Toxic Secretions Research Articles

Poisons, toxungens, and venoms: redefining and classifying toxic biological secretions and the organisms that employ them

Despite extensive study of poisonous and venomous organisms and the toxins they produce, a review of the literature reveals inconsistency and ambiguity in the definitions of 'poison' and 'venom'. These two terms are frequently conflated with one another, and with the more general term, 'toxin.' We therefore clarify distinctions among three major classes of toxins (biological, environmental, and anthropogenic or man-made), evaluate prior definitions of venom which differentiate it from poison, and propose more rigorous definitions for poison and venom based on differences in mechanism of delivery. We also introduce a new term, 'toxungen', thereby partitioning toxic biological secretions into three categories: poisons lacking a delivery mechanism, i.e. ingested, inhaled, or absorbed across the body surface; toxungens delivered to the body surface without an accompanying wound; and venoms, delivered to internal tissues via creation of a wound. We further propose a system to classify toxic organisms with respect to delivery mechanism (absent versus present), source (autogenous versus heterogenous), and storage of toxins (aglandular versus glandular). As examples, a frog that acquires toxins from its diet, stores the secretion within cutaneous glands, and transfers the secretion upon contact or ingestion would be heteroglandular-poisonous; an ant that produces its own toxins, stores the secretion in a gland, and sprays it for defence would be autoglandular-toxungenous; and an anemone that produces its own toxins within specialized cells that deliver the secretion via a penetrating wound would be autoaglandular-venomous. Adoption of our scheme should benefit our understanding of both proximate and ultimate causes in the evolution of these toxins.

Effects of natural flooding and manual trapping on the facilitation of invasive crayfish-native amphibian coexistence in a semi-arid perennial stream

Aquatic amphibians are known to be vulnerable to a myriad of invasive predators. Invasive crayfish are thought to have eliminated native populations of amphibians in some streams in the semi-arid Santa Monica Mountains of southern California. Despite their toxic skin secretions that defend them from native predators, newts are vulnerable to crayfish attacks, and crayfish have been observed attacking adult newts, and eating newt egg masses and larvae. For 15 years, we have observed invasive crayfish and native California newts coexisting in one stream in the Santa Monica Mountains. During that period, we monitored the densities of both crayfish and newt egg mass densities and compared these to annual rainfall totals. After three seasons of below average rainfall, we reduced crayfish numbers by manual trapping. Our long-term data indicated that crayfish did not fare well in years when rainfall is above the historic average. This invasive predator did not evolve with high velocity streams, and observations indicated that southern California storm events washed crayfish downstream, killing many of them. Newts exhibit increased reproduction in years when crayfish numbers were reduced. A comparison with a nearby stream that does not contain crayfish indicated that newt reproduction positively responded to increased rainfall, but that fluctuations were much greater in the stream that contains crayfish. We suggest that rainfall patterns help explain invasive crayfish/newt coexistence and that management for future coexistence may benefit from manual trapping.

New Perspectives on Ancient Granulomas

EDITORIAL article Front. Immunol., 15 November 2013Sec. Inflammation Volume 4 - 2013 | https://doi.org/10.3389/fimmu.2013.00345

Inhibition of human astrocyte and microglia neurotoxicity by calcium channel blockers

We examined the effects of L-type calcium channel blockers (CCBs) on toxicity exerted by activated human astrocytes and microglia towards SH-SY5Y human neuronal cells. The CCBs nimodipine (NDP) and verapamil (VPM) both significantly suppressed toxic secretions from human astrocytes and astrocytoma U-373 MG cells that were induced by interferon (IFN)-γ. NDP also inhibited neurotoxic secretions of human microglia and monocytic THP-1 cells that were induced by the combination of lipopolysaccharide and IFN-γ. In human astrocytes, both NDP and VPM reduced IFN-γ-induced phosphorylation of signal transducer and activator of transcription (STAT) 3. They also inhibited the astrocytic production of IFN-γ-inducible T cell α chemoattractant (I-TAC). These results suggest that CCBs attenuate IFN-γ-induced neurotoxicity of human astrocytes through inhibition of the STAT3 signaling pathway. L-type CCBs, especially NDP, might be a useful treatment option for a broad spectrum of neurodegenerative diseases, including Alzheimer disease, where the pathology is believed to be exacerbated by neurotoxic glial activation.

