有机氯农药硫丹的生殖毒性及其机制研究进展

硫丹作为一种广谱有机氯农药,在农业区域周边的土壤和水体中都存在较高残留,2011年被斯德哥尔摩公约列入持久性有机污染物(POPs)名单。硫丹已被证实对神经系统、心血管系统、肝、肾等具有毒性作用,关于其生殖毒性的研究很多,但潜在机制尚不完全清楚。本文总结了硫丹导致的不同动物的生殖毒性,并从生殖器官和生殖细胞损伤、氧化应激以及DNA损伤、生殖细胞周期阻滞及细胞凋亡等方面,对近年来硫丹生殖毒性及其作用机制研究进展进行综述,并对其中存在的问题进行讨论,以期有助于深入了解硫丹的毒性效应。     

Comparison of in vitro characteristics of and experimental lesions produced by a clinical and an environmental isolate of Aspergillus flavus

In the present study, two strains of Aspergillus flavus (one from a human corneal ulcer and one from the environment) were found to be strikingly similar in vitro in terms of thermotolerance, inability to grow in an anaerobic environment and in secreting proteinases; however, one obvious difference was that the clinical isolate produced 120 ppb of aflatoxin B1 in glucose salt medium while the environmental isolate did not produce this toxic metabolite. Alterations in the activities of acid phosphatase (ACP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and glutathione-S-transferase were observed in the liver, kidney and serum in an experimental rat model, irrespective of whether the animal had been challenged with the clinical isolate or the environmental isolate of A. flavus. In rats that had been challenged with the clinical isolate, a significant decrease in the activity of kidney ALP was noted, whereas in rats that had been challenged with the environmental isolate, the reverse was observed. While these differential alterations may have occurred due to differences in the toxin-producing ability of the two isolates, further investigation is warranted to clarify whether other phenotypic, or genotypic, differences are also involved.     

Effect of surfactants on phosphatase level of fresh water fish Labeo rohita

Alterations in the activity of enzymes Acid phosphatase (E.C.3.1.3.2) and Alkaline phosphatase (EC 3.1.3.1) in organs such as liver, gills and muscle of rohu following its exposure to surfactants viz. CTAB, SDS and Triton X-100 were analyzed. Different levels of exposure were given depending on the LC50 value of the surfactant used. Also, the influence of age and weight of the organisms was tested simultaneously. The activity of ACP in the tissues of fish exposed to all the three surfactants showed marked enhancement after exposure; the effect being highest in the liver followed by gill and muscle. Activity levels of ALP in different tissues of the fish exposed to the surfactants also showed an increase. Maximum increase was found in the liver followed by muscle, and gill. The increase in the levels of these enzymes indicates a stressful condition of the fish.     

Sub-chronic exposure to carbendazim induces biochemical and hematological alterations in male goats

The present investigation reports the effect of repeated (90 days) administration of carbendazim on the biochemical and hematological parameters in male goats. Carbendazim administered orally at a daily dose of 50 mg kg^?1 body weight for 90 consecutive days resulted in increased plasma concentration of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), creatinine and albumin, while alkaline phosphatase (ALP) and glucose levels were decreased. Decrease in total leukocyte (TLC) and neutrophil count and increase in lymphocyte count was observed in the treatment group. The findings of the present investigation indicate that sub-chronic exposure to carbendazim in male goats causes hepatic and slight kidney dysfunctions.     

Endosulfan induced changes in phospholipids in the freshwater female catfish, Heteropneustes fossilis (Bloch)

The catfish, H. fossilis were exposed to endosulfan for 30 days at sub-lethal concentration (0.002 ppm) during different phases of its annual reproductive cycle. Its impact on total (TP) and different phospholipids- phosphatidylcholine (PC), phosphatidylserine (PS), phosphatdylinositol (Pl) and phosphatidylethanolamine (PE) were measured in liver plasma and ovary. On pesticide exposure, during preparatory phase, the hepatic TP PC and PE were declined. The plasma levels of TP, PC and PS were declined with the elevation of PE whereas in ovary only PC was lowered after endosulfan exposure. During pre-spawning phase, the hepatic TP, PC and PE declined in liver plasma and ovary after endosulfan exposure. During spawning phase, only plasma and ovarian phospholipids showed decrease in their levels following endosulfan exposure. In the post-spawning phase, endosulfan elevated the levels of TP, PC and PS in ovary but had no effect on their levels in liver and plasma. During resting phase, the TP, PC and Pl were found to be decreasing its levels. Thus it appears that this pesticide interfere with phospholipids metabolism during annual reproductive cycle of this species.     

