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  • 机译 藤黄酸通过阻断脂多糖与髓样分化因子2结合来破坏Toll样受体4的激活。
    摘要:Our body’s immune system has defense mechanisms against pathogens such as viruses and bacteria. Immune responses are primarily initiated by the activation of toll-like receptors (TLRs). In particular, TLR4 is well-characterized and is known to be activated by gram-negative bacteria and tissue damage signals. TLR4 requires myeloid differentiation factor 2 (MD2) as a co-receptor to recognize its ligand, lipopolysaccharides (LPS), which is an extracellular membrane component of gram-negative bacteria. Gambogic acid is a xanthonoid isolated from brownish or orange resin extracted from Garcinia hanburyi. Its primary effect is tumor suppression. Since inflammatory responses are related to the development of cancer, we hypothesized that gambogic acid may regulate TLR4 activation. Our results demonstrated that gambogic acid decreased the expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-12, and IL-1β) in both mRNA and protein levels in bone marrow-derived primary macrophages after stimulation with LPS. Gambogic acid did not inhibit the activation of Interferon regulatory factor 3 (IRF3) induced by TBK1 overexpression in a luciferase reporter gene assay using IFN-β-PRD III-I-luc. An in vitro kinase assay using recombinant TBK1 revealed that gambogic acid did not directly inhibit TBK1 kinase activity, and instead suppressed the binding of LPS to MD2, as determined by an in vitro binding assay and confocal microscopy analysis. Together, our results demonstrate that gambogic acid disrupts LPS interaction with the TLR4/MD2 complex, the novel mechanism by which it suppresses TLR4 activation.
  • 机译 Hfe功能的丧失逆转了小鼠嗅觉锰暴露引起的识别记忆受损。
    摘要:Excessive manganese (Mn) in the brain promotes a variety of abnormal behaviors, including memory deficits, decreased motor skills and psychotic behavior resembling Parkinson’s disease. Hereditary hemochromatosis (HH) is a prevalent genetic iron overload disorder worldwide. Dysfunction in HFE gene is the major cause of HH. Our previous study has demonstrated that olfactory Mn uptake is altered by HFE deficiency, suggesting that loss of HFE function could alter manganese-associated neurotoxicity. To test this hypothesis, Hfe-knockout (Hfe−/−) and wild-type (Hfe+/+) mice mice were intranasally-instilled with manganese chloride (MnCl2 5 mg/kg) or water daily for 3 weeks and examined for memory function. Olfactory Mn diminished both short-term recognition and spatial memory in Hfe+/+ mice, as examined by novel object recognition task and Barnes maze test, respectively. Interestingly, Hfe−/− mice did not show impaired recognition memory caused by Mn exposure, suggesting a potential protective effect of Hfe deficiency against Mn-induced memory deficits. Since many of the neurotoxic effects of manganese are thought to result from increased oxidative stress, we quantified activities of anti-oxidant enzymes in the prefrontal cortex (PFC). Mn instillation decreased superoxide dismutase 1 (SOD1) activity in Hfe+/+ mice, but not in Hfe−/− mice. In addition, Hfe deficiency up-regulated SOD1 and glutathione peroxidase activities. These results suggest a beneficial role of Hfe deficiency in attenuating Mn-induced oxidative stress in the PFC. Furthermore, Mn exposure reduced nicotinic acetylcholine receptor levels in the PFC, indicating that blunted acetylcholine signaling could contribute to impaired memory associated with intranasal manganese. Together, our model suggests that disrupted cholinergic system in the brain is involved in airborne Mn-induced memory deficits and loss of HFE function could in part prevent memory loss via a potential up-regulation of anti-oxidant enzymes in the PFC.
