Acrylamide and its metabolite glycidamide can affect antioxidant defenses and steroidogenesis in Leydig and Sertoli cells

Acrylamide, which is commonly used in various industries, may also form in food products cooked in high temperatures. Glycidamide, the ultimate genotoxic metabolite of acrylamide, is generated within cells through CYP4502E1-mediated epoxidation. Recent studies have shown that acrylamide and/or glycidamide may cause infertility by disrupting spermatogenesis, decreasing germ cell production and sperm fertilization ability due to their toxic effects on the male reproductive system. This study aimed to determine some direct effects of acrylamide and glycidamide on antioxidant defenses and on steroidogenic enzymes of Leydig and Sertoli cells. For this purpose, mouse Leydig and Sertoli cells were exposed to acrylamide (0.01 or 1?mmol/L) or to glycidamide (0.001 or 0.5?mmol/L) for 24?h. Following the exposure, antioxidant enzyme activities (catalase, superoxide dismutase, glutathione peroxidase and γ-glutamyl transpeptidase), cellular antioxidant levels (glutathione) and steroidogenic enzyme activities (3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase) were calculated. It was shown that acrylamide and glycidamide may cause inhibition of antioxidant and steroidogenic enzymes in Leydig and Sertoli cells. In conclusion, acrylamide and glycidamide may alter testicular function, thereby disrupting male reproduction.     

Synthesis and in vitro anti-inflammatory activity of novel benzo[d] imidazolyl dihydrospiro[indoline-3,1′-isoindole]-2,4′,7′-triones

Synthesis of novel benzo[d]imidazolyldihydrospiro[indoline-3,1′-isoindole]-2,4′,7′-triones has been described. The key intermediate 2-[(2-sulfanyl-1H-benzo[d]imidazol-5-yl)amino]acetic acid is obtained by reacting 5-amino-2-mercapto benzimidazole and chloroacetic acid. The three-component reaction of 2-[(2-sulfanyl-1H-benzo[d]imidazol-5-yl)amino]acetic acid with isatin and 1,4-benzoquinone in the presence of 10 mol% of L-proline at ambient temperature afforded 2′-(2-mercapto-1H-benzo [d] imidazol-5-yl)-3′,3a′-dihydrospiro[indoline-3,1′-isoindole]-2,4′,7′(2′H,7a′H)-triones. All the synthesized compounds were evaluated for in vitro anti-inflammatory activity.     

4种具有α-季碳结构的对位壬基酚异构体的合成和表征

不同来源工业壬基酚混合物(t-NP)中对位壬基酚(p-NP)异构体的组成各不相同,各异构体之间在环境行为等方面也存在着较大差异,因此在壬基酚的环境归趋、生态毒性以及雌激素活性等研究中迫切需要t-NP中不同单个异构体作为模型化合物,然而目前市场上能购买到的直链壬基酚(4-n-NP)异构体不能作为代表.以苯酚和4种含分支结构的壬醇为原料(苯酚与壬醇摩尔比为4:1),以BF3为催化剂,按照Friedel-Crafts烷基化方法合成了t-NP中常见的4种烷基链具有α-季碳结构的对位壬基酚的异构体,即4(3′,5′-二甲基-3′-庚基)-苯酚(p353NP),4(3′,6′-二甲基-3′-庚基)-苯酚(p363NP),4(2′,6′-二甲基-2′-庚基)-苯酚(p262NP)和4(3′-甲基-3′-辛基)-苯酚(p33NP).合成的壬基酚粗产物用硅胶柱色谱法提纯后的纯度达99%,并经紫外可见分光光度计、荧光分光光度计、HPLC、GC-MS、1H-和13C-NMR进行了表征.合成的4种p-NP异构体可被用于壬基酚的雌激素活性、毒理、代谢和环境归趋等研究.     

