碘醚柳胺对大鼠胚胎毒性和致畸性

以23．0,51.8,116.4mg/kg碘醚柳胺在Wistar大鼠妊娠后7－15d口服，各剂量组吸收胎和死胎率增加，活胎率减少，但对胎鼠外观，骨骼和内脏无致畸性，高剂量组对胎鼠生长发育和孕体重增长有明显的负影响，表明碘西边柳胺对大鼠有胚胎毒性，无致畸作用，提出，在临床上怀孕动物应慎用。     

Bioprospecting of Less-Polar Fractions of Ericaria crinita and Ericaria amentacea: Developmental Toxicity and Antioxidant Activity

Ericaria crinita and Ericaria amentacea from the Adriatic Sea (Croatia) were investigated with respect to the presence of less-polar compounds for the first time after fractionation by solid-phase extraction (SPE). The composition of less-polar fractions of freeze-dried E. crinita (FdEc) and E. amentacea (FdEa) were analyzed by high-performance liquid chromatography–high-resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). The major identified compounds were: amides of higher aliphatic acids (palmitoleamide, linoleamide, palmitamide, oleamide and erucamide) and related compounds, carotenoid (fucoxanthin), chlorophyll derivatives (pheophytin a and b and their derivatives) and higher terpenes (loliolide, isoamijiol with its oxidation product), β-stigmasterol and (3β,6α)-14-methylergosta-8,24(28)-diene-3,6-diol). The toxic effects observed on the less-polar fractions obtained from Ericaria species on zebrafish Danio rerio embryos could be associated with the high abundance of all five detected amides. The antioxidant activity of the fractions was evaluated by means of five independent assays, including the reduction of the radical cation (ABTS), the oxygen radical absorbance capacity (ORAC), ferric-reducing antioxidant power (FRAP), the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay and the Folin–Ciocalteu method. A higher antioxidant activity of E. amentacea in comparison to that of the E. crinita fractions was found with IC₅₀ concentrations of 0.072 and 1.177 mg/mL, respectively. The correlation between the activity and the chemical composition revealed that the synergistic effect of different compounds impacted their antioxidant response.     

Albendazole sulphoxide enantiomers in pregnant rats' embryo concentrations and developmental toxicity

Three single oral doses (8.5, 10, and 14 mg/kg) of a racemic formulation of albendazole sulphoxide (ABZSO) were administered to pregnant rats on day 10 of gestation. Mother plasma and embryo concentrations of ABZSO enantiomers and albendazole sulphone (ABZSO(2)) were determined 9 h after administration. The (-)-ABZSO enantiomer showed higher peak concentrations in both maternal plasma and embryo than the (+) enantiomer. An increase in embryo concentrations of ABZSO enantiomers and ABZSO(2) was only observed when dose rose to 14 mg/kg. There was an increase in resorption when the dose increased, but significant differences were only found in the higher dose group when compared with the other groups. The incidence of external and skeletal malformations (mostly of the tail, vertebrae and ribs) rose significantly in the 10 mg/kg group, producing almost 20% and 90% of malformed fetuses, respectively, and gross external and skeletal abnormalities in the thoracic region and limbs were also found.     

氰戊菊酯对鲤科鱼类致突变效应的研究

通过统计草鱼(C tenopharyngodon idellus)外周血红细胞的微核率和斑马鱼(Brachydanio rerio)胚胎致畸率,研究了氰戊菊酯对鱼类的致突变效应。结果显示:氰戊菊酯对1龄草鱼的96 h半致死浓度(LC50)为60.62μg/L;1.2μg/L以上的氰戊菊酯能显著提高草鱼的微核率、核异常率以及总核异常率,三者的变化趋势均是随着暴露时间的延长先升高,达到峰值后再缓慢下降;微核率与空白对照组比较呈显著性差异。表明氰戊菊酯对草鱼染色体畸变有明显影响。在2～32μg/L的氰戊菊酯中,随着浓度的升高,斑马鱼的胚胎死亡率升高、出膜率降低、80%胚胎出膜时间延长,仔鱼畸形率升高,说明氰戊菊酯对斑马鱼胚胎及仔鱼有致畸作用。     