  • 机译 甲苯代谢中的族裔差异:暴露于甲苯的韩国工人与外国工人的比较
    摘要:The objectives of this study were to investigate the individual characteristics, lifestyle habits, exposure levels, and genetic diversity of xenobiotic-metabolizing enzymes involved in toluene metabolism in Korean and foreign workers exposed to toluene at a manufacturing plant. This study was conducted to determine the effects of culture or ethnicity on toluene metabolism. The results showed that blood and urinary toluene concentrations were dependent on the level of exposure to toluene. We analyzed the correlation between toluene metabolism and genetic diversity in glutathione S-transferase (GST) (M1), GSTT1, and cytochrome p-450 (CYP) 2E1*5 as well as lifestyle habits (smoking, drinking, and exercise habits). The results revealed significant correlations between toluene metabolism and GSTM1 and GSTT1 genetic diversity, as well as smoking and exercise.
  • 机译 超滤法制备的无PLA2的蜂毒的改良治疗谱
    摘要:Bee venom (BV) has long been used in traditional Eastern and Western medicine for chronic inflammation, pain and skin therapy. Human exposure to BV, however, often causes unwanted adverse effects and is even fatal in some cases. Phospholipase A2 (PLA2) of BV is now suspected to play a key role in these adverse effects. We investigated the potential use of PLA2-free bee venom (PBV) as a replacement for BV in cosmetic products. PBV prepared by molecular weight cut-off ultrafiltration exhibits a superior profile in comparison with regular BV, by inhibiting elastase activity and suppressing the induction of nitric oxide (NO) and metalloproteinase-9 (MMP-9), while retaining the effects of cell proliferation and protection against ultraviolet B (UVB)-induced damage in human dermal fibroblast cells. PBV thus appears to be more promising than BV as a cosmetic ingredient with a reduced potential for adverse reactions in the recipient.
  • 机译 草本卷烟主流烟气安全性评价
    摘要:Owing to the increase in price of cigarettes in Korea, herbal cigarettes have received increasing attention as a non-smoking aid; however, its safety has hardly been studied. We analyzed some of the toxic components in the mainstream smoke of herbal cigarettes, performed a mutagenicity test on smoke condensates for safety assessment, and compared the results with the corresponding values of a general cigarette with the same tar content. Herbal cigarette “A” was smoked using automatic smoking machine under ISO conditions in a manner similar to general cigarette “T”. The tar content measured was higher than that inscribed on the outside of a package. The mainstream smoke of herbal cigarette “A” did not contain detectable levels of tobacco-specific nitrosamines and nicotine. Carbon monoxide and benzo(α)pyrene contents in herbal cigarette “A” were higher than those in the general cigarette “T”. The phenolic contents such as hydroquinone, resorcinol, and catechol in herbal cigarette “A” were higher than those in the general cigarette “T”, but cresol contents in herbal cigarette “A” were lower than those in the general cigarette “T”. The content of aromatic amines such as 4-aminobiphenyl in herbal cigarette “A” was higher than that in the general cigarette “T”; however, this difference was not statistically significant. On the other hand, 1-aminonaphthalene, 2-aminonaphthalene, and 3-aminobiphenyl contents in herbal cigarette “A” were lower than those in the general cigarette “T”. The smoke condensates of herbal cigarette “A” exhibited a higher mutagenic potential than the condensates from the general cigarette “T” at the same concentration. We concluded that the mainstream smoke of herbal cigarette contains some toxic components, the smoke condensates of herbal cigarettes are mutagenic similar to general cigarette because of combustion products, and that the evaluation of the chemical and biological safety of all types of herbal cigarettes available on the market.