粗壮女贞中的新单萜配糖体

从粗壮女贞（Ｌｉｇｕｓｔｒｕｍ ｒｏｂｕｓｔｕｍ）叶子中分离鉴定了４个新的单萜配糖体,命名为粗壮女贞甙Ｄ、Ｇ、Ｈ和Ｌ．通过滤谱及化学方法,它们分别鉴定为香叶醇３‘－Ｏ－μ－Ｌ－南鼠李糖基－４’－顺式香豆酰基－β－Ｄ－吡喃葡萄糖甙（１）,６－羟基－３,７－二甲基－２Ｅ,７葵二烯醇３‘－Ｏ－α－Ｌ－吡喃鼠李糖基－４’反式香豆酰基－β－Ｄ－吡喃葡萄糖甙（２）,６－羟基－３,７－二甲基－２Ｅ,７－葵二烯醇     

EEDs对鱼类性激素合成途径干扰作用研究进展

环境内分泌干扰物(environmental endocrine disruptors,EEDs)是一类可以改变生物体内激素的合成、释放、运输、代谢、结合、作用或清除等一系列生物过程的外源物质。性激素的生物合成需要一系列酶的参与,体内和体外研究表明,性激素合成途径中的类固醇生成酶是EEDs通过非性激素受体介导途径发挥内分泌扰乱作用的重要靶点,性激素合成途径的扰乱可能导致生物体生殖系统受损。本文综述了EEDs对鱼类性激素合成底物和类固醇生成酶的影响、信号转导机制及其生殖危害;并对性激素合成途径中促性腺激素调控机理、多种转录因子间的相互作用、不同物种间类固醇生成酶的差异以及各内分泌轴线的相互作用研究进行了展望,以期为EEDs通过非性激素受体介导途径发挥内分泌干扰效应的机制研究提供思路。     

Regression models to estimate total concentrations of polybrominated diphenyl ethers: data from NHANES 2003–2004

The objective of this study was to develop regression models to estimate the total concentration of polybrominated diphenyl ethers in serum based on the known concentrations of a limited number of congeners. Because of the possible adverse health effects associated with the exposure to polybrominated diphenyl ethers, it is of interest to know their total concentrations. Data from the National Health and Nutrition Examination Survey for 2003–2004 (N = 1859) were used to develop regression models to estimate both wet weight and lipid-adjusted total concentrations. Only the knowledge of three congeners, namely, 2,2′,4,4′-tetrabromodiphenyl ether, 2,2′,4,4′,5-pentadibromodiphenyl ether, and 2,2′,4,4′,5,5′-hexabromodiphenyl ether was required to use these models. Other than the concentrations of these three congeners, age, gender, and smoking status were the only information needed to use these models. Optionally, models were developed that could also use the race/ethnicity of the participants. All models explained more than 98% of the known variability in the observed total concentration levels. Over 98% of the model generated, predicted values were found to be within 5% of the observed values.     

水源水中有机提取物生殖毒性评价和敏感检测指标的筛选（Reproductive Toxicity of Drinking Source Water and Selection of Sensitive Bioassays）

以原代培养的大鼠睾丸细胞为体外毒性试验靶细胞,采用支持细胞、生精细胞、间质细胞的形态、细胞活力、胞外乳酸脱氢酶(LDH)活力、细胞早期凋亡坏死率和间质细胞睾酮分泌量5种检测指标评价了X市和L市水源水中有机提取物的生殖毒性,并筛选了对痕量有机污染物敏感的生殖毒性指标.研究结果表明,两市水源水中有机提取物皆可引起支持细胞、间质细胞和生精细胞形态的变化,相比较而言,对生精细胞的影响更严重.X市水源水有机提取物对3种生殖细胞胞外LDH活力没有显著影响(p>0.05);而在L市水源水中有机提取物的暴露下,支持细胞和间质细胞胞外LDH活力显著增强(p<0.01).X市水源水中有机提取物可使间质细胞睾酮分泌量显著减少(p<0.01);而L市水源水有机提取物对间质细胞睾酮分泌量无明显影响(p>0.05).两市水源水有机提取物均能不同程度地诱发大鼠睾丸细胞损伤,生精细胞对环境毒物是比较敏感的细胞,细胞形态、活力、LDH活力、凋亡坏死率、睾酮分泌量等生殖毒理学检测指标可用于饮用水源地水质的评价.     

