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  • 1.

    【2hr】Toxicological Evaluation of Phytochemical Characterized Aqueous Extract of Wild Dried Lentinus squarrosulus (Mont.) Mushroom in Rats

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    机译 野生野生香菇（山）蘑菇的植物化学特征水提取物的毒理学评价
    摘要：Lentinus squarrosulus (Mont.) is an edible wild mushroom with tough fruiting body that belongs to the family Polyporaceae. It is used in ethnomedicine for the treatment of ulcer, anaemia, cough and fever. Recent studies have demonstrated its anticancer, anti-diabetic and antioxidant properties. However, little or no information is available regarding the bioactive components and toxicological study of wild dried L. squarrosulus. Therefore, this study investigated the bioactive components of aqueous extract of boiled wild dried L. squarrosulus and its toxicological effects in rats. The extract of L. squarrosulus was subjected to GC-MS analysis. The acute toxicity test was performed by oral administration of a single dose of up to 5,000 mg/kg extract of L. squarrosulus. In subacute study, the rats were orally administered extract of L. squarrosulus at the doses of 500, 1,000 and 1,500 mg/kg body weight daily for 14 days. The haematological, lipid profile, liver and kidney function parameters were determined and the histopathology of the liver and kidney were examined. The GC-MS analysis revealed the presence of bioactive compounds; 1-tetradecene, fumaric acid, monochloride, 6-ethyloct-3-yl ester, 9-eicosene, phytol, octahydropyrrolo[1,2-a]pyrazine and 3-trifluoroacetoxypentadecane. In acute toxicity study, neither death nor toxicity sign was recorded. In the sub-acute toxicity study, significant differences (p < 0.05) were observed on creatinine, aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglycerides and high-density lipoprotein cholesterol. Whilst no significant differences (p > 0.05) were observed on packed cell volume, heamoglobin, red blood cell, white blood cell and alkaline phosphatase, in all the tested doses. No histopathological alterations were recorded. Our findings revealed that aqueous extract of L. squarrosulus may have antimicrobial, antinocieptive and antioxidant properties based on the result of GC-MS analysis. Results of the toxicity test showed no deleterious effect at the tested doses, suggesting that L. squarrosulus is safe for consumption at the tested doses.
  • 2.

    【2hr】A 90-Day Repeated Oral Dose Toxicity Study of Alismatis Rhizoma Aqueous Extract in Rats

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    机译 大鼠毛ism水提物的90天重复口服剂量毒性研究
    摘要：Alismatis rhizoma (AR), the dried rhizome of Alisma orientale (Sam.) Juzep, is a well-known, traditional medicine that is used for the various biological activities including as a diuretic, to lower cholesterol and as an anti-inflammatory agent. The present study was carried out to investigate the potential toxicity of the Alismatis rhizoma aqueous extract (ARAE) following 90-day repeated oral administration to Sprague-Dawley rats. ARAE was administered orally to male and female rats for 90 days at 0 (control), 500, 1,000 and 2,000 mg/kg/day (n = 10 for male and female rats for each dose). Additional recovery groups from the control group and high dose group were observed for a 28-day recovery period. Chromatograms of ARAE detected main compounds with four peaks. Treatment-related effects including an increase in the red blood cells, hemoglobin, hematocrit, albumin, total protein, and urine volume were observed in males of the 2,000 mg/kg/day group (p < 0.05). However, the diuretic effect of ARAE was considered, a major cause of hematological and serum biochemical changes. The oral no-observed-adverse-effect level (NOAEL) of the ARAE was > 2,000 mg/kg/day in both genders, and no target organs were identified.
  • 3.

