Effect of Certain Toxicants on Gonadotropin-Induced Ovarian Non-Esterified Cholesterol Depletion and Steroidogenic Enzyme Stimulation of the Common Carp Cyprinus carpio in vitro

Isolated ovarian tissues from the common carp, Cyprinus carpio were incubated in vitro to obtain a discrete effect of four common toxicants of industrial origin, namely phenol, sulfide, mercuric chloride and cadmium chloride, on gonadotropin-induced alteration of nonesterified and esterified cholesterol and steroidogenic enzymes, △5-3β-HSD and 17β-HSD activity. Stage II ovarian tissue containing 30-40% mature oocytes were shown to be most responsive to gonadotropins in depleting only nonesterified cholesterol moiety and stimulating the activity of both. Safe doses of above mentioned toxicants when added separately to stage II ovarian tissue with oLH (1 μg/incubation) gonadotropin-induced depletion of nonesterified cholesterol and gonadotropin-induced stimulation of the activity of both enzymes was significantly inhibited. Esterified cholesterol remained almost unaltered. Findings clearly indicate the impairment of gonadotropin induced fish ovarian steroidogenesis by the four toxicants separately.

Histological Assessment and Transcriptome Analysis Provide Insights into the Toxic Effects of Perfluorooctanoic Acid to Juvenile Half Smooth Tongue Sole Cynoglossus semilaevis

Perfluorooctanoic acid(PFOA)is a widespread synthetic persistent organic pollutant that may enrich along the food chain and affect the growth,development,reproduction,and lipid metabolism of aquatic organisms,particularly the benthic organisms.How-ever,the toxic effects of PFOA on the half-smooth tongue sole Cynoglossus semilaevis,a commercial benthic fish in China,have rarely been reported.Because juvenile fish are sensitive to environmental pollutants,in the present study,histological assessment and tran-scriptome sequencing were performed to determine the short-term impact of PFOA on juvenile half-smooth tongue soles.Histologi-cal analysis showed that PFOA exposure caused hepatocyte rupture,intestinal villi breakage,increased goblet cell count,and brain ab-normal.Transcriptome results showed that some interesting signaling pathways,such as glycolysis/gluconeogenesis,PPAR signaling pathway and GABAergic synapse signaling pathway,were enriched after PFOA exposure.In addition,some metabolic,immune and neural genes were differentially expressed,which including ependymin,hbb1-like and gad 1,and they were up-regulated after 14 days of exposure.Transcriptome results also indicated that half-smooth tongue sole might improve energy metabolism in response to PFOA toxicity after 7 days of exposure.These findings provide a basis for studying the ecological effects of PFOA on marine benthic fishes.

Toxic Effects of Lanthanum, Cerium, Chromium and Zinc on Potamogeton Malaianus

The toxic effects of rare earth elements such as lanthanum, cerium and heavy metal elements such as chromium, zinc on Potamogeton malaianus Miq. were studied. The results show that the contents of chlorophyll and soluble protein increase to a certain degree and then decrease under La3+ Ce3+ Zn2+ stress, while there is a constantly dropping tendency under Cr6+ stress. The four ions have different effects on protective enzyme systems of Potamogeton malaianus. They can induce rises of the activities of catalase (CAT) and peroxides (POD) at lower concentration, however, with the increase of ions concentration, the activities decline. The change of SOD activity is exactly opposite to that of CAT and POD activity. It falls at first and rises later. An increasing tendency of MDA content appears with the increasing concentration. The toxicities of La3+, Zn2+, Ce3+ and Cr6+ become more serious in the order. The lethal concentration of Cr6+ to Potamogeton malaianus ranges from 0.5 to I mg(-1) that of Ce3+ and Zn2+ ranges from 3 to 5 mg(-1) and that of La3+ ranges from 7 to 10 mg(.)L(-1). The toxic mechanism of La3 + and Ce3+ is similar to that of Cr6+ and Zn2+.

