Genotoxicity studies on green tea catechin

The beneficial effects of tea catechins are well documented. We evaluated the genotoxic potential of a green tea catechin preparation using established genotoxicity assays, including a bacterial reverse mutation assay (Ames test), a chromosomal aberration assay in cultured Chinese hamster lung cells (CHL/IU), a mouse lymphoma L5178Y/tk assay, and a bone marrow micronucleus (MN) assay in ICR CD mice and SD rats. No significant increases in the number of revertant colonies were observed in the Ames test, but positive responses were observed in two in vitro assays: the chromosomal aberration assay and mouse lymphoma L5178/tk assay. However, the in vivo study demonstrated no significant increase in micronucleated polychromatic erythrocytes (MNPCE) in the bone marrow of both ICR CD mice and SD rats administered a high dose of the green tea catechin preparation up to 2000 mg/kg. Combined with favorable epidemiological information suggesting a chemopreventive effect of tea catechins on carcinogenesis, we conclude that green tea catechin presents no significant genotoxic concern under the anticipated conditions of use. These results are consistent with other genotoxicity studies of tea catechins, which show minimal, if any, genotoxic potential.     

Beneficial effects of Undaria pinnatifida ethanol extract on diet-induced-insulin resistance in C57BL/6J mice

This study was performed to evaluate the beneficial effect of Undaria pinnatifida ethanol extract (UEFx) on insulin resistance in diet-induced obese mice. A high-fat diet was supplemented with the UEFx at 0.69% (wt/wt) dose, which contains an equivalent amount of 0.02% fucoxanthin (wt/wt), or with Fx at 0.02% (wt/wt) dose in diet. After 9 weeks, both UEFx supplement significantly lowered the amount of visceral fat, the size of adipocyte, the fasting blood glucose concentration, the plasma insulin and the insulin resistance index similar to pure as shown by Fx supplement, compared to the high-fat (HF) control group. Blood glucose level was negatively correlated with hepatic glucokinase activity (r = −0.533, p < 0.05), whereas positively correlated with hepatic gluconeogenic enzyme activities (r = 0.463, p < 0.05 for glucose-6-phosphatase; r = 0.457, p < 0.05 for phosphoenolpyruvate carboxykinase). Ratio of hepatic glucokinase/glucose-6-phosphatase and glycogen content were significantly elevated by the UEFx and Fx supplements. Supplementation of the UEFx as well as Fx seemed to stimulate the β-oxidation activity and inhibit the phosphatidate phosphohydrolase activity resulting in a decrease in the hepatic lipid droplet accumulation. The results indicate that the UEFx can prevent insulin resistance and hepatic fat accumulation that is partly mediated by modulating the hepatic glucose and lipid homeostasis in the high fat-induced obese mice.     

Genotoxicity studies on a high-purity rebaudioside A preparation

Rebaudioside A (Reb A) is a steviol glycoside isolated from the leaves of the Stevia rebaudiana plant. This non-nutritive, natural sweetener is reported to be 250–450 times sweeter than sucrose and has potential for wide use in the US diet, and is used in Japan and South America today. The safety of Reb A has been investigated in several recently published studies and information on genotoxicity is described herein. Reb A was investigated for its potential to induce genotoxicity in three in vitro and two in vivo assays (conducted according to OECD guidelines). Reb A was non-mutagenic in an Ames test using Salmonella typhimurium and Escherichia coli, in a chromosomal aberration test using Chinese Hamster V79 cells and in a mouse lymphoma assay using L5178Y+/− cells, all studies were conducted at concentrations up to 5000 μg/ml, with and without metabolic activation. Also, Reb A was non-genotoxic in a bone marrow micronucleus test in mice at doses up 750 mg/kg bw and in an unscheduled DNA synthesis test in rats at 2000 mg/kg bw. These studies provide additional evidence that Reb A is not genotoxic at the doses tested and further support the generally recognized as safe determination of Reb A.     