  • 机译 亚急性暴露于眼刺激性化学品后评估家兔的全身毒性
    摘要:Eye is a highly vascularised organ. There are chances that a foreign substance can enter the systemic circulation through the eye and cause oxidative stress and evoke immune response. Here the eyes of rabbits were exposed, for a period of 7 days, to 5 known ocular irritants: Cetyl pyridinium chloride (CPC), sodium salicylate (SS), imidazole (IMI), acetaminophen (ACT) and nicotinamide (NIC). The eyes were scored according to the draize scoring. Blood collected from the treated rabbit were analyzed for haematological and biochemical parameters. After sacrifice, histological analysis of the eye and analysis of pro-inflammatory biomarkers (IL-1α, IL-1β, IL-8 and TNF-α) in the cornea using ELISA was carried out. Spleen was collected and the proliferation capacities of spleenocytes were analyzed. Liver and brain were collected and assessed for oxidative stress. The eye irritation potential of the chemicals was evident from the redness and swelling of the conjunctiva and cornea. Histopathological analysis and ELISA assay showed signs of inflammation in the eye. However, the haematological and biochemical parameters showed no change. Spleenocyte proliferations showed only slight alterations which were not significant. Also oxidative stress in the brain and liver were negligible. In conclusion, chemicals which cause ocular irritation and inflammation did not show any systemic side-effects in the present scenario.
  • 机译 蓝色金银花浓缩液对小鼠的单次口服剂量毒性试验
    摘要:The objective of this study was to obtain single oral dose toxicity information for concentrated and lyophilized powder of blue honeysuckle (Lonicera caerulea L., Caprifoliaceae; BHcL) in female and male ICR mice to aid in the process of developing natural origin medicinal ingredients or foods following proximate analysis and phytochemical profile measurement. The proximate analysis revealed that BHcL had an energy value of 3.80 kcal/g and contained 0.93 g/g of carbohydrate, 0.41 g/g of sugar, 0.02 g/g of protein, and 0.20 mg/g of sodium. BHcL did not contain lipids, including saturated lipids, trans fats, or cholesterols. Further, BHcL contained 4.54% of betaine, 210.63 mg/g of total phenols, 159.30 mg/g of total flavonoids, and 133.57 mg/g of total anthocyanins. Following administration of a single oral BHcL treatment, there were no treatment-related mortalities, changes in body weight (bw) or organ weight, clinical signs, necropsy or histopathological findings up to 2,000 mg/kg bw, the limited dosage for rodents of both sexes. We concluded that BHcL is a practically non-toxic material in toxicity potency.
  • 机译 亚双孢小夜蛾幼虫冻干粉的亚慢性口服剂量毒性。
    摘要:The objective of this study was to investigate the toxicological information of freeze-dried powder from Allomyrina dichotoma (A. dichotoma) larvae as a food ingredient. The powder, suspended in distilled water, was administered once daily by oral gavage to four groups of Sprague-Dawley (SD) rats at dose levels of 0 (vehicle control), 250, 850, and 2500 mg/kg/day. After 13 wks of repeated administration, the standard toxicological parameters such as mortality, clinical signs, body weight, food consumption, ophthalmologic examination, clinical pathology, organ weights and macro/microscopic examination were applied for assessment of general toxicity. In addition, serum IgE and histamine levels were determined to evaluate allergenicity. The freeze-dried powder from A. dichotoma larvae did not produce treatmentrelated changes or findings in any toxicological parameters in either sex of any dosed groups except for slight increases in serum histamine levels at 2500 mg/kg/day. The changes were considered not to be adverse since the magnitude was minimal. In conclusion, the NOAEL (No Observed Adverse Effect Level) of the freeze-dried powder from A. dichotoma larvae was determined to be 2500 mg/kg/day or more in both sexes of SD rats and it is considered a candidate to be edible material.
  • 机译 紫草紫杉提取物在狗中的单剂量和重复剂量口服毒性研究
    摘要:Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day.
  • 机译 毒理学相关金属对人类表观遗传调控的影响
    摘要:Environmental toxicants such as toxic metals can alter epigenetic regulatory features such as DNA methylation, histone modification, and non-coding RNA expression. Heavy metals influence gene expression by epigenetic mechanisms and by directly binding to various metal response elements in the target gene promoters. Given the role of epigenetic alterations in regulating genes, there is potential for the integration of toxic metal-induced epigenetic alterations as informative factors in the risk assessment process. Here, we focus on recent advances in understanding epigenetic changes, gene expression, and biological effects induced by toxic metals.