    【2hr】Comparative In Vitro Toxicity Study of Docetaxel and Nanoxel, a Docetaxel-Loaded Micellar Formulation Using Cultured and Blood Cells

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    机译 比较多西他赛和纳诺西尔的体外毒性研究，多西他赛装载的胶束配方使用培养的和血细胞
    摘要：Nanoxel-PMTM (Nanoxel) is a docetaxel-loaded methoxy-poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA). This newly developed and marketed nanoformulation exhibits an improved pharmacokinetic profile, efficacy, and safety. Although the safety of Nanoxel to docetaxel as well as its bioequivalence must be clinically confirmed, all biological activities have not been examined in in vitro or in vivo studies. Here, the toxicity in a cultured cell system and the effects on blood cells were tested with Nanoxel and docetaxel. The in vitro cytotoxicity of Nanoxel was found to be comparable to or slightly lower than that of docetaxel depending on the concentrations tested or the cell types. Neither docetaxel nor Nanoxel induced erythrocytes hemolysis and produced reactive oxygen species up to 100 μM. However, Nanoxel was able to enhance the aggregatory response of platelets to collagen, whereas docetaxel attenuated such aggregation in a range of 50–100 μM, while thrombin-induced aggregation was not affected by either of them. Docetaxel or Nanoxel did not alter basal level of Ca2+ and 5-hydroxytryptamine-evoked Ca2+ transient in vascular smooth muscle cells. These results suggest that the mPEG-PDLLA micellar formulation alters the toxicological properties of docetaxel, and that extra cautions are needed when evaluating the safety of nanomedicine.
  • 4.

    【2hr】Subacute Oral Toxicity and Bacterial Mutagenicity Study of a Mixture of Korean Red Ginseng (Panax ginseng C.A. Meyer) and Salvia plebeia R. Br. Extracts

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    机译 韩国红参（Panax ginseng C.A. Meyer）和丹参（Salvia plebeia R. Br。）混合物的亚急性口服毒性和细菌致突变性研究。提取物
    摘要：As various populations are rapidly becoming an aging society worldwide and interest in health issues has increased, demand for functional foods including herbal products has increased markedly to maintain a healthy state which has led to safety issues about their intake as an inevitable result. The objective of this study was to identify the safety profile of a Korean red ginseng and Salvia plebeia R. Br. extract mixture (KGC-03-PS) which is a valuable ingredient that can be used as a functional food. In the present study, the subacute oral toxicity and bacterial reverse mutagenicity of KGC-03-PS were evaluated. Sprague Dawley rats were administered KGC-03-PS orally for 28 days by gavage. Daily KGC-03-PS dose concentrations were 0, 500, 1,000, or 2,000 mg/kg body weight (bw) per day. Bacterial reverse mutation test with KGC-03-PS dose levels ranging from 312.5 to 5,000 μg/plate was carried out by OECD test guideline No. 471. Five bacterial strains (Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2) were tested in the presence or absence of metabolic activation by plate incorporation method. There were no toxicological effects related with test substance in the clinical evaluation of subacute oral toxicity test including clinical signs, body weight, and food consumption. Moreover, no toxicological changes related to KGC-03-PS were observed in the hematological and serum biochemical characteristics as well as in the pathological examinations, which included organ weight measurements and in the gross- or histopathological findings. KGC-03-PS did not induce an increase in the number of revertant colonies in all bacterial strains of the bacterial reverse mutation test. The no-observed-adverse-effect level of KGC-03-PS is greater than 2,000 mg/kg bw/day, and KGC-03-PS did not induce genotoxicity related to bacterial reverse mutations under the conditions used in this study.
  • 5.

    【2hr】Acute and Repeated 28-Day Oral Dose Toxicity Studies of Thymus vulgaris L. Essential Oil in Rats

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    机译 百里香对大鼠百日草的急性和重复28天口服剂量毒性研究
    摘要：Thymus vulgaris L. is widely used as an ingredient in cooking and in herbal medicine. However, there is little information about its toxicity. The present study was performed to evaluate the acute and repeated 28-day oral dose toxicity of thyme essential oil in rats. For the acute toxicity test, two groups of three rats were used. The rats received a single dose of essential oil: 300 or 2,000 mg/kg of body weight (bw). The rats were observed individually during the first four hours, and then daily until day 14. For the toxicity test with repeated doses, four groups of 10 rats were used. Doses of 100, 250, and 500 mg/kg/day were tested for 28 days. At the end of the experiment, blood was collected and the animals were sacrificed. Histopathological examination showed that in the lungs of rats given the 2,000 mg/kg bw dose, polymorph nuclear infiltrates, hemosiderin macrophages, and interstitial space thickening were present. In the repeated dose study, all rats survived the 28-day treatment period and apparently showed no signs of toxicity. The hematological and biochemical parameters were not altered. The histopathological study of the organs showed severe changes in the lung, with the dose of 500 mg/kg/day; in the other organs, no alterations were observed or the changes were slight. The body weight was only altered in male rats given the 500 mg/kg dose. The relative weight of the organs did not show any significant changes. Our studies revealed that the essential oil of Thymus vulgaris has moderate oral toxicity according to the results of the acute test, whereas the results of the 28-day oral toxicity test suggest that the no-observed-adverse effect level (NOAEL) is greater than 250 mg/kg/day.
  • 6.

