Cd were absent in all fruit samples, while Cr was only detected in grapes obtained from Cairo and Fayoum governorates and exceeded the maximum permissible limit (0.10 mg kg−1). Nickel and Cu were detected in all fruit samples. Nickel was reduced more than copper after washing process of grapes especially in samples obtained from Alexandria and Giza governorates. After peeling process, Cu was extremely reduced in orange samples obtained from the following governorates in descending order Cairo, Alexandria, El-Fayoum and Giza. Estimated daily intake of heavy metals in fruit samples were found to be higher than that of the tolerable daily intake, indicating potential risk to human health. Therefore, to decrease the risk to human health, fruits must be washed well before eating to decrease heavy metal concentrations.
  • 机译 标准化的Kaempferia parviflora提取物的毒理学评估:亚慢性和致突变性研究
    摘要:Kaempferia parviflora (KP), also known as Krachai-dam in Thailand, belongs to the family Zingiberaceae and has been used traditionally to improve blood flow and treat inflammatory, allergic, and gastrointestinal disorders. The objective of this study was to investigate the safety profile of a standardized hydroalcoholic KP rhizome extract via mutagenicity and sub-chronic toxicity evaluations using in vitro and in vivo techniques. The in vitro mutagenicity of KP extract was assessed via reverse mutation tests using Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and Escherichia coli WP2 uvrA. The sub-chronic toxicity profile was evaluated after daily oral administration of KP extract to Sprague-Dawley rats for 90 days. General toxicological parameters were monitored weekly. After the treatment period, blood was collected for hematological and biochemical analyses and certain organs were removed for macroscopic and histopathological analyses.Reverse mutation tests revealed that KP extract did not induce gene mutations at any of the concentrations tested. In the sub-chronic toxicity test, a few changes were observed, including increased salivation in the animals administered high-dose KP extract (249 mg/kg body weight (bw)/day). No toxicologically relevant changes were observed in the biochemical analysis. Sub-chronic administration of KP extract increased platelet levels in animals administered low-dose KP extract (25 mg/kg bw/day). However, the hematological and biochemical parameters remained within normal physiological ranges for the animal species. No toxicological changes were observed in the macroscopic and histopathological analyses performed in this study. These results demonstrate that KP extract is not genotoxic and that 90-day oral administration of the doses tested did not result in toxicity. Therefore, KP extract has a high safety margin for daily use.
  • 机译 急性有机磷酸盐中毒中的肺血栓形成-有机磷毒性中血栓前预处理的病例报道和文献综述
    摘要:ObjectiveAcute organophosphate (OP) poisonings are presented with acetylcholine-receptor overstimulation. There have been a few case reports of thrombotic complications in acute OP poisonings, as well as prolonged thrombosis preconditions in patients who survived this type of intoxications. The paper presents a case with pulmonary thrombosis (PT) that develops in the subacute phase of intentional acute OP poisoning, treated only with atropine, as well as a literature overview of OP-induced prothrombotic toxicity.
  • 机译 岩藻依聚糖对HepG2癌细胞的增殖,细胞周期进程,遗传损伤和凋亡细胞死亡的抗癌作用
    摘要:Keywords: Fucoidan, HepG2 cells, Cell cycle, Genetic damage, Apoptosis, Seaweed, Natural biopolymer