褐藻糖胶抗血栓研究进展

褐藻糖胶是一种酸性硫酸化多糖，有多种生物活性和药理作用，其抗血栓活性尤为明显。褐藻糖胶能够抑制凝血酶的产生及活性，提高组织型纤溶酶原活化剂对纤溶酶原的激活作用，从而具有抗血栓形成和溶栓功能。     

Genotoxicity studies on the root extract of Polygala tenuifolia Willdenow

The root of Polygala tenuifolia Willdenow has been used for the treatment against insomnia, amnesia, depression, palpitations with anxiety, and memory improvement. However, there is no sufficient background information on toxicological evaluation of the root to given an assurance of safety for developing dietary supplements and functional foods. As part of a safety evaluation, the potential genotoxicity of the root extract of P. tenuifolia was evaluated using a standard battery of tests (bacterial reverse mutation assay, chromosomal aberrations assay, and mouse micronucleus assay). In a reverse mutation assay using four Salmonella typhimurium strains and Escherichia coli, the extract did not increase the number of revertant colonies in any tester strain with or without metabolic activation by S9 mix, and did not cause chromosomal aberration in short-period test with the S9 mix or in the continuous (24 h) test. A bone marrow micronucleus test in ICR mice dosed by oral gavage at doses up to 2000 mg/kg/day showed no significant or dose dependent increase in the frequency of micronucleated polychromatic erythrocytes (PCE). These results indicate that ingesting the rot extract P. tenuifolia is not genotoxic at the proper dose.     

岩藻聚糖硫酸酯降血糖作用机制的研究进展

糖尿病是以高血糖和胰岛素抵抗为特征的内分泌和代谢系统疾病,已成为世界范围内一种普遍疾病。岩藻多糖基于其特定的化学结构,如单糖组成和糖苷键,具有良好的降糖作用和理想的糖尿病治疗潜力。岩藻聚糖硫酸酯具有多种生物活性,但其结构复杂、高分子量和高粘性的特性限制了其应用,而低分子量岩藻多糖粘度低、溶解度好,且研究表明低分子量岩藻多糖具有更好的降血糖作用,因此其低分子量产物的研究具有重大意义。本文讨论了岩藻多糖的结构特征,包括主干结构、糖苷键位置、单糖类型、硫酸盐含量,着重介绍了多糖分子量和降血糖活性的关联,继而引申出低分子量降血糖作用及其作用机理,以期为明晰岩藻多糖的构效关系及进一步的应用提供理论基础。     

Genotoxicity of two mouthwash products in the Drosophila Wing-Spot Test

In this study, genotoxicity of two mouthwash products (chlorexidin, benzidamine–HCl) were investigated in the Drosophila Wing-Spot Test which makes use of the wing cell markers multiple wing hairs (mwh) and flare (flr) and detects both mitotic recombination and various types of mutational events. Induced mutations are detected as single mosaic spots on the wing blade of surviving adults that show either the multiple wing hairs or flare phenotype. Induced recombination leads to mwh and flr twin spots and also, to some extent, to mwh single spots. Recording of the frequency and the size of different spots is allowed for a quantitative determination of the mutagenic and recombinogenic effects. Trans-heterozygous third-instar larvae were treated at different concentrations of the mouthwash products. Chlorexidin exposure concentrations were 0.5, 1 and 2 mg/ml. Benzidamine–HCl exposure concentrations were 0.38, 0.75 and 1.5 mg/ml. In addition, the observed mutations were classified according to size and type of mutation per wing. Both chlorexidin and benzidamine–HCl were genotoxic in terms of total mutations per wing at the highest doses. Survival rates of flies used in the experiments were significantly lower than those of the control group, with both mouthwash products showing toxic effects on Drosophila melanogaster larvae.     

岩藻聚糖硫酸酯及其模拟物的制备研究进展

岩藻聚糖硫酸酯(fucoidan)是1种富含α-L-岩藻糖的硫酸化多糖,通常存在于海洋褐藻和棘皮动物中.天然fucoidan多糖主要从海洋生物中提取获得,经物理、化学或生物酶法可控降解制备其低聚糖与寡糖,其多样的生物活性已被广泛报道;化学合成是获得结构清晰的fucoidan寡糖的高效途经之一,有助于进行深入地构效关系研...     

Hypolipidemic effect of fucoidan from Laminaria japonica in hyperlipidemic rats

In this study, we investigated the effect of fucoidan polysaccharide sulfuric acid ester (FPS) from Laminaria japonica Aresch (Laminariaceae) on hyperlipidemic rats. FPS notably reduced the concentration of serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) of hyperlipidemic rats and increased the concentration of high-density lipoprotein cholesterol (HDL-C) and the activities of lipoprotein lipase (LPL), hepatic lipoprotein (HL), and lecithin cholesterol acyltransferase (LCAT).     

