The effect of various dietary fibres on tissue concentration and chemical form of mercury after methylmercury exposure in mice

The whole-body retention of mercury after exposure of BALB/c mice to methylmercury was measured in animals fed fibre-free, 5% pectin, 5% cellulose or 5, 15 or 30% wheat bran diets. The rate of elimination of mercury was dependent on the diet fed, with dietary bran increasing the rate of elimination. The incorporation of 15 or 30% bran in the diet of the mice decreased the total mercury concentration in the brain, blood and small intestine, although the effects were significant only in those animals on 30% bran diet. The fibres had little effect on mercury levels in other tissues. The proportion of mercury found in the mercuric form was significantly greater in liver, kidneys and gut of mice fed bran. The results suggest that dietary bran may reduce the levels of mercury in the brain after methylmercury exposure and may therefore reduce the neurotoxic effects of the organomercurial. We suggest that wheat bran exerts its effects on mercury retention and brain level via a modification of the metabolic activity of the gut microflora.     

Critical influence of chloride ions on silver ion-mediated acute toxicity of silver nanoparticles to zebrafish embryos

Abstract

The toxicity of silver nanoparticles (AgNP) to aquatic organisms, including zebrafish (Danio rerio), has been demonstrated, but differing opinions exist on the contribution of the physical properties of the particles themselves and the free dissolved silver ions (Ag⁺) to the observed effects. High concentrations of chloride ions (Cl^?) in the routinely used exposure media can cause precipitation of Ag⁺ as AgCl, as well as complexation of silver in diverse soluble chlorocomplexes, thus masking the contribution of dissolved silver to AgNP toxicity. In the present study, we formulated a zebrafish exposure medium with a low chloride content and exposed zebrafish embryos to AgNO₃ or carbonate-coated AgNP. The severity of toxicity caused by both silver forms depended on the time of exposure start, with younger embryos being most sensitive. Toxicity caused by both AgNO₃ and AgNP was of the same order of magnitude when compared based on the total dissolved silver concentration and could be prevented by addition of the Ag⁺ chelator cysteine. Further, we have analyzed the data from several previous studies to evaluate the influence of interactions between Ag⁺ and Cl^? on silver toxicity to zebrafish embryos. Our analysis demonstrates that the acute toxicity of AgNP to zebrafish embryos is largely mediated by Ag⁺. The influence of particle size and coating can at least partially be explained by the differences in Ag⁺ dissolution. High Cl^? levels in the exposure medium indeed have a pivotal influence on the resulting toxicity of AgNP, appearing to significantly attenuate toxicity in several studies. This consideration should influence the choice of exposure medium to be used when evaluating and comparing AgNP toxicity.     

Modulating effects of dietary fats on methylmercury toxicity and distribution in rats

Fish consumption is the most important source of human exposure to methylmercury (MeHg). Since fish is also a rich source of n-3 polyunsaturated fatty acids, this study was conducted to examine the effects of dietary fats on MeHg-induced acute toxicity in rats. Weanling male Sprague Dawley rats were administered semi-purified casein-based isocaloric diet containing soy oil, seal oil, docosahexaenoic acid (DHA), fish oil, or lard for 28 days. Rats were then gavaged with 0, 1, or 3 mg MeHg/kg body weight (BW) per day and fed the same diet for 14 consecutive days. On 43rd day of the experiment, rats were sacrificed and blood samples were collected and analyzed for hematology. Liver and spleen were removed, fixed, and examined for pathological changes. Blood, feces, liver, and brain were analyzed for total mercury and/or MeHg contents. Serum samples were analyzed for clinical markers of hepatic injury and immunoglobulin. Total mercury contents in all tissues measured increased with dose. Mercury excretion in feces increased with dose and duration of MeHg treatment. Both diets and MeHg showed significant effects and interacted significantly on many of the toxicological endpoints measured. Many of the effects of MeHg were diet-dependent. For example, in the rats fed the lard diet, 3mg MeHg/kg BW significantly increased relative liver and spleen weight as compared with vehicle control; whereas in rats fed the fish oil, soy oil, seal oil, or DHA, this effect of MeHg was less obvious or absent, suggesting a protective effect of these diets. MeHg at 3mg/kg BW significantly decreased serum albumin level in all except DHA dietary groups, implying a protection by the DHA diet on this parameter. Only in the lard dietary group, did 3mg MeHg/kg BW significantly increase serum bilirubin level, indicating an enhancing effect of this diet on MeHg toxicity. MeHg suppressed the adaptive immune system and stimulated the innate immune system in rats in a diet-dependent fashion. The seal oil diet provided more resistance, while the fish oil diet rendered greater sensitivity to these effects of MeHg on the immune system. These results imply significant modulating effects of dietary fats on MeHg toxicity which may translate into more severe or protective clinical outcomes. Therefore, dietary fats are important factors to be considered in the risk assessment of MeHg exposure.     

