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  • 机译 使用药代动力学模型外推工业化学品的肝浓度以预测肝毒性
    摘要:In this review, we describe the absorption rates (Caco-2 cell permeability) and hepatic/plasma pharmacokinetics of 53 diverse chemicals estimated by modeling virtual oral administration in rats. To ensure that a broad range of chemical structures is present among the selected substances, the properties described by 196 chemical descriptors in a chemoinformatics tool were calculated for 50,000 randomly selected molecules in the original chemical space. To allow visualization, the resulting chemical space was projected onto a two-dimensional plane using generative topographic mapping. The calculated absorbance rates of the chemicals based on cell permeability studies were found to be inversely correlated to the no-observed-effect levels for hepatoxicity after oral administration, as obtained from the Hazard Evaluation Support System Integrated Platform in Japan (r = −0.88, p < 0.01, n = 27). The maximum plasma concentrations and the areas under the concentration-time curves (AUC) of a varied selection of chemicals were estimated using two different methods: simple one-compartment models (i.e., high-throughput toxicokinetic models) and simplified physiologically based pharmacokinetic (PBPK) modeling consisting of chemical receptor (gut), metabolizing (liver), and central (main) compartments. The results obtained from the two methods were consistent. Although the maximum concentrations and AUC values of the 53 chemicals roughly correlated in the liver and plasma, inconsistencies were apparent between empirically measured concentrations and the PBPK-modeled levels. The lowest-observed-effect levels and the virtual hepatic AUC values obtained using PBPK models were inversely correlated (r = −0.78, p < 0.05, n = 7). The present simplified PBPK models could estimate the relationships between hepatic/plasma concentrations and oral doses of general chemicals using both forward and reverse dosimetry. These methods are therefore valuable for estimating hepatotoxicity.
  • 机译 对亲电子应激和活性硫作为调节分子的适应性反应
    摘要:We are exposed to numerous xenobiotic electrophiles on a daily basis through the environment, lifestyle, and dietary habits. Although such reactive species have been associated with detrimental effects, recent accumulated evidence indicates that xenobiotic electrophiles appear to act as signaling molecules. In this review, we introduce our findings on 1) activation of various redox signaling pathways involved in cell proliferation, detoxification/excretion of electrophiles, quality control of cellular proteins, and cell survival during exposure to xenobiotic electrophiles at low concentrations through covalent modification of thiol groups in sensor proteins, and 2) negative regulation of reactive sulfur species (RSS) in the modulation of redox signaling and toxicity caused by xenobiotic electrophiles.
  • 机译 镉,锰和砷的毒理学与金属转运体的作用特别相关
    摘要:The transport systems for metals play crucial roles in both the physiological functions of essential metals and the toxic effects of hazardous metals in mammals and plants. In mammalian cells, Zn transporters such as ZIP8 and ZIP14 have been found to function as the transporters for Mn(II) and Cd(II), contributing to the maintenance of Mn homeostasis and metallothionein-independent transports of Cd, respectively. In rice, the Mn transporter OsNramp5 expressed in the root is used for the uptake of Cd from the soil. Japan began to cultivate OsNramp5 mutant rice, which was found to accumulate little Cd, to prevent Cd accumulation. Inorganic trivalent arsenic (As(III)) is absorbed into mammalian cells via aquaglyceroporin, a water and glycerol channel. The ortholog of aquaporin in rice, OsLsi1, was found to be an Si transporter expressed in rice root, and is responsible for the absorption of soil As(III) into the root. Since rice is a hyperaccumulator of Si, higher amounts of As(III) are incorporated into rice compared to other plants. Thus, the transporters of essential metals are also utilized to incorporate toxic metals in both mammals and plants, and understanding the mechanisms of metal transports is important for the development of mitigation strategies against food contamination.