The remarkable Boophone disticha (L.f.) Herb. (Amaryllidaceae); survivor from the northern tropical savanna woodlands to the South African semi-arid Karoo

My first memory of this spectacular plant dates from the 1940’s when I roamed the granitic, miombo woodlands east of Harare (Salisbury). I removed a large bulb and planted it in our garden. When our gardener (a local) saw the plant, he was quite alarmed and warned me of the extremely toxic bulb secretion, now a recognized poisonous alkaloid. From this first experience, the plants followed my long migration southwards from the tropics to the arid desert-like Northern Cape, finally, to my surprise, to appear in the western Succulent Karoo biome, which experiences winter rainfall unlike the northern tropics where heavy summer downfalls all but drown the plants. In South Central Africa, the plants seem to be confined to the watershed, frequently on granitic sandveld. The extremely large bulbs are covered with a thick layer of papyraceous scales, skeletal remnants of leaves long dried. These scales rise above the soil level and serve to protect the developing flower bud and later the newly emerged leaves. The giant bulbs are evolutionarily well adapted to store moisture and under a semi desert environment or during periodic seasonal droughts can endure until more favourable conditions prevail. The origin of the generic name Boophone means “ox-killer” and in the south, the plant is known as “gifbol” —poisonous ball— by the local people. In the Northern and Western Cape Provinces, the traditional Khoi inhabitants use the plant for a variety of medicinal complaints in spite of its proven toxicity. The wide, dry outer bulb scales are used as a dressing, applied to boils or septic wounds. However, the secretion, if taken internally, can cause death but surprisingly stock nibble the leaves without apparent ill effect. The bulbs measure up to 15 × 13 cm, with leaves growing in a broad fan (distichous) up to 25 cm high. Individual leaves twist slightly along their length and are coloured greyishto dark green. In the tropics, the inflorescence appears in spring before the leaves and just before the first rains arrive. The peduncle is very stout carrying a dense, rounded ball of very numerous (100 or more) brightly coloured red-pink to dark pink flowers with long pedicels which elongate even further, and stiffen during maturity, to carry the dried seed capsules. Seed distribution occurs after the 30 cm long peduncle

Antibacterial properties of contact defensive secretions in neotropical Crematogaster ants

Crematogaster ants use their contact venoms to compete with other ants. Although those venoms are used primarily as repellent and toxic secretions, they may have other functions. The present study aimed to test the antibacterial property of abdominal venom of three neotropical Crematogaster ant species (C. distans, C. pygmaea and C. rochai) against gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Enterococcus faecalis and Staphylococcus aureus) bacteria. Sterile filter paper was soaked with C. distans, C. pygmaea or C. rochai crude venom and placed on an agar dish that was inoculated with bacterial suspensions. The agar dish was incubated overnight at 37ºC and examined for zones of growth inhibition. For each tested venom and bacterial strain, three venom concentrations were used, with six replicates for each concentration: 1, 2 and 4 DGE (Dufour's gland equivalent). The venom of C. pygmaea, but not those of C. rochai and C. distans, inhibited the growth of all tested gram-positive and gram-negative bacterial strains. This is the first evidence of antibacterial properties of contact venoms in Crematogaster ants and it supports the claim that ant venoms are multifunctional. It is hypothesized that only C. pygmaea venom showed antibacterial activities due to its nesting habits.