    【2hr】Subacute Toxicity of Nerium oleander Ethanolic Extract in Mice

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    机译 夹竹桃乙醇提取物对小鼠的亚急性毒性
    摘要：Nerium oleander (N. oleander) is a well-known poisonous shrub that is frequently grown in gardens and public areas and contains numerous toxic compounds. The major toxic components are the cardiac glycosides oleandrin and neriin. The aim of our study was to evaluate the toxic effects of an ethanolic N. oleander leaf extract on haematological, cardiac, inflammatory, and serum biochemical parameters, as well as histopathological changes in the heart. N. oleander extract was orally administered for 14 and 30 consecutive days at doses of 100 and 200 mg of dried extract/kg of body weight in 0.5 mL of saline. The results showed significant increases in mean corpuscular volume, white blood cell counts, platelet counts, interleukins (IL-1 and IL-6), tumour necrosis factor alpha, C reactive protein, alanine aminotransferase, lactate dehydrogenase, creatine kinase and creatine kinase MB, especially at high doses. Marked pathological changes were perceived in the heart tissue. Thus, it can be concluded that exposure to N. oleander leaf extract adversely affects the heart and liver.
  • 7.

    【2hr】Gestational Exposure to Pesticides Induces Oxidative Stress and Lipid Peroxidation in Offspring that Persist at Adult Age in an Animal Model

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    机译 在动物模型中，妊娠期接触农药会导致成年后持续存在的后代产生氧化应激和脂质过氧化。
    摘要：Pesticide exposure may induce biochemical alterations including oxidative stress and lipid peroxidation. However, in the context of developmental origin of health and disease, putative trans-generational effect of exposure to pesticides are insufficiently studied. We therefore aimed to evaluate the biochemical effect of gestational exposure to four pesticides on female Wistar rats and their offspring at adult age. We studied 30 female nulliparous Wistar rats divided into 5 equal groups. Group 1 served as the control group and received distilled water while group 2, 3, 4 and 5 received orally pesticide 1 (imidacloprid), pesticide 2 (chlorpyrifos), pesticide 3 (imidacloprid + lambda cyhalothrin) and pesticide 4 (oxamyl) respectively once daily throughout gestation at a dose equivalent to 1/10 lethal dose 50. The mothers were followed up until one month post gestation. The offspring were followed up from birth until adult age (12 weeks). In all animals at each time point we evaluated malondialdehyde (MDA), oxidative stress and liver function enzymes. There was similar variation of total body weight in all the groups during and after gestation. However, Female Wistar rats of the exposed groups had significant alterations in liver SOD (−30.8% to +64.1%), catalase (−38.8% to −85.7%) and GSH (−29.2% to −86.5%) and; kidney catalase (> 100%), GSH (> 100%). Moreover, MDA, alanine transaminase (ALT) and aspartate transaminase (AST) levels were significantly higher in pesticide exposed rats compared to the control group. Similar alterations in antioxidant enzymes, MDA and liver function enzymes were observed in offspring of treated rats evidenced at weaning and persisting until adult age. Exposure to pesticides causes oxidative stress and lipid peroxidation in exposed female Wistar rats and their offspring. The persistence in offspring at adult age suggests transgenerational adverse effects.
  • 8.