  • 机译 使用电子病历和人类遗传数据库进行药物警戒研究的未来方向
    摘要:Adverse drug reactions (ADRs) constitute key factors in determining successful medication therapy in clinical situations. Integrative analysis of electronic medical record (EMR) data and use of proper analytical tools are requisite to conduct retrospective surveillance of clinical decisions on medications. Thus, we suggest that electronic medical recording and human genetic databases are considered together in future directions of pharmacovigilance. We analyzed EMR-based ADR studies indexed on PubMed during the period from 2005 to 2017 and retrospectively acquired 1161 (29.6%) articles describing drug-induced adverse reactions (e.g., liver, kidney, nervous system, immune system, and inflammatory responses). Of them, only 102 (8.79%) articles contained useful information to detect or predict ADRs in the context of clinical medication alerts. Since insufficiency of EMR datasets and their improper analyses may provide false warnings on clinical decision, efforts should be made to overcome possible problems on data-mining, analysis, statistics, and standardization. Thus, we address the characteristics and limitations on retrospective EMR database studies in hospital settings. Since gene expression and genetic variations among individuals impact ADRs, pharmacokinetics, and pharmacodynamics, appropriate paths for pharmacovigilance may be optimized using suitable databases available in public domain (e.g., genome-wide association studies (GWAS), non-coding RNAs, microRNAs, proteomics, and genetic variations), novel targets, and biomarkers. These efforts with new validated biomarker analyses would be of help to repurpose clinical and translational research infrastructure and ultimately future personalized therapy considering ADRs.
  • 机译 对基于细胞的发育毒性试验的可预测性的影响分开发展了两个十年
    摘要:Many in vitro developmental toxicity assays have been proposed over several decades. Since the late 1980s, we have made intermittent attempts to introduce in vitro assays as screening tests for developmental toxicity of in-house candidate products. Two cell-based assays which were developed two decades apart were intensively studied. One was an assay of inhibitory effects on mouse ascites tumor cell attachment to a concanavalin A-coated plastic sheet surface (MOT assay), which we studied in the early days of assay development. The other was an assay of inhibitory effects on the differentiation of mouse embryonic stem cell to beating heart cells (EST assay), which we assessed more recently. We evaluated the suitability of the assays for screening in-house candidates. The concordance rates with in vivo developmental toxicity were at the 60% level. The EST assay classified chemicals that inhibited cell proliferation as embryo-toxic. Both assays had a significant false positive rate. The assays were generally considered unsuitable for screening the developmental toxicity of our candidate compounds. Recent test systems adopt advanced technologies. Despite such evolution of materials and methods, the concordance rates of the EST and MOT systems were similar. This may suggest that the fundamental predictivity of in vitro developmental toxicity assays has remained basically unchanged for decades. To improve their predictivity, in vitro developmental toxicity assays should be strictly based on elucidated pathogenetic mechanisms of developmental toxicity.
  • 机译 7-MEGATM 500减轻无毛小鼠皮肤中紫外线B诱导的光老化
    摘要:The purpose of this study was to investigate the effect of 7-MEGA™ 500 on the improvement of skin aging in an UVB-induced photo-aging model of hairless mice. The dorsal skin of hairless mice was exposed to UVB three times a week for 12 weeks to induce skin wrinkle. After inducing the wrinkle, 7-MEGA™ 500 was orally administered once a day for 4 weeks. Skin thickness, skin barrier function, and wrinkle indicators were improved by treatment with 7-MEGA™ 500. Both gene and protein expression levels of MMP-3 and c-Jun in skin were significantly decreased by 7-MEGA™ 500. Therefore, the intake of 7-MEGA™ 500 is thought to have a positive effect on the improvement of skin aging, although further studies are needed.
  • 机译 1,2-二氯丙烷(1,2-DCP)诱导的皮炎血管生成
    摘要:1,2-Dichloropropane (1,2-DCP) has been used as an industrial solvent and a chemical intermediate, as well as in soil fumigants. Human exposure may occur during its production and industrial use. The target organs of 1,2-DCP are the eyes, respiratory system, liver, kidneys, central nervous system, and skin. Repeated or prolonged contact may cause skin sensitization. In this study, 1,2-DCP was dissolved in corn oil at 0, 2.73, 5.75, and 8.75 mL/kg. The skin of mice treated with 1,2-DCP was investigated using western blotting, hematoxylin and eosin staining, and immunohistochemistry. 1,2-DCP was applied to the dorsal skin and both ears of C57BL/6J mice. The thickness of ears and the epidermis increased significantly following treatment, and the appearance of blood vessels was observed in the dorsal skin. Additionally, the expression of vascular endothelial growth factor, which is tightly associated with neovascularization, increased significantly. The levels of protein kinase-B (PKB), phosphorylated PKB, mammalian target of rapamycin (mTOR), and phosphorylated mTOR, all of which are key components of the phosphoinositide 3-kinase/PKB/mTOR signaling pathway, were also enhanced. Taken together, 1,2-DCP induced angiogenesis in dermatitis through the PI3K/PKB/mTOR pathway in the skin.