Modeling familial Alzheimer's disease with induced pluripotent stem cells

Alzheimer's disease (AD) is the most common form of age-related dementia, characterized by progressive memory loss and cognitive disturbance. According to the amyloid cascade hypothesis, a prevailing theory of AD pathology, accumulation of toxic Aβ42, in the brain is the initiator of AD pathogenesis, subsequently leading to the formation of neurofibrillary tangles, and consequently neuronal loss. Mutations of presenilin 1 (PS1) and presenilin 2 (PS2), which are catalytic components of γ-secretase, are causative factors for autosomal dominant early-onset familial AD (FAD). Induced pluripotent stem cell (iPSC) technology provides a new method for elucidating the molecular basis of human diseases, including neurodegenerative diseases. Here we generate iPSCs from fibroblasts of FAD patients with mutations in PS1 (A246E) and PS2 (N141I), and characterize the differentiation of these cells into neurons. We find that FAD-iPSC-derived differentiated neurons have increased toxic Aβ42 secretion, recapitulating the molecular pathogenesis of mutant presenilins. Furthermore, secretion of Aβ42 from these neurons sharply responds to γ secretase inhibitors and modulators, indicating the potential for identification and validation of candidate drugs. Our findings demonstrate that the FAD-iPSC-derived neuron is a valid model of AD and provides an innovative strategy for the study of late-onset neurodegenerative diseases.

Skin glands, poison and mimicry in dendrobatid and leptodactylid amphibians

In amphibians, secretions of toxins from specialized skin poison glands play a central role in defense against predators. The production of toxic secretions is often associated with conspicuous color patterns that warn potential predators, as it is the case of many dendrobatid frogs, including Ameerega picta. This species resembles the presumably nontoxic Leptodactylus lineatus. This study tests for mimicry by studying the morphology and distribution of skin glands, components of skin secretion, and defensive behavior. Dorsal skin was studied histologically and histochemically, and skin secretions were submitted to sodium dodecyl sulfate polyacrylamide gel electrophoresis, reversed phase high performance liquid chromatography and assays for proteolytic activity. We found that poison glands in A. picta are filled with nonprotein granules that are rich in carbohydrates, while L. lineatus glands present protein granules. Accordingly, great amounts of proteins, at least some of them enzymes, were found in the poison of L. lineatus but not in that of A. picta. Both species differ greatly on profiles of gland distribution: In L. lineatus, poison glands are organized in clusters whose position coincides with colored elements of the dorsum. These regions are evidenced through a set of displays, suggesting that poison location is announced to predators through skin colors. In contrast, A. picta presents lower densities of glands, distributed homogeneously. This simpler profile suggests a rather qualitative than quantitative investment in chemical defense, in agreement with the high toxicity attributed to dendrobatids in general. Our data suggest that both species are toxic or unpalatable and transmit common warning signals to predators, which represents a case of Müllerian mimicry.

Argovin, a novel natural product secreted by the fungus Meira argovae, is antagonistic to mites

A metabolite of the fungus Meira argovae Boekhout, Scorzetti, Gerson & Sztejnberg (Exobasidiomycetidae) was assayed as an antagonist of mites. Separation of extracted fungal metabolites by reversed phase liquid chromatography (RPLC), with subsequent testing of the obtained fractions, allowed us to isolate a single mite-antagonistic fraction (also active against a bacterium) that primarily includes one major component. This active compound (herein termed ‘argovin’) was identified by analyzing its spectral characteristics as 4,5-dihydroxyindan-1-one, which has previously only been described as a product of chemical reactions. The growth rate of the fungus was higher at a neutral pH than at an acidic one. Meira argovae adjusts the pH of its media to values optimal for its colony growth and toxic secretions. RPLC-cleaned argovin at 0.2 mg ml−1 killed 100% of a population of the citrus rust mite, Phyllocoptruta oleivora (Ashmead) (Acari: Eriophyidae). This trait may be used to control citrus rust mites in the field, as well as for toxin production for industrial and pharmaceutical uses.

Antipredator Skin Secretions of the Long-toed Salamander (Ambystoma macrodactylum) in Its Northern Range

