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  • 1.

    【2hr】Assessment of rabbit spermatozoa characteristics after amygdalin and apricot seeds exposure in vivo

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    机译 杏仁核和杏籽体内暴露后兔精子特性的评估
    摘要：This study evaluates rabbit spermatozoa motility parameters after in vivo administration of amygdalin and apricot seeds during a 28-day period. Apricot seeds are potentially useful in human nutrition and amygdalin is the major cyanogenic glycoside present therein. The rabbits were randomly divided into the five groups (Ctrl-Control, P1, P2, P3, P4) with 4 males in each group. Control group received no amygdalin/apricot seeds while the experimental groups P1 and P2 received a daily intramuscular injection of amygdalin at a dose 0.6 and 3.0 mg/kg b.w. respectively during 28 days. P3 and P4 received a daily dose 60 and 300 mg/kg b.w. of crushed apricot seeds mixed with feed during 28 days, respectively. CASA system was used to evaluate for motility, progressive motility, curvilinear velocity, amplitude of lateral head displacement and beat cross frequency. Intramuscular application of amygdalin resulted in a significant time- and dose-dependent decrease of spermatozoa motility as well as progressive motility. On the other hand, oral consumption of apricot seeds had no significant effect either on the rabbit spermatozoa motility or progressive motility over the entire course of the study. The analysis of the other motion characteristics revealed a similar trend depicting a continuous, time- and dose-dependent decrease of all parameters following intramuscular AMG administration, with significant differences particularly for the dose 3.0 mg AMG/kg b.w. On the other hand, oral administration of apricot seeds had no significant impact on spermatozoa motility parameters. The present study suggests that short-term intramuscular application of amygdalin decreased rabbit spermatozoa motility in vivo. Whereas, consumption of apricot seeds did not induce any change in rabbit spermatozoa in vivo. Our findings suggest dose-dependent negative effect of pure amygdalin, but not apricot seeds on the rabbit spermatozoa parameters.
  • 2.

    【2hr】Immunosuppressant drug tacrolimus induced mitochondrial nephrotoxicity, modified PCNA and Bcl-2 expression attenuated by Ocimum basilicum L. in CD1 mice

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    机译 免疫抑制药他克莫司诱导线粒体肾毒性，修饰了罗勒果油在CD1小鼠中减弱的PCNA和Bcl-2表达
    摘要：Abbreviations: ABC, Avidin-Biotin- Peroxidase; ANOVA, analysis of variance; BUN, blood urea nitrogen; DNPH, dinitrophenylhydrazine; DPPH, 2,2-Diphenyl-1-picrylhydrazyl; EOBPV, Egyptian Organization for Biological Products and Vaccines; GPx, glutathione peroxidase; GSH, glutathione; H&E, hematoxylin and eosin; H2O2, hydrogenperoxide; IAEC, Institutional Animals Ethics Committee; IC, inhibitory concentration; Ip, intraperitoneal; mLPO, mitochondrial lipid peroxidation; Mn-SOD, Mn-superoxide dismutase; NP-SH, nonprotein thiol; OB, Ocimum basilicum; OPA, orthophosphoric acid; PC, protein carbonyl; PCNA-ir, proliferating cell nuclear antigen immunoreactivity; ROS, reactive oxygen species; TAC, tacroliumsKeywords: Tacrolimus, Nephrotoxicity, PCNA, Bcl-2, Ocimum basilicum

    Abstract

    Tacrolimus (TAC) is used sporadically as an immunosuppressive agent for organ transplantation, but its clinical used is limited due to its marked nephrotoxicity. Ocimum basilicum L. (Lamiaceae) (OB) had been shown to possess antioxidant, anti-inflammatory and nephroprotective activity, and effective at improving renal inflammation and glomerular. In our study, we aim to evaluate the efficacy of the OB against TAC-induced mitochondrial nephrotoxicity in CD1 mice. Mice were randomly divided into four groups. Group 1 (control group); administered orally with normal saline (1 mL/kg) for two weeks; Group 2 (OB extract treated-group) (500 mg/kg b.wt) gavaged once/day for two weeks; Group 3 (TAC-treated group) (3 mg/kg b.wt, administered ip once a day for two weeks); and Group 4; (TAC plus OB extract treated-group). Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. The OB extract was high in phenolic content (50.3 mg/g of gallic acid equivalent), total flavonoids (14.5 mg/g CE equivalent). The potential antioxidant efficacy of the extract (IC50) was 24.5 μg/mL. OB pretreatment significantly improved the TAC-induced changes in biochemical markers of nephrotoxicity for instance blood urea nitrogen (BUN), creatinine, total protein, and albumin (P < 0.01, when compared with TAC treated group). Also, it significantly restored the increase activities of TBARS, protein carbonyl (PC) (P < 0.001, when compared to healthy control group) and decreased activities of nonprotein thiol (NP—SH) levels, Mn-superoxide dismutase (Mn-SOD) and glutathione peroxidase (GPx) antioxidants of mitochondria. The nephroprotective efficacy of the OB leaves extract was further evident by histopathological analysis together with the PCNA-ir and Bcl2. The upshot of the present study revealed that the OB possessed significant antioxidant and nephroprotective activity and had a preventive effect on the biochemical alterations and histological changes in TAC-treated mice.
  • 3.