Genotoxicity and morphological changes induced by the alkaloid monocrotaline, extracted from Crotalaria retusa, in a model of glial cells

Plants of Crotalaria genus (Leguminosae) present large amounts of the pyrrolizidine alkaloid monocrotaline (MCT) and cause intoxication to animals and humans. Therefore, we investigated the MCT-induced cytotoxicity, morphological changes, and oxidative and genotoxic damages to glial cells, using the human glioblastoma cell line GL-15 as a model. The comet test showed that 24 h exposure to 1-500 μM MCT and 500 μM dehydromonocrotaline (DHMC) caused significant increases in cell DNA damage index, which reached 42-64% and 53%, respectively. Cells exposed to 100-500 μM MCT also featured a contracted cytoplasm presenting thin cellular processes and vimentin destabilisation. Conversely, exposure of GL-15 cells to low concentrations of MCT (1-10 μM) clearly induced megalocytosis. Moreover, MCT also induced down regulation of MAPs, especially at the lower concentrations adopted (1-10 μM). Apoptosis was also evidenced in cells treated with 100-500 μM MCT, and a later cytotoxicity was only observed after 6 days of exposure to 500 μM MCT. The data obtained provide support for heterogenic and multipotential effects of MCT on GL-15 cells, either interfering on cell growth and cytoskeletal protein expression, or inducing DNA damage and apoptosis and suggest that the response of glial cells to this alkaloid might be related to the neurological signs observed after Crotalaria intoxication.     

Genotoxicity and subchronic toxicity studies of DHA-rich oil in rats

Polyunsaturated fatty acids, including docosahexaenoic acid (DHA), are natural constituents of the human diet. DHA-algal oil is produced through the use of the non-toxigenic and non-pathogenic marine protist, Ulkenia sp. The safety of DHA-algal oil was assessed in a subchronic toxicity study and in genotoxicity studies. In a 90-day study, rats were orally administered water or DHA-algal oil at concentrations of 0, 500, 1000, and 2000 mg/kg in combination with 2000, 1500, 1000 or 0 mg/kg DHA-containing fish oil, respectively. Additional animals were administered water, 2000 mg/kg DHA-algal oil, or 2000 mg/kg fish oil for 90 days, followed by a 4-week recovery phase. No treatment-related effects were observed in clinical observations, food and water consumption, mortality, gross pathology, and histopathology. Increased body weights and liver weights in oil-treated groups were attributed to the large lipid load and were not regarded as toxicologically significant. Furthermore, no treatment-related differences in the measured parameters between the DHA-algal oil and fish oil groups were detected. In genotoxicity experiments, DHA-algal oil exerted no mutagenic activity in various bacterial strains, nor did it induce chromosomal aberrations in Chinese hamster fibroblast cells. These results support the safety of DHA-algal oil as a dietary source of DHA.     

注射用伏立康唑前药的遗传及生殖毒性研究

目的 研究注射用伏立康唑前药(Voriconazole prodrug,VP)的遗传及生殖毒性.方法 分别采用Ames试验、中国仓鼠肺细胞(CHL)染色体畸变试验、小鼠骨髓微核试验,观察VP的遗传毒性,并通过伴随毒动学试验了解其血浆暴露量;生殖毒性研究了注射用VP对SD大鼠胚胎-胎仔发育毒性的影响,于SD大鼠妊娠第6～ 15天连续iv给药(30、60、120 mg· kg-1·d-1),于妊娠第20天剖检,分析其生殖毒性.结果 遗传毒性的Ames试验、CHL试验和微核试验中,结果均显示为阴性;伴随毒动学试验表明:受试物在小鼠体内呈线性消除;胚胎-胎仔发育毒性试验中,受试物高剂量组中胎鼠头颅骨和/或胸骨异常的数量与溶媒对照组相比显著增加.结论 注射用VP未见明显遗传毒性;受试物在120 mg·kg-1剂量下对胎鼠骨骼发育有一定的毒性作用,未见其他生殖毒性.     