Effects of acetaminophen (paracetamol) in the embryonic development of zebrafish,Danio rerio

Acetaminophen, or paracetamol is an over‐the‐counter analgesic generally used by all groups of people, including pregnant women. The present investigation aims to elucidate the effects of acetaminophen on the development of zebrafish Danio rerio in which embryogenesis is ex utero. Developing eggs (n = 30) were exposed to different doses (0, 1, 5, 10, 50 and 100 µg L^?1) of the drug in triplicate and observations were made hourly until gastrulation and once in 24 h thereafter for seven consecutive days. Acetaminophen induced anomalies at different levels of development in a dose‐dependent manner, causing impairment in (1) the early development, (2) hatching, (3) organogenesis (by altering the rate of apoptosis), (4) larval growth and morphometry, (5) tail and tail‐fin formation, (6) pigmentation and (7) larval behavior and survival. The results of the present study clearly reveal that acetaminophen interfered with the normal embryonic development, growth, behavior and survival of D. rerio larvae. Copyright © 2009 John Wiley & Sons, Ltd.     

The effect of DDT and dieldrin on skeletal muscle fibres

The effects of the chlorinated hydrocarbon insecticides, DDT and dieldrin, on the electrical activity of skeletal muscle fibres of the clawed toad, Xenopus laevis, were investigated by means of intracellular microelectrodes. Both compounds caused an increase in the amplitude of the negative afterpotential and a slowing-down of the falling phase of the action potential, without affecting the resting potential. Neither DDT nor dieldrin caused repetitive activity. It is concluded that the increase in the duration of the action potential, measured at a potential level of ?50 mV, may be responsible for part of the effects of these insecticides on the mechanical response of skeletal muscle.     

Effects of particle size and coating on nanoscale Ag and TiO2 exposure in zebrafish (Danio rerio) embryos

Abstract

Manufactured metal (oxide) nanoparticles are entering the aquatic environment with little understanding on their potential health impacts for exposed organisms. Adopting an integrative approach, we investigated effects of particle size and coating on biological responses for two of the most commonly used metal (oxide) nanoscale particles, silver (Ag) and titanium dioxide (TiO₂) in zebrafish embryos. Titanium dioxide nanoparticles (nominally, 4 nm, 10 nm, 30 nm and 134 nm) had little or no toxicity on the endpoints measured. Ag both in nano form (10 nm and 35 nm) and its larger counterpart (600–1600 nm) induced dose-dependent lethality and morphological defects, occurring predominantly during gastrula stage. Of the silver material tested 10 nm nanoparticles appeared to be the most toxic. Coating Ag nanoparticles with citrate or fulvic acid decreased toxicity significantly. In situ hybridisation analysis identified the yolk syncytial layer (YSL) as a target tissue for Ag-nano toxicity where there was a significant induction of the heavy metal stress response gene, metallothionein 2 (Mt2) at sub-lethal exposures. Coherent Anti-stroke Raman Scattering (CARS) microscopy provided no evidence for silver particles crossing the chorionic membrane in exposed embryos. Collectively, our data suggest that silver ions play a major role in the toxicity of Ag nanoparticles.     