  • 机译 拟南芥水提取物的毒理学评价及其抗高尿酸血症的潜力
    摘要:Although the dried root of Saposhnikovia divaricata (Turcz.) Schischk. (Umbelliferae) is a popular medicinal plant in East Asia, there has been no systemic toxicological evaluation of a water extract of Saposhnikoviae Radix (SRE). In this experiment, an oral acute and 13-week subchronic toxicological evaluations of SRE (500–5,000 mg/ kg body weight) were performed in both sexes of Crl:CD(SD) rats. Based on the results from mortality, clinical signs, effects on body weight and organ weight, clinical biochemistry, hematology, urinalysis, and histopathology, significant acute, 4-week repeated dose range finding (DRF) and 13-week subchronic toxicity of SRE was not observed in either sex of rats; thus, the no observed adverse effect level (NOAEL) was 5,000 mg (kg/day). To identify anti-hyperuricemia potential of SRE, the suppressive effect of SRE was determined in mice challenged with potassium oxonate (PO; 250 mg/kg) via intraperitoneal injection for 8 days (each group; n = 7). SRE supplementation suppressed the uric acid level in urine through significant xanthine oxidase (XO) inhibitory activity. Kidney dysfunctions were observed in PO-challenged mice as evidenced by an increase in serum creatinine level. Whereas, SRE supplementation suppressed it in a dose-dependent manner. Collectively, SRE was safe up to 5,000 mg (kg/day) based on NOAEL found from acute and 13-week subchronic toxicological evaluations. SRE had anti-hyperuricemia effect and lowered the excessive level of uric acid, a potential factor for gout and kidney failure.
  • 机译 韩国消费者接触防晒喷雾和防晒霜的研究
    摘要:When conducting risk assessments of cosmetic ingredients, it is important that reliable exposure information is obtained for cosmetic products. As cosmetics are becoming more diverse, continuous effort must be made to obtain exposure data that reflect their growth and usage trends. The usage pattern of cosmetics, such as the application area and amount used, may differ by product type and also by country. We conducted a survey to compare the amount of sun spray and sun cream used in a usage environment in South Korea. The study was conducted on Haeundae Beach, one of the most popular beaches in South Korea. A total of 1,255 beachgoers participated in this study; 604 and 651 participants used the sun spray and sun cream, respectively, while sunbathing and enjoying water activities on the beach for one day. Exposure was analyzed following a probabilistic method. On comparing all subjects, it was found that the group that used sun spray (mean: 44.52 g/day) used significantly more product (p = 0.000) than those who used sun cream (mean: 20.51 g/day). By analyzing the daily exposure of sun spray and sun cream per unit body weight according to age and gender, the exposure amount of sun spray and sun cream was found to be highest among 2~9 year-old girls (mean for sun spray: 2.51 g/kg/day, p95: 5.50 g/kg/day, mean for sun cream: 0.79 g/kg/day, p95: 1.79 g/kg/day). The amount of sun spray used is approximately twice that of sun cream. Among both the sun spray and sun cream groups, the exposure amount per unit body weight was highest in girls younger than 10. These factors should be considered when conducting risk assessments of sun spray and sun cream.
  • 机译 明胶的皮内递送减少了皮下脂肪组织中的脂肪积累
    摘要:Subcutaneous adipose tissue (SAT) accumulation is a constitutional disorder resulting from metabolic syndrome. Although surgical and non-surgical methods for reducing SAT exist, patients remain non-compliant because of potential adverse effects and cost. In this study, we developed a new minimally-invasive approach to achieve SAT reduction, using a microneedle (MN) patch prepared from gelatin, which is capable of regulating fat metabolism. Four gelatin types were used: three derived from fish (SA-FG, GT-FG 220, and GT-FG 250), and one from swine (SM-PG 280). We applied gelatin-based MN patches five times over 4 weeks to rats with high-fat diet (HD)-induced obesity, and determined the resulting amount of SAT. We also investigated the histological features and determined the expression levels of fat metabolism-associated genes in SAT using hematoxylin and eosin staining and western blotting, respectively. SAT decreased following treatment with all four gelatin MN patches. Smaller adipocytes were observed in the regions treated with SA-FG, GT-FG 250, and SM-PG 280 MNs, demonstrating a decline in fat accumulation. The expression levels of fat metabolism-associated genes in the MN-treated SAT revealed that GT-FG 220 regulates fatty acid synthase (FASN) protein levels. These findings suggest that gelatin MN patches aid in decreasing the quantity of unwanted SAT by altering lipid metabolism and fat deposition.