柳叶忍冬的化学成分研究

从柳叶忍冬95%乙醇提取物中首次分离并鉴定了20个化合物: ( )-cycloolivil (1)、( )-fraxiresinol (2)、prinsepiol(3)、软脂酸(4)、对甲基苯酚(5)、2,4-二羟基-3,6-二甲基苯甲酸甲酯(6)、洋芹素(7)、木犀草素(8)、5,7,4′-三羟基黄酮醇7-O-β-D-吡喃葡萄糖苷(9)、槲皮素(10)、染料木素(11)、5,4′-二羟基-7-甲氧基异黄酮(12)、染料木素5-O-β-D-吡喃葡萄糖苷(13)、5,4′-二羟基-7-甲氧基异黄酮5-O-β-D-吡喃葡萄糖苷(14)、5,7,4′-三羟基双氢黄酮7-O-β-D-吡喃葡萄糖苷(15)、丁二酸(16)、( )-儿茶素(17)、( -)-表儿茶素(18)、谷甾醇(19)和胡萝卜苷(20).应用波谱方法及与已知品对照进行结构鉴定.其中,化合物10、17和18是抑制血管紧张素转化酶的活性成分.表4参63     

Activity of nucleoside triphosphate diphosphohydrolase, 5′-nucleotidase,and adenosine deaminase in cattle fed on pastures treated with different nitrogen fertilizers

The aim of this study was to evaluate nucleoside triphosphate diphosphohydrolase, 5′-nucleotidase, and adenosine deaminase activities in cattle fed on cuttings from pastures fertilized with urea compared to animals fed on cuttings from organically fertilized or from non-fertilized pastures. Blood samples were collected up to 9 h after feeding, and nitrite and enzyme activities were evaluated. The animals feeding on urea-fertilized pasture suffered subclinical intoxication. Serum nitrite levels increased by about 50% and adenosine deaminase activity increased almost sixfold 4 and 6 h after feeding on urea-fertilized pasture, and adenosine deaminase in platelets almost doubled 6 and 9 h after feeding. In platelets, nucleoside triphosphate diphosphohydrolase activity with adenosine triphosphate as substrate increased 2, 4, 6 and 9 h after feeding while nucleoside triphosphate diphosphohydrolase with adenosine diphosphate as substrate and 5′-nucleotidase activities increased only 9 h after feeding. Increased activities of these enzymes may be implicated in the pathophysiology of subclinical intoxication since they are involved in many biochemical functions.     

曲霉sp.136的化学成分研究

从曲霉sp.136的固体发酵物中分离得到6个化合物.应用波谱分析及与已知品对照的手段将它们鉴定为烟曲霉酸(1)、(20S,22E,24R)-5α,8α-表二氧-麦角甾-6,22-二烯-3β-醇(2)、β-谷甾醇(3)、(2S,3S,4R)-2-[(2′R)-2′-羟基二十四烷酰氨基]-1,3,4-三羟基十八烷(4)、4-羟基苯乙酸(5)和烟碱酸(6).图1参5     

PFOS青春期暴露对成年期雄性大鼠的生殖毒性

为探究青春期的PFOS暴露对成年后的SD大鼠的生殖毒性,对出生后第21天(PND21)的SD大鼠经口灌胃不同剂量的PFOS(5、10和20mg·kg~(-1)),连续染毒7d,在出生后第56天(PND56)时,对各染毒组SD大鼠的体质量、精子数量、血清中的睾酮浓度,以及睾丸间质细胞睾酮合成的相关基因mRNA水平进行了检测。结果显示,10mg·kg~(-1)剂量组大鼠体质量较对照组明显下降(P<0.01);精子数量在10mg·kg~(-1)和20mg·kg~(-1)剂量组明显降低(P<0.05);血清中睾酮浓度随着PFOS剂量的加大有明显下降的趋势,20mg·kg~(-1)剂量组显著低于对照组(P<0.05);类/胆固醇相关基因star和cyp11α1的mRNA表达水平明显下调。研究表明,青春期的PFOS暴露会导致睾酮合成途径中相关因子的功能缺失,破坏成熟睾丸间质细胞的功能,致使睾酮水平降低,并抑制精子生成,从而破坏生殖系统的功能。     

Bestimmung von Nitrodiphenylaminen und verwandten Verbindungen im Sickerwasser einer Rüstungsaltlast

Goal, Scope and Background

Nitrodiphenylamines can be found at abandoned military sites where the explosive 2,2′,4,4′,6,6′-hexanitrodiphenylamine (hexyl) or diphenylamine as a stabilizer of smokeless powder was handled. Aim of the present study is the development of HPLC methods for the analysis of contaminants which can be expected in particular under aerobic conditions at premises which are contaminated by nitrodiphenyl-amines and related compounds.

