Antispermatogenic effects of artemether: An animal model

Various antimalarial drugs have been shown to exert different adverse effects; however, scanty information is available for artemether-induced potential side effects. The present study assessed effects of artemether on lipid profile, sperm count, and histological features of testes in an animal model. The mean total cholesterol, high-density lipoproteins, low-density lipoproteins, triglyceride, and total proteins in mice-administered artemether were higher compared with controls. The mean sperm counts in mice treated with artemether were reduced when compared with controls. In addition, it was observed that artemether affected the histopathology of seminiferous epithelia and Leydig cells. Evidence indicates that artemether exerts adverse effects in mice testes.     

Biochemical evaluation of hepatotoxicity in mice due to administration of artemether

Effects of artemether administration on liver and selected biochemical parameters were evaluated. Eighty albino mice were divided into four equal groups. Group 1 was given water which served as control, while groups 2, 3, and 4 were given 1.2, 2.4, or 4.8 mg kg^?1 body weight artemether intramuscularly for five consecutive days. On day 6 all mice were sacrificed by cervical dislocation and blood was collected for analysis of alanine and aspartate transaminases, alkaline phosphatase, copper, and total proteins. Liver tissues were prepared for histological studies. It was found that the serum alanine and aspartate transaminase and alkaline phosphatase activities were higher in groups treated with artemether compared to control. The serum concentrations of copper and total proteins were lower than control. The histological features of liver tissues after administration of artemether showed histopathological alterations. These findings showed that artemether administration may have reversible adverse effects on mouse hepatocytes.     

Histopathological effects of artemether on selected organs in rat

Dose and treatment-duration neurotoxic effects are reported for artemisinin drugs of mostly the liposoluble derivatives; and yet artemether, the only parenteral formulation of the artemisinin series available in Nigeria is fat-soluble and also has a treatment-duration of 5–7 days (in an attempt to delay recrudescence). Since parenteral drugs are usually resorted to in severe/complicated or multidrug-resistant malaria against the oral artemisinin co-formulated therapies (ACT), this study is aimed to investigate the pathological changes on selected tissues (if any), in rats, of the normal 7-days artemether-injections when used both in the normal and higher doses. Artemether was administered i.p., at three dose levels, equivalent to therapeutic dose (1.5 mg kg^?1) as well as 5 and 10 times higher (7.5 and 15 mg kg^?1). A three percentage v/v Tween 80 vehicle was used for the control experiment. The pathological changes in the kidney, heart, liver, and lungs evaluated using percentage mean organ:body-weight ratio showed no changes in the organs. No histopathological effect was observed in the organs of rats treated with 1.5 mg kg^?1. However, rats treated with 7.5 and 15 mg kg^?1 revealed necrositic lesions with mononuclear cellular-infiltration in the liver and brain. The liver had focal area necrosis, while the brain had liquefactive necrosis, neuronal degeneration, congested blood vessels, hemorrhage, and vacuolations. The interstitial spaces of the glomerulus and renal tubules of one kidney from rats that received 15 mg kg^?1 had focal area fibrositic-necrosis.     

Tissue distribution and neurotoxic effects of domoic acid in a prominent vector species, the northern anchovy Engraulis mordax

The planktivorous northern anchovy is a prominent vector of the phycotoxin domoic acid (DA) to organisms at higher trophic levels, including fish-eating seabirds and mammals. Although there are abundant data reporting DA-induced excitotoxic symptoms in higher vertebrates, to date there has been no reported evidence of neurotoxic effects in lower vertebrate vectors such as fish. To explain this apparent lack of toxicity, it has been suggested that DA may not reach the brain in anchovies and/or that fish are not as sensitive neurologically to DA. In the present study, intracoelomic (IC) injection of DA, at doses ranging from 1 to 14 μg DA g⁻¹ total fish weight, resulted in severe neurotoxic symptoms such as spinning, disorientation, inability to school, and mortality, indicating that anchovies are neurologically susceptible and that DA crosses the blood–brain barrier in fish. An ED₅₀ of 3.2 μg DA g⁻¹ total body weight was determined via IC injection of DA in 83 anchovies. Comparable intraperitoneal injection studies with mice, rats, and monkeys report similar DA-induced neurotoxic symptoms at doses near 3.2 μg DA g⁻¹, suggesting a similar neurologic sensitivity and mechanism of toxicity between anchovies and mammals. DA tissue distribution measurements from freshly collected field-exposed anchovies and orally gavaged anchovies indicate that DA uptake from the gastrointestinal tract does occur. Levels as high as 1,175 μg DA g⁻¹ were measured in anchovy viscera, while muscle and brain tissue DA levels were 3 orders of magnitude lower, indicating low but measurable DA uptake. Further evidence is needed to confirm that uptake is sufficient during field events to induce symptoms in anchovies. Our work provides the first reported evidence of neurotoxic symptoms in fish and suggests that anchovies may be affected by DA during toxic diatom blooms. If sufficient uptake occurs, DA-induced neurotoxic symptoms and mortality may make fish easier prey targets, thereby selecting for the highest toxin levels transferred, as well as providing a possible pathway for the transfer of DA to benthic communities. Received: 19 May 2000 / Accepted: 29 November 2000     