非暴露式气管滴注3种典型纳米材料对大鼠肝、肾的毒性效应

为探讨纳米二氧化硅(Nano-SiO2)、纳米四氧化三铁(Nano-Fe3O4)和单壁碳纳米管(SWCNTs)对大鼠肝、肾的毒性效应,将49只雄性Wistar大鼠随机分为7组,包括生理盐水对照组,以及3种纳米材料的低剂量组(2mg·mL-1)和高剂量组(10mg·mL-1),采用非暴露式气管滴注法染毒,每2d染毒1次,每次每只0.2mL,共染毒5周,眼眶取血后处死大鼠,称肝、肾重量计算脏器系数,测定大鼠血清中反映肝、肾功能的生化指标,并对肝、肾进行病理学观察.结果表明,1)3种纳米材料均可导致大鼠体重明显降低,但对肝、肾脏器系数无明显影响;2)病理学观察发现,3种纳米材料均可导致大鼠肝细胞轻度脂肪变性,肾脏则无明显改变;3)3种纳米材料均可导致大鼠肝功能异常,部分肝功能指标如谷草转氨酶(AST)、碱性磷酸酶(ALP)、谷丙转氨酶(ALT)等出现显著降低;4)3种纳米材料均可导致大鼠肾功能异常,部分肾功能指标如尿酸(UA)、肌酐(CREA)、尿素氮(BUN)等出现显著升高或降低.以上结果提示,经呼吸道染毒的Nano-SiO2、Nano-Fe3O4和SWCNTs均可对大鼠肝、肾产生一定的毒性效应.     

Histopathological alterations of Nile tilapia, Oreochromis niloticus in acute and subchronic alachlor exposure

Histopathological alterations in Nile tilapia, Oreochromis niloticus, aged 3 months and subjected to acute and subchronic alachlor exposure were studied by light microscopy LC50 values of alachlor for 24 hr 48 hr, 72 hr and 96 hr were 963.6, 563, 448, and 381.9 microg l(-1), respectively and the maximum acceptable toxicant concentration (MATC) was 350 microg l(-1). Fish were exposed to 381.9 (acute) and 35 microg l(-1) (sub-chronic) of alachlor for 24, 48, 72 and 96 hr and 90 days, respectively Gill lamellae and kidney tubules were the primary target organs for the acute toxic effect of alachlor while in the subchronic exposure, the toxic effect on the gills was less marked than that of the kidneys and liver Gill alterations included edema of the epithelial cell system, aneurisms with some ruptures, hypertrophy and hyperplasia of epithelial cells. The liver showed hydropic swelling of hepatocytes and vacuolation. Lipid vacuoles were observed in hepatocytes in the second and third month of subchronic exposure. The kidney showed hydropic swelling of tubular cells, lipid vacuole accumulation in many tubules, and nuclear pyknosis. The findings of this study could be used as a guideline forbiomonitoring programs on populations of Nile tilapia cultured near alachlor contaminated areas.     

Acute toxicity effect of the venom of the marine snail, Conus zeylanicus

Acute toxicity of the venom of Conus zeylanicus was studied to evaluate its risk and toxic factors in view of human safety The lethality of the crude venom (LD50 -60 mg/kg via i.p.) in mice was associated with increased heart rate and strong muscular hind limb paralysis, skeletal muscle paralysis, dyspnea, loss of spontaneous activity followed by respiratory failure. The effect on vital tissues revealed liver tissues were disrupted with hemorrhagic necrosis and the lung showed the pathogenic changes of diffused inflammation of the parenchyma and obliteration of the alveolar space. In brain, edema was observed throughout the parenchyma and the kidney shows the tubules with cloudyswelling of the lining cells and the parenchyma inflammation and few inflammatory cells infiltration.     

Effect of fenvalerate technical grade on acetyl cholinesterase activity in Indian bullfrog Haplobatrachus tigerinus (Daudin)

Indian bullfrog Haplobatrachus tigerinus (Daudin) was exposed to sublethal dose (1/3 of LC50 I.E. 1.166 mg/kg) of fenvalerate technical grade and the effect was studied on the specific activity of acetyl cholinesterase in the different tissues of frog viz., brain, muscle, liver, kidney and testis at different time periods viz., 3,6, 12, 24, 48 and 72 hours. The inhibition of specific activity of acetyl cholinesterase was in the order of kidney > brain > muscle > liver > testis. A significant inhibition was noticed in kidney at 12 hours (-64.33%) and no effect was noticed at 3 hours in testis (+0.67%). The AChE activity was inhibited in first three hours of administration of fenvalerate in all the tissue tested. The inhibition continued upto 6 hours or 2 hours in different tissue but the recovery was started by 24 hours and almost completed by 72 hours.     