    【2hr】Toxicological safety evaluation of freeze-dried Protaetia brevitarsis larva powder

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    机译 冻干百日咳博德特氏菌幼虫粉的毒理学安全性评估
    摘要：White-spotted flower chafer (Protaetia brevitarsis) is an edible insect and its larva was used as a traditional Asian medicine. It’s a promising material as a novel food source because of its nutritional components. In this study, as part of the preclinical toxicity program, we evaluated the toxicity of freeze-dried P. brevitarsis larva powder to develop a novel food material. In a single-dose oral toxicity study in rats, there were no changes in mortality, clinical observations, and body weight in rats administered 5000 mg/kg P. brevitarsis larva powder. In a 13-week oral repeated dose toxicity study in rats, there were no adverse effects or changes in mortality, clinical observations, body weight, food consumption, ophthalmology, clinical pathology, necropsy, organ weight, and histopathology at doses of 300, 1000, and 3000 mg/kg/day. In identification of allergic reactions, P. brevitarsis larva powder induced no increases of serum immunoglobulin E and histamine concentrations over 13 weeks of oral administration in rats. In a genotoxicity assessment, P. brevitarsis larva powder didn’t provoke bacterial reverse mutations, chromosomal aberrations, and micronucleated reticulocytes. Therefore, freeze-dried P. brevitarsis larva powder shows no evidence of toxic and mutagenic changes under the experimental conditions of the present in vitro and in vivo studies.
  • 4.

    【2hr】Toxicodynamics of Lead, Cadmium, Mercury and Arsenic- induced kidney toxicity and treatment strategy: A mini review

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    机译 铅，镉，汞和砷引起的肾脏毒性和治疗策略的毒理动力学：小型综述
    摘要：Environmental pollution has become a concerning matter to human beings. Flint water crisis in the USA pointed out that pollution by heavy metal is getting worse day by day, predominantly by Lead, Cadmium, Mercury and Arsenic. Despite of not having any biological role in flora and fauna, they exhibit detrimental effect following exposure (acute or chronic). Even at low dose, they affect brain, kidney and heart. Oxidative stress has been termed as cause and effect in heavy metal-induced kidney toxicity. In treatment strategy, different chelating agent, vitamins and minerals are included, though chelating agents has been showed different fatal drawbacks. Interestingly, plants and plants derived compounds had shown possible effectiveness against heavy metals induced kidney toxicity. This review will provide detail information on toxicodynamics of Pb, Cd, Hg and As, treatment strategy along with the possible beneficiary role of plant derived compound to protect kidney.
  • 5.

    【2hr】The investigation of effect of alpha lipoic acid against damage on neonatal rat lung to maternal tobacco smoke exposure

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    机译 α-硫辛酸对新生大鼠肺暴露于母体烟草烟雾的伤害作用的研究
    摘要：Keywords: Alpha lipoic acid, Lung, Neonate, Tobacco smoke, Pregnancy