Genotoxicity studies on licorice flavonoid oil (LFO)

Licorice flavonoid oil (LFO) is a new functional food ingredient. In this study, the genotoxicity of LFO was investigated using a test battery of three different methods. In a reverse mutation assay using four Salmonella typhimurium strains and Escherichia coli, LFO did not increase the number of revertant colonies in any tester strain with or without metabolic activation by rat liver S9 mix. In a chromosomal aberration test using Chinese hamster lung (CHL/IU) cells, LFO did not induce any chromosomal aberrations either in the short period test without rat liver S9 mix or in the continuous treatment (24 h or 48 h) test. However, in the short-period test with rat liver S9 mix, LFO induced structural chromosomal aberrations at concentrations higher than 0.6 mg/mL. A bone marrow micronucleus test using male F344 rats was initially conducted. The animals were dosed by oral gavage at doses up to 5000 mg/kg/day. No significant or dose-dependent increases in the frequency of micronucleated polychromatic erythrocytes (MNPCE) were observed and the high dose suppressed the ratio of polychromatic erythrocytes (PCE) to total erythrocytes. Subsequently, a liver and peripheral blood micronucleus test using male F344 rats was conducted. No micronuclei induction either in hepatocytes or PCE was observed even at the highest dose of 5000 mg/kg/day. From the findings obtained from the genotoxicity assays performed in this study and the published pharmacokinetic studies of LFO, it appears unlikely that dietary consumption of LFO will present any genotoxic hazard to humans.     

Genotoxicity testing of low molecular weight fucoidan from brown seaweeds

Fucoidan extracts from brown seaweed have anticoagulant, antithrombotic, and antiviral activities. Low molecular weight fucoidan (LMF) obtained by acid hydrolysis of high molecular weight fucoidan showed more favorable bioactivity. Despite extensive work on LMF bioactivities, detailed studies on the genotoxicity of LMF have not been conducted. As part of a safety evaluation, the potential genotoxicity of LMF was evaluated using a standard battery of tests (bacterial reverse mutation assay, chromosomal aberrations assay, and mouse micronucleus assay). The LMF was determined not to be genotoxic under the conditions of the reverse mutation assay, chromosomal aberrations assay, or mouse micronucleus assay. In a reverse mutation assay using four Salmonella typhimurium strains and Escherichia coli, LMF did not increase the number of revertant colonies in any tester strain regardless of metabolic activation by S9 mix, and did not cause chromosomal aberration in short tests with the S9 mix or in the continuous (24 h) test. A bone marrow micronucleus test in ICR mice dosed by oral gavage at doses up to 2000 mg/kg body weight/day showed no significant or dose-dependent increases in the frequency of micronucleated polychromatic erythrocytes. Use of LMF is presently expected to be safe, as anticipated intake is small compared to doses administered in the genotoxicity assays and may prove to be a useful bioactive agent after further toxicity research.     

Safety assessment of EPA-rich triglyceride oil produced from yeast: Genotoxicity and 28-day oral toxicity in rats

The 28-day repeat-dose oral and genetic toxicity of eicosapentaenoic acid triglyceride oil (EPA oil) produced from genetically modified Yarrowia lipolytica yeast were assessed. Groups of rats received 0 (olive oil), 940, 1880, or 2820 mg EPA oil/kg/day, or fish oil (sardine/anchovy source) by oral gavage. Lower total serum cholesterol was seen in all EPA and fish oil groups. Liver weights were increased in the medium and high-dose EPA (male only), and fish oil groups but were considered non-adverse physiologically adaptive responses. Increased thyroid follicular cell hypertrophy was observed in male high-dose EPA and fish oil groups, and was considered to be an adaptive response to high levels of polyunsaturated fatty acids. No adverse test substance-related effects were observed on body weight, nutritional, or other clinical or anatomic pathology parameters. The oil was not mutagenic in the in vitro Ames or mouse lymphoma assay, and was not clastogenic in the in vivo mouse micronucleus test. In conclusion, exposure for 28 days to EPA oil derived from yeast did not produce adverse effects at doses up to 2820 mg/kg/day and was not genotoxic. The safety profile of the EPA oil in these tests was comparable to a commercial fish oil.     