  • 机译 鞘脂(生物利用度高的姜黄素)预防高脂饮食诱导的小鼠肝脂肪变性的发展
    摘要:Curcumin, a hydrophobic polyphenol isolated from the Curcuma longa L. plant, has many pharmacological properties, including antioxidant, anti-inflammatory, and chemo-preventive activities. Curcumin has been shown to have potential in preventing nonalcoholic fatty liver disease (NAFLD). However, the low bioavailability of curcumin has proven to be a major limiting factor in its clinical adoption. Theracurmin, a highly bioavailable curcumin that utilizes micronized technology showed improved biological absorbability in vivo. The aim of this study was to investigate the role of theracurmin in modulating hepatic lipid metabolism in vivo. A fatty liver mouse model was produced by feeding mice a high fat diet (HFD; 60% fat) for 12 weeks. We found that treatment for 12 weeks with theracurmin significantly lowered plasma triacylglycerol (TG) levels and reduced HFD-induced liver fat accumulation. Theracurmin treatment lowered hepatic TG and total cholesterol (T-CHO) levels in HFD-fed mice compared to controls. In addition, theracurmin administration significantly reduced lipid peroxidation and cellular damage caused by reactive oxygen species in HFD-fed mice. Overall, these results suggest that theracurmin has the ability to control lipid metabolism and can potentially serve as an effective therapeutic remedy for the prevention of fatty liver.
  • 机译 癌症性别差异的分子标记
    摘要:Cancer is one of the common causes of death with a high degree of mortality, worldwide. In many types of cancers, if not all, sex-biased disparities have been observed. In these cancers, an individual’s sex has been shown to be one of the crucial factors underlying the incidence and mortality of cancer. Accumulating evidence suggests that differentially expressed genes and proteins may contribute to sex-biased differences in male and female cancers. Therefore, identification of these molecular differences is important for early diagnosis of cancer, prediction of cancer prognosis, and determination of response to specific therapies. In the present review, we summarize the differentially expressed genes and proteins in several cancers including bladder, colorectal, liver, lung, and non-small cell lung cancers as well as renal clear cell carcinoma, and head and neck squamous cell carcinoma. The sex-biased molecular differences were identified via proteomics, genomics, and big data analysis. The identified molecules represent potential candidates as sex-specific cancer biomarkers. Our study provides molecular insights into the impact of sex on cancers, suggesting strategies for sex-biased therapy against certain types of cancers.
  • 机译 5-氯-2-甲基异噻唑-3(2H)-One / 2-甲基异噻唑-3(2H)-One(CMIT / MIT)在化妆品中用作防腐剂的风险评估
    摘要:The mixture of 5-chloro-2-methylisothiazol-3(2H)-one (CMIT) and 2-methylisothiazol-3(2H)-one (MIT), CMIT/MIT, is a preservative in cosmetics. CMIT/MIT is a highly effective preservative; however, it is also a commonly known skin sensitizer. Therefore, in the present study, a risk assessment for safety management of CMIT/MIT was conducted on products containing 0.0015% of CMIT/MIT, which is the maximum MIT level allowed in current products. The no observed adverse effect level (NOAEL) for CMIT/MIT was 2.8 mg/kg bw/day obtained from a two-generation reproductive toxicity test, and the skin sensitization toxicity standard value for CMIT/MIT, or the no expected sensitization induction level (NESIL), was 1.25 μg/cm2/day in humans. According to a calculation of body exposure to cosmetics use, the systemic exposure dosage (SED) was calculated as 0.00423 mg/kg bw/day when leave-on and rinse-off products were considered. Additionally, the consumer exposure level (CEL) amounted to 0.77512 μg/cm2/day for all representative cosmetics and 0.00584 μg/cm2/day for rinse-off products only. As a result, the non-cancer margin of safety (MOS) was calculated as 633, and CMIT/MIT was determined to be safe when all representative cosmetics were evaluated. In addition, the skin sensitization acceptable exposure level (AEL)/CEL was calculated as 0.00538 for all representative cosmetics and 2.14225 for rinse-off products; thus, CMIT/MIT was considered a skin sensitizer when all representative cosmetics were evaluated. Current regulations indicate that CMIT/MIT can only be used at concentrations 0.0015% or less and is prohibited from use in other cosmetics products. According to the results of this risk assessment, the CMIT/MIT regulatory values currently used in cosmetics are evaluated as appropriate.