  • 机译 线粒体和线粒体氧化还原生物学全景
    • 作者:Aekyong Kim
    • 刊名:Toxicological Research
    • 2014年第4期
    摘要:Mitochondria dysfunction was first described in the 1960s. However, the extent and mechanisms of mitochondria dysfunction’s role in cellular physiology and pathology has only recently begun to be appreciated. To adequately evaluate mitochondria-mediated toxicity, it is not only necessary to understand mitochondria biology, but discerning mitochondrial redox biology is also essential. The latter is intricately tied to mitochondrial bioenergetics. Mitochondrial free radicals, antioxidants, and antioxidant enzymes are players in mitochondrial redox biology. This review will provide an across-the-board, albeit not in-depth, overview of mitochondria biology and mitochondrial redox biology. With accumulating knowledge on mitochondria biology and mitochondrial redox biology, we may devise experimental methods with adequate sensitivity and specificity to evaluate mitochondrial toxicity, especially in vivo in living organisms, in the near future.
  • 机译 癌症中的线粒体DNA体细胞突变
    • 作者:Aekyong Kim
    • 刊名:Toxicological Research
    • 2014年第4期
    摘要:Cancer cells are known to drastically alter cellular energy metabolism. The Warburg effect has been known for over 80 years as pertaining cancer-specific aerobic glycolysis. As underlying molecular mechanisms are elucidated so that cancer cells alter the cellular energy metabolism for their advantage, the significance of the modulation of metabolic profiles is gaining attention. Now, metabolic reprogramming is becoming an emerging hallmark of cancer. Therapeutic agents that target cancer energy metabolism are under intensive investigation, but these investigations are mostly focused on the cytosolic glycolytic processes. Although mitochondrial oxidative phosphorylation is an integral part of cellular energy metabolism, until recently, it has been regarded as an auxiliary to cytosolic glycolytic processes in cancer energy metabolism. In this review, we will discuss the importance of mitochondrial respiration in the metabolic reprogramming of cancer, in addition to discussing the justification for using mitochondrial DNA somatic mutation as metabolic determinants for cancer sensitivity in glucose limitation.
  • 机译 线粒体:肝病的治疗潜力及超越
    摘要:Mitochondrial integrity is critical for maintaining proper cellular functions. A key aspect of regulating mitochondrial homeostasis is removing damaged mitochondria through autophagy, a process called mitophagy. Autophagy dysfunction in various disease states can inactivate mitophagy and cause cell death, and defects in mitophagy are becoming increasingly recognized in a wide range of diseases from liver injuries to neurodegenerative diseases. Here we highlight our current knowledge on the mechanisms of mitophagy, and discuss how alterations in mitophagy contribute to disease pathogenesis. We also discuss mitochondrial dynamics and potential interactions between mitochondrial fusion, fission and mitophagy.
  • 机译 甲基胆碱对小鼠肝细胞的转化导致上皮-间充质转化相关的表型变化
    摘要:Environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) have been implicated in cancer development and progression. However, the effects of PAHs on carcinogenesis are still poorly understood. Here, we characterized a mouse cancer cell line BNL 1ME A. 7R.1 (1MEA) derived by transformation of non-tumorigenic liver cell line BNL CL.2 (BNL) using 3-methylcholanthrene (3MC), a carcinogenic PAH. RT-PCR and immunoblot analysis were used to determine the expression level of mRNA and proteins, respectively. To determine functionality, cell motility was assessed in vitro using a transwell migration assay. Both mRNA and protein levels of E-cadherin were significantly decreased in 1MEA cells in comparison with BNL cells. While the expression levels of mesenchymal markers and related transcription factors were enhanced in 1MEA cells, which could lead to increase in cell motility. Indeed, we found that 7-day exposure of BNL cells to 3-MC reduced the level of the adhesion molecule and epithelial marker Ecadherin and increased reciprocally the level of the mesenchymal marker vimentin in a dose-dependent manner. Taken together, these results indicate that the process of epithelial-mesenchymal transition (EMT) may be activated during premalignant transformation induced by 3-MC. A mechanism study to elucidate the relation between 3-MC exposure and EMT is underway in our laboratory.