    【2hr】Comparative and Interactive Biochemical Effects of Sub-Lethal Concentrations of Cadmium and Lead on Some Tissues of the African Catfish (Clarias gariepinus)

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    机译 亚致命浓度的镉和铅对非洲Cat鱼（Clarias gariepinus）某些组织的比较和相互作用的生化作用
    摘要：Cadmium is a strong toxic heavy metal which presents in paints and liquid wastes and causes oxidative stress in fish. On the other hand, lead is widely used for different purposes, e.g. lead pipes, it targets vital organs such as liver and kidney causing biochemical alterations. The present study evaluates the effects of 60 days exposure to Cd and Pb either single or combined together in African catfish. Sixty-four fishes were divided into 3 groups and exposed to CdCl2 (7.02 mg/L) or PbCl2 (69.3 mg/L) or a combination of them along with control group. Activities of acid phosphatase (ACP), lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G-6-PDH) were estimated. Moreover, gill, liver and kidney were assayed for activities of superoxide dismutase (SOD), catalase (CAT) and levels of glutathione (GSH) and malondialdehyde (MDA). Individual exposure showed that both Cd and Pb significantly decreased LDH activity and SOD activity in the kidney. Pb significantly increased G-6-PDH activity and decreased GSH level in the gill. CAT activity in liver and kidney elevated significantly on Cd exposure while lead caused a significant depletion in the liver and significant elevation in the kidney. Both Cd and Pb significantly increased MDA levels in liver and kidney while Pb increased its level in gills. The combined exposure resulted in normalization of LDH, G-6-PDH activity, and CAT activity in liver and kidney as well as GSH level in both tissues and MDA in gill and kidney. The combination increased SOD activity and MDA level in liver and decreased SOD activity in kidney and GSH level in gills. In conclusion, the antioxidant system of African catfish was adversely affected by prolonged exposure to Cd and Pb. The combined exposure caused less damage than individual exposure and returned most parameters to those of controls.
  • 9.

    【2hr】Effect of Citrus macroptera Fruit Pulp Juice on Alteration of Caspase Pathway Rendering Anti-Proliferative Activity against Ehrlich’s Ascites Carcinoma in Mice

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    机译 柑桔果肉果汁对小鼠胱天蛋白酶途径表达抗艾氏腹水癌增殖的影响
    摘要：Citrus macroptera (Rutaceae) has long been used in folk medicine in Bangladesh. Considering the folkloric context, this study was aimed to scrutinize anti-proliferative activity of C. macroptera fruit pulp juice (CMFPJ) against Ehrlich’s ascites carcinoma (EAC). The anti-proliferative capacity of CMFPJ was investigated and confirmed primarily using MTT assay. In vivo anti-proliferative aptitude of CMFPJ was investigated with 25, 50, and 100 mg/kg/day intraperitoneal (i.p.) treatment. Anti-proliferative efficacy of CMFPJ was assessed based on EAC growth inhibition. CMFPJ inhibited EAC growth in vitro in a dose-dependent manner. And the percentages of in vivo EAC growth inhibition were 19.53, 49.2, and 68.9% at 25, 50, and 100 mg/kg CMFPJ respectively. CMFPJ significantly induced expression of apoptosis regulatory genes caspase-8, caspase-9, cytochrome-c, and caspase-3. This considerable anti-cancer activity was perhaps due to combinatorial effect of lectin, polyphenols, and flavonoids present in CMFPJ.
  • 10.

    【2hr】Cinnamomum camphora Leaves Alleviate Allergic Skin Inflammatory Responses In Vitro and In Vivo