"Current" advances in mechanically skinned skeletal muscle fibres

1. In skeletal muscle, excitation-contraction (E-C) coupling describes a cascade of cellular events initiated by an action potential (AP) at the surface membrane that ultimately results in muscle contraction. Being able to specifically manipulate the many processes that constitute E-C coupling, as well as the many factors that modulate these processes, has proven challenging. 2. One of the simplest methods of gaining access to the intracellular environment of the muscle fibre is to physically remove (mechanically skin) the surface membrane. In doing so, the myoplasmic environment is opened to external manipulation. 3. Surprisingly, even though the surface membrane is absent, it is still possible to activate both twitch and tetanic force responses in a mechanically skinned muscle fibre by generating an AP in the transverse tubular system. This proves that all the key steps in E-C coupling are retained in this preparation. 4. By using this technique, it is now possible to easily manipulate the myoplasmic environment and observe how altering individual factors affects the normal E-C coupling sequence. The effect of important factors, such as the redox state of the cell, parvalbumin and the sarcoplasmic reticulum Ca2+-ATPase, on twitch and tetanic force can now be specifically investigated independent of other factors.     

Metabolism of third generation synthetic cannabinoids using zebrafish larvae

Synthetic cannabinoids are the second largest group of new psychoactive substances reported by the United Nations Office on Drugs and Crime in the last decade and case reports bring attention to its high potency effects and its severe toxicity, including fatalities. Moreover, synthetic cannabinoids are usually entirely metabolized and metabolic pathways for many new generation synthetic cannabinoids are still unknown. In this study, the metabolism of five third generation synthetic cannabinoids was evaluated using zebrafish (Danio rerio) larvae as 24-h in vivo model studied within 5 days after fertilization. The studied synthetic cannabinoids were MMB-CHMICA, ADB-CHMICA, ADB-CHMINACA, MDMB-CHMCZCA, and NNL-3, and the respective metabolites were identified by liquid chromatography-high resolution tandem mass spectrometry. Eleven, six, fourteen, eleven, and four metabolites were identified for MMB-CHMICA, ADB-CHMICA, ADB-CHMINACA, MDMB-CHMCZCA, and NNL-3, respectively, and metabolic pathways have been proposed. The use of zebrafish larvae, with a high degree of physiological and genetic homology to humans, is an emerging tool very useful for the identification of metabolic pathways of psychoactive substances. Results obtained in this study compared well with metabolites obtained previously for the same target molecules or structural analogous after in vitro incubation with human or rat hepatocytes. Thus, potential biomarkers for the evaluated compounds are the O-demethylated metabolite for MMB-CHMICA; the oxidative deamination to hydroxyl metabolite for ADB-CHMICA; hydroxyl metabolites at cyclohexylmethyl, tert-butyl, and indazole moieties for ADB-CHMINACA; hydroxyl metabolites at carbazole core, tert-butyl, or cyclohexylmethyl tail moieties for MDMB-CHMCZCA; and amide hydrolyzed, defluorinated, and dihydroxilated metabolite for NNL-3.     

Effects of perinatal coexposure to methylmercury and polychlorinated biphenyls on neurobehavioral development in mice

Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are environmental pollutants that cause neurobehavioral deficits in humans. Because exposures to MeHg and PCBs occur through fish consumption, it is necessary to clarify the effects of the interaction of the two pollutants. Therefore, we investigated the effects of perinatal exposure to MeHg and PCBs on the neurobehavioral development in mice. Female mice (C57BL/6Cr) were divided into four groups according to the type of exposure: (1) vehicle control, (2) MeHg alone, (3) PCBs alone, and (4) MeHg + PCBs. The MeHg-exposed groups were fed with a diet containing 5 ppm MeHg (as Hg), from 4 weeks before mating, throughout pregnancy, and lactation. The PCB-exposed groups were given a commercial mixture of PCBs, Aroclor 1,254, at 18 mg/kg body weight in corn oil by gavage every 3 days from day 5 after breeding and continued until postnatal day (PND) 20. Before weaning, an assessment of eye opening showed the interactive effects between MeHg and PCBs on PND 12: The coexposure group showed a similar response to the control group, whereas the MeHg- and PCB-exposed groups showed a high response than the former two groups. We also observed delay in development of grasp reflex by MeHg exposure on PNDs 12 and 14. When the offspring mice were 8 weeks old, the group exposed to PCBs alone showed increases in the frequencies of excrement defecation and urine traces in an open-field test. Analysis of the latency revealed the antagonistic interaction between the MeHg and PCBs: The latency increased by either MeHg or PCB exposure was decreased by coexposure. Treatment with MeHg decreased the distance walked by the mice, and MeHg interacted with PCBs. Moris' water maze test showed that the MeHg-treated mice took a long time to reach the submerged platform; however, this MeHg exposure showed no interaction with PCB exposure. The spontaneous locomotion activity of the mice was not affected by the chemical exposure at 9 weeks of age. These behavioral changes were not accompanied by any histopathological changes at the levels of the frontal cortex-caudoputamen, hippocampus-amygdala, brainstem and cerebellum. These results show that perinatal coexposure to MeHg and PCBs produces no additive or synergistic effects. This phenomenon needs to be further investigated.     

Effects of methylmercury on zinc-thionein levels of rat liver

The induction of metallothionein synthesis by administration of methylmercury chloride was studied. A repetitive sc dose of methylmercury chloride to rats in amounts of 10 mg/kg/day for 3 days produced profund hypozincemia and 3-fold increase of hepatic zinc bound to metallothionein by the initial 24 h. The incorporation of ³⁵S-cysteine into hepatic metallothionein was about 4 times larger for rats treated with methylmercury, which was comparable with it for rats treated with cadmium, than for control rats. These results suggest the induction of de novo synthesis of metallothionein by administration of methylmercury, although methylmercury was found to be unable to bind to produced metallothionein both in vivo and in vitro. A stress produced by methylmercury administration appears to be involved in the induction of hepatic zinc-thionein by methylmercury, though its mechanism is not clear.This work was supported by Grant-in-Aid (1979) for scientific research from the Ministry of Education of Japan, the chief of the research group was Dr. T.Tsubaki, Institute of Brain Research, School of Medicine, Niigata University     

An investigation of the effects of methylmercury in rats fed different dietary fats and proteins: testicular steroidogenic enzymes and serum testosterone levels.