Toxic effects of acetochlor, methamidophos and their combination on nifH gene in soil

Toxic effects of two agrochemicals on nifH gene in agricultural black soil were investigated using denaturing gradient gel electrophoresis （DGGE） and sequencing approaches in a microcosm experiment. Changes of soil nifH gene diversity and composition were examined following the application of acetochlor, methamidophos and their combination. Acetochlor reduced the nifH gene diversity （both in gene richness and diversity index values） and caused changes in the nifH gene composition. The effects of acetochlor on nifH gene were strengthened as the concentration of acetochlor increased. Cluster analysis of DGGE banding patterns showed that nifH gene composition which had been affected by low concentration of acetochlor （50 mg/kg） recovered firstly. Methamidophos reduced nifH gene richness that except at 4 weeks. The medium concentration of methamidophos （150 mg/kg） caused the most apparent changes in nifH gene diversity at the first week while the high concentration of methamidophos （250 mg/kg） produced prominent effects on nifH gene diversity in the following weeks. Cluster analysis showed that minimal changes of nifH gene composition were found at 1 week and maximal changes at 4 weeks. Toxic effects of acetochlor and methamidophos combination on nifH gene were also apparent. Different nifH genes （bands） responded differently to the impact of agrochemicals： four individual bands were eliminated by the application of the agrochemicals, five bands became predominant by the stimulation of the agrochemicals, and four bands showed strong resistance to the influence of the agrochemicals. Fifteen prominent bands were partially sequenced, yielding 15 different nifH sequences, which were used for phylogenetic reconstructions. All sequences were affiliated with the alpha- and beta-proteobacteria, showing higher similarity to eight different diazotrophic genera.

ZnO,TiO_2,SiO_2,and Al_2O_3 Nanoparticles-induced Toxic Effects on Human Fetal Lung Fibroblasts

Objective This study aims to investigate and compare the toxic effects of four types of metal oxide （ZnO, TiO2, SiO2, and Al2O3） nanoparticles with similar primary size （-20 nm） on human fetal lung fibroblasts （HFL1） in vitro.Methods The HFL1 cells were exposed to the nanoparticles, and toxic effects were analyzed by using MTT assay, cellular morphology observation and Hoechst 33 258 staining.Results The results show that the four types of metal oxide nanoparticles lead to cellular mitochondrial dysfunction, morphological modifications and apoptosis at the concentration range of 0.25-1.50 mg/mL and the toxic effects are obviously displayed in dose-dependent manner. ZnO is the most toxic nanomaterials followed by TiO2, SiO2, and Al2O3 nanoparticles in a descending order.Conclusion The results highlight the differential cytotoxicity associated with exposure to ZnO, TiO2, SiO2, and Al2O3 nanoparticles, and suggest an extreme attention to safety utilization of these nanomaterials.

Toxic Effects of Tetrabromobisphenol A on Thyroid Hormones in SD Rats and the Derived-reference Dose

The present study determined the thyroid hormone interference of tetrabromobisphenol A （TBBPA） in Sprague-Dawley （SD） rats, and the derived-reference dose （RfD） of different endpoint effects on mammals based on experimental results and data collection. Based on repeated exposure toxicity tests on mammals and extensive research, the present study used BMDS240 Software to derive a benchmark dose, and analyzed the accuracy and uncertainty, and similarity with other studies. Test results on triiodothyronine （T3）, thyroxine （T4）, and thyroid stimulating hormone （TSH） demonstrated that all the indicators presented a non-monotonous dose-effect relationship clearly, except TSH in male rats exposed to 0-1000 mg/kg BW per day. Therefore, RfDs were derived from different critical effects. In summary, RfD for mammals in the present study was found to be 0.6 mg/kg per day.