Natal dispersal in two mice species with contrasting social systems

We compared the natal dispersal behaviour of two mice species under laboratory conditions. Natal dispersal is a movement of an animal from its birthplace to its breeding area. This behaviour is known to be influenced by the mating system. In polygamous species, males are more likely to disperse, while in most of the monogamous species, both sexes disperse. Our subjects, the house mouse (Mus musculus) and the mound-building mouse (Mus spicilegus) are two sympatric species of the genus Mus. Both are native in Hungary, but they differ in their habitat type mating system and overwintering strategy. The house mouse is a polygynous species and adapted to human environment, known for mature and reproduce early. On the contrary, the mound-building mice are monogamous, and they inhabit extensively used agricultural fields, where they spend the unfavourable winter period in nest chambers under mounds, which they construct from soil and plant material. Successful overwintering for this species demands delayed maturity and reduced dispersion during the winter. Our results showed that the natal dispersal of these two species differ; both sexes of the mound-building mice dispersed later than the house mice, where a difference between sexes also occurs; house mice males dispersed earlier than females. The mound-building mice showed no sexual dimorphism in this behaviour.     

Swimming speed alteration of larvae of Balanus Amphitrite as a behavioural end-point for laboratory toxicological bioassays

In this study, we investigate the feasibility of developing a new behavioural toxicity bioassay (Swimming Speed Alteration test—SSA test) with larvae of Balanus amphitrite (Crustacea Cirripedia). This organism was chosen as a model for different reasons: it is present all over the world, simple to be reared, easily available, and also because barnacles play an important role in the coastal ecosystem. In addition, all the operations related to the rearing and test execution are comparatively cheap. This bioassay was performed with several classes of chemical pollutants (antifouling biocides, neurotoxic pesticides, and heavy metals) and with environmental samples (sediment elutriates). The measurement of swimming speed, by means of video-graphic techniques, proved to be a valid instrument in highlighting the sub-lethal levels of toxicity caused by the different tested samples. In conclusion, the SSA test is able to provide in a biomonitoring program a good behavioural integrated output, which is also repeatable, sensitive, easily interpretable, and truly representative of a broad range of toxic compounds and environmental toxic matrices which are, generally, very complex and difficult to analyse. For all of these reasons, it could be proposed as a non-specific behavioural end-point. Physical and Chemical Impacts on Marine Organisms, a Bilateral Seminar Italy-Japan held in November 2004.     

二氧化硫体内衍生物对小鼠的显性致死作用

采用二氧化硫(SO2)衍生物亚硫酸钠和亚硫酸氢钠(二者的物质的量之比为3:1)腹腔注射的方法,研究其对雄性小鼠生殖细胞的遗传毒性.结果表明,雄鼠经SO2衍生物染毒后再与雌鼠交配,导致:(1)雌鼠受孕率下降,显性致死率增高,且均有明确的剂量-效应关系;(2)胚胎生长迟缓,活胎平均重量下降.研究得出结论:SO2及其衍生物对雄性小鼠有生殖毒性作用.表2参14     

Comparison of 1-(2-naphthyloxymethylcarbonyl) pyrrolidine,PP-20/DPJ,newly synthesized compound with the nootropic drug piracetam in normal and aluminum-induced neurotoxic state

Nootropic drugs like piracetam, oxiracetam, and nifiracetam are used as memory enhancers. They are thought to directly influence the energetic processes in the brain and produce elevated acetylcholine levels, but they lack protecting therapeutic potentials. Thus, there is a continuing effort directed towards developing a new cognition-enhancing agent, which would be more effective than the currently available drugs, and 2-Naphthyloxy derivatives (PP-20/DPJ) were consequently developed. This in vivo study was designed to compare the memory enhancing potential of PP-20/DPJ with the known nootropic agent, piracetam, in aluminum (Al)-induced neurotoxic model. Results indicated that PP-20/DPJ improved the short-term memory and cognitive behaviors similar to piracetam. Further, both the compounds were equally effective in elevating the acetylcholinesterase and Mg⁺-ATPase enzyme activity in both the brain regions after Al treatment. Thus the current study suggests, that PP-20/DPJ acts as both a cognition-enhancing agent and as a metabolic enhancer.     