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    机译 樟脑叶可减轻体内和体外的过敏性皮肤炎症反应
    摘要：In this study, we investigated the therapeutic potential of Cinnamomum camphora leaves on allergic skin inflammation such as atopic dermatitis. We evaluated the effects of C. camphora leaves on human adult low-calcium high-temperature keratinocytes and atopic dermatitis mice. C. camphora leaves inhibited Macrophage-derived chemokine (an inflammatory chemokine) production in interferon-γ (10 ng/mL) stimulated Human adult low-calcium high-temperature keratinocytes in a dose dependent manner. C. camphora leaves suppressed the phosphorylation of janus kinase signal transducer and activator of transcription 1. C. camphora leaves also suppressed the phosphorylation of extracellular signal-regulated kinase 1/2, a central signaling molecule in the inflammation process. These results suggest that C. camphora leaves exhibits anti-inflammatory effect via the phosphorylation of signal transducer and activator of transcription 1 and extracellular signal-regulated kinase 1/2. To study the advanced effects of C. camphora leaves on atopic dermatitis, we induced experimental atopic dermatitis in mice by applying 2,4-dinitrochlorobenzene. The group treated with C. camphora leaves (100 mg/kg) showed remarkable improvement of atopic dermatitis symptoms: reduced serum immunoglobulin E levels, smaller lymph nodes with reduced thickness and length, decreased ear edema, and reduced levels of inflammatory cell infiltration in the ears. Interestingly, the effects of C. camphora leaves on atopic dermatitis symptoms were stronger than those of hydrocort cream, a positive control. Taken together, C. camphora leaves showed alleviating effects on the inflammatory chemokine production in vitro and atopic dermatitis symptoms in vivo. These results suggest that C. camphora leaves help in the treatment of allergic inflammation such as atopic dermatitis.
  • 11.

    【2hr】In Vitro Cytotoxicity of Zinc Oxide Nanoparticles in Cultured Statens Seruminstitut Rabbit Cornea Cells

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    机译 氧化锌纳米颗粒在体外培养的Statest Seruminstitut兔角膜细胞中的细胞毒性
    摘要：The possibility of eye exposure for workers participating in manufacturing of nanoparticles or consumers using products containing nanoparticles has been reported, but toxicity studies on the eye are scarce. In this study, cytotoxicity of five nanoparticles including silver, ceria, silica, titanium and zinc were tested using Statens Seruminstitut Rabbit Cornea (SIRC) cells. When cells were treated with nanoparticles with concentrations of 1–100 μg/mL for 24 hr, zinc oxide nanoparticles showed higher toxicity to cornea cells. LC50 of zinc oxide nanoparticles was less than 25 μg/mL but those of other nanoparticles could not be calculated in this test, which means more than 100 μg/mL. Generation of reactive oxygen species was observed, and expression of apoptosis related biomarkers including Bax and Bcl-2 were changed after treatment of zinc oxide nanoparticles, while no other significant toxicity- related changes were observed in cornea cells treated with Ag, CeO2, SiO2 and TiO2 nanoparticles.
  • 12.

    【2hr】Role of G Protein-Coupled Estrogen Receptor in Cancer Progression

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    机译 G蛋白偶联的雌激素受体在癌症进展中的作用。
    • 作者：Joohee Jung
    • 刊名：Toxicological Research
    • 2019年第3期
    摘要：Cancer is the leading cause of mortality worldwide. In cancer progression, sex hormones and their receptors are thought to be major factors. Many studies have reported the effects of estrogen and estrogen receptors (ERs) in cancer development and progression. Among them, G protein-coupled estrogen receptor (GPER), a G proteincoupled receptor, has been identified as an estrogen membrane receptor unrelated to nuclear ER. The mechanism of GPER, including its biological action, function, and role, has been studied in various cancer types. In this review, we discuss the relation between GPER and estrogen or estrogen agonists/antagonists and cancer progression.
  • 13.

    【2hr】Effects of Methadone Maintenance Therapy on Thyroid Function of Adult Men

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    机译 美沙酮维持治疗对成年男性甲状腺功能的影响
    摘要：One of the major challenges in methadone maintenance therapy (MMT) for drug dependence is the physiological side effects on endocrine hormones. Because of the key role of the thyroid gland in the normal functioning of the human body and brain, this study examined the effect of MMT on thyroid function. Thyroid hormones (T3, T4, and thyroid-stimulating hormone (TSH)) were evaluated in normal and user treated with MMT who were referred to the Province Clinical & Pathology Center of Urmia, Iran. The study was conducted for three months using the Case Series method. A total of 270 samples were collected, 215 were from individuals who were not treated, whereas 55 were from men treated with methadone. Average levels of T3 and T4 in non-treated sample of men are 1.34 ± 0.02 ng/mL and 90.96 ± 1.38 ng/mL while the corresponding values for patients treated with methadone are 1.39 ± 0.04 ng/mL for T3 and 94.57 ± 2.72 ng/mL for T4. Mean TSH levels of the non-treated group and the methadone consuming group were 1.75 ± 0.08 μIU/mL and 3.17 ± 0.45 μIU/mL, respectively. These results indicate that although men treated with methadone had higher levels of T3, T4, and TSH than normal individuals, only the difference in TSH level was significant. The importance of this difference among individuals on methadone maintenance programs should be investigated in larger samples over long periods of time. Additionally, the effects of methadone treatment on women should be examined.
  • 14.