Toxicity of cypermethrin on total lipids and free fatty acids in liver,muscle, kidney and ovary of Clarias batrachus (L) and recovery response

Alterations in the levels of lipid metabolites, total lipids and free fatty acids, were studied in physiologically important tissues viz; liver, muscle, kidney and ovary of a freshwater edible fish Clarias batrachus. The fish was exposed to sublethal concentration (1/3 of LC50 value for 96?h) of a synthetic pyrethroid insecticide, cypermethrin for 1, 5 and 10 days. After 10 days of exposure, fish were released into fresh water and total lipids and free fatty acids were determined at intervals of 1, 5 and 10 days to assess fish recovery response after cessation of cypermethrin exposure. Fish showed an increased rate of lipogenesis in liver, muscle, kidney and ovary during the exposure period followed by a decrease after transfer of fish into fresh water. There was also an elevation in liver and kidney free fatty acids contents, while the muscle and ovary free fatty acid contents were reduced during exposure period. The alterations in free fatty acids were restored to near normal values after 10 days of cessation of exposure.     

Variations in carbohydrate metabolism during gonad maturation in female turbot (Scophthalmus maximus)

Several carbohydrate metabolism pathways were studied in four different tissues (liver, gonad, kidney and white muscle) of female turbot (Scophthalmus maximus) at three different stages of gonad maturation, i.e., previtellogenesis, early vitellogenesis and late vitellogenesis. During carbohydrate metabolism in the liver, the only major change noticed throughout vitellogenesis was increased glycolytic activity at early vitellogenesis. The major changes observed in the gonad during vitellogenesis were an increased use of exogenous glucose and increased gluconeogenesis, which were reflected in increased glucose levels throughout vitellogenesis accompanied by a small increase in glycogen levels. Changes observed in carbohydrate metabolism in the kidney pointed to increased gluconeogenesis during early vitellogenesis. Finally, during ovarian maturation, the muscle mobilized proteins whose constituent amino acids could have been used in other tissues either as substrates for gluconeogenesis or for protein synthesis. As an overall conclusion, changes in the carbohydrate metabolism of female turbot during maturation are quite marked in the gonad, kidney and white muscle, in contrast to other species, in which major changes have been previously reported to occur in the liver.     

稻米来源镉对生长期猪的生长特性及不同脏器组织镉蓄积的影响

环境中的镉污染对动植物及人类都带来了极大的危害。目前,多数镉毒理研究关注其无机状态,而来源于稻米的有机态镉的毒害作用报道较少。为评估稻米来源镉对生长期猪的毒性作用,选用初始体重为30 kg左右的健康生长猪28头,随机分为体重无明显差异的2组,即对照组与稻米来源镉组(试验组),研究稻米来源镉对生长期猪(生长及育肥全阶段)的生长特性及不同脏器组织镉蓄积的影响。结果表明,在生长及育肥阶段,试验组与对照组相比:1)生长特性无显著差异(P0.05);2)育肥期组织游离氨基酸含量,除肌肉中的赖氨酸显著降低外(P0.05),血浆、肝脏、肾脏及肌肉中其他游离氨基酸水平均无显著差异(P0.05);3)心脏、肝脏、脾脏、肾脏、肺脏、胃、小肠、大肠、骨骼中镉蓄积量显著增高(P0.05),而肌肉、血液中无显著差异(P0.05),脂肪、皮中未检出镉。日粮使用大比例镉超标稻米后镉在各脏器和组织中的蓄积规律为肾脏肝脏小肠脾肺大肠胃血液骨头心腿肌背肌脂肪、皮。由此可见,镉超标稻米对生长期猪的生长特性未产生显著的影响,稻米来源镉主要蓄积于肝脏和肾脏,而主流食用组织肌肉和血液中镉的蓄积量较少。     

Influence of endosulfan and monocrotophos exposure on the activity of NADPH cytochrome C reductase (NCCR) of Labeo rohita (Ham)

The response of NADPH cytochrome C reductase (NCCR) activity in liver of Labeo rohita fish exposed to the pesticides, 0.25 microgl(-1) endosulfan and 2 mg/l monocrotophos was studied. In terms of specific enzyme activity (mU/mg protein) a significant level of NCCR was observed in the liver tissues of Labeo rohita exposed to the pesticides, when compared to the control fish (2.460 mU/mg protein). Increase of NCCR activity was more in the liver of the fish exposed to monocrotophos (4.595 mU/mg protein) than those exposed to endosulfan (2.850 mU/mg protein). The results demonstrate that the pesticides, endosulfan and monocrotophos, interfere with NADPH dependent monoxygenase mechanism and are effective inducers of NADPH cytochrome C reductase. The activity of NCCR in the liver tissue of Labeo rohita may serve as a useful tool for monitoring aquatic pollution.     