  • 机译 铅对铁超负荷小鼠模型中重复行为和多巴胺代谢的影响
    摘要:Exposures to lead (Pb) are associated with neurological problems including psychiatric disorders and impaired learning and memory. Pb can be absorbed by iron transporters, which are up-regulated in hereditary hemochromatosis, an iron overload disorder in which increased iron deposition in various parenchymal organs promote metal-induced oxidative damage. While dysfunction in HFE (High Fe) gene is the major cause of hemochromatosis, the transport and toxicity of Pb in Hfe-related hemochromatosis are largely unknown. To elucidate the relationship between HFE gene dysfunction and Pb absorption, H67D knock-in Hfe-mutant and wild-type mice were given drinking water containing Pb 1.6 mg/ml ad libitum for 6 weeks and examined for behavioral phenotypes using the nestlet-shredding and marble-burying tests. Latency to nestlet-shredding in Pb-treated wild-type mice was prolonged compared with non-exposed wild-types (p < 0.001), whereas Pb exposure did not alter shredding latency in Hfe-mutant mice. In the marble-burying test, Hfe-mutant mice showed an increased number of marbles buried compared with wild-type mice (p = 0.002), indicating more repetitive behavior upon Hfe mutation. Importantly, Pb-exposed wild-type mice buried more marbles than non-exposed wild-types, whereas the number of marbles buried by Hfe-mutant mice did not change whether or not exposed to Pb. These results suggest that Hfe mutation could normalize Pb-induced behavioral alteration. To explore the mechanism of repetitive behavior caused by Pb, western blot analysis was conducted for proteins involved in brain dopamine metabolism. The levels of tyrosine hydroxylase and dopamine transporter increased upon Pb exposure in both genotypes, whereas Hfe-mutant mice displayed down-regulation of the dopamine transporter and dopamine D1 receptor with D2 receptor elevated. Taken together, our data support the idea that both Pb exposure and Hfe mutation increase repetitive behavior in mice and further suggest that these behavioral changes could be associated with altered dopaminergic neurotransmission, providing a therapeutic basis for psychiatric disorders caused by Pb toxicity.
  • 机译 土生白僵菌工人(一种大黄蜂)的免疫调节作用,对CFA诱导的大鼠足水肿的提取物
    摘要:To develop a composition for enhancing immunity, based on alcohol extracts of the bumblebee as an active ingredient, bumblebee ethanol extracts were evaluated for their protective effect in chronic models of inflammation, adjuvant induced rat arthritis. B. terrestris worker extract (SDIEX) and, B. hypocrita sapporoensis lava an pupa extract (SPDYBEX), significantly decreased paw edema in arthritic rats, at a dose 100 mg/kg, respectively. The cytokine levels related inflammation of COX-2, sPLA2, VEGF, and TNF-α, were decreased, compared to positive control, indomethacin (5 mg/kg). Histopathological data demonstrated decreases inflammatory activity, hind paw edema, and repaired hyaline articular cartilage in DRG over a 2 wk administration. HPLC and GC-MS analysis of SDIEX and SPDYBEX revealed the presence of cantharidin.
  • 机译 茶水提取物对无毛小鼠的抗皱作用
    摘要:Tea flavonoids and polyphenols are well known for their extraordinary antioxidant activity which is considered important for anti-aging processes in animals. This study evaluated the anti-wrinkle effects of three different kinds of tea (Camellia sinensis) water extracts (CSWEs) including green, white, and black teas using a photoaged hairless mouse model. Data showed that the CSWE-treatment greatly improved skin conditions of mice suffering from UVB-induced photoaging, based on the parameters including the skin erythema index, moisture capacity, and transepidermal water loss. In addition, the wrinkle measurement and image analysis of skin replicas indicated that CSWEs remarkably inhibited wrinkle formation. In histological examination, the CSWE-treated mice exhibited diminished epidermal thickness and increased collagen and elastic fiber content, key signatures for skin restoration. Furthermore, the reduced expression of MMP-3, a collagen-degradative enzyme, was observed in the skin of CSWE-treated animals. Interestingly, comparative data between green, white, and black tea indicated that the anti-wrinkle activity of white tea and black tea is equally greater than that of green tea. Taken together, these data clearly demonstrated that CSWEs could be used as an effective anti-wrinkle agent in photoaged animal skin, implying their extended uses in therapeutics.