Influences of Chloropazine, Nimodipine and Their Combination on the Toxic Effects of Cadmium in Liver and Kidney of Mice

The influences of the calmodulin antagonist chlorpromazine (CPZ), and calcium channel blocker nimodipine (NIMO) and their combination on cadmium (Cd) poisoning of mice were studied. A seties of biochemical parameters including urinary enzyme activities, blood and urine Cd levels, metallothionein (MT) contents in liver and kidney, hepatic ultrastructure and Ca2+ -Mg2+ AT-Pase activity in erythrocyte membrane were determined. Animal models for Cd poisoning were established by peritoneal injection of 1/5 LD50 CdCl2. The experimental groups were protected by administration of CPZ, NIMO and CPZ and NIMO in combination l h before the injection of CdCl2. Five days later, samples were collected for analysis. The data showed that Crs could protect kidney tissue against Cd-induced damage, as the urinary γ-glutamyl traspepti dase (γ- GT ) and N- acetyl-β-D-glucosaminidase (NAG) activities were reduced significantly. There was neither evidence of the protective effect of NIMO on kidney tissue nor an indication of a synergistic effecf of Crs and NIMO.Both CPZ and NIMO showed a considerable protective effect against the deerease in Ca2+ -Mg2+ AT-Pase activity, and a synergistic action was observed. Cd content in blood was reduced significanily by CPZ or the combination of CPZ and NIMO, but elevated by NIMO. Both CPZ and NIMO consideraby increased MT contents in livers and kidneys and ameliorated damaged to the hepatic ultrastructures caused by Cd. The results indicated that these inhibitors could protect mice against the toxic effects of Cd in liver and kidney tissues, while CPZ was more efficient than NIMO. The combination of CPZ and NIMO exerted a synergistic action. The protective action of these two drugs might be relevent to the function of MT.

Monitoring bioaccumulation and toxic effects of hexachlorobenzene using the polyurethane foam unit method in the microbial communities of the Fuhe River,Wuhan

Hexachlorobenzene （HCB） is a chlorinated aromatic hydrocarbon that was widely used for seed dressing in prevention of fungal growth on crops, and also as a component of fireworks, ammunition, and synthetic rubbers. Because of its resistance to degradation and mobility, HCB is widely distributed throughout the environment and is accumulated through food chains in different ecosystems. In this study, a preliminary investigation was carried out on the bioaccumulation and the toxic effects of HCB in the microbial （protozoan in particular） communities in the Fuhe River, Wuhan, a water body receiving industrial wastewaters containing HCB and other pollutants, using the standardized polyurethane foam units （PFU） method. Field samples were taken from eight stations established along the Fuhe River in January and August 2006. The concentration ratios of HCB in microbial communities and in water were 9.66-18.64, and the microbial communities accumulated 13.29-56.88 μg/L of HCB in January and 0.82-10.25 μg/L HCB in August. Correlation analysis showed a negative correlation between the HCB contents in the microbial assemblage, and the number of species and the diversity index of the protozoan communities. This study demonstrated the applicability of the PFU method in monitoring the effects of HCB on the level of microbial communities.

Investigation of the immune effects of Scutellaria baicalensis on blood leukocytes and selected organs of the chicken＇s lymphatic system

Background： The health of chickens and the welfare of poultry industry are central to the efforts of addressing global food security. Therefore, it is essential to study chicken immunology to maintain and improve its health and to find novel and sustainable solutions. This paper presents a study on investigation of the effect of Scutellaria baicalensis root（SBR） on the immune response of broiler chicken, especially on lymphocytes and heterophils reactivity, regarding their contribution to the development of immunity of the chickens.Methods： The 121-day-old Hubbard Hi-Y male broiler hybrids were randomly assigned to four treatment groups,three SBR supplemented groups（0.5, 1.0, and 1.5% of SBR） and one control group. Each treatment was replicated five times with six birds per replicate pen in a battery brooder. Blood was collected after 3-（rd） and 6-（th）wk of the experiment, and hemoglobin and hematocrit values were determined, as well as total leukocyte count and differential count were performed. Nitroblue tetrazolium test and phagocytosis assay as nonspecific immune parameters and humoral immune responses to the antigenic challenge by sheep red blood cells were performed.Moreover, the ability of peripheral blood lymphocytes to form radial segmentation（RS） of their nuclei was analyzed.Body weight and relative weight of spleen, liver, and bursa of Fabricius were recorded.Results： Results showed that mean heterophile/lymphocyte ratio increased in the SBR groups compared to the control group and the blood of the chickens showed lymphocytic depletion. The results also demonstrated that the relative weight of bursa of Fabricius and spleen in groups fed with SBR significantly decreased compared to the control group. This study also showed that the addition of SBR significantly inhibited the formation of RS of nuclei compared to some cytotoxic substances.Conclusion： We found that SBR supplementation should be carefully evaluated when given to poultry. The excess intake of SBR supplementation may cause immunologic inhibition and may negatively affect the development of immune organs. SBR has inhibited the formation of radial segmentation nuclei showing antimetastatic properties and also the phagocytosis of chicken heterophils.