Methods

A list of 13 compounds which can be expected at these explosives factories was deduced from literature studies. HPLC methods were developed for the analytes. Water samples from the unsaturated zone of a former hexyl-producing factory were collected by suction cups and the material was analysed according to these procedures to demonstrate the practicability of the new methods and to verify the existence of the postulated compounds in the environment of the former nitration plant.

Results and Conclusion

The new HPLC methods are suitable for the exploration of sites contaminated by nitrodiphenylamines. Beside some hexyl its intermediates 1-chloro-2,4-dinitrobenzene, 2,4-dinitrodiphenylamine und 2,2′,4,4′-tetranitrodiphenylamine were identified in the leachate water.

Recommendation and Perspective

It is advisable to include at least these 4 compounds in the examination of former hexyl-producing plants. Several unknown peaks were observed in the HPLC-chromatogram. It is recommendable to perform further investigations of the unidentified compounds to compile a final list of analytes for military sites polluted by nitrodiphenylamines.     

台湾海峡水域的β—葡萄糖苷酶活性

本研究分别在1997年8月10日至8月19日，1998年2月20日至3月7日，对台湾海峡进行现场调查研究，在九个断面20个站位取得水文、化学和生物学综合参数，研究该海域β－葡萄糖苷酶活性（βGlcA)，细菌生物量及生产力的时空动态，主要结果如下①夏季台湾海峡南部各站位βGlcA的值为1．94mmol/L^-1h^-1，变化幅度大于（0．31－8．1nmol/L^-1h^-1；冬季海峡北部βGlcA平均值为0．86nmol/L^-1h^-1，变化幅度大（0．34－1．89nmol/L^-1h^-1)远小于夏季。②以碳的转化量表示，夏冬两季的βGlcA分别为0．14μgL6-1h^-1和0．062μgL6-1h^-1，分别高于这两个季节的细菌生产力。③从离岸到近岸，细菌胞外酶活性升高。④该海域胞牙酶活性与细菌的二次生产力的相关性不够明显。⑤βGlcA的剖面分布及周日变化与细菌生产力的相关性不很明显。⑥表层水游离态的细菌的βGlcA，在整个海区的分布特征与该水层的总βGlcA分布特征相似。     

ZnO纳米粒子通过线粒体通路抑制小鼠光感受器细胞Na~+/K~+-ATP酶表达和活性的作用研究

氧化锌(ZnO)纳米粒子已被发现具有生物毒性,氧化应激被认为是最重要的因素之一。前期实验证实,ZnO纳米粒子能显著减少锰超氧化物歧化酶(Mn SOD)蛋白的表达,降低Mn SOD活性。本文通过检测乳酸脱氢酶(LDH)释放、线粒体活性氧(ROS)水平和膜电位(Δφm)、延迟整流钾电流变化和Na~+/K~+-ATP酶的表达及活性等变化,检测ZnO纳米粒子对小鼠光感受器细胞的细胞毒作用。结果表明,ZnO纳米粒子可显著增强小鼠光感受器细胞中LDH的释放、增加线粒体内ROS水平并下调Δφm、阻断延迟整流钾电流,同时降低Na~+/K~+-ATP酶的表达及活性,从而对小鼠视网膜光感受器细胞产生细胞毒作用,提示ZnO纳米粒子可通过线粒体通路引起氧化应激,从而抑制小鼠光感受器细胞Na~+/K~+-ATP酶表达和活性,产生细胞毒性,导致细胞死亡。本文的研究结果有助于理解ZnO纳米粒子引起细胞毒性的作用机理。     

Biologie du chinchard de la Mer Noire (Trachurus meditarraneus ponticus)

A study has been made regarding the action of the hydrocortisone, testosterone and 17β-estradiol on isolated liver and spleen tissue homogenates or slices of male and female adults of the fish Trachurus mediterraneus ponticus. The results showed a decrease of the oxygen uptake and of the cytochrome oxydase and succinic dehydrogenase activity of the liver homogenate after hydrocortisone administration, while this hormone increased significantly the lactic acid production in both tissues. Testosterone acted in an opposite manner to hydrocortisone by increasing the intensity of oxygen consumption and the succinic dehydrogenase activity, but decreased the lactic acid production of the liver and spleen tissue preparations. Estradiol decreased the oxygen consumption of the liver, the cytochrome oxydase activity and the lactic acid production in both tissues of female Trachurus mediterraneus ponticus.     