  • 机译 赤uru提取物对Triton WR-1339所致高脂血症大鼠肝脏氧化应激的保护作用
    摘要:Saururus chinensis has been reported to contain compounds such as lignans, alkaloids, diterpenes, flavonoids, tannins, steroids, and lipids. Fermentation is commonly used to break down certain undesirable compounds, to induce effective microbial conversion, and to improve the potential nutraceutical values. Previous studies have reported that the fermentation process could modify naturally occurring constituents, including isoflavons, saponins, phytosterols, and phenols, and could enhance biological activities, specifically antioxidant and antimicrobial properties. The probiotic strains used for fermentation exert beneficial effects and are safe. In this study, the antioxidative effects of the Bacillus subtilis fermentation of Saururus chinensis were investigated in a rat model with Triton WR-1339-induced hyperlipidemia by comparing the measured antioxidative biological parameters of fermented Saururus chinensis extract to those of nonfermented Saururus chinensis extract. Fermentation played a more excellent role than nonfermentation in ultimately protecting the body from oxidative stress in the liver of the experimental rats with Triton WR-1339-induced hyperlipidemia.
  • 机译 大鼠尿贮藏条件对肾毒性生物标志物的影响
    摘要:Recently, there has been an increase in the use of several nephrotoxicity biomarkers in preclinical experiments. In addition, it has been indicated that the result may have been influenced by secondary factors, such as sample storage condition or storage period. In this study, we have assessed the variation in urinary nephrotoxicity biomarkers as a result of urine storage conditions and storage period of the urine. Urine was sampled from specific pathogen-free Sprague-Dawley rats (19 weeks old), which were housed individually in hanged stainless steel wire mesh cages. Urine was stored at 20℃, at 4℃, or at −70℃ after sampling. The levels of the biomarkers such as beta-2 microglobulin (B2M), cystatin-C (Cys-C), N-acetyl-β- D-glucosaminidase (NAG), micro albumin (MA), micro protein (MP) were measured at 6, 24, 48 and 144 hr after sampling. The B2M level was significantly decreased at 6, 24, 48, and 144 hr compared to 0 hr at −70℃ (p < 0.05, p < 0.01, p < 0.05, and p < 0.05, respectively) and 24 and 144 hr at 20℃ (p < 0.01, p < 0.01, respectively). The Cys-C level was significantly decreased at 144 hr compared to 0 hr at 4℃ (p < 0.01), at 20℃ (p < 0.05) and at 70℃ (p < 0.01). MP and MA levels were not different for 144 hr in all storage conditions. Taken together, B2M and Cys-C levels were modulated by storage temperature and period. For the enhancement of test accuracy, it is suggested that strict protocols be established for samples to minimize the effects of the storage conditions on the detected levels of biomarkers.
  • 机译 鱼类脑和肾脏中痕量铜的实时检测以进行医学诊断
    摘要:For the detection of trace copper to be used in medical diagnosis, a sensitive handmade carbon nanotube paste electrode (PE) was developed using voltammetry. Analytical optimized conditions were found at 0.05 V anodic peak current. In the same conditions, various common electrodes were compared using stripping voltammetry, and the PE was found to be more sharply sensitive than other common electrodes. At optimum conditions, the working ranges of 3~19 μgL−1 were obtained. The relative standard deviation of 70.0 μgL−1 was determined to be 0.117% (n = 15), and the detection limit (S/N) was found to be 0.6 μgL−1 (9.4 × 10−9 M). The results were applied in detecting copper traces in the kidney and the brain cells of fish.

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