CHEMICAL CAUSES : ARTHROPODA
 

Chelicerata

• Arachnida
• Acari
• Parasitiformes
• Ixodida (ticks)
• Ixodidae (hardbacked ticks)
• Amblyomma
• Amblyomma americanum
• Dermacentor
• Dermacentor andersoni
• Dermacentor variabilis
• Ixodes
• Ixodes holocyclus (a.k.a. Australian paralysis tick)


Epidemiology : in grey fox (Urocyon cinereoargenteus), llamas, domestic animals such as dogs and cats, livestock, and in some cases, humans along the eastern coast of Australia. It most frequently occurs in the spring and summer months but can be seen at any time of year. Children aged 1-5 years are most commonly affected. The tick is usually found in the scalp, often behind the ear.
=> holocyclotoxin, produced in tick salivary glands, inhibits relase of ACh causing a severe toxicosis as well as hypersensitivity reactions in humans. Tick paralysis in animals is usually fatal in the absence of speedy antitoxin treatment and human hypersensitivity may result in life-threatening anaphylaxis. The current treatment for severe tick paralysis is in the form of a polyclonal dog antiserum, but this antiserum treatment is expensive and effective only in the early stages of paralysis causing a high incidence of acute allergy and serum sickness
=> tick paralysis
• Araneae

=> arachnidism / araneism / arachnoidism : the condition produced by the bite of a venomous spider; envenomation by a spider
• necrotic arachnidism : spider envenomation marked by necrosis at the site of the bite, resulting in slow-healing, ulcerating lesions. Spider bites are often used as a default diagnosis for idiopathic dermal necrosis, despite the lack of solid evidence.
• Araneomorphae
• Entelegynae
• Agelenidae
• Agelena
• Agelena opulenta

=> agelenin : it blocks P-type voltage-gated Ca²⁺ channels.
• Agelenopsis
• Agelenopsis aperta

=> w-agatoxin-TK has D-serine in its peptide at position 46 : it blocks P-type voltage-gated Ca²⁺ channels.
• Hololena
• Hololena curta

=> Hololena toxin (peptide) : it blocks P-type voltage-gated Ca²⁺ channels
• Araneoidea
• Araneidae
• Araneus spp. (e.g. Araneus gemma)

=> toxic peptide : it is an antagonist of Glu receptors
• Argiope
• Argiope aurantia

=> argiopine

=> argiotoxin₆₃₆
• Theridiidae
• Latrodectus (a.k.a. black widows)
• Latrodectus mactans (a.k.a. Lactrodectus schuchii, black widow)
• Latrodectus tredecimguttatus (a.k.a. black widow spider, malmignatta)


• Latrodectus hasselti (a.k.a. black widow, redback spider)
=> a-latrotoxin / black widow spider venom (BWSV) binds neurexin 1 and increases ACh release.
• Tetragnathidae
• Nephila
• Nephila clavata (a.k.a. Joro spider)

=> Joro spider toxins (JSTX) :
• 2,4-dihydroxyphenylacetyl-L-asparaginylcadaverine group => blocking quisqualate Glu receptors.


• indoleacetyl group
• nephilatoxins : they cause histamine release from mast cells
• Nephila clavipes (a.k.a. banana or garden spider)

=> phoneutriatoxin : it slows Na⁺ channels inactivation
• Nephila maculata (a.k.a. giant wood spider or golden web spider)

=> NSTX-3

• Lycosoidea
• Lycosidae
• Lycosa spp. (wolf spider)

=> necrosing factor
• Ctenidae
• Phoneutria
• Phoneutria nigriventer (a.k.a. Brazilian armed spider)

=> toxic peptide
• Haplogynae
• Plectreuridae
• Plectreurys
• Plectreurys tristis

=> toxic peptide : it blocks N-type Ca²⁺ channels
• Mygalomorphae
• Hexathelidae
• Atrax
• Atrax robustus (a.k.a. funnel web spider)

=> verustoxin : it opens Na⁺ channels
=> robustotoxin : it opens Na⁺ channels
=> g-aminobutyric acid (GABA)
=> spermine
• Theraphosidae (tarantulas)
• Eurypelma
• Eurypelma californicum

=> toxic peptide : it blocks P-type Ca² channels
• Grammostola
• Grammostola spatulata (a.k.a. South American rose or Chilean fire tarantula)