    Abstract

    This study was carried out to determine the changes in the lungs of the rat pups exposed to tobacco smoke during pregnancy period and to investigate the protective effects of alpha lipoic acid, which is administered during pregnancy, on these changes.Spraque-Dawley female rats were divided into four groups: control, tobacco smoke (TS), tobacco smoke + alpha lipoic acid (TS + ALA) and alpha lipoic acid (ALA). The rats in control group were untreated. Rats were exposed to TS twice a day for one hour starting from eight weeks before mating and during pregnancy. 20 mg / kg of ALA was administered to rats. On 7th and 21st days 7 of the pups from each group were decapitated. Histological, morphometric, biochemical and quantitative real-time RT-PCR analyzes were performed.Histopathological and biochemical changes were observed in TS group. While a significant decrease was observed both in SP-A and VEGF immunoreactivities and mRNA levels, caspase-3 immunoreactivity and TUNEL positive cells were increased in TS group.It is suggested that prenatal TS exposure leads to morphological and histopathological changes on lung development by causing oxidative damage in lungs of neonatal rats and the maternal use of ALA can provide a limited protective effect on the neonatal lung development against this oxidative stress originating from TS. Although pregnant women are increasingly aware on health risks of smoking, environmental tobacco smoke exposure is still a widespread problem. For this reason, it is thought that this damage can be partially reduced by some antioxidant supplements in pregnancy.
  • 6.

    【2hr】Crosstalk between GSK-3, c-Fos, NFκB and TNF-α signaling pathways play an ambitious role in Chitosan Nanoparticles Cancer Therapy

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    机译 GSK-3，c-Fos，NFκB和TNF-α信号通路之间的串扰在壳聚糖纳米粒子癌症治疗中起着雄心勃勃的作用
    摘要：Keywords: Chitosan nanoparticles, HCC, Inflammatory markers, Apoptotic markers

    Abstract

    Nanotechnology is a promising era of medicine for developing targeted drug delivery system. Chitosan nanoparticles (CNPs) have attracted increasing attention for their wide applications as anticancer drugs. This article is concerned with the therapeutic index of chitosan nanoparticles against diethyl nitrosamine (DEN) induced hepatocellular carcinoma (HCC). HCC was induced in rats via repeated DEN administration in a dose of 200 mg/kg BW IP, 2 weeks later rats received (2 ml/kg BW) CCl4 orally for 2 months followed by daily treatment with chitosan nanoparticles in an oral dose of 12 mg/kg for 1 month. Then the gene expression of glycogen synthase kinase-3 (GSK-3), (c-FOS), nuclear factor kappa-B (NFκB) and tumor necrosis factor- α (TNF-α) were reported in rats sera and the correlation between GSK-3, C-Fos, NFƘB and TNF-α and liver tumorigenesis was investigated. The results elucidated that DEN significantly increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Marked increments in serum malondialdehyde (MDA) and nitric oxide (NOx) levels along with a slight reduction of glutathione (GSH) level were evidenced in HCC. Liver injury triggered an inflammatory response by enhancing the mRNA gene expression of NFκB and TNF-α. DEN effectively activated apoptotic markers GSK-3 and c-FOS. Oral administration of CNPs alleviated the oxidative, inflammatory and apoptotic hazards induced via DEN. The histopathological examination reinforced these results. The present study highlights the anti-inflammatory and anti-apoptotic potentials of CNPs against DEN-induced HCC.
  • 7.

    【2hr】Toxic effects of Lambda-cyhalothrin, on the rat thyroid: Involvement of oxidative stress and ameliorative effect of ginger extract

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    机译 氟氯氰菊酯对大鼠甲状腺的毒性作用：氧化应激的参与和姜提取物的改善作用
    摘要：Abbreviations: LCT, Lambda-cyhalothrin; SOD, superoxide dismutase; CAT, catalase; TSH, thyroid-stimulating hormone; MDA, malondialdehyde; AD, Alzheimer's disease; PD, Parkinson’s disease; PCO, protein carbonyl; T3, triiodothyronine, T4, thyroxine; PAS, Periodic acid–Schiff; ALT, plasma alanine aminotransferase; AST, aspartate aminotransferase; GPx, glutathione peroxidase; GR, glutathione reductase; GST, glutathione-S-transferase; CC14, carbon tetrachloride; DMBA, 7,12-dimethylbenz(a)anthracene; DMA, lipid peroxidan marker; ALK-P, alkaline phosphatase; GSH, glutathione; ROS, reactive oxygen species; TL, distance of DNA migration from the center to the nuclear core; TI, percent of genomic DNA that migrated during electrophoresis from the nuclear core to the tailKeywords: Lambda-cyhalothrin, Ginger, Thyroid, Histochemistry, Antioxidant