An ecotoxicological view on neurotoxicity assessment

The numbers of potential neurotoxicants in the environment are raising and pose a great risk for humans and the environment. Currently neurotoxicity assessment is mostly performed to predict and prevent harm to human populations. Despite all the efforts invested in the last years in developing novel in vitro or in silico test systems, in vivo tests with rodents are still the only accepted test for neurotoxicity risk assessment in Europe. Despite an increasing number of reports of species showing altered behaviour, neurotoxicity assessment for species in the environment is not required and therefore mostly not performed. Considering the increasing numbers of environmental contaminants with potential neurotoxic potential, eco-neurotoxicity should be also considered in risk assessment. In order to do so novel test systems are needed that can cope with species differences within ecosystems. In the field, online-biomonitoring systems using behavioural information could be used to detect neurotoxic effects and effect-directed analyses could be applied to identify the neurotoxicants causing the effect. Additionally, toxic pressure calculations in combination with mixture modelling could use environmental chemical monitoring data to predict adverse effects and prioritize pollutants for laboratory testing. Cheminformatics based on computational toxicological data from in vitro and in vivo studies could help to identify potential neurotoxicants. An array of in vitro assays covering different modes of action could be applied to screen compounds for neurotoxicity. The selection of in vitro assays could be guided by AOPs relevant for eco-neurotoxicity. In order to be able to perform risk assessment for eco-neurotoxicity, methods need to focus on the most sensitive species in an ecosystem. A test battery using species from different trophic levels might be the best approach. To implement eco-neurotoxicity assessment into European risk assessment, cheminformatics and in vitro screening tests could be used as first approach to identify eco-neurotoxic pollutants. In a second step, a small species test battery could be applied to assess the risks of ecosystems.     

Chemopreventive role of Indigofera aspalathoides against 20-methylcholanthrene-induced carcinogenesis in mouse

This investigation was undertaken to evaluate the chemopreventive effect of hydroalcoholic extract of Indigofera aspalathoides (HAIA) against 20-methylcholanthrene (20-MC)-induced carcinogenesis in mice. Tumor was induced by single subcutaneous administration of 20-MC (200 µg per mouse) in Swiss albino mice. After 24 h of 20-MC administration, HAIA was administered at the doses of 250 and 500 mg kg^?1 body weight orally for 90 consecutive days. Mice of all groups were observed for 15 weeks to record tumor incidence (fibrosarcoma) and survival time. After 15 weeks the mice were sacrificed for the estimation of hematological profiles like hemoglobin (Hb), white blood cell (WBC), red blood cell (RBC), and liver biochemical parameters, namely lipid peroxidation, reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT). HAIA treatment markedly reduced tumor incidence and prolonged the life span of sarcoma-bearing mice as compared to 20-MC control mice. Hematological profiles were significantly (p < 0.001) restored to normal levels in HAIA-treated mice as compared to 20-MC control mice. HAIA treatment significantly (p < 0.001) modulated the aforesaid liver biochemical parameters as compared to 20-MC control. The results concluded that I. aspalathoides demonstrated a remarkable chemopreventive effect in chemical-induced carcinogenesis in mouse. The potential chemopreventive action may be due to its antioxidant and detoxifying properties.     

Evaluating the Predicted Local Extinction of a Once-Common Mouse

Abstract:  In an earlier paper ( Pergams & Nyberg 2001 ) we found that the proportion of the prairie deer mouse ( Peromyscus maniculatus bairdii ), among all local Peromyscus museum specimens collected in the Chicago region, had significantly declined over time. This proportion changed from about 50% before 1900 to <10% in the last 25 years. Based on this proportion a regression model predicted the local extinction of the prairie deer mouse in 2009. To evaluate that prediction, we estimated current deer mouse abundance by live trapping small mammals at 15 preserves in Cook and Lake counties, Illinois (USA) at which prairie deer mice had previously been caught or that still contained their preferred open habitat. In 1900 trap nights, 477 mammals were caught, including 251 white-footed mice ( P. leucopus ), but only one prairie deer mouse. The observed proportion of Peromyscus that were prairie deer mice, 0.4%, was even lower than the 4.5% predicted for 2000. Here we also introduce a simple, new community proportions model, which for any given geographic region compares the proportions of species recently caught with the proportions of species in museums. We compared proportions of seven species collected in Cook and Lake counties and examined by Hoffmeister (1989) with proportions of these species that we caught. Ten percent of the museum community was prairie deer mice, but only 0.2% of our catch was. The current local scarcity of the prairie deer mouse is consistent with the regression-based prediction of its eminent local extinction. More conservation attention should be paid to changes in relative abundance of once-common species.     