Protective Effects of Calcium Antagonists on Cadmium-induced Toxicity in Rats

Protective effects of calcium antagonists, chlorpromazine (CPZ) and nimodepine (NI-MO), on cadmium-induced toxicity were investigated. After giving CdCl2 (0. 44mg Cd/kg,ip), CPZ (5mg/kg, ip) or NIMO (8mg/kg, po) were administered every day to Sprague-Dawley (S. D. ) rats for a week. Then, urinary N- acetyl-β-D- glucosaminidase (NAG ), uri -nary cadmium and bloocl cadmium were measured. The accumulation of cadmium in the kid-ney cortex, content of renal calmodulin, hemoglobin and the ultrastructural damage of proxi-mal convoluted tubules of rats were examined three weeks after the last administration. Re-sults indicated that the calcium antagonists partly protected against toxic effects induced bycadmium in different manners. These data provide further evidence for the new hypothesisthat the cross effect of cadmium and calcium in calmodulin regulated systems may be responsi-ble for the mechanism of cadmium intoxication. 'The results suggested that the calcium antag-onists could be a new and promising approach in the therapy of heavy metaLinduced diseases

Toxic effect of dinoflagellate Alexandrium species on Cladocera Moina mongolica Daday

The main objective of this study was to investigate toxic effects of the dinoflagellate Alexandrium species, on cladocera Moina mongolica in the laboratory. Ten strains of Alexandrium species, including Alexandrium tamarense （AT-6, ATHK, ATCI02, ATCI03 and AT5-1）, A. catenella （ACDH）, A. affine （AC-1 and AS-1）, A. lusitanicum and A A. tamarense （ATHK, ATCI02 and AT5-1） and A minutum were tested. The results showed that affine （AC-1 and AS-1）, but not A. tamarense （AT-6 and ATCI02）, A. catenella （ACDH）, A. lusitanicum and A. minutum had significantly negative effects on the survival of M. mongoliea; when exposed to these ten strains of Alexandrium species in densities of 3 000 cells/cm^3 for 7 d, respecyively. M. mongolica could feed on A. tamarense （AT-6, ATHK, ATCI02, ATCI03 and AT5-1）, A. eatenella, A. lusitanieum and A. minutum, but exhibited little or no grazing on A. affine （AC-1 and AS-1）, based on the changes in gut pigment af- ter exposure to alga for 1 and 12 h. A. affine AC-1, which had the strongest toxicity on the survival of M. mongolica, was chosen to further study the negative effects on M. mongolica. The results showed that the effect of A. affine AC-1 on the survival of M. mongolica was density-dependent, and its lethal effects on one-day, two-day and three-day old M. mongolica were exacerbated with increasing age; The whole algal culture, re-suspended algal cells, cell fragments and cell contents all had adverse impacts on the survival of M. mongolica. Moreover, both juvenile numbers and life-span time of M. mongolica were decreased significantly when they were cultured in A. affine AC-1 of 10 and 50 cells/cm^3, combined with 3×10^6 cells/cm^3 of Chlorella spp., respectively. As a non-PSP producer, A. affine may produce other toxins, responsible for the strong negative effects on M. mongolica.