=> grammotoxin SIA : it blocks Ca²⁺ channels
=> phrixotoxin : it blocks K⁺ channels
=> voltage-sensor toxin (VSTX1) reaches its target by partitioning into the lipid membrane^ref
• Hysterocrates
• Hysterocrates gigas (a.k.a. African tarantula)

=> SNX-482 : it blocks R-type voltage-gated Ca²⁺ channels
• Ornithoctonus
• Ornithoctonus huwena (a.k.a. Chinese (golden) earth tiger, Chinese bird spider)

=> HWTX-I : it blocks Ca²⁺ channels
Venom from a tarantula that is native to the West Indies contains three inhibitor cysteine knot (ICK) peptides that target the capsaicin receptor (TRPV1), an excitatory channel expressed by sensory neurons of the pain pathway. In contrast with the predominant role of ICK toxins as channel inhibitors, these previously unknown 'vanillotoxins' function as TRPV1 agonists, providing new tools for understanding mechanisms of TRP channel gating. Some vanillotoxins also inhibit voltage-gated potassium channels, supporting potential similarities between TRP and voltage-gated channel structures. TRP channels can now be included among the targets of peptide toxins, showing that animals, like plants (for example, chilli peppers), avert predators by activating TRP channels on sensory nerve fibres to elicit pain and inflammation^ref
• Scorpiones (scorpions)

=> scorpionism
• Buthoidea
• Buthidae : the most toxic species of Mexico and the USA
• Androctonus
• Androctonus australis (a.k.a. Sahara scorpion)

=> kaliotoxin 2 (KTX2) : it blocks K⁺ channels
• Androctous mauretanicus
• Androctonus mauretanicus mauretanicus

=> kaliotoxin (KTX) : it blocks K⁺ channels
• Buthus
• Buthus occitanus
• Buthus occitanus mardochei (Moroccan scorpion)^ref
• Centruroides
• Centruroides margaritatus

=> margatoxin : it blocks K⁺ channels
• Centruroides noxius (a.k.a. Mexican scorpion). Approximately 250 species of scorpions exist in Mexico, of this, only 8 have medical importance. All of this species are contained in 11 genus belonging to 4 of the 6 families of scorpions known today. In Mexico, the most dangerous genus of scorpions is Centruroides, and the most potent venom belongs to C. noxius^{ref1, ref2, ref3}. The venom of C.noxius is composed mainly by a great spectrum of proteins, lipids, amino acids, nucleotides and inorganic salts. Cn2 toxin, as the greater number of known voltage dependent Na⁺ channel specific toxins, is constituted by 68 amino acid residues and stabilized by 4 disulfide bridges^ref, and corresponds approximately to the 7% of the total venom, being the most abundant and toxic protein in it, with a LD₅₀ in mice of 125 ng/20g. Its lethal activity lies on its specificity for blocking Na⁺ channels in excitable membranes^ref

=> noxiustoxin : it blocks Na⁺ channels
• Leiurus
• Leirus quinquestriatus (a.k.a. Egyptian scorpion)

=> charybdotoxin : it blocks "maxi" (g = 100-250 pS) K⁺ channels
=> agitoxins (AgTX) 1-3 (peptides) : they block Shaker K⁺ channels
• Mesobuthus
• Mesobuthus martensii (a.k.a. Buthus martensii, Chinese scorpion)

=> BmKTX : it blocks K⁺ channels
=> BmTXKS1 & TM-601 / chlorotoxin-like peptide, an inhibitor of small-conductance Cl^- channels. It binds to malignant brain tumor cells with high affinity and does not seem to bind to normal brain tissue. Preclinical studies suggest that ¹³¹I–TM-601 may be an effective targeted therapy for the treatment of glioma. The safety, biodistribution, and dosimetry of intracavitary-administered ¹³¹I-TM-601 was evaluated in patients with recurrent glioma. 18 adult patients (17 with glioblastoma multiforme and one with anaplastic astrocytoma) with histologically documented recurrent glioma and a Karnofsky performance status of  60% who were eligible for cytoreductive craniotomy were enrolled. An intracavitary catheter with subcutaneous reservoir was placed in the tumor cavity during surgery. 2 weeks after surgery, patients received a single dose of ¹³¹I-TM-601 from one of three dosing panels (0.25, 0.50, or 1.0 mg of TM-601), each labeled with 10 mCi of ¹³¹I. Intracavitary administration was well tolerated, with no dose-limiting toxicities observed. ¹³¹I-TM-601 bound to the tumor periphery and demonstrated long-term retention at the tumor with minimal uptake in any other organ system. Nonbound peptide was eliminated from the body within 24 to 48 hours. Only minor adverse events were reported during the 22 days after administration. At day 180, 4 patients had radiographic stable disease, and one had a partial response. 2 of these patients further improved and were without evidence of disease for > 30 months. A single dose of 10 mCi ¹³¹I-TM-601 was well tolerated for 0.25 to 1.0 mg TM-601 and may have an antitumoral effect. Dosimetry and biodistribution from this first trial suggest that phase II studies of ¹³¹I-TM-601 are indicated^ref.
• Mesobuthus tamulus (a.k.a. eastern Indian red scorpion)