    Abstract

    Lambda-cyhalothrin (LCT) is a synthetic pyrethroid that is widely used to control insecticide. Ginger is a traditional plant that is widely used as a spice or folk medicine. This study evaluates the antioxidant effect of ginger extract on thyroid toxicity induced by LCT in albino rats. Adult Rats were divided into 4 experimental groups: Group 1: control, Group 2: oral ginger treatment (24 mg/ml, 3 days/week for 4 weeks), Group 3: oral LCT treatment (1/100 LD50, 3 days/week for 4 weeks), Group 4: oral LCT and ginger mixture treatment. The histological results of LCT group showed degenerated follicles with reduced colloids, congestion of blood vessels and hyperaemia between the follicles. Histochemically, depletion of glycogen and proteins was recorded in follicular cells and colloids. The biochemical results of LCT treated group revealed a decrease in T3, T4, SOD and CAT, while TSH and MDA were increased. The comet assay showed that LCT significantly induced DNA damage in the thyroid gland. However, treating rats with LCT plus ginger led to an improvement in the histological structure of the thyroid, with noticeable increases in glycogen and protein deposition. Also, LCT plus ginger increase in T3, T4 and the antioxidant enzymes SOD and COT were detected concomitantly with a decrease in TSH and MDA as well as a significant reduction in DNA damage. LCT affected the thyroid function and structure. On the other hand, ginger has a preventative effect against the histological damage and biochemical toxicity caused by the (LCT) insecticide.
  • 8.

    【2hr】Complex toxicity as disruption of adipocyte or osteoblast differentiation in human mesenchymal stem cells under the mixed condition of TBBPA and TCDD

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    机译 TBBPA和TCDD混合条件下人间充质干细胞中脂肪细胞破坏或成骨细胞分化的复杂毒性
    摘要：People are frequently and unintentionally exposed to many chemical compounds, such as environmental pollutants and endocrine-disrupting chemicals (EDCs), in food and from the atmosphere. In particular, endocrine-disrupting TBBPA and dioxins are found in human breast milk and in the body. Conventional studies evaluate toxicity by administering a single substance to cells or animals, but evaluation of the toxicity of mixtures of these ingested compounds is essential for “true” toxicological assessment. We evaluated toxic effects in vitro using human mesenchymal stem cells (hMSCs). TBBPA increased the number of lipid droplets, and upregulated the expression of adipocyte-related mRNA, aP2 and LPL, through a PPARγ-dependent mechanism. TCDD suppressed lipid droplets and adipocyte-related mRNA levels. Adipocyte differentiation was stimulated by TBBPA and inhibited by TCDD in a dose-dependent manner. TBBPA did not influence osteoblast differentiation, but TCDD suppressed ALP staining and activity, calcium deposition, and osteoblast-related mRNA levels. In a mixture of TBBPA and TCDD, TBBPA inhibited TCDD suppression of adipocyte and osteoblast differentiation in a dose-dependent manner. Interestingly, we observed lipid droplets in TBBPA-treated cells differentiated into osteoblasts. These results suggest that TBBPA and TCDD disrupted differentiation into adipocytes and osteoblasts and contributes to a more complete toxicological understanding of exposure to these chemical substances.
  • 9.

    【2hr】Contamination by neonicotinoid insecticides and their metabolites in Sri Lankan black tea leaves and Japanese green tea leaves

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    机译 斯里兰卡红茶和日本绿茶中新烟碱类杀虫剂及其代谢产物的污染
    摘要：Keywords: Neonicotinoid, Tea, Japan, Sri Lanka, Dinotefuran

    Abstract

    Tea is one of the world’s most popular beverages due to health promoting effects. Despite these, there have been concerns about the adverse effects of tea contamination by neonicotinoid insecticides. Only a handful of studies on neonicotinoid insecticides in tea have been carried out and this study was therefore performed to determine the concentrations of seven neonicotinoid insecticides and 20 metabolites in Japanese green tea leaves, and black tea leaves from Sri Lanka; and assess the Maximum Daily Intake (MDI) of neonicotinoid insecticides. From the results, the seven parent compounds were detected in Japanese tea leaves and beverages. Dinotefuran (3004 ng/g) was found at the highest level in green tea leaves. Ten of the 20 metabolites were detected in Japanese tea products. Dinotefuran-urea (92%) and thiacloprid-amide (89%) were most frequently detected in Japanese tea leaves. Clothianidin-urea (100 ng/g) was found at the highest level in green tea leaves. Neonicotinoid insecticides and metabolites were not detected in Sri Lankan black tea leaves. The concentrations and MDI of neonicotinoid insecticides in tea leaves were below the Maximum Residual Levels (MRLs) and Acceptable Daily Intakes (ADIs), respectively.
  • 10.