Methylmercury (MeHg) is a testicular toxicant causing reduced steroidogenic enzyme activity, reduced serum testosterone (T) and abnormal spermatogenesis in mammals and fowl. It is also known that certain diets can alter androgen metabolism in rats. Previously we have shown that diets used in the current study impact circulating androgen levels and testicular steroidogenic enzyme activities in Sprague Dawley rats in the absence of MeHg. In the present study, we have investigated the impact of imposing an environmental contaminant (MeHg) commonly found in marine mammals and fish onto the rats' dietary intake of different proteins and lipids in order to determine if the different diets could modify MeHg toxicity in rats. Therefore, we examined the effects of MeHg on testicular steroidogenic enzymes and serum testosterone in rats fed diets containing either different protein sources (casein, fishmeal, whey) or different lipid sources (soybean oil, docosahexaenoic acid (DHA), seal oil, fish oil, lard). Male rats 42-45 days of age (18 per group) were assigned to different experimental diets for 28 days after which 6 rats in each group were gavaged daily with 0, 1 or 3 mg/kg body weight (BW)/day MeHg chloride in 5 mM Na(2)CO(3) solution for 14 days while being maintained on their diets. On the 43rd day of dosing, rats were sacrificed and blood plasma and testes frozen (-80 degrees C) until analysis. Microsomal steroidogenic enzyme activities (3beta-HSD, 17-OHase, C-17, 20-lyase, 17beta-HSD) were measured radiometrically. Serum testosterone was determined using ELISA kits. Testis weights were not affected by MeHg. MeHg at 3 mg/kg BW/day caused a reduction (>50%) in the activity of C-17, 20-lyase in all three protein diets and similar reductions in 17-OHase activity were seen in the casein and whey protein fed rats. At 3 mg/kg BW/day, MeHg reduced 17-OHase activity in the DHA diet but had no effect on 3beta-HSD activity and no inhibitory effects on 17beta-HSD activity. MeHg (3 mg/kg BW/day) caused significant reductions in serum T in the whey, soybean oil and fish oil groups. Interestingly, fishmeal protein but not fish oil offered some protection with respect to maintaining steroidogenic enzyme activities and serum T levels in rats dosed with MeHg. In conclusion, these studies show that different lipid diets can alter the toxic effects of MeHg on male rat steroidogenesis in terms of serum testosterone and steroidogenic enzyme activities.     

Muscarinic receptors mediate the endocrine‐disrupting effects of an organophosphorus insecticide in zebrafish

The glucocorticoid cortisol, the end product of hypothalamus‐pituitary‐interrenal axis in zebrafish (Danio rerio), is synthesized via steroidogenesis and promotes important physiological regulations in response to a stressor. The failure of this axis leads to inability to cope with environmental challenges preventing adaptive processes in order to restore homeostasis. Pesticides and agrichemicals are widely used, and may constitute an important class of environmental pollutants when reach aquatic ecosystems and nontarget species. These chemical compounds may disrupt hypothalamus‐pituitary‐interrenal axis by altering synthesis, structure or function of its constituents. We present evidence that organophosphorus exposure disrupts stress response by altering the expression of key genes of the neural steroidogenesis, causing downregulation of star, hsp70, and pomc genes. This appears to be mediated via muscarinic receptors, since the muscarinic antagonist scopolamine blocked these effects.     

Developmental disturbances of the fetal brain in guinea-pigs caused by methylmercury

Pregnant guinea-pigs of Hartley strain were orally administered methylmercuric chloride once at a dose of 7.5 mg Hg/animal (weighing 500–800 g) on one of days 21, 28, 35, 42 or 49 (3–7 weeks) of gestation. They were killed on day 63 (9 weeks) and their fetuses were removed. Both maternal and fetal blood, brain, liver and kidney, and fetal hair, urine, gastric content and amniotic fluid as well, were sampled for mercury analysis. The fetal brains were also examined pathologically. The maternal kidney contained mercury at a high concentration but the fetal kidney did not. The mercury concentration was strikingly high in the fetal hair, but fairly low in the urine, gastric contents and amniotic fluid. Mercury distributed unevenly in various brain regions of both dams and fetuses after treatment at 6 and 7 weeks of pregnancy (3 and 2 weeks before sampling). The concentration was high in the neopallium and archipallium, followed by the paleopallium, diencephalon and mesencephalon, but low in the rhombencephalon, including cerebellum. Mercury contents were relatively low and distributed almost evenly in various brain regions of both the dams and fetuses following treatment at 3, 4, and 5 weeks of pregnancy. Morphologically, the fetal brains were disturbed in the development following treatment at 3, 4 and 5 weeks of pregnancy. The cerebral cortex was thinned, the nucleus caudatus putamen and the hippocampal formation were reduced in size, and the lateral ventricles were dilated. However, the histological architecture of the cerebral cortex was not strikingly maldeveloped; only a slight disarrangement of the cellular alignment was noted. Following treatment at 6 and 7 weeks of pregnancy, focal degeneration of the neuronal cells was observed in the fetal neocortex; the severe cases showed spongy degeneration and dysgenetic hydrocephalus.     