=> iberiotoxin (IbTX) : it blocks K⁺ channels
• Parabuthus
• Parabuthus schlechteri (a.k.a South African scorpion)

=> parabutoporin : it is a  a pore-forming peptide
• Parabuthus transvaalicus (a.k.a South African fattail scorpion)

=> kurtoxin : it blocks T-type voltage-gated Ca²⁺ channels
• Tityus
• Tityus serrulatus (a.k.a. Brazilian scorpion)

=> tityustoxin-K : it blocks K⁺ channels
• Scorpionoidea
• Scorpionidae
• Pandinus
• Pandinus imperator

=> pandinotoxins (PiTX-K) a and b : they block voltage-gated K⁺ channels
• crab poisoning
• Zosimus aeneus
• Atergatis floridus
• Lophozozymus pictor
• Demania spp.

Hexapoda

• Insecta
• Pterygota
• Neoptera
• Endopterygota
• Amphiesmenoptera
• Lepidoptera
• Glossata
• Neolepidoptera
• Heteroneura
• Ditrysia
• Obtectomera
• Bombycoidea
• Saturniiformes
• Saturniidae
• Saturniinae
• Attacini
• Hyalophora
• Hyalophora cecropia

=> cecropin A, an antibacterial polypeptide
• Noctuoidea
• Notodontidae
• Thaumetopoeinae
• Thaumetopoea
Thaumetopoea processionea (a.k.a. oak processionary caterpillars) : the larvae of a moth species that is widely distributed in central and southern Europe and occasionally found in more northern countries, such as The Netherlands, Sweden and the UK. As is to be expected from its name, the caterpillar feeds on oak leaves and, occasionally, on leaves of walnut trees. Older caterpillars, that is 3rd to 6th larval instars, are covered with numerous (estimated at 63 000 per fully grown larva!) pointed poisonous hairs (setae) that contain an urticating toxin (thaumetopoein). Their purpose is defensive, to protect against predators. Similar hairs are found in the caudal tuft of adult moths, but it is the larvae that cause most problems. When people come into contact with air-borne hairs, they can cause pruritus, dermatitis, conjunctivitis and occasionally respiratory distress, including asthma. A papular rash is a common symptom^{ref1, ref2}. In 1995, 165 soldiers and civilians from the U.S. military base in Heidelberg sought treatment for acute dermatitis resulting from exposure to hairs of oak processionary caterpillars^ref. There are many other moth species that cause various forms of dermatitis in various countries, from the Americas to Asia. (Incidentally, in southeast Asia, there are moths (Calyptra species) whose proboscis is modified for piercing the skin of mammals and sucking up blood)
• Hymenoptera
• Apocrita
• Aculeata
• Apoidea
• Apidae
• Apis spp. (bees)
• Apis mellifera
• Tetragonisca angustula
• apisination : poisoning by the sting of bees.