Monitoring of cellular enzymes in the serum of electroplating workers at Coimbatore

Chromium compounds are potent toxic and carcinogenic substances. With respect to toxicity, hepatic and renal toxicity have been reported both in workers and in animals exposed to chromium (VI). Chromium (VI) compounds induces DNA damage in vivo and in cultured cells as well as the cytotoxicity evaluated by the leakage of lactate dehydrogenase. The present study reports the cytotoxicity of chrome platers who are employed from 8 to 25 years in electroplating industries at Coimbatore, Tamilnadu. Blood samples were collected and estimated for glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and total protein in the serum. The study revealed that there is a significant elevation in the level of LDH, ALP, CPK and transaminases and a decrease in total protein in serum. The results of the study suggests that chromium (VI), a hepatotoxic chemical may perhaps damage the plasma membrane resulting in leakage of enzymes in to the serum of chromeplaters.     

Characterization of enzymes responsible for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) detoxification pathway in lungs of Chinese population: Carbonyl reduction and glucuronidation

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most potent carcinogens found in mainstream and sidestream smoke and considered to be a causative agent for lung cancer in active and passive smokers. Carbonyl reduction followed by glucuronidation is considered to be the main detoxification pathway of NNK. Microsomal 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD 1) and cytosolic carbonyl reductase (CR) are responsible for NNK carbonyl reduction, and UDP-glucuronosyltransferase 1A4 (UGT1A4) and UDP-glucuronosyltransferase 2B7 (UGT2B7) catalyze 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) glucuronidation. To better characterize this pathway, the expression and kinetics of 11β-HSD 1 and CR, as well as the expression of UGT1A4 and UGT2B7, was investigated in lungs of Chinese people. Kinetic studies for 11β-HSD 1 and CR showed that there was large inter-individual variability in the capacity for NNK carbonyl reduction. Compared with cytosol, there was increased catalytic efficiency for NNAL formation in microsomes. The higher activities of both 11β-HSD 1 and CR were observed in lung tissues of males than females. UGT1A4 and UGT2B7 mRNA were detected in lungs from a variety of different patients and wide inter-individual variations were observed. These observations should be useful in improving the risk estimates and prevention of lung cancer for the Chinese population exposed to tobacco smoke.     

Metabolic and molecular stress responses of the gilthead seabream Sparus aurata during long-term exposure to increasing temperatures

Tolerance to a changing climate regime and persistence in the natural environment depends on the limited capacity to acclimate to changing temperatures. The present study aimed to identify and characterize thermal limits of the Mediterranean fish Sparus aurata as well as the processes providing heat protection during exposure to high temperatures. Processes studied included heat shock protein expression, protein kinase activity and metabolic adjustments. Molecular responses were addressed through the expression of Hsp70 and Hsp90 and the phosphorylation of stress-activated protein kinases, p38 mitogen-activated protein kinase (p38 MAPK) and cJun-N-terminal kinases (JNKs). Thermal impacts on metabolic capacities were assessed by studying the maximum activities of citrate synthase (CS), malate dehydrogenase (MDH) and 3-hydroxyacyl CoA dehydrogenase (HOAD) as well as pyruvate kinase (PK) and lactate dehydrogenase (L-LDH). The expression of Hsp70 and hsp90 was activated when the fish were exposed to temperatures beyond 20°C. Increased phosphorylation of p38 MAPK and JNKs indicated the parallel activation of MAPK signaling cascades and the potential involvement of MAPKs in the induction of Hsp genes. Exposure to extreme temperatures beyond 24°C caused an increase in the enzymatic activity of PK and LDH indicating an enhanced glycolytic potential.