    【2hr】Safety profile of 40% Garcinol from Garcinia indica in experimental rodents

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    机译 Gar藤中40％藤黄酚在实验啮齿动物中的安全性
    摘要：The present study was taken up to evaluate the single dose acute toxicity, 28 days and 90 days repeated dose toxicity and reproductive/developmental toxicity of standardized 40% Garcinol in experimental rodents. The studies were conducted in compliance with OECD principles of good laboratory practice, guidelines for testing of chemicals no.420, 407, 408 and 421 respectively. Single dose acute oral toxicity was conducted on female Wistar rats as sighting study step-I (300 mg/kg) & sighting study step-II (2000 mg/kg) and main study (2000 mg/kg). Sub-acute, sub-chronic and reproductive/developmental studies were conducted in Wistar rats divided equally in vehicle control, 20, 50 and 100 mg/kg dose group along with recovery groups for vehicle control and high dose. Reproductive/developmental study was carried out for minimum of 28 days and in females during pregnancy and 4 days post partum. There were no abnormal clinical signs/behavioural changes, reproductive and developmental parameters, gross and histopathological changes as well as no alteration in the body weight, body temperature, haematology and other biochemical parameters in all the four studies. 40% Garcinol has a low toxicity profile in rodents and had no observed effects under experimental conditions used.
  • 11.

    【2hr】Glutathione and Inter-α-trypsin inhibitor heavy chain 3 (Itih3) mRNA levels in nicotine-treated Cd44 knockout mice

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    机译 尼古丁治疗的Cd44基因敲除小鼠中的谷胱甘肽和α-胰蛋白酶抑制剂重链3（Itih3）mRNA水平
    摘要：Chemical compounds studied in this article: l-Nicotine (89594), l-Glutathione reduced, also GSH (124886), l-Glutathione oxidized or oxiglutatione, also GSSG (65359), β-Nicotinamide adenine dinucleotide 2′-phosphate or NADPH (16218775), Dimethyl sulfoxide or DMSO (679), 5-Sulfosalicylic acid dihydrate (2723734), 5,5′-Dithiobis(2-nitrobenzoic acid) or DTNB (6254), 4-Vinylpyridine (7502)Keywords: Chronic oral nicotine treatment, Hyaluronan receptor, Pre-Alpha-Inhibitor, Oxidative stress, Hepatic disease, Gender

    Abstract

    Cluster of differentiation 44 (Cd44), a hyaluronan receptor, and the secreted hyaluronan-binding protein Inter-α-trypsin Inhibitor Heavy chain 3 (Itih3) play an important role in cancer and oxidative stress. Smoking of tobacco reduces Itih3 in the plasma and activates hyaluronan signaling through Cd44, but the impact of Cd44 on Itih3 expression is unknown. Here, we studied changes induced by the tobacco component nicotine on the glutathione (GSH) antioxidant system and Itih3 gene expression in Cd44 knockout mice. Cd44 deficiency decreased baseline total GSH and oxidized glutathione (GSSG) levels in the liver compared to wildtype mice. However, contrary to wildtype mice, chronic oral nicotine administration (200 μg/ml) failed to further reduce total GSH and GSSG in Cd44 mice. Sex differences with lowered glutathione levels in females was also detectable only in wildtype but not Cd44 knockout mice. Itih3 mRNA levels in the liver and hypothalamus were not affected by nicotine, Cd44 genotype or sex. Nonetheless, the correlation between Itih3 and total GSH levels in the liver (r = 0.42, p < 0.05) suggested a role of Itih3 in glutathione metabolism in WT mice. Again this effect was diminished in Cd44 knockout mice. The disappearance of nicotine effects, sex differences and correlations between Itih3 and total GSH in Cd44 knockout mice compared to wildtype animals suggests an interaction between nicotine, Cd44 and/or sex-dependent signaling in the regulation of glutathione metabolism.
  • 12.