=> apamin : it blocks "low conductance" (g = 5-15 pS) K⁺ channels
=> mellitin : it activates phospholipase A₂
=> phospholipase A₂
=> MCD-peptide : it blocks voltage-gated K⁺ channels
=> peptide 401 (mast cells degranulating peptide)
• apiotherapy : treatment of multiple sclerosis with bee venom, which is likely to induce an immune deviation from a T_h1 to a T_h2 polarization^{ref1, ref2, ref3, ref4, ref5}
• honey : a sweet-tasting substance deposited by the honeybee, which contains between 62 and 83% glucose and fructose, and small amounts of sucrose, dextrin, and malic and acetic acids; its pH is 3.8 to 4.3.
• beeswax derived from the honeycomb of Apis mellifera; was excipient in beauty care
• white wax / bleached beeswax : the bleached, purified beeswax, used as an ingredient in several ointments
• yellow wax / cera flava / unbleached beeswax : the purified beeswax; used as a stiffening agent in pharmaceutical preparations and as an ingredient of yellow ointment. It was formerly used internally, in the treatment of diarrhea
• hive products
• pollen
• royal jelly, introduced for few decades in dietetic meet show a great commercial passion
• major royal jelly proteins (MRJPs), secreted by nurse bees into the royal jelly.
• MRJP1
• MRJP2
• 70 kDa glycoprotein major royal jelly protein 3 (MRJP3) suppresses IL-4 production
• 350-kDa royal jelly glycoprotein (RJGP) / apisin stimulates the proliferation of human monocytes
• 10-hydroxy-2-decenoic acid (10-HDA) has antimicrobial properties
• royal jelly 57-kDa protein
• furosine is a suitable index for assessing the quality and freshness of royal jelly
• apisimin
• vitellogenin is a female-specific glucolipoprotein yolk precursor produced by all oviparous animals. Its expression is under hormonal control, and the protein is generally synthesized directly before yolk deposition. In the honeybee (Apis mellifera), vitellogenin is not only synthesized by the reproductive queen, but also by the functionally sterile workers. In summer, the worker population consists of a hive bee group performing a multitude of tasks including nursing inside the nest, and a forager group specialized in collecting nectar, pollen, water, and propolis. Vitellogenin is synthesized in large quantities by hive bees. When hive bees develop into foragers, their juvenile hormone titers increase, and this causes cessation of their vitellogenin production. This inverse relationship between vitellogenin synthesis and juvenile hormone is opposite to the norm in insects, and the underlying proximate processes and life-history reasons are still not understood. Hive bees use the jelly to feed larvae, queen, workers, and drones. This finding suggests that the evolution of a brood-rearing worker class and a specialized forager class in an advanced eusocial insect society has been directed by an alternative utilization of yolk protein
• propolis is a resinous substance collected by honeybees from plant sources. It has numerous biologic activities including antibiotic, antifungal, antiviral, anti-inflammatory and analgesic properties. The anti-tumor mechanism may be mediated by preventing oxidative damage and induction of apoptosis.

=> 4-feruoyl quinic acid
=> 5-ferruoyl quinic acid
=> artepillin C is an antioxidant
=> cinnamic acid derivatives
• drupanin
• baccharin
=> caffeic acid phenethyl ester (CAPE) has many biological and pharmacological activities including antioxidant, anti-inflammation, antiviral action, and anticancer effect : it inhibits heme oxygenase 1 (HO-1), suppresses T-cell activation by inhibiting both NF-kB-dependent and NF-AT-dependent transcriptional activity (without affecting the degradation of cytoplasmic IkBa). p38 MAPK mediates the CAPE-induced p53-dependent apoptosis in C6 glioma cells
• Vespoidea
• Formicidae
• Myrmicinae
• Solenopsidini
• Solenopsis : the fire ants, a genus of stinging ants, which may attack humans, inflicting painful burning stings and causing local or systemic reactions
• Solenopsis geminata (a.k.a. tropical fire ant) is indigenous to the United States
• Solenopsis saevissima richteri (a.k.a. black fire ant) is a viciously aggressive South American species that has now gained a foothold in North America.
• Vespidae (wasps)

=> philanthotoxin (PhTX) : it blocks Glu receptors (or non competitive inhibitor of N AChR ??)
=> b-pompilidotoxin (b-PMTX)
• Vespa
• Vespa basalis (a.k.a. Taiwan hornet)

=> mastoparan B (MP-B) is an antimicrobial cationic tetradecapeptide amide (LKLKSIVSWAKKVL-CONH₂)
• Paraneoptera; Hemiptera; Euhemiptera; Neohemiptera; Prosorrhyncha; Heteroptera; Euheteroptera; Neoheteroptera; Panheteroptera; Cimicomorpha; Reduvioidea
• Reduviidae
• Melanolestes : the corsairs, a genus of biting insects
• Melanolestes picipes : the “black corsair” or “kissing bug”; its bite much resembles the sting of a wasp, but it is often much more serious.
• Loxosceles laeta is the Chilean recluse spider, commonly know as the violin, fiddleback, or corner spider. It is the most venomous of the recluse spiders. Bites of these spiders can be minor, or cause severe necrotizing ulcers that can take weeks to months to heal. Death from renal failure may occur in 3-4 percent of cases. This spider is related to the brown recluse spider found in North America^ref. In Peru it caused 2264 incidents in 2006^ref

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