    Abstract

    The centre of the attraction of this article is inevitably associated with fucoidan polymers in terms of brown seaweed such as Turbinaria conoides. Fucoidan is a sulphated polysaccharide constitutes fucose as a major principle sugar along with other monosugars such as glucuronic acid, xylose and galactose. The core value of fucoidan in terms of various cancer types were substantially exhibited through targeting the key apoptotic molecules and subsequently mitigate the toxicity that are essentially included in the chemotherapeutic agents and radiation. The pragmatic investigation about the anti-cancer effect of fucoidan in a hepatoblastoma-derived (HepG2) cell line was thoroughly analyzed by the typical techniques such as cell viability, colony formation, cell migration, cell cycle progression, genetic damage and apoptosis along with their nuclear morphology and mitochondrial membrane potential. Following the analyzes, the cell viability was precisely evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. And hence, cell cycle arrest and apoptosis was appropriately examined staining with propidium iodide (PI) and annexin V-fluorescein isothiocyante (FITC) by flowcytometer, respectively. Primarily, genetic damage by fucoidan in HepG2 cell line was evaluated by following Trevigen’s comet assay kit. In addition, alteration of nuclear content and mitochondrial membrane potential were also detected with Hoechst and mitochondrial membrane potential dye (JC-1: 5,5′6,6′-tetrachloro-1,1′3,3′tetraethylbenzimi-dazolycarbocyanine iodide) by fluorescence microscopy, respectively. The results of the present study showed that cells constituted with fucoidan/quercetin standard at 50, 100 and 200 μg/ml exhibited cell viability about 71, 60 & 40/80, 65 & 45%, respectively. The above recorded effect of fucoidan was a concentration-dependant inhibition on the basis of decline in colony forming and cell migration potential of HepG2 cancer cells. Compared with untreated control, fucoidan consituted cells were significantly (p ≤  0.05) accumulated proliferative cells in the G0/G1 phase of the cell cycle in a concentration dependent manner. Increasing concentration of fucoidan (50,100 and 200 μg/ml) was remarkably enhanced the DNA damage which reflected through tail moment value of 3.8, 7.1 & 12.8 folds with respect to the untreated control. Fucoidan induced total apoptotic cells were observed ∼20–40% at 50–200 μg/ml concentrations. The apoptotic cell formation effected by change in the nuclear content and mitochondrial membrane potential was confirmed in HepG2 cancer cells under fluorescence microscopy. It was eventually concluded that the fucoidan display promising anti-cancer activity against HepG2 cancer cells by promoting the inhibition of cell proliferation, migration and cell arrest on concentration dependent-manner that was well correlated with genetic damage and apoptosis.
  • 机译 遗传多态性决定农药毒性:最新进展
    摘要:Keywords: Pesticides, Carcinogens, Genetic polymorphisms, Gene-environment interactions, Occupational health