Experimental Podophyllotoxin (Bajiaolian) Poisoning:Ⅲ. Biochemical Bases for Toxic Effects

The biochemical mechanism underlying the toxicity of podophyllotoxin is investigated.Previous studies from our laboratories suggested that hepatocytes were extremely sensitive to the toxicity of podophyllotoxin and a disruption of protein synthesis was suspected.Dose-response and time-course studies on the effects of podophyllotoxin on protein, RNA,and DNA syniheses on hepatocellular cultures were made. Inhibitions of protein, RNA,and DNA syntheses were demonstrated, and a direct correlated dose-response relationshipon such effects was also evident. Inhibition of protein synthesis appeared to be a direet toxic effect of podophyllotoxin and occurred independently from that of RNA. The reduction of DNA synthesis was reflected by a reduction of H3-thymidine incorporation,which is believed to be the consequence of inhibition on the mitotic activity by podophyllotoxin

Intratracheally Administered Liposomal α-Tocopherol Protects the Lung against Long-Term Toxic Effects of Paraquat

Paraquat is a broad-spectrum herbicide known to produce lung injury via oxidative stress-mediated mechanisms. Different pharmacological strategies have been explored to reduce the formation of these reactive oxygen species and/or prevent their toxic effects in the treatment of paraquat poisoning. The present study was carried out to investigate whether the antioxidant (L-tocopherol, incorporated into liposomes and delivered directly to the lungs of rats, could protect the organ against the long-term toxic effects of paraquat.Plain liposomes (composed of dipalmitoylphosphatidylcholine, DPPC) or α-tocopherol liposomes (8 mg α-tocopherol/kg body weight) were administered intratracheally to animals 24 h prior to an intraperitoneal injection of paraquat dichloride (20 mg/kg) and rats wefe killed 0, 1, 4, 6, 8, 10, 12, 16, 19 or 24 days after paraquat treatment. Results of this study showed that lungs of animals treated with paraquat were extensively damaged,as evidenced by significant increases in lung weight and decreases in lung angiotensin converting enzyme (ACE) and alkaline phosphatase enzyme (AKP) activities. Moreover,paraquat treatme; resulted in a significant reduction in the number of neutrophils in the blood of rats with a concurrent increase in the pulmonary myeloperoxidase activity,suggestive of neutrophil infiltration in the lungs of treated animals. Pretreatment of rats with liposomes alone did not significantly alter the paraquat-induced changes of all parameters examined. On the other hand, pretreatment of rats with (t-tocopherol liposomes,24 h prior to paraquat challenge, attenuated paraquat-induced changes in ACE, AKP and myeloperoxidase activities but failed to prevent increases in lung weight. Thus, pretreatment of rats with liposome-associated α-tocopherol appears to protect the lung against some of the toxic effects of paraquat

Toxic Effects of Pirimiphos-methyl Residues on Rats

This study analyzes the level of total and bound pirimiphos-methyl residues in treated wheat grain and its toxic effects on rats.Wheat grain was treated with[(14)~C]pirimiphos-methyl of 16.36 mCi/mmol specific activity to determine the bioavailability of bound residues in rats.At the same time,grain was treated with nonlabeled pirimiphos-methyl as required to determine any possible toxic effects of bound residues in a subacute feeding study in rats.Two dose levels were used:10 and 100 ppm(the former being the recommended dose level in practical treatment). Estimation of the type of residues was performed at intervals of 0,30,90,120,150,and 180 days.During and after the animal feeding study,changes in body weight gain,organ weight, cholinesterase activity,serum enzyme activity,and hematology were investigated.There is an indication that bound residues of the pesticide pirimiphos-methyl provoke toxic effects to some extent.1989 Academic Press.Inc.

Toxic Effects of Bound Malathion Residues in Rats

The level of bound malathion residues in treated wheat grain and its toxic effects on rats were investigated. Wheat grain was treated with [14C] malathion (specific activity: 2.76 MBq/mg) to determine the bioavailability of bound residues in rats. At the same time, grain was treated with nonlabeled malathion to test for possible toxic effects of bound residues in a subchronic (90 days) feeding study in rats at two dose levels. 10 and 100 ppm.It was observed that the level of malathion-bound residues amounted to 11.28% of the applied dose (for six months). Also, it was noted that the main route of [14C]-malathion excretion was through the urine. This signifies that grain-bound malathion was bioavailable. In subchronic test on rats bound malathion residues (both dose levels) induced effects to some extent in organ weight (spleen and adrenals), and blood ChE activity. In both, males and females, there was an increase in SGPT activity (lower dose), and in alkaline phosphatase in females (higher dose). Hematological data showed changes only in hemoglobin concentration in males (both dose levels).