有机磷酸酯对斑马鱼的早期神经毒性作用研究

国内外研究已证实,有机磷酸酯广泛分布于多种环境介质中,但目前仍缺乏足够的数据阐明有机磷酸酯具有早期神经毒性效应及其可能的毒性作用机制。本研究采用模式动物斑马鱼(Danio rerio)作为研究对象,选择了环境中3种典型的有机磷酸酯类化合物包括磷酸三苯酯(TPP)、2-乙基己基二苯基磷酸酯(EHDPP)和磷酸三(2-氯)乙酯(TCEP),从斑马鱼运动行为、氧化应激和神经发育关键基因的转录等方面阐述有机磷酸酯的早期神经毒性作用及可能的作用机制。研究发现,TPP(0.1和1 mg·L~(-1))、EHDPP(0.2和2 mg·L~(-1))和TCEP(0.5和5 mg·L~(-1))可能通过诱导氧化应激并下调神经发育关键基因(mbp和syn2a)的转录从而显著抑制斑马鱼的运动行为。本研究可以为有机磷酸酯类阻燃剂及其替代产品的生产、使用和危险度评估提供直接依据。     

Aluminium and Alzheimer's disease: is there a causal connection?

At the present time there seems to be sufficient evidence to conclude that aluminium may, at least under some circumstances, be neurotoxic. Furthermore, several studies have found increased amounts of aluminium in specific brain structures of people who have died with Alzheimer's disease. From the available evidence it is not possible, however, to draw any firm conclusions regarding the possible role of aluminium in the aetiology or pathogenesis of Alzheimer's disease.Even though there is some evidence from ecological studies that exposure to aluminium at least from drinking water may be causally linked to the development of Alzheimer's disease, it is still entirely possible that the accumulation of aluminium in the brains of people with this disorder is a secondary phenomenon. There is a lack of data relating individual exposure to aluminium with subsequent risk of developing the disease.A case-control study currently being carried out in Norway will seek to collect individual exposure data with particular emphasis on aluminium exposure from drinking water sources. The design of this study is presented.     

Defensive behavior of the black widow spider Latrodectus hesperus (Araneae: Theridiidae)

Summary When threatened, the black widow spider, Latrodectus hesperus, emits an adhesive, viscous web, pulls the strand from its spinnerets with its fourth pair of legs, and spreads its appendages. This behavior positions the web over the delicate abdomen, increases the area of protection, and enables the spider to place the web onto the offender, if necessary.In laboratory interactions, the viscous web protected black widows from mice (Peromyscus spp.). Mature female spiders, which had their spinnerets blocked and hence could not discharge the viscid silk, escaped less often than did black widows that were not experimentally altered.The viscid silk is palatable to mice and it appears that the deterrent effect of the web is due solely to mechanical irritation.The defensive behavior is elicited most often from mature females, which may suffer greater predation than other age groups. Males lose the ability to produce the defensive web at maturity and may shift their energy resources totally into reproductive effort.     

Adverse effects of mercuric chloride on thyroid of mice, Musculus albinus and pattern of recovery of the damaged activity

The protective role of "essentiale phospholipids" (EPL) on mercury induced thyroid dysfunction with special reference to cholesterol, thyroid peroxidase and thyroxine activity in mice were investigated. The animals were treated with 0.5 ml/day of 0.5 ppm aqueous mercuric chloride for a period of 7, 14 and 21 days. For the recovery 175 mg of EPL was given to mice (already treated with HgCl2) for a period of 7, 14 and 21 days. Daily treatment of HgCl2 for 7, 14 and 21 days decreased serum cholesterol, TPO and T4 activity. Simultaneous administration of EPL (25 mg/mice) restored thyroid function in mice by maintaining serum thyroid hormone concentration almost normal. It increased serum cholesterol, TPO and T4 activity. It appears that the protective effect of EPL against HgCl2 induced thyroid dysfunction is mediated through its antioxidative action.     