Amikacin-induced Fin Reduction is Mediated by Autophagy

Despite its medical use, little is known about the mechanisms underlying amikacin-induced embryotoxicity, including fin reduction, in zebrafish. In this study, we examined the expression of well-known autophagy markers mTOR (target of rapamycin), atg10 (autophagy-related gene), atg12 and LC3 (mammalian homolog of Atg8) in amikacin-treated zebrafish embryos. Our results indicated that the mRNA expression level of atg12 in the amikacin-treated group was significantly increased by 1.5-fold (p<0.05) compared with the corresponding mock control group, while the expression levels of atg10 and mTOR were significantly decreased by 0.74-fold (p<0.05) and 0.58-fold (p<0.05), respectively. Western blot analysis revealed that LC3 protein expression was induced by amikacin. Taken together, these data suggest that amikacin-induced fin reduction is mediated by fin cell autophagy.     

Toxicity of a synthetic phenolic antioxidant,butyl hydroxytoluene (BHT), in vertebrate model zebrafish embryo (Danio rerio)

The synthetic antioxidant 3,5‐di‐tert‐butyl‐4‐hydroxytoluene (BHT) is widely used as an additive in the food, cosmetic and plastic industries to increase the tenability of food and plastic for the past 70 years. BHT is degraded to 3,5‐di‐test‐butyl‐4‐hydroxybenzaldehyde (BHT‐CHO) in mammals, as well as in the natural environment such as in river and water. The average daily intake of BHT for human being is estimated to be 0.3 mg/kg body weight. Even though it is considered safe for human at authorized level, but its ubiquitous presence in the aquatic environment and the controversial toxicological data are of great concern for human as well as aquatic life. The experimental findings of zebrafish embryo toxicity test (ZFET) showed that the acute toxicity of 96‐hr (LC₅₀) exposure during the embryogenic stage was found to be 4.388 mg/L and the effective concentration (EC₅₀) was 1.375 mg/L. The reduce heart rate from the sublethal concentrations indicates the chemical to be cardiotoxic but a further review is to be needed. The Teratogenic Index (TI) calculated to be 3.19, which implies the compound may be a potential teratogen in aquatic life. The findings obtained in this study will stretch more evidence regarding developmental toxicity of BHT, which will be of much importance in further risk assessment of ecotoxicological studies.     

川楝素对昆明小鼠的胚胎毒性研究

取体重18~25 g雌鼠,超数排卵后与公鼠合笼。获得的孕鼠随机分为 6 组,分别用于研究川楝素对孕鼠2 细胞胚、桑椹胚、囊胚3个时期胚胎的毒性。每个时期均设对照组,以小鼠腹腔注射1/30半数致死量(LD50)的川楝素剂量对以上3个时期试验组孕鼠染毒2次,对照组孕鼠用等量PBS注射。研究其着床时期胚胎毒性时不对小鼠进行超数排卵,但试验组孕鼠染毒3次,对照组孕鼠用等量PBS注射。最后计数、观察4个时期孕鼠子宫内的胚胎数量和形态。结果表明:2 细胞胚、桑椹胚、囊胚时期试验组胚胎总数与对照组相比,没有统计学上差异(P>0 05); 2 细胞期试验组正常胚胎、异常胚胎数量与对照组相比,也无统计学上的差异(P> 0 05);桑椹胚、囊胚时期试验组正常胚胎、异常胚胎数量与对照组相比,具有极显著差异(P<0 01)。3 次染毒对着床后的胚胎毒性最大,子宫内胚胎几乎全部溶解,无法计数。母体组织病理切片观察发现川楝素对主要器官心、肝、肺、肾、子宫仅有轻微损害,提示腹腔注射小剂量川楝素对怀孕小鼠具有特定的胚胎毒性。     