  • 机译 Drometrizole(一种用作紫外线吸收剂的化妆品成分)的风险评估
    摘要:As the use of cosmetics has greatly increased in a daily life, safety issues with cosmetic ingredients have drawn an attention. Drometrizole [2-(2′-hydroxy-5′-methylphenyl)benzotriazole] is categorized as a sunscreen ingredient and is used in cosmetics and non-cosmetics as a UV light absorber. No significant toxicity has been observed in acute oral, inhalation, or dermal toxicity studies. In a 13-week oral toxicity study in beagle dogs, No observed adverse effect level (NOAEL) was determined as 31.75 mg/kg bw/day in males and 34.6 mg/kg bw/day in females, based on increased serum alanine aminotransferase activity. Although drometrizole was negative for skin sensitization in two Magnusson-Kligman maximization tests in guinea pigs, there were two case reports of consumers presenting with allergic contact dermatitis. Drometrizole showed no teratogenicity in reproductive and developmental toxicity studies in which rats and mice were treated for 6 to 15 days of the gestation period. Ames tests showed that drometrizole was not mutagenic. A long-term carcinogenicity study using mice and rats showed no significant carcinogenic effect. A nail product containing 0.03% drometrizole was nonirritating, non-sensitizing and non-photosensitizing in a test with 147 human subjects. For risk assessment, the NOAEL chosen was 31.75 mg/kg bw/day in a 13-week oral toxicity study. Systemic exposure dosages were 0.27228 mg/kg bw/day and 1.90598 mg/kg bw/day for 1% and 7% drometrizole in cosmetics, respectively. Risk characterization studies demonstrated that when cosmetic products contain 1.0% of drometrizole, the margin of safety was greater than 100. Based on the risk assessment data, the MFDS revised the regulatory concentration of drometrizole from 7% to 1% in 2015. Under current regulation, drometrizole is considered to be safe for use in cosmetics. If new toxicological data are obtained in the future, the risk assessment should be carried out to update the appropriate guidelines.
  • 机译 化妆品中乙基己基二甲基PABA的风险评估
    摘要:Ethylhexyl dimethyl para-aminobenzoic acid (PABA) is an oily yellow liquid derivative of water-soluble PABA commonly used in sunscreen. Ethylhexyl dimethyl PABA is widely used as an ingredient in many cosmetics at an average concentration of 1.25% (0.5–2.0%) in Korea. Previous studies, including those involving animals, have demonstrated that ethylhexyl dimethyl PABA is toxic to the following four organs: testis, epididymis, spleen, and liver. In addition, experiments using human keratinocytes found that ethylhexyl dimethyl PABA inhibits cell growth and DNA synthesis at low concentrations, and halted the cell cycle of MM96L cells (human melanoma cell line) at the G1 phase. Despite limited clinical data in humans, many studies have confirmed increased mutagenicity of ethylhexyl dimethyl PABA following exposure to sunlight, which suggests that this molecule is likely to contribute to onset of sun-induced cancer despite protecting the skin through absorption of UVB. For risk assessment, the no observed adverse effect level (NOAEL) chosen was 100 mg/kg bw/day in a 4 weeks oral toxicity study. Systemic exposure dosage (SED) was 0.588 mg/kg bw/day for maximum use of ethylhexyl dimethyl PABA in cosmetics. Based on the risk assessment and exposure scenarios conducted in this study, the margin of safety (MOS) was calculated to be 180.18 for a sunscreen containing 8% ethylhexyl dimethyl PABA, which is the maximum level allowed by the relevant domestic authorities.