硫丹对草鱼乙酰胆碱酯酶及抗氧化酶活性的影响

研究了硫丹暴露对草鱼肝脏、肌肉抗氧化酶及脑乙酰胆碱酯酶活性的影响。结果表明,硫丹24 h暴露可诱导草鱼脑AChE活性,当暴露时间延长或质量浓度升高时,AChE活性表现为受抑制,120 h较高质量浓度组抑制率为41.8%和56.2%,抑制率与暴露时间呈良好的线性相关。硫丹暴露24 h后,草鱼肝脏及肌肉SOD、GSH-Px活性受到显著影响,表现出先诱导后缓慢降低的趋势,120 h后SOD活性显著低于对照组水平,GSH-Px活性与对照组无显著差异。在抗氧化酶受到影响的同时,鱼体脂质过氧化LPO程度不断上升,组织MDA含量逐渐增大,96 h达到最高值。硫丹可影响草鱼AChE及抗氧化酶活性,其变化可作为生物标志物,来评价化学污染物对水生动物的生物学效应。     

A correlative study on liver glycogen and endosulfan toxicity in Heteropneustes fossilis (Bloch.)

The biochemical tests were conducted to find out the relationship between liver glycogen and endosulfan toxicity on a catfish, Heteropneustes fossilis (Bloch.) using 0.00075, 0.00050 and 0.000375 ppm concentrations for 15, 30, 45 and 60 days of exposure periods. The quantity of liver glycogen showed decreasing trend as concentration of toxicant increased. The depletion in glycogen contents is greatly affiliated to cellular damage in hepatic cells.     

基于谷胱甘肽结合作用定量研究微囊藻毒素的解毒代谢机制

基于谷胱甘肽(GSH)解毒作用探讨了微囊藻毒素-RR(MCRR)在不同动物肝脏和肾脏合作下的代谢机制。通过人工合成MCRR的谷胱甘肽代谢物(MCRR-GSH),腹腔注射至鲫鱼和大鼠体内,利用液相色谱串联质谱技术(LC-MS/MS)定量检测MCRR-GSH及其下游半胱氨酸代谢物(MCRR-Cys)在组织内的代谢动力学变化。在72 h的暴露实验中,实验组鲫鱼和大鼠体内均定量检测到MCRR-GSH和MCRR-Cys。MCRR-GSH在肾脏中的浓度显著高于其他组织(P0.05),鲫鱼和大鼠体内累积浓度分别是(0.161±0.001)和(0.116±0.005)μg·g~(-1)DW。同样的,MCRR-Cys主要分布于鲫鱼和大鼠的肾脏组织。鲫鱼肾脏中MCRR-Cys的浓度出现明显的波动,而肝脏和胆汁内的MCRR-Cys浓度却呈现出上升的趋势;大鼠肾脏内MCRR-Cys的浓度呈缓慢下降的趋势,浓度范围为(8.899±0.817)μg·g~(-1)DW至(3.336±0.263)μg·g~(-1)DW。基于以上结果推测,微囊藻毒素在肝脏和肾脏合作下的解毒过程为:MC在肝脏内经GSH结合作用生成的代谢物MC-GSH随血液循环转运至肾脏,在肾脏内MCGSH快速地转化为下游代谢物MC-Cys以促进排泄。     

Impact of industrial effluents on the biochemical composition of fresh water fish Labeo rohita

In acute toxicity (96 hr) experiment the fingerlings of freshwater fish Labeo rohita was exposed to tannery, electroplating and textile mill effluents. The LC0 and LC50 concentrations were 15% and 20% for tannery effluents, 3% and 6% for electroplating effluents and 18% and 22% for textile mill effluents respectively. It was found that, electroplating effluent was more toxic than tannery and textile mill wastes. After acute toxicity experiments for different industrial effluents, various tissues viz. gill, liver, muscle and kidney were obtained separately from control, LC0 and LC50 groups. These tissues were used for biochemical estimations. The glycogen content in all the tissues decreased considerably upon acute toxicity of three industrial effluents except muscle in LC50 group of tannery effluent and kidney in LC50 group of textile mill effluent, when compared to control group. The total protein content decreased in all tissues in three effluents except gills in LC50 group of tannery effluent, kidney in LC50 group of electroplating effluent and kidney in LC0 group of textile mill effluent. In general total lipid content decreased in all tissues after acute exposure when compared to control group. The results obtained in the present study showed that, the industrial effluents from tannery, electroplating and textile mills caused marked depletion in biochemical composition in various tissues of the fish Labeo rohita after acute exposure.     