    Abstract

    Occupational and environmental exposure to pesticides may induce harmful effects on human health by promoting the development of a wide range of disorders. Some of the most recently hypothesized mechanisms are oxidative stress and epigenetic modifications, however biological effects seem to be modulated mainly by the occurrence of genetic polymorphisms. The susceptibility to exposure can be evaluated by studying the most common polymorphisms of genes involved in the metabolism of organophosphorus compounds (cytochrome P450, glutathione transferase, acetyltransferases or paraoxonase 1). The aim of this article is to review recent literature data concerning the influence of genetic polymorphisms on pesticides-induced oxidative damage.
  • 机译 停药后双氯芬酸的生殖毒性作用增强:褪黑激素的治疗​​作用研究
    摘要:Although there are several reports on the toxic actions of sodium diclofenac (DF), there is dearth information on its effect on the male reproductive system. Therefore, the study investigated the effects of DF and melatonin in male rats. Twenty rats were used in this study, which lasted for 6 weeks. The control group (vehicle treated) received normal saline (0.1 ml/day, p.o.). In the experimental groups, DF was administered during the first (group 2) and last (group 3) three weeks of the study. However, in group 4, melatonin was administered for 3 weeks, after 3 weeks of treatment with DF. DF and melatonin were administered at 1 and 10 mg/kg b.w./day (p.o.) respectively. The results showed that unlike melatonin, DF had no effect on gonadotrophins; however, it caused significant decreases in GNRH and testosterone, but a significant increase in prolactin. Melatonin attenuated the pro-antioxidant and pro-inflammatory effects of DF, which caused significant decreases in SOD, TAC, CAT, but significant elevations in LDH, MDA, uric acid and CRP. Moreover, the hormone reversed the adverse effect of DF on sperm count, sperm motility and sperm morphology. There were slight evidence of the precipitation of imbalance in lipid metabolism by DF and the antidyslipidaemic action of melatonin. Compared to DF, DF recovery showed more adverse effects on prolactin, testosterone, LDH, MDA, UA, CRP, semen parameters (except sperm motility), TC, LDL-c, HDL-c and phospholipid. The histological results agreed with the biochemical assays. In conclusion, the reproductive toxicity effects of DF seem to escalate after withdrawal; however, these effects could be attenuated by treatment with melatonin.
  • 机译 没食子酸能从双酚A诱导的氧化应激介导的损伤中离体保护大鼠肝线粒体
    摘要:Humans are often exposed to bisphenol A (BPA), the monomer of polycarbonate plastics and epoxy resins, through BPA contaminated drinking water, beverages and foods, packaged in polycarbonate plastic bottles and cans coated with epoxy resins due to leaching. Several research groups have reported that BPA may cause damage of mitochondria in liver, kidney, heart and brain cells by inducing oxidative stress. The antioxidant efficacy of gallic acid (GA), a polyphenol compound obtained from plants, against different toxicants induced oxidative stress has been well established. The aim of the present study was to examine the protective efficacy of GA against BPA induced oxidative damages of the rat liver mitochondria ex vivo. In our study, we have found a significant decrease in the intactness of mitochondria; a significant increase (P ≤ 0.001) in the levels of lipid peroxidation end product (i.e. malondialdehyde) and protein carbonylation product; and also a significant decrease (P ≤ 0.001) in the reduced glutathione content; when mitochondria were incubated with BPA (160 μM/ml) only. These results indicate that BPA probably causes damage to the cellular macromolecules through oxidative stress. We have observed significant counteractions (P ≤ 0.001) against BPA induced alterations in mitochondrial intactness, lipid peroxidation and protein carbonylation products formation and reduced glutathione content when mitochondria were incubated with BPA and GA (20 μg/ml/ 40 μg/ml/ 80 μg/ml) in combination in a dose-dependent manner. Gallic acid also showed significant restorations (P ≤ 0.001) of the activities of antioxidant enzymes, Krebs cycle enzymes, respiratory chain enzymes and thiolase when mitochondria were incubated with BPA and dosage of GA (20 μg/ml/ 40 μg/ml/ 80 μg/ml) in combination compared to BPA incubated mitochondria. Furthermore, GA significantly (P ≤ 0.001) counteracted the BPA induced decrease in tryptophan and NADH auto-fluroscence levels in mitochondria. This result suggests that GA protects the mitochondria probably by reducing the oxidative stress. Besides, GA protects the mitochondrial surface from BPA induced oxidative damages as viewed under the scanning electron microscope. Considering all the results, it can be concluded that GA shows potent efficacy in protecting the rat liver mitochondria ex vivo from BPA induced oxidative stress mediated damages.
  • 机译 聚苯乙烯和顺马来酸酐的纳米颗粒衍生物和酸性樱桃岩的合成,用于去除水溶液中的镍离子
    摘要:In this study, Prunus Cerasus Rock (PCR) and Poly (Styrene – co- Maleic Anhydride) modified with Melamine-Oxalic acid (SMA-MO) were used to prepare a cheap adsorbent through chemical modification. The maximum removal was observed at pH = 6.0 and adsorbent dose 1.5 g/L for initial Nickel -ions concentration 30 mg/L. Study of temperature effect proved that the process is endothermic. Langmuir and Freundlich isotherm models were used for equilibrium adsorption data. Langmuir isotherm proved to be a better fit. Pseudo first order and pseudo second order kinetic models were applied to analyze the kinetic mechanism of adsorption.
  • 机译 长期毒死exposure暴露对大鼠运动和慢,快抽搐骨骼肌收缩力的影响
    摘要:AimInvestigate the effect of dietary exposure to chlorpyrifos on locomotion and contraction of soleus andextensor digitorum longus (edl) involved in locomotion. Methods: Rats were fed diets containing 1 or 5 mg kg−1 of chlorpyrifos for six weeks. Locomotion has been assessed weekly using beam walking and beam balance tests. Soleus and edl were removed to study contractile properties, myofibrillar protein content and myosin heavy chain isoforms.
  • 机译 金角莓果对大鼠致癌前黄曲霉毒素的保护作用
    摘要:Keywords: Aflatoxins, Biochemical parameters, Cape-golden berry, Carcinogenic impacts, Liver tissues, Corrective action