    【2hr】Short term exposure to titanium, aluminum and vanadium (Ti 6Al 4V) alloy powder drastically affects behavior and antioxidant metabolites in vital organs of male albino mice

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    机译 短期暴露于钛，铝和钒（Ti 6Al 4V）合金粉中会严重影响雄性白化病小鼠重要器官的行为和抗氧化代谢产物
    摘要：Keywords: Titanium aluminium vanadium Alloy, Albino mice, Behavior, Hematology, Antioxidants

    Abstract

    Titanium, Aluminum and Vanadium (Ti 6Al 4V) alloy are frequently used as surgical implant but regarding their compatibility in living systems is limited. Ti 6Al 4V was prepared from high purity constituents and Ti 6Al 4V alloy powder (25 mg/ml solvent/Kg body weight) was gavaged to albino mice for 8 days. A saline treated control group was maintained in parallel. A series of behavioral (rota rod, light and dark box, open field and novel object) test performance, complete blood count, selected serum (HDL cholesterol, LDL cholesterol, creatinine, cholesterol and triglycerides) parameters, antioxidant metabolites from vital organs (superoxide dismutase, catalase and lipid peroxidation) from vital organs and body weight were determined in both treatments. It was observed that rota rod test performance in male (P = 0.05) and novel object recognition capability in female mice (P = 0.04) were significantly reduced as compared to their respective control groups. Body weight, complete blood count and studied serum parameters remained unaffected when compared between two treatments of both genders. Concentration of superoxide dismutase in liver (P = 0.008), heart (P = 0.01) and lungs (P = 0.05) was significantly elevated while catalase concentration in liver (P = 0.001) was significantly decreased in female albino mice that were exposed to 25 mg/ml solvent/kg body weight of Ti 6 A l 4 V alloy powder. In case of male albino mice, superoxide dismutase concentration in lungs was reduced (P = 0.05) in mice exposed to Ti 6 A l 4 V alloy powder.In conclusion, our results indicated that short term exposure to 25 mg/ml solvent/Kg body weight of Ti-6Al-4V alloy powder supplementation had adversely affected selected aspects of behavior of albino mice in a gender specific manner. Analysis of antioxidant parameters in vital organs has demonstrated that the applied dose of Ti-6Al-4V alloy powder can disturb the H₂O₂ associated metabolic pathways in albino mice, especially in female mice. As this alloy is part of surgical implants, so we recommend that their effects in living systems must be extensively explored under variable dose and exposure time conditions to know more about their biocompatibility.
  • 13.

    【2hr】Evaluation of selenium nanoparticles and doxorubicin effect against hepatocellular carcinoma rat model cytogenetic toxicity and DNA damage

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    机译 硒纳米颗粒和阿霉素对肝癌大鼠模型细胞遗传毒性和DNA损伤的评价
    摘要：The present study aimed to demonstrate the potent role of nanoselenium and Doxorubicin in retrogression of genotoxicity induced in hepatocellular carcinoma rat model by studying chromosomal aberration, micronuclei formation, DNA fragmentation as well as comet assay. Male rats hepatocellular carcinoma model were treated with Se-Nanoparticles, Doxurobicin (DOX) and the combination of both. The results revealed the protective effect of nanoselenium, Doxorubicin and their combination on bone marrow cytogenetic toxicity by decreasing chromosomal aberrations and micronuclei formation as well as their effects on rat's liver by decreasing DNA damage. Nevertheless, the treatment with nanoselenium either alone or in combination with Doxorubicin was more effective than treatment with doxorubicin alone.
  • 14.

    【2hr】Aflatoxin B1 residues in human livers and their relationship with markers of hepatic carcinogenesis in São Paulo, Brazil

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    机译 巴西圣保罗人肝脏中的黄曲霉毒素B1残留及其与肝癌发生标志物的关系
    摘要：Keywords: AFB1, Hepatocellular carcinoma, Cirrhosis, Markers

    Abstract

    In this study, hepatic biopsies from autopsy cases in São Paulo, Brazil, showing hepatocellular carcinoma (HCC, n = 8), cirrhosis associated with viral hepatitis (VC, n = 20), cirrhosis associated with alcoholism (AC, n = 20), and normal livers (NL or controls, n = 10) were subjected to determination of aflatoxin B1 (AFB1) and its main metabolites, and of markers of hepatic carcinogenesis Only non-metabolized AFB1 was detected in 13 samples (27.1%, N = 48) of liver disorders (HCC, VC and AC), at levels between 10.0 and 418.0 pg/g (mean: 76.6 ± 107.7 pg/g). Immuno-labeling of p53, cyclin D1, p21, β-catenin, and Prohibitin (PB) increased mainly in HCC patients, in relation to the controls. AFB1+ samples of HCC presented higher expressions of p53, cyclin D1, p21, and β-catenin compared with AFB1-livers. In contrast, p27, p16, and Rb immuno-labeling decreased in HCC, VC, and AC samples, compared with NL, with lowest values in AFB1+ samples for all liver disorders. Compared with NL, gene expression of cyclin D1 and PB in AFB1+ samples of HCC and AC were also higher, along with higher gene expression of p21 in VC and AC AFB1+ livers. Results indicated that patients with liver disorders were exposed to dietary aflatoxins, and that residual AFB1 in liver negatively affected the p53 and protein Rb pathways in HCC. Moreover, the presence of AFB1 in cirrhotic livers warrants concern about the potential contribution of dietary aflatoxin to disease progression during VC and AC.
  • 15.