Toxic Effects of an Anionic Detergent on the Lipid Constituents of Various Cell Types of the Gill Epithelium of Rita rita:A Histochemical Investigation

Rita rita exposed to a concentration of 6.9 mg per liter(96-h LC_(50)of an anionic detergent, dodecylbenzene sodium sulfonate)exhibited a gradual decrease in the lipid moieties of the epi- thelial cells,club cells,and goblet mucous cells lining the gill arch and gill filament epithelium. However,in time,no reaction of any of the lipid moieties could be observed,indicating the absence of the same,using various histochemical techniques.The results are discussed in light of the mechanistic understanding of detergent action.1989 Academic Press,Inc.

Toxic Effects of Four Commonly-used Agrochemicals on Arma chinensis and Picromerus lewisi

This study was conducted to investigate the toxic effects of four different agrochemicals on Arma chinensis and Picromerus lewisi . Cypermethrin·phoxim, imidacloprid and fenvalerate had higher toxic effects on A. chinensis and P. lewisi . After the application of the agrochemicals, the released stink bugs could not well survive and propagate. Though the herbicide （glyphosate ammonium） had no direct toxic effects on A. chinensis and P. lewisi , their survival and propagation were affected after the application of the herbicide into natural environment. Therefore, to ensure better survival and propagation of the two kinds of stink bugs in natural environment, local agrochemical management should be strengthened, and the concept of green environmental protection should be constructed and popularized.

Acute Toxic Effects of Mercuric Chloride on the Mucocytes of the Epithelial Lining of the Accessory Respiratory Organ and Skin of the Air Breathing Catfish Heteropneustes fossilis（Bloch）^1

Acute toxicity of 0.3 ppm mercuric chloride on the mucocytes of the branchial diverticulum and skin of Heteropneustes fossilis results in cyclic increases followed by decreases in the density, area occupancy and volume at different intervals of exposure. The alterations in the two tissues do not follow the same path perhaps due to different modes of action of the mercury salt: The skin comes under direct contact effects, while the branchial diverticulum may be affected by hormonal imbalance caused by a stress effect.

Effect of TCDD on Maternal Toxicity and Chorionic Gonadotropin──Bioactivity in the Immediate Post-implantation Period of Macaque

The purpose of this experiment was to observe the alterations in bioactivity of chorionic gonadotropin (CG) associated with early fetal loss (EFL), induced by the environmental toxin TCDD (2,3,7,8\|tetrachlorodibenzo\| p \|dioxin) in the cynomolgus macaque. Ten of twelve females administered single doses of 1, 2 or 4 μg/kg TCDD on gestational day (GD) 12 had EFL from ten to twenty days later. Seven control animals treated only with the vehicle had normal pregnancies. Blood samples were repeatedly collected for hormone evaluation, from two days before treatment to thirty\|one days following treatment. Immunoreactive monkey chorionic gonadotropin (mCG) was measured in serum using ELISA, and bioactive mCG was measured using a luminescence LH/CG bioassay. No change in immunoreactive mCG levels was detected as a result of TCDD, treatment, but bioactive mCG levels were significantly lower in TCDD\|treated animals compared to controls. This change in bioactivity of mCG was also reflected in the ratio of mCG bioactivity to mCG immunoreactivity (B/I ratio) which began to rise in normal pregnancies by GD 20, but did not rise in TCDD treated animals. These results demonstrate that normal pregnancy in the monkey, as in humans, is characterized by a post\|implantation change in the B/I ratio of CG. These findings therefore suggest that changes in the production of bioactive CG may be used as a biomarker of environmental toxicant exposures which lead to EFL.

Clinical Observation on the Efficacy Enhancing and Toxicity Attenuating Effect of Nuzhen Yangyin Granule to the Anti-Parkinsonism Therapy Mainly with Medopa

Objective: To observe and assess the efficacy enhancing and toxicity attenuating effect of Nuzhen Yangyin Granule (NYG) to the anti-parkinsonism (paralysis agitans) therapy with medopa and ar-tane. Methods: Adopting the randomized double-blinded method, the effect of adding NYG to 30 patients with Parkinsonism in the treated group,