    Abstract

    Aflatoxins are harmful compounds that induced carcinogenic impacts on tissues. It could generate oxidative stress causing cells damage. Bioactive substances from natural plants could avoid mycotoxins’ bad impacts. Cape-goldenberry (CGB), a source of active substances, was vacuum-dried at 30 °C then milled. Fresh and dried CGB-powder properties were estimated. Animal experiment was designed using six rat-groups to evaluate CBG effect to reduce harmful effect of aflatoxins. Rats treated groups were orally administrated by aflatoxins (AFs) with or without CGB in diets. Blood parameters, liver and kidney functions, serum lipids, and liver histological changes were estimated. The CGB powder showed several time doubles of phenolics, flavonoids, and antioxidants than fresh fruits. Diet supplementation by CGB of AFs-treated rats showed enhancement in final weight, food efficiency, and weight gain compared to AFs treatment only. Also, liver and kidney functions, liver enzymes, iron level, tumors indicator, and serum lipids of AFs- rats. Moreover, total protein, albumin, and globulin reduction by AFs have been improved by CGB presence in diets. Histopathological studies for AFs-rats liver showed dilated blood sinusoids with aggregation of inflammatory, Kupffer cell hyperplasia, degenerated hepatocytes, and apoptotic cells. However, in AFs-rat groups fed CGB in diets, liver hepatocytes appeared to be almost normal similar to the control. Results pointed out that CGB recorded a corrective action for aflatoxin B1 and G1 toxicity. This was recorded for the blood and serum parameters, and liver enzymes. This CGB action avoiding AFs-toxicity was more clearly declared in the liver tissues.
  • 机译 花椰菜Pinia cauliflora(Mart。)Kausel对家兔的药理安全性
    摘要:Abbreviations: ABG, Arterial blood gas; ANOVA, One-way analysis of variance; ASE, Accelerated solvent extraction; BB, Buffer Base; BE, Base Excess; BEecf, Base excess in the extracellular fluid compartment; Ca++, Calcium; cHCO3, Bicarbonate concentration; Cl, Chloride; CNS, Central nervous system; ctCO2 (B), Concentration of total carbon dioxide of whole blood; ctCO2 (P), Concentration of total carbon dioxide in plasma; ctO2, Concentration of total oxygen; DBP, Diastolic blood pressure; ECG, Electrocardiography; EEPC, Ethanol extract of Plinia cauliflora; GAE, Gallic acid equivalent; H+, Hydrogen ion dissociated; Hct, Hematocrit; HHb, Deoxyhemoglobin; K+, Potassium; LA, Left arm; LC-DAD-MS, Liquid chromatography coupled to a diode array detector and mass spectrometer; LL, Left leg; MAP, Mean arterial pressure; Na+, Sodium; Na₂CO₃, Sodium carbonate; O2Hb, Oxyhemoglobin; P50, Half of the maximum hemoglobin saturation; PCO2, Partial pressure of carbon dioxide; pH, Potential of hydrogen; PO2, Partial pressure of oxygen; RA, Right arm; RL, Right leg; S.E.M, Standard error of the mean; SBP, Systolic blood pressure; SO2, Level of hemoglobin-saturation by oxygen; tHb, Hemoglobin; UFLC, Ultra fast liquid chromatographKeywords: Cardiovascular, Irwin test, Myrtaceae, Respiratory, Toxicology

    Abstract

    Fruit peels of Plinia cauliflora (Mart.) Kausel are widely used in Brazilian traditional medicine, but no studies have proved the safety of its pharmacological effects on the respiratory, cardiovascular, and central nervous systems. The present study assessed the safety pharmacology of P. cauliflora in New Zealand rabbits. First, an ethanol extract (EEPC) was selected for the pharmacological experiments and chemical characterization. Then, different groups of rabbits were orally treated with EEPC (200 and 2000 mg/kg) or vehicle. Acute behavioral and physiological alterations in the modified Irwin test, respiratory rate, arterial blood gas, and various cardiovascular parameters (i.e., heart rate, blood pressure, and electrocardiography) were evaluated. The main secondary metabolites that were identified in EEPC were ellagic acid, gallic acid, O-deoxyhexosyl quercetin, and the anthocyanin O-hexosyl cyanidin. No significant behavioral or physiological changes were observed in any of the groups. None of the doses of EEPC affected respiratory rate or arterial blood gas, with no changes on blood pressure or electrocardiographic parameters. The present study showed that EEPC did not cause any significant changes in respiratory, cardiovascular, or central nervous system function. These data provide scientific evidence of the effects of this species and important safety data for its clinical use.
  • 机译 埃及马齿Extract提取物对实验性功能性和组织病理学改变的大鼠的镉毒性的肝肾保护作用
    摘要:Keywords: Cadmium, Chemistry, Histopathology, Kidney, Liver, P. oleracea, Rat