Distasteful, noxious, and toxic secretions from skin glands have been demonstrated to play important antipredatory roles in amphibians. Previous studies suggest that the Long-toed Salamander (Ambystoma macrodactylum), a widely distributed urodele found near the northern limit of its range in northern British Columbia, is distasteful to predators. The source of this distastefulness has not been exclusively identified. Our objectives were to isolate the skin secretions of the Long-toed Salamander through electrical stimulation of its granular glands and bioassay this secretion for antipredatory effects with crayfish. Previous studies suggested that proteins play an important role in these secretions; therefore, we tested for their presence and utility. The feeding response of crayfish to control food pellets was compared to pellets incorporating raw salamander skin secretions and to pellets incorporating boiled secretions. Significantly more crayfish consumed the control pellets than the raw skin secretion pellets, indicating unpalatability of these skin secretions. Thus, skin secretions appear to have an important antipredatory function. Skin secretions tested positive for presence of proteins, but the feeding response of crayfish to raw and boiled secretions was not significantly different, indicating that proteins were either only partially denatured by boiling, or are not exclusively responsible for the antipredatory nature of the secretions. A very low concentration of secretion was required to illicit a significant antifeedant response in crayfish, and we discuss the possible implications of this in relation to a proposed dual function of the Long-toed Salamander's granular glands in nutrient storage and the energetic requirements of an amphibian in its northern range.

Identical Skin Toxins by Convergent Molecular Adaptation in Frogs

The Tree of Life is rife with adaptive convergences at all scales and biological levels of complexity. However, natural selection is not likely to result in the independent evolution of identical gene products. Here we report such a striking example of evolutionary convergence in the toxic skin secretions of two distantly related frog lineages. Caeruleins are important decapeptides in pharmacological and clinical research [1] and are commonly believed to represent a single evolutionary class of peptides [2-4]. Instead, our phylogenetic analyses combining transcriptome and genome data reveal that independently evolved precursor genes encode identical caeruleins in Xenopus and Litoria frogs. The former arose by duplication from the cholecystokinin (cck) gene, whereas the latter was derived from the gastrin gene. These hormone genes that are involved in many physiological processes diverged early in vertebrate evolution, after a segmental duplication during the Cambrian period. Besides implicating convergent mutations of the peptide-encoding sequence, recurrent caerulein origins entail parallel shifts of expression from the gut-brain axis to skin secretory glands. These results highlight extreme structural convergence in anciently diverged genes as an evolutionary mechanism through which recurrent adaptation is attained across large phylogenetic distances.

Anting behaviour with millipedes by the dendrocolaptid bird Xiphocolaptes albicollis in southeastern Brazil

Several bird species practice anting. While anting a bird holds an ant or other arthropod that produces toxic or irritating secretions and rubs it on the plumage. Here I describe the White-collared Woodcreeper (Xiphocolaptes albicollis) rubbing its body with millipedes of the orders Spirostreptida and Polydesmida while foraging among banana stumps or at bromeliad clumps in southeastern Brazil. On three occasions I recorded the bird holding a millipede in the bill and rubbing it against its chest, belly, and wings. From time to time the millipede was "chewed", and hammered against the substratum and then rubbed on the plumage again. After a while the millipede was ingested or dropped. Bromeliads harbour a rich fauna that includes mosquitoes, ticks, spiders, and snakes, and some of them may be potential hazards to birds that forage among the accumulated plant debris. The toxic secretions of millipedes may act as a deterrent against some of these hazardous animals, and the woodcreeper's behaviour also reduces the noxiousness of a toxic prey before ingestion.

Comparative experimental tests of natricine antipredator displays, with special reference to the apparently unique displays in the Asian genus, Rhabdophis

Nuchal glands are unique organs known in only twelve Old World natricine species (three genera) including Rhabdophis tigrinus tigrinus. The glands of R. t. tigrinus contain a toxic secretion that may be derived from its toxic toad diet. A series of peculiar antipredator behaviors, for example neck arch, neck butt, and dorsal-facing posture, are exhibited by R. t. tigrinus, and a functional association between this behavior and the nuchal glands has been suggested. To investigate the ubiquitousness of these putatively unique displays among snakes, antipredator responses of 27 taxa of natricine snakes, both with and without nuchal glands, were studied using a common testing procedure. Three of four taxa with nuchal glands exhibited neck arch, neck butt, and dorsal-facing posture. None of the remaining 23 taxa, which do not possess the glands, showed neck arch and neck butt. Principal-components analysis indicated the association of the above three displays along with the behaviors termed neck flatten and head elevation, confirming the presence of a series of nuchal gland-related behaviors. These results support the assumption that the suite of peculiar displays is associated with the deterrent effects of the nuchal gland secretion.