    【2hr】Alterations of Antioxidant Status and Mitochondrial Succinate Dehydrogenase Activity in the Liver of Wistar Strain Albino Rats Treated with by Ethanol Extracts of Annona senegalensis Pers (Annonaceae) Stem Bark

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    机译 塞内加尔番荔枝（Annonaceae）茎皮乙醇提取物处理Wistar株白化病大鼠肝脏抗氧化状态和线粒体琥珀酸脱氢酶活性的变化
    摘要：Numerous ethnomedicinal uses have been attributed to different parts of Annona senegalensis (ASE), including its uses as food and food additives. The present study investigated toxicological and antioxidant effects of 28 days administration of ethanol extracts of ASE stem bark to Wistar strain albino rats. Acute toxicity test was done to determine lethal dose in Wistar rats while sub-acute toxicity test was conducted on rats divided into four groups (A - control, B - 50 mg/kg, C - 100 mg/kg, D - 150 mg/kg, respectively and treated for 28 days. Oxidative stress markers in liver and kidney as well as hepatic succinate dehydrogenase activity in the mitochondrial and post mitochondrial fractions (PMF) were evaluated. The LD50 value of ASE was > 2,000 mg/kg. White blood cell counts gradually increased, but red blood cell counts and haematocrits level decreased significantly (p < 0.05) by about 50%. Liver enzymes in the serum and mitochondrial succinate dehydrogenase activity increased significantly (p < 0.05). Superoxide dismutase and catalase activities also increased in liver mitochondria and PMF while malondialdehyde (MDA) and reduced glutathione levels increased only in the PMF. Furthermore, only MDA levels increased significantly in the kidney after 28 days extract administration. Histopathological examination showed hepatic necrosis and no obvious signs of nephrotoxicity. Anona senegalensis is relatively safe, but prolonged ingestion could induce oxidative stress and impair ATP synthesis through the modulation of the activity of mitochondrial succinate dehydrogenase.
  • 15.

    【2hr】Protective Effects of Plathymenia reticulata and Connarus favosus Aqueous Extracts against Cadmium- and Mercury-Induced Toxicities

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    机译 网状疟原虫和短吻夜蛾水提取物对镉和汞诱导的毒性的保护作用
    摘要：The extracts of Plathymenia reticulata and Connarus favosus are widely used in the folk medicine. The potential protective effects of these extracts have been evaluated against cadmium in the yeast Saccharomyces cerevisiae, and against mercurial contamination in zebrafish Danio rerio. In yeast, both extracts efficiently protected the Δycf1 mutant strain exposed to cadmium chloride restoring the growth, the expression of stress-response genes and decreasing the level of oxidative stress. In zebrafish, the supplementation of methylmercury-contaminated diet with both plant extracts similarly protected fish through the suppression of the methylmercury-induced lipid peroxidation, decrease of acetylcholinesterase activity, and restoring the expression levels of stress-response genes. This study particularly demonstrates the protective potential of both aqueous extracts against methylmercury, and could represent an interesting alternative for the Amazonian fish-eating communities to cope with the impact of chronic exposure to contaminated diets.
  • 16.