    Abstract

    The study was designed to clarify the hapato-nephroprotective effects of purslane ethanolic extract (PEE) against cadmium toxicity. Cadmium (Cd) is a toxic heavy metal. Cd occurs as environmental and food/ feed contamination causing public and animals health hazards. Liver and kidney are the main target organs for acute and chronic cadmium toxicity. Portulaca oleracea is rich in several vitamins, minerals, antioxidant components, and omega-3 fatty acids mainly α-linolenic acid and eicosapentaenoic acid. Results showed significant elevation of the liver and kidney functions, lipid profile and lipid peroxidation. In contrast to the antioxidants enzymatic were greatly decreased. The hepatic and renal tissues showed severe degeneration and necrosis accompanied by severe congestion and multifocal hemorrhages in Cd intoxicated rats. All parameters and tissues showed no changes in rates-treated with both Cd and purslane extract as compared with the control rats. The administration of PEE provided a significantly protection against Cd-induced hepato-nephrotoxicity.
  • 机译 为单一化学物质和化学混合物的风险特征提出新方法的建议:与源有关的危险商(HQS)和危险指数(HIS)以及逆境特定的危险指数(HIA)
    摘要:A hazard quotient (HQ) for a single chemical and the hazard index (HI) for a mixture of chemicals were first described as approaches for risk characterisation by the EPA. HQ is defined as the ratio of exposure to an appropriate reference dose such as the ADI. HI is the sum of the HQs of the chemicals in a mixture. HQ and HI have been used to characterise risk after various exposure scenarios. However, both approaches have a significant limitation in the way they are used. The accurate use of HQ or HI requires estimation of aggregate exposure, that is, exposure to a given chemical(s) from all possible relevant sources. In many studies, risk is assessed assuming exposure from a specific source such as, consumption of water or a specific food item, in which chemical(s) concentration(s) have been measured. In this case the classic HQ/HI approach can result in significant underestimation of risk. For this purpose, we developed an alternative approach, named as Source Related HQ (HQs) where HQS is the ratio of the exposure from the specific source of interest to the respected reference values. According to our approach the HQS, before being compared to the reference dose, should be adjusted by a correction factor, in order to simulate aggregated exposure. A correction factor can be calculated based on the permitted exposure contribution from the specific source to the permitted aggregated exposure. Another important limitation specific to the HI approach is the use of chemical specific ADIs that do not correspond to the same critical effect. In this study, we present an analysis based on the individual critical effects, in order to derive the critical effect and an adversity specific Hazard Index (HIA) and risk characterisation for the whole mixture.
  • 机译 鹰嘴豆素介导的自噬激活在体内和体外对鱼藤酮诱导的神经毒性具有保护作用
    摘要:Rotenone (ROT) is an environmental neurotoxin which has been demonstrated to cause characteristic loss of dopamine (DA) neurons in Parkinson’s disease (PD). Icariin (ICA) is a flavonoid glucoside isolated from Herba Epimedii that has been shown to display neuroprotective functions. The present study evaluated protective effects of ICA on ROT-induced neurotoxicity and determined the modulation of ICA on the regulation of autophagy in vivo and in vitro. Rats were treated with ROT (1.0 mg/kg/day) with a co-administration of ICA (15 or 30 mg/kg/day) for 5 weeks. Immunohistochemical analysis showed a significant loss in DA neurons in the substantia nigra (SN) of rats treated with ROT, accompanied by an increase in the accumulation of α-synuclein and a compromised mitochondrial respiration. However, co-administration of ICA potently ameliorated the ROT-induced neuronal cell injury and improved mitochondrial function and decreased the accumulation of α-synuclein. ROT treatment resulted in a decrease in the protein expression of LC3-II and Beclin-1, and an increase in the protein level of P62, and upregulated the activation of mammalian target of rapamycin (mTOR), whereas ICA significantly reversed these aberrant changes caused by ROT. Furthermore, the neuroprotective effect of ICA was further verified in PC12 cells. Cells treated with ROT displayed an increased cytotoxicity and a decreased oxygen consumption which were rescued by the presence of ICA. Furthermore, ROT decreased the protein expression level of LC3-II, enhanced Beclin-1 expression, and activated phosphorylation of mTOR, whereas ICA markedly reversed this dysregulation of autophagy caused by ROT in the PC12 cells. Collectively, these results suggest that ICA mediated activation of autophagic flux confers a neuroprotective action on ROT-induced neurotoxicity.
  • 机译 静脉和管饲法对雄性和雌性Hsd:Sprague Dawley SD大鼠全氟丁烷磺酸盐(PFBS),全氟己烷-1-磺酸(PFHxS)和全氟辛烷磺酸(PFOS)的毒代动力学
    摘要:Keywords: Perfluorinated alkyl acids, Perfluorinated chemicals, Rats, Toxicokinetics, PFBS, PFHxS, PFOS