    【2hr】Microcystins in water and in microalgae

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    机译 水和微藻中的微囊藻毒素
    摘要：Microcystins have been the subject of increasingly alarming popular and scientific articles, which have taken as their unquestionable foundation the provisional Guideline of 1 μg/L established by the WHO Panel on microcystins levels in water, and mechanically translated by the Oregon government as 1 μg/g of Klamath Aphanizomenon flos aquae microalgae. This article underlines the significant limitations and ultimately scientific untenability of the WHO Guideline on microcystins in water, for being based on testing methodologies which may lead to a significant overestimation of the toxicity of microcystins. I propose criteria for the realization of new experimental studies on the toxicity of microcystins, based on the essential understanding that drinking water is contaminated by whole cyanobacterial microalgae rather than purified microcystins, while it is important to differentiate between water and cyanobacterial supplements. It is indeed a mistake to automatically apply standards that are proper for water to cyanobacterial supplements, as they have different concentrations of the antioxidant substances that inactivate or significantly reduce the toxicity of microcystins, a fact that also require that each cyanobacterial supplement be tested individually and through realistic testing methodologies.
  • 16.

    【2hr】Performance of a whole-body human dust inhalation challenge exposure chamber

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    机译 人体粉尘吸入挑战暴露室的性能
    摘要：BackgroundEvaluation of the performance of a whole-body human dust exposure chamber is presented in this report.
  • 17.

    【2hr】An allied approach for in vitro modulation of aldose reductase, sorbitol accumulation and advanced glycation end products by flavonoid rich extract of Coriandrum sativum L. seeds

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    机译 富含黄ian种子类黄酮提取物体外调节醛糖还原酶，山梨糖醇积累和高级糖基化终产物的相关方法
    摘要：Abbreviations: PKC, protein kinase C; DAG, diacyl glycerol; NADPH, nicotinamide adenine dinucleotide phosphate; DPPH, 2,2-diphenyl-1-picrylhydrazyl; AG, aminoguanidineKeywords: C. sativum, FCS, AGEs, Sorbitol, ALR

    Abstract

    Traditional herbal medicines are attaining more popularity and are being widely practiced. Coriandrum sativum L. is one of the oldest herbal medicinal plants valued for its nutritional and medicinal properties. Present investigation was focussed on evaluation of attenuating potential of flavonoid rich extract of C. sativum (FCS) seeds against pathogenic markers of diabetic complications i.e. advanced glycation end products (AGEs), sorbitol and aldose reductase (ALR); by using in-vitro methods. Gas chromatography–mass spectrometry (GC–MS) and Infrared spectroscopy of FCS revealed the presence of different flavonoids.Results demonstrated that FCS has produced 79.80% inhibition of AGEs formation. Additionally, FCS was effective against sorbitol accumulation and ALR inhibition with IC50 values of 221 μg/ml and 6.08 μg/ml respectively. Molecular docking was conducted against three binding site for ALR, RAGEs and sorbitol dehydrogenase to explore their binding interactions with identified flavonoids. The constituents F2, F4 and F6 have shown good binding interactions with all the receptors. The visualisation of the docked complexes revealed the occurrence of hydrophobic forces and hydrogen bonding in receptor and docked constituents.The results were in support with experimental inhibitory activities of FCS against these biomarkers and provide a considerable basis for the identification and development of new inhibitors.
  • 18.