Nephrotoxicity of mercuric chloride, methylmercury and cinnabar-containing Zhu-Sha-An-Shen-Wan in rats

Cinnabar (HgS) is used in traditional medicines, and total Hg content is used for risk assessment of cinnabar-containing traditional medicines such as Zhu-Sha-An-Shen-Wan (ZSASW). Is ZSASW or cinnabar toxicologically similar to common mercurials? Adult Sprague–Dawley rats were gavaged with ZSASW (1.4 g/kg), cinnabar (0.2 g/kg), HgCl₂ (0.02 g/kg), MeHg (0.001 g/kg), or saline daily for 60 days, and toxicity was determined. Animal body-weight gain was decreased by HgCl₂ and MeHg. Blood urea nitrogen (BUN) was increased by MeHg. Histology showed severe kidney injury following MeHg and HgCl₂ treatments, but mild after ZSASW and cinnabar. Renal Hg contents were markedly increased in the HgCl₂ and MeHg groups but were not elevated in the ZSASW and cinnabar groups. The expression of kidney injury molecule-1 was increased 50-fold by MeHg, 4-fold by HgCl₂, but was unaltered by ZSASW and cinnabar; the expression of matrilysin was increased 3-fold by MeHg. In contrast, the expression of N-cadherin was decreased by HgCl₂. Thus, ZSASW and cinnabar are much less nephrotoxic than HgCl₂ and MeHg, indicating that chemical forms of mercury underlie their disposition and toxicity.     

Effects of methylmercury on postnatal neurobehavioral development in mice

Eighty ICR mice were randomly assigned to one of four groups given daily intraperitoneal injections of 0, 0.1, 1 or 3 mg/kg MeHg chloride respectively from postnatal days (PD) 15–17, and then tested with the Morris water maze on PD45. After that the mice were sacrificed by cervical dislocation, and the protein levels of NMDA receptor subtypes in the hippocampus were measured by Western blot analysis. A significant increase in the latency (F = 2.88, P < 0.05) before finding the platform was observed in the 1 and 3 mg/kg MeHg exposure groups. Further, the 3 mg/kg MeHg exposure group also had a longer swim distance (F = 2.97, P < 0.05) for finding the platform. In the probe test, the MeHg exposure groups displayed a smaller number of platform crossings when the hidden platform was moved, but this did not reach statistical significance. Western blot analysis results showed significant increases in the levels of NR1, NR2A and NR2B proteins of the hippocampus in the 1 and 3 mg/kg MeHg exposure groups. Overall, the current study found that MeHg exposure at 1 and 3 mg/kg doses during the postnatal brain growth spurt induces subtle and persistent learning deficits, and the neurobehavioral abnormalities of MeHg-exposed mice might be ascribed to alteration of the gene expression of specific NMDA receptor subunits in the hippocampus.     

Development of reflexes in neonatal mice prenatally exposed to methylmercury and selenite

The development of reflexes in neonates exposed prenatally to methylmercury and selenite was investigated. Pregnant mice were assigned to one of 4 treatments; methylmercury (MeHg), selenite(Se), combination of 2 compounds (MeHg X Se) and saline control (NaCl). Mice were injected subcutaneously (s.c.) on day 9 of gestation. The dose of each compound was 30 mumol/kg. Mercury (Hg) concentrations in the neonatal brain and liver of the MeHg X Se group were slightly lower than in the MeHg group. The results of behavioral examination revealed that the MeHg X Se group showed significantly improved development compared with the MeHg group. These facts suggest the possibility that selenium compounds have protective effects against methylmercury neurotoxicity in fetuses and neonates.     