    Abstract

    Perfluorinated alkyl substances (PFAS) are persistent contaminants that have been detected in the environment and in humans. With the PFAS chemical class, there are perfluorinated alkyl acids, many of which have been associated with certain toxicities. Because toxicity testing cannot feasibly be conducted for each individual PFAS, the National Toxicology Program (NTP) designed studies to compare toxicities across different subclasses of PFAS and across PFAS of different chain lengths to better understand the structure-toxicity relationship. Pharmacokinetic studies were conducted in parallel to these toxicity studies to facilitate comparisons across PFAS and to provide context for human relevance. Here, the toxicokinetic parameters of perfluorobutane sulfonate (PFBS), perfluorohexane-1-sulphonic acid (PFHxS), or perfluorooctane sulfonate (PFOS) after a single intravenous or gavage administration in male and female Hsd:Sprague-Dawley rats are reported. Concentrations of these PFAS were measured in the liver, kidney, and brain. Plasma half-life increased with longer chain length after gavage administration: PFBS- males averaged 3.3 h, females 1.3 h; PFHxS- males averaged 16.3 days, females 2.1 days; PFOS- males and females averaged ˜ 20 days. There were dose-dependent changes in clearance and systemic exposure for all administered chemicals and the direction of change was different in PFOS compared to the others. Liver:plasma ratios of PFOS were the highest followed by PFHxS and PFBS, while brain:plasma ratios were low in all three sulfonates. Sex differences in plasma half-life and tissue distribution were observed for PFBS and PFHxS, but not PFOS. These data provide a direct comparison of the kinetics of three different perfluoroalkyl sulfonic acids and allow for the contextualization of toxicity data in rats for human risk assessment of this chemical class.
  • 机译 急性和亚急性口服未成熟阿克西(Blighia sapida)水果提取物的神经毒性和肝毒性作用的评估
    摘要:Keywords: Ackee, Toxicity, Seizure, Brain, Liver, Oxidative stress

    Abstract

    Ackee (Blighia sapida) is a commonly eaten fruit that is indigenous to West Africa and Jamaica. Ackee poisoning in young children have been reported in parts of Nigeria due to consumption of the unripe fruits. This study was designed to identify potential mechanisms of acute and sub-acute toxicity of unripe B. sapida fruit extract (BSE).Acute toxic effect was investigated in mice of either sex administered BSE 2000 mg/kg. The sub-acute toxicity effects were investigated in mice of either sex that received 28 days repeated administration of BSE (100 and 500 mg/kg, p.o.). Locomotor activity and memory performance were measured as well as seizure vulnerability in PTZ-induced model. Liver enzymes were assessed in the serum. Acetylcholinesterase, oxidative stress parameters and histopathological changes were assessed in the brain and liver tissues.Signs and symptoms of toxicity such as urination, tremor, depressed locomotion and death were observed in acute toxicity test. Sub-acute dosing caused significant impairment in locomotor activity and memory performance in mice. Seizure threshold was shortened in BSE-treated compared to control mice. Brain acetylcholinesterase activity was significantly increased. Alkaline phosphatase (ALP) was significantly elevated in mice that received BSE (500 mg/kg). Furthermore, BSE caused significant increase in oxidative stress expressed in nitrite, malondialdehyde, reduced glutathione and catalase in the brain and liver tissues. Histological staining revealed neuronal damage of brain hippocampus and hepatocellular swelling and necrosis.Blighia sapida unripe fruit extract increased susceptibility to seizure and impaired locomotor and memory function. The biochemical and histopathological findings revealed potential toxicity mechanisms related to neurotoxicity and hepatotoxicity.
  • 机译 运动有益于对有机磷酸酯毒性的心脏,自主和炎症反应
    摘要:The organophosphate, diisopropyl fluorophosphate (DFP), may impair cardiovascular, autonomic and immune function while exercise training is thougt to be restorative. Experiments determined effects of wheel exercise in C57B1 male mice, testing cardiovascular and autonomic function and characterization of the immunological profile. Sedentary (S) and exercise (ET) groups were treated with corticosterone (CORT) followed by injection of DFP. This model was associated with systolic and diastolic dysfunction in the S group, measured using echocardiography (ECHO). Chronic exercise ameliorated the cardiac deficit. Autonomic balance, accessed by heart rate variability (HRV), showed increased sympathetic and decreased parasympathetic modulation in S group. Autonomic balance in ET mice was not affected by DFP. Our DFP model resulted in mild neuroinflammation seen by increased IL5, IL12 and MIP2 in brain and plasma IL6 and IL1a. DFP had a negative impact on cardiac/autonomic function and inflammatory markers, effects reduced by exercise. Data suggest a beneficial effect of exercise training on the cardiovascular and autonomic responses to DFP/CORT.

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