    【2hr】Potential role of the common food additive manufactured citric acid in eliciting significant inflammatory reactions contributing to serious disease states: A series of four case reports

    包量

    机译 常见食品添加剂制造的柠檬酸在引发导致严重疾病状态的重大炎症反应中的潜在作用：一系列四个病例报告
    摘要：Citric acid naturally exists in fruits and vegetables. However, it is not the naturally occurring citric acid, but the manufactured citric acid (MCA) that is used extensively as a food and beverage additive. Approximately 99% of the world’s production of MCA is carried out using the fungus Aspergillus niger since 1919. Aspergilus niger is a known allergen. The FDA placed MCA under the category of GRAS without any research to substantiate this claim. In 2016, 2.3 million tons of MCA were produced, predominantly in China, and approximately 70% is used as a food or beverage additive. There have been no scientific studies performed to evaluate the safety of MCA when ingested in substantial amounts and with chronic exposure. We present four case reports of patients with a history of significant and repetitive inflammatory reactions including respiratory symptoms, joint pain, irritable bowel symptoms, muscular pain and enervation following ingestion of foods, beverages or vitamins containing MCA. We believe that ingestion of the MCA may lead to a harmful inflammatory cascade which manifests differently in different individuals based on their genetic predisposition and susceptibility, and that the use of MCA as an additive in consumable products warrants further studies to document its safety.
  • 19.

    【2hr】Acute toxicity studies of the South African medicinal plant Galenia africana

    包量

    机译 南非药用植物非洲榄仁的急性毒性研究
    摘要：Abbreviations: DPM, disintegrations per minute; ECVAM, European Centre for the Validation of Alternative Methods (ECVAM); G. africana, Galenia africana; GHS, globally harmonized aystem; GLP, good laboratory practice; HCA, hexylcinnamicaldehyde; LD50, lethal oral dosage; LLNA, local lymph node assay; MTT, methylthiazoldiphenyl-tetrazolium bromide (MTT); NAD, no abnormalities detected; OECD, Organization for Economic Co-operation and Development; PBS, phosphate buffered saline; SI, stimulation index; WHO, World Health OrganizationKeywords: Galenia africana, Acute toxicity, Skin irritation, Episkin, Dermal sensitization, Local lymph node assay

    Abstract

    BackgroundMedicinal plants are used by a large proportion of the global population as complementary and alternative medicines. However, little is known about their toxicity. G. africana has been used to treat wounds, coughs and skin diseases and is used in cosmetic formulations such as lotions and shampoos.
  • 20.

    【2hr】Comparison of transcriptome responses to glyphosate, isoxaflutole, quizalofop-p-ethyl and mesotrione in the HepaRG cell line

    包量

    机译 在HepaRG细胞系中对草甘膦，异草二氟醚，喹喔啉-对-乙基和甲基磺草酮的转录组反应的比较
    摘要：Use and thus exposure to quizalofop-p-ethyl, isoxaflutole, mesotrione and glyphosate, which are declared as active principles in commercial formulations of herbicides, is predicted to rapidly increase in coming years in an effort to overcome the wide-spread appearance of glyphosate-resistant weeds, especially in fields where glyphosate-tolerant genetically modified crops are cultivated in the USA. Thus, there is an urgent need for an evaluation of metabolic effects of new pesticide ingredients used to replace glyphosate. As the liver is a primary target of chemical pollutant toxicity, we have used the HepaRG human liver cell line as a model system to assess the toxicological insult from quizalofop-p-ethyl, isoxaflutole, mesotrione and glyphosate by determining alterations in the transcriptome caused by exposure to three concentrations of each of these compounds, including a low environmentally relevant dose. RNA-seq data were analysed with HISAT2, StringTie and Ballgown. Quizalofop-p-ethyl was found to be the most toxic of the pesticide ingredients tested, causing alterations in gene expression that are associated with pathways involved in fatty acid degradation and response to alcoholism. Isoxaflutole was less toxic, but caused detectable changes in retinol metabolism and in the PPAR signalling pathway at a concentration of 1 mM. ToxCast data analysis revealed that isoxaflutole activated PPAR gamma receptor and pregnane X responsive elements in reporter gene assays. Glyphosate and mesotrione caused subtle changes in transcriptome profiles, with too few genes altered in their function to allow a reliable pathway analysis. In order to explore the effects of glyphosate in greater depth and detail, we undertook a global metabolome profiling. This revealed a decrease in free long chain fatty acids and polyunsaturated fatty acid levels at the lowest concentration (0.06 μM) of glyphosate, although no effects were detected at the two higher concentrations tested, perhaps suggesting a non-linear dose response. This surprising result will need to be confirmed by additional studies. Overall, our findings contribute to filling the knowledge gap regarding metabolic toxicity that can potentially arise from exposure to these four herbicide active principles.
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