Genotoxicity studies in the ST cross of the Drosophila wing spot test of sunflower and soybean oils before and after frying and boiling procedures

Sunflower and soybean oils were tested for genotoxicity in the Drosophila wing somatic mutation and recombination assay. Results indicate that both oils produce genotoxic effects when tested without any previous frying or boiling processes. Boiling sunflower oil during fifteen, thirty and sixty minutes significantly increased its genotoxic response; nevertheless, after frying potatoes this oil showed a significant decrease in the genotoxic activity. On the other hand, boiling and frying soybean oil in the same conditions results in a decrease of its genotoxic potential. We have also detected that the amount of total polar materials increases significantly in oils submitted to frying or boiling process. Nevertheless, in oils obtained after frying potatoes, the amount of TPM was higher than after boiling. It is suggested that this effect is probably due to the amount of non-volatile TPM, the fatty acid composition of the oils, the types of frying oil, the high frying temperature and time, and the number of boiling and frying. This is the first study reporting genotoxicity data in Drosophila for the boiling and frying of both sunflower and soybean oils.     

三七护肝胶囊的遗传毒性评价

摘 要 目的：对三七护肝胶囊的急性毒性和遗传毒性进行研究,评价其毒理学安全性。方法: 对三七护肝胶囊进行小鼠经口急性毒性试验、Ames试验、小鼠骨髓细胞微核试验、小鼠精子畸形试验。结果: 三七护肝胶囊对小鼠的急性毒性最大耐受剂量（MTD）大于20 g·kg^-1,属无毒物质;各剂量组Ames试验、微核试验和精子畸形试验结果均为阴性。结论: 在本试验条件下,三七护肝胶囊属于无毒级物质,未显示有遗传毒性作用。     

褐藻糖胶药理活性研究进展

褐藻糖胶是一类来自于海洋褐藻和无脊椎动物的杂多糖,主要成分为硫酸化的岩藻糖及少量的半乳糖、甘露糖、木糖及糖醛酸等。现有研究表明,褐藻糖胶具有诸多药理活性,如抗氧化、抗肿瘤、抗凝血、免疫调节、抗菌抗病毒、降糖降血脂、神经保护等。本文对褐藻糖胶目前研究的主要药理活性进行了总结,以期为其进一步研究和开发提供参考。     

Safety studies of LP20 powder produced from heat-killed Lactobacillus plantarum L-137

The safety of LP20 and its prototype, a powder, with potential use in food, produced from a mixture of dextrin and heat-killed Lactobacillus plantarum L-137, was assessed in an acute study in mice, and in an in vitro bacterial reverse mutation assay, an in vitro chromosome aberration assay, and an in vivo mouse micronucleus assay. LP20 prototype was not acutely toxic when administered to male and female Slc:ICR mice by single gavage at 2000 mg/kg bw. Dosing was not associated with mortality, clinical signs, changes in bodyweight, or macroscopic abnormalities. The LD₅₀ in mice was greater than 2000 mg/kg bw. There was no evidence of genotoxicity of LP20 in the Ames assay (0–5000 μg/plate) or in the in vitro chromosome aberration assay with Chinese hamster lung fibroblasts (0–5000 μg/mL). Administration of two consecutive daily doses of 500, 1000, or 2000 mg/kg bw by gavage to male Crlj:CD-1 mice was not associated with an increased incidence of micronuclei and did not alter the ratio of polychromatic to normochromatic erythrocytes. These studies show that LP20 powder is not acutely toxic and is without genotoxic activity both in vitro and in vivo.     

Genotoxic and antimutagenic activities of extracts from pseudocereals in the Salmonella mutagenicity assay

Extracts of amaranth (Amaranthus L.), sorghum (Sorghumbicolor L.) and Japanese millet (Echinochloafrumentacea L.) were evaluated for mutagenicity in Salmonellatyphimurium strains TA98, TA100 and TA102. All three pseudocereal extracts were also assessed for their antimutagenic properties against the direct mutagens 2-nitrofluorene (2NF) for strain TA98, 3-(5-nitro-2-furyl)acrylic acid (5NFAA) for TA100 and H₂O₂ for TA102 strain and against the indirect mutagen aflatoxin B₁ (AFB₁). No mutagenicity was induced by any of the pseudocereal extracts when tested at concentrations as high as 50 mg/ml. All three extracts showed similar antimutagenicity against 5NFAA and no antimutagenicity against 2NF. The number of revertants induced by H₂O₂ extract was inhibited in order amaranth > Japanese milet > sorghum. All extracts were effective in the inhibition of mutagenic activity of aflatoxin B₁. The total polyphenol content as well as the amount of the flavonoids and phenolic acids as main component of polyphenolics were also determined.