硫丹对草鱼Ⅰ相、Ⅱ相酶活性及DNA损伤的影响

研究了硫丹对草鱼肝脏Ⅰ相酶氨基比林-N-脱甲基酶（APND）和红霉素-N-脱甲基酶（ERND）、Ⅱ相酶谷胱甘肽-S-转移酶（GST）活性及DNA受损细胞彗星尾长（TL）和尾部DNA含量（%TDNA）的影响。试验共设置0.18、0.36和0.71μg.L-1 3个暴露浓度组和1个空白对照组,分别在试验24、72、120和168 h时取样测定各指标。结果表明,24 h时,0.36和0.71μg.L-1暴露组草鱼肝脏APND活性与对照组相比显著升高（P〈0.05或P〈0.01）,72 h时受到显著抑制（P〈0.01）;120 h后各暴露组APND活性与对照组相比均表现为受到显著抑制（P〈0.05或P〈0.01）。ERND活性总体表现为受诱导。GST活性总体呈先受诱导后受抑制的变化趋势;0.36和0.71μg.L-1暴露组GST活性均在72 h时达到最高值,之后随暴露时间的延长缓慢降低,并在168 h时表现为受抑制;0.18μg.L-1暴露组在120 h时达到最大值,之后降低,168 h时GST活性与对照组水平相当。经硫丹暴露后,草鱼肝脏细胞DNA明显受损,TL与%TDNA均随硫丹浓度的升高或暴露时间的延长而增加,且相关显著。硫丹可影响草鱼肝脏Ⅰ相、Ⅱ相代谢酶活性,并对肝细胞DNA造成遗传损伤。     

Negative health effects in rats fed on sardine fishes

An adequate human diet should satisfy the requirements for energy and nutritive components including essential polyunsaturated fatty acids, essential amino acids, mineral components, vitamins, and fat. The benefits of the fish consumption are, however, often counteracted by toxic metals such as lead present in fish meat. Adverse effects of toxic metals on the aquatic environment and human health have aroused increasing interest in recent years. The achievement of an appropriate balance between the risks and benefits associated with fish consumption has therefore become a key health issue in current research. Therefore, we studied health impacts associated with the consumption of sardine fish, one of the most commonly consumed fish species throughout the world. Hepatic damages associated with the consumption of white or red muscle of sardine fish were explored and evaluated using a rat model. Rats were fed for 60 days with white or red sardine meat. Findings revealed (1) an elevated level of uric acid in the blood, (2) an accumulation of lead in the liver, (3) an atrophy of the liver, (4) an increase in plasma aspartate aminotransferase and alanine aminotransferase activities, and (5) an oxidative stress in the liver, including increased levels of lipid peroxidation and enhanced activities of superoxide dismutase, catalase, and glutathione peroxidase. Several abnormalities were also observed in liver histology. The alterations observed in the animals can be attributed to both the accumulation of lead and the high levels of purine in the sardine meat. The findings show that special attention should be given to the health effects associated with high intakes of sardine meat, particularly dark-meat sardine.     

Histopathological impact of industrial wastewater on the vital organs of Oreochromis mossambicus

The acute toxicity of paper mill wastewater to Oreochromis mossambicus was investigated with the lethal concentration (LC50) value 6.5% for 96?h exposure. This concentration was used as a baseline to study the effects of paper mill effluent on histopathological changes in gills, liver, kidney, and brain of fish. In the gills, filament cell proliferation, cellular infiltration, hemorrhage, and epithelial lifting were observed. In the liver, vacuolation of hepatocytes and necrosis were noted. In kidney, exfoliation and swollen with pyknotic nuclei were identified. Similarly, the brain also showed enlarged pyramidal cells, binucleated nuclei, vacoulation, and necrosis. These changes occurred predominantly in 21days following exposure of fish to the industrial waste water. Paper mill wastewater was found to be highly toxic to fish.