Environmental and Seasonal Variation in the Diet of Elachistocleis bicolor (Guérin-Méneville 1838) (Anura: Microhylidae) from Northern Uruguay

We studied the diet of Elachistocleis bicolor captured in pine, eucalypt, and unmodified environments in Uruguay. Comparisons between seasons (active, inactive) and among three environments (pine, eucalypt, unmodified), were made using rarefaction analyses, importance indices, and non-parametric tests. Elachistocleis bicolor has a specialized diet composed mainly of Pheidole and Solenopsis ants and termites. The diet of E. bicolor includes a high number of prey per individual, suggesting active search as a foraging strategy. The consumption of myrmicine ants (i.e., Solenopsis) represents a source for potential toxic skin secretions that in E. bicolor may be used to avoid being attacked in the ant nests used for shelter during aestivation, as occurs in the microhylid Phrynomantis microps. Diets in forested environments were richer in both periods, which may reflect the colonization of opportunistic ant species in these environments. Ants were more important in the eucalyptus plantations, particularly in the inactive period, whereas termites were more important in the pine plantations mainly in the inactive period. These environmental and seasonal differences in diet are consistent with the temperature and humidity tolerances of ants and termites, which are the main prey of E. bicolor.

Tests of aggregative preferences of wandering salamanders (Aneides vagrans)

Plethodontid salamanders usually exhibit territorial spacing patterns and behaviors. Previous works suggest that plethodontids from Vancouver Island, Canada lack strong territoriality. In one Vancouver Island species, Aneides vagrans, salamanders may even be found in the field in small aggregations. We investigated preferences of A. vagrans for occupied vs unoccupied cover objects and for cover objects occupied by conspecifics of different age/size classes. We also tested A. vagrans preferences for conspecific vs heterospecific salamanders in an attempt to determine if the lack of territoriality by A. vagrans is species-specific and perhaps related to habitat segregation. A. vagrans did not avoid occupied cover objects or exhibit a preference for occupied vs unoccupied sites. Age class did not affect cover object choice. A. vagrans did not avoid heterospecifics that exhibit the highest degree of resource overlap (Plethodon vehiculum), which we believe might be attributable to a benign and resource-rich habitat, although alternative explanations exist. A. vagrans did avoid syntopic newts (Taricha granulosa), though this is probably due to toxic newt skin secretions.

RETRACTED: γ-Cleavage-Independent Functions of Presenilin, Nicastrin, and Aph-1 Regulate Cell-Junction Organization and Prevent Tau Toxicity In Vivo

Genetic analysis of familial Alzheimer's disease has revealed that mutations in the gamma-secretase enzyme presenilin promote toxic Abeta secretion; however, presenilin mutations might also influence tau hyperphosphorylation and neurodegeneration through gamma-secretase-independent mechanisms. To address this possibility and determine whether other components of the gamma-secretase complex possess similar regulatory functions, we analyzed the roles of presenilin, nicastrin, and aph-1 in a Drosophila model for tau-induced neurodegeneration. Here, we show that presenilin and nicastrin prevent tau toxicity by modulating the PI3K/Akt/GSK3beta phosphorylation pathway, whereas aph-1 regulates aPKC/PAR-1 activities. Moreover, we found that these transmembrane proteins differentially regulate the intracellular localization of GSK3beta and aPKC at cell junctions. Inhibition of gamma-secretase activity neither interfered with these kinase pathways nor induced aberrant tau phosphorylation. These results establish new in vivo molecular functions for the three components of the gamma-secretase complex and reveal a different mechanism that might contribute to neuronal degeneration in Alzheimer's disease.