    【2hr】Receptor Binding Affinities of Synthetic Cannabinoids Determined by Non-Isotopic Receptor Binding Assay

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    机译 通过非同位素受体结合测定法测定合成大麻素的受体结合亲和力
    摘要：A major predictor of the efficacy of natural or synthetic cannabinoids is their binding affinity to the cannabinoid type I receptor (CB1) in the central nervous system, as the main psychological effects of cannabinoids are achieved via binding to this receptor. Conventionally, receptor binding assays have been performed using isotopes, which are inconvenient owing to the effects of radioactivity. In the present study, the binding affinities of five cannabinoids for purified CB1 were measured using a surface plasmon resonance (SPR) technique as a putative non-isotopic receptor binding assay. Results were compared with those of a radio-isotope-labeled receptor binding assay. The representative natural cannabinoid Δ9-tetrahydrocannabinol and four synthetic cannabinoids, JWH-015, JWH-210, RCS-4, and JWH-250, were assessed using both the SPR biosensor assay and the conventional isotopic receptor binding assay. The binding affinities of the test substances to CB1 were determined to be (from highest to lowest) 9.52 × 10−13 M (JWH-210), 6.54 × 10−12 M (JWH-250), 1.56 × 10−11 M (Δ9-tetrahydrocannabinol), 2.75 × 10−11 M (RCS-4), and 6.80 ×10−11 M (JWH-015) using the non-isotopic method. Using the conventional isotopic receptor binding assay, the same order of affinities was observed. In conclusion, our results support the use of kinetic analysis via SPR in place of the isotopic receptor binding assay. To replace the receptor binding affinity assay with SPR techniques in routine assays, further studies for method validation will be needed in the future.
  • 17.

    【2hr】Inhalation of Bacterial Cellulose Nanofibrils Triggers an Inflammatory Response and Changes Lung Tissue Morphology of Mice

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    机译 吸入细菌纤维素纳米纤维会触发炎症反应并改变小鼠的肺组织形态
    摘要：In view of the growing industrial use of Bacterial cellulose (BC), and taking into account that it might become airborne and be inhaled after industrial processing, assessing its potential pulmonary toxic effects assumes high relevance. In this work, the murine model was used to assess the effects of exposure to respirable BC nanofibrils (nBC), obtained by disintegration of BC produced by Komagataeibacter hansenii. Murine bone marrow-derived macrophages (BMMΦ) were treated with different doses of nBC (0.02 and 0.2 mg/mL, respectively 1 and 10 μg of fibrils) in absence or presence of 0.2% Carboxymethyl Cellulose (nBCMC). Furthermore, mice were instilled intratracheally with nBC or nBCMC at different concentrations and at different time-points and analyzed up to 6 months after treatments. Microcrystaline Avicel-plus® CM 2159, a plant-derived cellulose, was used for comparison. Markers of cellular damage (lactate dehydrogenase release and total protein) and oxidative stress (hydrogen peroxidase, reduced glutathione, lipid peroxidation and glutathione peroxidase activity) as well presence of inflammatory cells were evaluated in brochoalveolar lavage (BAL) fluids. Histological analysis of lungs, heart and liver tissues was also performed. BAL analysis showed that exposure to nBCMC or CMC did not induce major alterations in the assessed markers of cell damage, oxidative stress or inflammatory cell numbers in BAL fluid over time, even following cumulative treatments. Avicel-plus® CM 2159 significantly increased LDH release, detected 3 months after 4 weekly administrations. However, histological results revealed a chronic inflammatory response and tissue alterations, being hypertrophy of pulmonary arteries (observed 3 months after nBCMC treatment) of particular concern. These histological alterations remained after 6 months in animals treated with nBC, possibly due to foreign body reaction and the organism’s inability to remove the fibers. Overall, despite being a safe and biocompatible biomaterial, BC-derived nanofibrils inhalation may lead to lung pathology and pose significant health risks.
  • 18.

    【2hr】Subchronic and Reproductive/Developmental Toxicity Studies of Tetrahydrocurcumin in Rats

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    机译 四氢姜黄素对大鼠的亚慢性和生殖/发育毒性研究
    摘要：Tetrahydrocurcumin (THC) is a major metabolite of curcumin, which is obtained from Curcuma longa. THC has various benefits and overcomes the bioavailability issue of curcumin. To establish it as a pharmacologically active molecule, its safety profile has to be determined. Thus, the present study aimed to determine the preclinical safety profile of THC in a 90-day subchronic and reproductive/developmental toxicity study in Wistar rats. THC at oral doses of 100, 200, and 400 mg/kg was administered daily for 90 days. Rats in the recovery group were kept for 14 days after treatment termination. The animals were observed for treatment-related morbidity, mortality, and changes in clinical signs, clinical pathology, and histopathology. In the reproductive/developmental toxicity study, THC at 100, 200, and 400 mg/kg was administered orally to rats and the reproductive/developmental parameters in adult male and female rats and pups were observed. THC at up to 400 mg/kg/day of did not have any significant effect on all parameters in male and female rats in both toxicity studies. Thus, 400 mg/kg/day can be considered as the no-observed-adverse-effect-level of THC in rats.
  • 19.