  • 机译 化妆品防腐剂三氯生的风险评估
    摘要:Triclosan (TCS) is an antimicrobial compound used in consumer products. The purpose of current study was to examine toxicology and risk assessment of TCS based on available data. Acute toxicities of oral, transdermal and inhalation routes were low, and phototoxicity and neurotoxicity were not observed. Topical treatment of TCS to animal caused mild irritation. TCS did not induce reproductive and developmental toxicity in rodents. In addition, genotoxicity was not considered based on in vitro and in vivo tests of TCS. It is not classified as a carcinogen in international authorities such as International Agency for Research on Cancer (IARC). No-observed-adverse-effect level (NOAEL) was determined 12 mg/kg bw/day for TCS, based on haematoxicity and reduction of absolute and relative spleen weights in a 104-week oral toxicity study in rats. Percutaneous absorption rate was set as 14%, which was human skin absorption study reported by National Industrial Chemicals Notification and Assessment Scheme (NICNAS) (2009). The systemic exposure dosage (SED) of TCS has been derived by two scenarios depending on the cosmetics usage of Koreans. The first scenario is the combined use of representative cosmetics and oral care products. The second scenario is the combined use of rinse-off products of cleansing, deodorants, coloring products, and oral care products. SEDs have been calculated as 0.14337 mg/kg bw/day for the first scenario and 0.04733 mg/kg bw/day for the second scenario. As a result, margin of safety (MOS) for the first and second scenarios was estimated to 84 and 253.5, respectively. Based on these results, exposure of TCS contained in rinse-off products, deodorants, and coloring products would not pose a significant health risk when it is used up to 0.3%.
  • 机译 EDTA和吡啶酮锌联合暴露对大鼠吡啶酮吸收的影响
    摘要:Zinc pyrithione (ZnPT) is a coordination complex of zinc and has been used widely as an anti-dandruff agent in shampoos. Many shampoos contain both ZnPT and EDTA, a chelating agent speculated to increase ZnPT absorption, thereby raising concerns about neurotoxicity. Here, we investigated the effect of EDTA on ZnPT absorption by direct comparison of ZnPT and pyrithione (PT) concentrations in shampoo formulations, and by pharmacokinetic analysis of ZnPT, PT, and 2-methanesulfonylpyridine (MSP), the main ZnPT metabolite, in rat plasma or urine following exposure to shampoo containing ZnPT alone or a combination of ZnPT and EDTA. Approximately 17.3% of ZnPT was converted to PT by the addition of EDTA in the shampoo formulation. Plasma ZnPT and PT concentrations were not measured up to 24 hr after treatment with shampoo containing 1% ZnPT or 1% ZnPT + 2% EDTA in all rats. However, PT amount in 24-hr urine sample, MSP concentration in plasma, and MSP amount in 24-hr urine sample were approximately 4-, 2.6-, and 2.7-fold higher, respectively, in the 1% ZnPT + 2% EDTA shampoo group than in the 1% ZnPT shampoo group. As confirmed by the formulation analysis and in vivo pharmacokinetic analysis, the exposure of ZnPT could be increased by the absorption of PT due to partial dissociation of ZnPT into PT.
  • 机译 离子对反相高效液相色谱法同时测定化妆品中的半胱胺和半胱胺
    摘要:Cysteamine has been used in cosmetics as an antioxidant, a hair straightening agent, and a hair waving agent. However, recent studies indicate that cysteamine can act as an allergen to hairdressers. The objective of this study was to develop and validate a simple and effective reversed-phase high-performance liquid chromatography (RP-HPLC) method for the measurement of cysteamine and its dimer, cystamine. Sodium 1-heptanesulfonate (NaHpSO) was used as an ion-pairing agent to improve chromatographic performance. Separation was performed on a Gemini C18 column (250 mm × 4.6 mm, 5 μm particle size) using a mobile phase composed of 85:15 (v/v) 4 mM NaHpSO in 0.1% phosphoric acid:acetonitrile. UV absorbance was monitored at 215 nm. The RP-HPLC method developed in this study was validated for specificity, linearity, limit of detection, limit of quantitation, precision, accuracy, and recovery. Cysteamine and cystamine were chromatographically resolved from other reducing agents such as thioglycolic acid and cysteine. Extraction using water and chloroform resulted in the recovery for cysteamine and cystamine ranging from 100.2–102.7% and 90.6–98.7%, respectively. This validated RP-HPLC method would be useful for quality control and monitoring of cysteamine and cystamine in cosmetics.
  • 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.
  • 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.

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