Joro Spider Toxin
Introduction
Joro spider toxin (JSTX), as the name implies, was isolated from the venom of the Joro spider (Nephila clavata) in the 1980s; a synthetic preparation is now available. JSTX is a potent, non-competitive, irreversible, or slowly reversible, antagonist of glutamate receptors. There is, however, debate concerning its specificity at the various ionotropic glutamate receptors, in that JSTX has been shown to inhibit NMDA receptors Nemeth et al (1992) as well as having an effect at AMPA receptors. More recent reports provide robust evidence that JSTX is probably a specific antagonist at Ca++-permeable AMPA receptors Lino et al (1996), Savidge and Bristow (1998).
Toxic Encephalopathies I: Cortical and Mixed Encephalopathies
Spiders
Spider venoms are generally quite complex and contain multiple elements that are potentially toxic. Few spider species have large enough and strong enough fangs to make them a threat to adult humans, but young children can be vulnerable to their bites. The venom of the Latrodectus (widow) spiders contain a neurotoxin with high concentrations of leucine and isoleucine, as well as lower concentrations of tyrosine. While its primary target is the peripheral nervous system, there is evidence of CNS activity, and varying degrees of headache, dizziness, and restlessness occur acutely.
Spider, Black Widow
Mechanism of Toxicity
Black widow spider venom contains several different protein fractions. However, the high-molecular-weight neurotoxin is the only fraction that is of clinical significance. This neurotoxin acts at the neuromuscular synapse damaging nerve terminals and causing the release and ultimately the depletion of such neurotransmitters as alpha-aminobutyric acid, norepinephrine, and acetylcholine. Neurotransmitter release is most likely responsible for hypertension, muscle fasciculation, and muscle spasms experienced by victims of a bite. Generalized muscle weakness and labored breathing may develop in severe cases. While the venom of the black widow spider has been characterized as being more potent than that of many poisonous snakes, the small amount of venom injected limits the extent of toxicity.
Neuroparasitology and Tropical Neurology
Spider venom composition
Spider venom is a combination of dozens of active substances than can be grouped, according to their chemical nature, into: (a) low-molecular-weight substances (biogenic amines, carbohydrates, salts, and ions), (b) peptides (linear and disulfide-containing peptides), and (c) high-molecular-weight substances (enzymatic and nonenzymatic proteins) (Volkova et al., 1995; Escoubas et al., 2000; de Oliveira et al., 2005; Schroeder et al., 2008; Vassilevski et al., 2009; Dias-Lopes et al., 2010; Diego-Garcia et al., 2010). The spider venom apparatus consists of a pair of venom glands located in the cephalic part of the arthropod. Venom glands are connected to the chelicerae, which are appendages located in the mouth of spiders. The distal part of each chelicerae is a mobile hollow fang that penetrates the skin during a bite, injecting venom into the prey (Cavusoglu et al., 2005). Spiders have evolved in such a way that they are able to calculate the amount of injected venom, according to the size of the prey and its resistance to the venom. Moreover, the venom may be species-specific, showing high toxicity for some taxons (such as insects) while being completely harmless to others. This is the basis for the potential production of insecticides from some spider venom components (Rohou et al., 2007).
Relevant components of the venom may have necrotic (cytolytic) or neurotoxic activity (Vassilevski et al., 2009). These actions are mainly related to the primary objective of the venom, i.e., to immobilize and kill the prey. Cytolytics include linear peptides and enzymes that have necrotic activity against cytoplasmic membranes of the prey, and neurotoxins are polyamines, disulfide-containing peptides and proteins, that act against electro-excitable cell membranes through a variety of mechanisms, including activation of voltage-gated ion channels, exhaustive release of neuromediators, and antagonism of glutamate receptors (Volkova et al., 1995; Reyes-Lugo et al., 2009). Other biogenic amines found in the venom of spiders are known to cause pain, while others may interfere with the prey’s physiological status by enhancing blood vessel permeability or through inhibition of angiotensin-converting enzyme (Vassilevski et al., 2009). Probably the toxins with more clinical importance are the high-molecular-weight proteins sphingomyelinases and α-latrotoxin. The former are necrotic toxins found in the venom of Loxosceles spp., with the ability to cause intravascular hemolysis and dermonecrosis (de Oliveira et al., 2005), and the latter is a potent neurotoxin found in the venom of Latrodectus spp.
Animals, Poisonous and Venomous
Toxicity
Funnel spider venom is harmful in humans and other primates, but not necessarily all mammals. The venom is a complex mixture; however, the neurotoxic components that contribute to symptoms are known as the Ç-atracotoxins. These may slow sodium current inactivation, with resultant firing of action potentials. The excessive release and eventual depletion of sympathetic neurotransmitters lead to a biphasic symptomatic response, which may range from mild to severe toxicity. The first phase is characterized by local effects, including a painful bite site, with swelling, redness, and fang marks. General symptoms during this first phase can also include perioral numbness, severe facial and tongue spasms, piloerection, nausea, vomiting, abdominal cramps, salivation, lacrimation, and profuse sweating. Difficulty in breathing may be experienced, along with high blood pressure, an irregular heartbeat, and mental confusion. In the second phase, which may occur several hours after cessation of secretions, victims of envenomation can experience extremely low blood pressure, decreased respirations, noncardiogenic pulmonary edema, and cardiac arrest.
