Abstract
Brown spider envenomation results in dermonecrosis with gravitational spreading characterized by a marked inflammatory reaction and with lower prevalence of systemic manifestations such as renal failure and hematological disturbances. Several toxins make up the venom of these species, and they are mainly peptides and proteins ranging from 5–40 kDa. The venoms have three major families of toxins: phospholipases-D, astacin-like metalloproteases, and the inhibitor cystine knot (ICK) peptides. Serine proteases, serpins, hyaluronidases, venom allergens, and a translationally controlled tumor protein (TCTP) are also present. Toxins hold essential biological properties that enable interactions with a range of distinct molecular targets. Therefore, the application of toxins as research tools and clinical products motivates repurposing their uses of interest. This review aims to discuss possibilities for brown spider venom toxins as putative models for designing molecules likely for therapeutics based on the status quo of brown spider venoms. Herein, we explore new possibilities for the venom components in the context of their biochemical and biological features, likewise their cellular targets, three-dimensional structures, and mechanisms of action.
Highlights
Venom Contents and Cellular TargetsSpider venoms are mixtures of biologically active peptides, proteins, glycoproteins, and small organic molecules which interact with cellular and molecular targets to trigger severe, sometimes fatal effects
Other cells targeted by venom toxins are fibroblasts that after exposure deregulated the expression of cytokines genes CXCL1, CXCL2, IL-6, and IL-8 mediators of inflammatory response activation [17]
PcTx1 toxin was neuroprotective in focal ischemia studies conducted in adult mouse: intracerebroventricular administration of this inhibitor cystine knot (ICK) peptide was able to reduce the percentage of the ipsilateral hemisphere infarct by more than 50% after 1 h of transient middle cerebral artery occlusion [58]
Summary
Spider venoms are mixtures of biologically active peptides, proteins, glycoproteins, and small organic molecules which interact with cellular and molecular targets to trigger severe, sometimes fatal effects. Brown spider venom toxins are associated with many cellular changes followed by envenomation, either in humans or in animal-based models for experimental exposure. Brown spider venom toxins exhibit indirect and robust activity on blood vessel endothelial cells that cause deregulated activation of leukocytes. Other cells targeted by venom toxins are fibroblasts that after exposure deregulated the expression of cytokines genes CXCL1, CXCL2, IL-6, and IL-8 mediators of inflammatory response activation [17]. Venom exposure causes hemolysis and morphological changes that seem to depend on a mechanism reflecting a direct effect on cell surface phospholipids such as sphingomyelin and lysophosphatidylcholine leading to the influx of a calcium-mediated pathway by an L-type channel [18,19,20]; and another complement-dependent pathway with the activation of an endogenous metalloprotease, which degrades glycophorins and activates complement and lysis [21]. The cell surface of renal epithelial cells is targeted by brown spider venom toxins and suffer direct cytotoxicity [27,28]
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