Impact of a risk-benefit advisory on fish consumption and dietary exposure to methylmercury in France

We designed the CORAI (COnsumer Risk Advisory Inquiry) study to observe consumer reactions' after an advisory revealing risk of methylmercury contamination together with benefits of Long-Chain Poly Unsaturated Fatty Acids of the n-3 variety (LC n-3 PUFA). The message was very close to the ones commonly delivered by national food agencies and included recommendations for women of childbearing age and children below 15 years old. Two groups of subjects including consumers at risk were selected. Participants recorded the frequency of their fish consumption detailed by species for them and their family over a one-month period one month before, a month immediately after and 3 month after the advisory. Results were compared between consumers receiving the advisory and controls. Results show that the message revelation led to a significant decrease in total fish consumption which is greater for children below 6 years old than for the children between 6 and 15 years old and women. The consumption of the most contaminated fish quoted in the advisory, rarely consumed and poorly known by French consumers did not decrease in any group despite the advice to avoid their consumption. The consumption of other fish products quoted in the advisory but frequently consumed and better known, as canned tuna, did decrease and was a major contributor to the overall reduction of exposure for the advised group. Before the information, about 3% of women of childbearing age are exceeding the PTWI for MeHg and both the average and the high percentiles of the exposure to MeHg are decreasing significantly in the advised group. Regarding the number of subjects of the advised group exceeding the PTWI, they were 6, 3 and 2, respectively, in May, June and September. Accompanying questionnaires show that consumers imperfectly memorize most of the fish species quoted in the recommendation. This paper concludes that consumer advisory, which is a major tool for risk management, has a minimal effect under our experimental conditions to reduce the exposure of groups at risk. Messages to be carried to consumers should be carefully tested for long term memorization in order to become more effective.     

Effects of quinidine,procaine amide,and N-propyl-ajmaline on skeletal muscle

Summary Membrane and action potentials of rat diaphragm fibres were measured in vitro as affected by quinidine, procaine amide, and N-propyl-ajmaline in concentrations of 10^–5 to 10^–4 g/ml.All three drugs had immediate effects on the action potential; the effects progressed the faster, the higher the concentration: the de- and repolarization were slowed, the duration increased, the overshoot decreased. Later (e.g., 1 h after application of 10^–5 g/ml quinidine) the resting potential started to decrease and the fibres became inexcitable.Electrical threshold was increased and the refractory period was prolonged by all three drugs, most effectively by N-propyl-ajmaline, least by procaine amide. All drugs abolished myotonic symptoms produced by reduction of extracellular chloride.Quinidine and N-propyl-ajmaline (10^–5 to 10^–4 g/ml) produced a transitory increase of contraction force, on prolonged drug action the muscle went into contracture. Procaine amide always had a negative inotropic effect. All drugs increased contraction time.This work was supported by the Deutsche Forschungsgemeinschaft.     

Combined toxicity of silica nanoparticles and methylmercury on cardiovascular system in zebrafish (Danio rerio) embryos

This study was to investigate the combined toxicity of silica nanoparticles (SiNPs) and methylmercury (MeHg) on cardiovascular system in zebrafish (Danio rerio) embryos. Ultraviolet absorption analysis showed that the co-exposure system had high absorption and stability. The dosages used in this study were based on the NOAEL level. Zebrafish embryos exposed to the co-exposure of SiNPs and MeHg did not show any cardiovascular malformation or atrioventricular block, but had an inhibition effect on bradycardia. Using o-Dianisidine for erythrocyte staining, the cardiac output of zebrafish embryos was decreased gradually in SiNPs, MeHg, co-exposure groups, respectively. Co-exposure of SiNPs and MeHg enhanced the vascular endothelial damage in Tg(fli-1:EGFP) transgenic zebrafish line. Moreover, the co-exposure significantly activated the oxidative stress and inflammatory response in neutrophils-specific Tg(mpo:GFP) transgenic zebrafish line. This study suggested that the combined toxic effects of SiNPs and MeHg on cardiovascular system had more severe toxicity than the single exposure alone.