Bioprospecting of Less-Polar Constituents from Endemic Brown Macroalga Fucus virsoides J. Agardh from the Adriatic Sea and Targeted Antioxidant Effects In Vitro and In Vivo (Zebrafish Model)

The endemic brown macroalga Fucus virsoides J. Agardh from the Adriatic Sea was in the focus of the present research. The volatiles of fresh (FrFv) and air-dried (DrFv) samples of F. virsoides obtained by headspace solid-phase microextraction (HS-SPME) and hydrodistillation (HD) were analyzed by gas chromatography equipped with flame ionization detector and mass spectrometry (GC-FID/MS). The major HS-FrFv compound was pentadecane (61.90–71.55%) followed by pentadec-1-ene (11.00–7.98%). In HS-DrFv, pentadec-1-ene was not present, and few lower aliphatic compounds appeared, as well as benzaldehyde and benzyl alcohol. In HD-FrFv, particularly abundant were alkenes (such as pentadec-1-ene (19.32%), or (E)-pentadec-7-ene (8.35%)). In HD-DrFv, more oxidation products were present (e.g., carbonyl compounds such as tridecanal (18.51%)). The fatty acids profile of freeze-dried sample (FdFv) after conversion to methyl esters was determined by GC-FID, and oleic acid was dominant (42.28%), followed by arachidonic acid (15.00%). High-performance liquid chromatography-high-resolution mass spectrometry with electrospray ionization (HPLC-ESI-HRMS) was used for the screening of less polar fractions (F3 and F4) of F. virsoides. Mono- and diglycerides of stearic, palmitic, oleic, and arachidonic acids were found. Terpenoids and steroids comprised the compounds C₂₀H₃₀₍₃₂₎O₂ and C₂₉H₄₈O₍₂₎. Among carotenoids, fucoxanthin was identified. Chlorophyll derivatives were also found (C₅₅H₇₄₍₇₂₎N₄O_(5-7)), dominated by pheophytin a. The antioxidant activity of the fractions was investigated by in vitro assays (oxygen radical absorbance capacity (ORAC), reduction of radical cation (ABTS•⁺), 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay, and ferric reducing antioxidant power (FRAP)) and by in vivo zebrafish model (along with fish embryotoxicity). In vitro experiments proved good radical scavenging abilities of F3 and F4 fractions, which were additionally supported by the protective effect against hydrogen peroxide-induced oxidative stress in zebrafish embryos.     

茶树花对大鼠致畸作用的研究

为研究茶树花对SD大鼠母体及胎仔的致畸毒性,将交配成功的SD孕鼠随机分为4组,每组至少12只。设供试茶树花提取物0．50、1．00、2．00g／kg三个剂量组及阴性对照组,分别在妊娠的7～16天灌胃给予。妊娠期间记录孕鼠体重,于妊娠第20天断头处死孕鼠,记录着床数、活胎数、死胎数和吸收胎数;检查胎鼠外观、内脏和骨骼,并称胎鼠体重,量体长。结果显示,除低剂量组（0．50g／kg）胎鼠体长显著高于对照组外（P〈0．01）,其余剂量组对孕鼠和胎鼠的各项毒效应观察指标与对照组相比均无显著差异。表明在本试验条件下,茶树花对孕鼠生长和胚胎发育无不良影响和致畸作用。     

胚胎毒理体外实验及雄性生殖毒理实验研究概述

寻找并建立简便、快捷、能真实准确的反映化学物质或药物对人类生殖健康危害程度的实验方法是目前国内外研究的热点,胚胎毒理体外实验及雄性生殖毒理实验是评价化学物质致畸的两种重要方法。本文主要介绍了这两种方法在评价化学物质危害性方面近几年国内外的研究应用及其利弊。