    【2hr】Embryotoxic and Teratogenic Effects of Tartrazine in Rats

    包量

    机译 酒石黄对大鼠的胚胎毒性和致畸作用
    摘要：Tartrazine (TAZ) is one of the most commonly used artificial dyes for foods and drugs. We determined the effect of TAZ on fetal development by examining morphological, visceral, and skeletal malformations in rat fetuses following daily oral administration of TAZ to pregnant Wistar rats at the 6th–15th day of gestation. TAZ at 0.45 and 4.5 mg/kg induced 6.0 and 7.1% fetal resorptions, as well as 10.0 and 10.5% fetal mortality, respectively. Fetal body weight and length were significantly lower in the groups treated with TAZ at 0.45 (3.97 ± 0.21 g and 27.3 ± 0.54 mm, respectively) and 4.5 mg/kg (3.48 ± 0.15 g and 23.22 ± 1.02 mm, respectively) than in the control group (4.0 ± 0.15 g and 30.01 ± 0.42 mm, respectively). TAZ at 0.45 and 4.5 mg/kg induced hepatic damage (20 and 33.3%, respectively), dark brown pigmentation due to hemosiderin in the splenic parenchyma (16.7 and 21.7%, respectively), as well as destructed and necrotic renal tubules (16.7 and 26.7%, respectively) in the fetuses. Moreover, TAZ at 0.45 and 4.5 mg/kg caused one or more missing coccygeal vertebrae (20 and 40%, respectively), missing sternebrae (6 and 10%, respectively), missing hind limbs (24 and 4%, respectively), and irregular ribs (16 and 20, respectively) in the fetuses. We concluded that TAZ has embryotoxic and teratogenic potentials in rats.
  • 20.

    【2hr】Zinc Oxide Nanoparticles Exhibit Both Cyclooxygenase- and Lipoxygenase-Mediated Apoptosis in Human Bone Marrow-Derived Mesenchymal Stem Cells

    包量

    机译 氧化锌纳米粒子在人骨髓来源的间充质干细胞中均表现出环氧合酶和脂氧合酶介导的凋亡。
    摘要：Nanoparticles (NPs) have been recognized as both useful tools and potentially toxic materials in various industrial and medicinal fields. Previously, we found that zinc oxide (ZnO) NPs that are neurotoxic to human dopaminergic neuroblastoma SH-SY5Y cells are mediated by lipoxygenase (LOX), not cyclooxygenase-2 (COX-2). Here, we examined whether human bone marrow-derived mesenchymal stem cells (MSCs), which are different from neuroblastoma cells, might exhibit COX-2- and/or LOX-dependent cytotoxicity of ZnO NPs. Additionally, changes in annexin V expression, caspase-3/7 activity, and mitochondrial membrane potential (MMP) induced by ZnO NPs and ZnO were compared at 12 hr and 24 hr after exposure using flow cytometry. Cytotoxicity was measured based on lactate dehydrogenase activity and confirmed by trypan blue staining. Rescue studies were executed using zinc or iron chelators. ZnO NPs and ZnO showed similar dose-dependent and significant cytotoxic effects at concentrations ≥ 15 μg/mL, in accordance with annexin V expression, caspase-3/7 activity, and MMP results. Human MSCs exhibited both COX-2 and LOX-mediated cytotoxicity after exposure to ZnO NPs, which was different from human neuroblastoma cells. Zinc and iron chelators significantly attenuated ZnO NPs-induced toxicity. Conclusively, these results suggest that ZnO NPs exhibit both COX-2- and LOX-mediated apoptosis by the participation of mitochondrial dysfunction in human MSC cultures.
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