Biochemical alterations in rat brain following aluminum exposure: Protection with centrophenoxine

Aluminum (Al) is a neurotoxicant potentially affecting ionic, cholinergic, and dopaminergic neurotransmission in the central nervous system. These alterations are known to be associated with learning ability, adaptive responses, and other aspects of behavior. The present experiment was designed to study the neurotoxic consequences of Al exposure on neurotransmitters like dopamine (DA), serotonin (5-HT), norepinephrine (NE) along with the activity of acetylcholinesterase (AChE). Furthermore, Centrophenoxine (CpH) was administered as a post treatment to evaluate its potential in Al-induced neurotoxicity. The cognitive functions and memory loss were also studied after both Al and CpH administration. Al was administered orally at a dose of 40?mg?kg^?1?day^?1 for a period of 8 weeks, whereas CpH was administered intraperitoneally at a dose of 100^?1?mg?kg^?1?day^?1 for a period of 6 weeks. The study was carried out in four regions of the brain, namely cerebrum, cerebellum, medulla oblongata, and hypothalamus. A significant reduction in AChE activity and different neurotransmitters was observed after Al exposure in the regions. CpH as a post treatment proved beneficial in restoring these alterations. Al exposure also affected the cognitive functions and short-term memory, which were significantly improved following CpH post treatment.     

Maternal investment, sex-differential prospects, and the sex ratio in wild house mice

In a population of first-generation offspring from wild-caught house mice (Mus musculus domesticus), previous evidence suggested that male fitness is more strongly affected by an increase in body weight than female fitness. This paper shows that in these mice the young are weaned at heavier weights the smaller the litter and the better the maternal body condition. These effects persisted into adulthood and were less pronounced in female young. However, contrary to expectation from conventional sex ratio theory, maternal condition and litter size had no detectable effect on sex ratios. Also, litter size did not affect sex ratios in two populations of laboratory-kept, wild-caught western (M. m. domesticus) and eastern house mice (M. m. musculus). Wild house mice, therefore, appear not to adaptively manipulate the sex ratio of offspring. It is argued that this absence of sex ratio trends might not be maladaptive, but rather that models currently used to predict sex ratio trends in rodents may not be valid. Received: 13 March 1997 / Accepted after revision: 9 August 1997     

复方阿苯达唑/伊维菌素及其单药的体内外致突变性研究

农业生产上常用的阿苯达唑和伊维菌素均有一定的致突变性。为了解伊维菌素和阿苯达唑按1:24形成固定剂量复方的致突变性,以及复方和单药致突变性的差异,采用Ames试验、小鼠骨髓微核试验和小鼠精子畸变试验进行复方阿苯达唑/伊维菌素及其单药的致突变性研究。结果表明,复方阿苯达唑/伊维菌素能提高小鼠骨髓嗜多染红细胞的微核率和精子畸形率,但在单复方的比较中发现,单药的微核率和精子畸形率均高于复方,表明复方毒性有所降低。同时,无论是复方还是单药均不能提高组氨酸缺陷型沙门氏菌的突变率。以上表明,虽然复方阿苯达唑/伊维菌素致突变毒性低于单药,但仍然是一种能引起小鼠骨髓微核率和精子畸形率升高的致突变阳性药物,因此需警惕该药物的食品残留问题及对生态环境的危害。     

Low-level copper exposures increase visibility and vulnerability of juvenile coho salmon to cutthroat trout predators

Copper contamination in surface waters is common in watersheds with mining activities or agricultural, industrial, commercial, and residential human land uses. This widespread pollutant is neurotoxic to the chemosensory systems of fish and other aquatic species. Among Pacific salmonids (Oncorhynchus spp.), copper-induced olfactory impairment has previously been shown to disrupt behaviors reliant on a functioning sense of smell. For juvenile coho salmon (O. kisutch), this includes predator avoidance behaviors triggered by a chemical alarm cue (conspecific skin extract). However, the survival consequences of this sublethal neurobehavioral toxicity have not been explored. In the present study juvenile coho were exposed to low levels of dissolved copper (5-20 microg/L for 3 h) and then presented with cues signaling the proximity of a predator. Unexposed coho showed a sharp reduction in swimming activity in response to both conspecific skin extract and the upstream presence of a cutthroat trout predator (O. clarki clarki) previously fed juvenile coho. This alarm response was absent in prey fish that were exposed to copper. Moreover, cutthroat trout were more effective predators on copper-exposed coho during predation trials, as measured by attack latency, survival time, and capture success rate. The shift in predator-prey dynamics was similar when predators and prey were co-exposed to copper. Overall, we show that copper-exposed coho are unresponsive to their chemosensory environment, unprepared to evade nearby predators, and significantly less likely to survive an attack sequence. Our findings contribute to a growing understanding of how common environmental contaminants alter the chemical ecology of aquatic communities.