Chapter 11.6 Clays and Clay Minerals as Drugs

Publisher SummaryThis chapter discusses the applications of clays and clay materials as drugs. Clay minerals are efficient against several aggressors that cause major disorders of the gut. These beneficial effects of clay minerals (on the gastrointestinal mucosa) are associated with two mechanisms of action: (1) adsorption of the aggressors or their toxic secretions and (2) modification of the thickness and rheological properties of the adherent mucus, reinforcing the natural defenses of the gastrointestinal mucosa. At the surface of the gut, a mucus gel adheres to the epithelial cells of the mucosa. This adherent mucus is dynamic, being continuously secreted by the calceiform cells and regularly eroded by environmental aggressors present in the gut lumen. The mucus gel is largely composed of glycoprotein polymers, lipids, and proteins linked together by covalent bonds. It acts as a physical barrier protecting the mucosa against penetration by extraneous molecules and mechanical injury. By maintaining a pH gradient and competing with the epithelial surface for microorganisms, the mucus gel also acts as a chemical barrier.

The inguinal macroglands of the frog Physalaemus nattereri (Leptodactylidae): structure, toxic secretion and relationship with deimatic behaviour

AbstractAmphibian skin is characterized by the presence of mucous glands, related to cutaneous breathing, reproduction and water balance, and granular glands, related to the production of toxins used in defence. In some species the granular glands can form accumulations in certain regions of the body. This is the case for inguinal macroglands of the leptodactylid frog Physalaemus nattereri, where these structures form a pair of black discs associated with deimatic behaviour. The morphology of the inguinal macroglands and their secretion were studied in this species and correlated to deimatic behaviour. The inguinal macroglands are formed from elongated granular glands that, in contrast with the granular glands of the rest of the skin, have small spherical granules with a proteinic content. In the dermis of the whole body, except for the inguinal macroglands and the inguinal region, a well‐developed calcified dermal layer is observed. During deimatic behaviour these macroglands discourage a potential predator from attacking, but if visual cues are insufficient and the predator persists in the attack, a toxic secretion is eliminated in its mouth. This elimination is favoured by the absence of a calcified dermal layer in the macroglands, which makes the dermal region softer than the rest of the dorsal skin.

Pathogenicity of bacterium, Xenorhabdus nematophila isolated from entomopathogenic nematode (Steinernema carpocapsae) and its secretion against Galleria mellonella larvae

The entomopathogenic bacterium, Xenorhabdus nematophila was isolated from the hemolymph of Galleria mellonella infected with Steinernema carpocapsae. The bacterial cells and its metabolic secretions have been found lethal to the Galleria larvae. Toxic secretion in broth caused 95% mortality within 4 d of application whereas the bacterial cells caused 93% mortality after 6 d. When filter and sand substrates were compared, the later one was observed as appropriate. Similarly, bacterial cells and secretion in broth were more effective at 14% moisture and 25 degrees C temperature treatments. Maximum insect mortality (100%) was observed when bacterial concentration of 4x10(6) cells/ml was used. Similarly, maximum bacterial cells in broth (95%) were penetrated into the insect body within 2 h of their application. However, when stored bacterial toxic secretion was applied to the insects its efficacy declined. On the other hand, when the same toxic secretion was dried and then dissolved either in broth or water was proved to be effective. The present study showed that the bacterium, X. nematophila or its toxic secretion can be used as an important component of integrated pest management against Galleria.

Use of Entomopathogenic Bacterium Pseudomonas putida (Enterobacteriaceae) and its Secretion Against Greater Wax Moth, Galleria mellonella Pupae

The bacterium from Pseudomonas putida from Steinernema abbasi and its metabolic secretions caused the mortality of the Galleria mellonella pupae. Experiments were conducted in sand and filter paper on time exposure, temperature, moisture, dose and time of penetration of bacterium in pupae and tested stored or dried toxic metabolites using G. mellonella pupae as a test target organism. Death of pupae was probably due to the toxic metabolites. Pseudomonas putida cells were recovered from the haemocoele when bacterial cells were applied to the G. mellonella pupae indicating that bacterial cells can enter the haemocoele in the absence of nematode vector. Penetration of bacterium was found rapidly after application on G. mellonella pupae. Pseudomonas putida or its toxic secretions can be used as a microbial control for insect control. The experimental results indicate that there is possibility of using P. putida and its toxic secretions as a biopesticide and can contribute in the development of new microbial and biological control against insect pests.