Scorpion venoms consist of a complex of several toxins that exhibit a wide range of biological properties and actions, as well as chemical compositions, toxicity, and pharmacokinetic and pharmacodynamic characteristics. These venoms are associated with high morbility and mortality, especially among children. Victims of envenoming by a scorpion suffer a variety of pathologies, involving mainly both sympathetic and parasympathetic stimulation as well as central manifestations such as irritability, hyperthermia, vomiting, profuse salivation, tremor, and convulsion. The clinical signs and symptoms observed in humans and experimental animals are related with an excessive systemic host inflammatory response to stings and stings, respectively. Although the pathophysiology of envenomation is complex and not yet fully understood, venom and immune responses are known to trigger the release of inflammatory mediators that are largely mediated by cytokines. In models of severe systemic inflammation produced by injection of high doses of venom or venoms products, the increase in production of proinflammatory cytokines significantly contributes to immunological imbalance, multiple organ dysfunction and death. The cytokines initiate a cascade of events that lead to illness behaviors such as fever, anorexia, and also physiological events in the host such as activation of vasodilatation, hypotension, and increased of vessel permeability.

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Bougainvillea is widely used in traditional Mexican medicine to treat several diseases. This study was designed to characterize the chemical constituents of B. x buttiana extracts with antioxidant and cytotoxic activities using different solvents. The extraction solvents used were as follows: distilled water (dH2O), methanol (MeOH), acetone (DMK), ethanol (EtOH), ethyl acetate (EtOAc), dichloromethane (DCM), and hexane (Hex) (100%) at an extraction temperature of 26 °C. Analysis of bioactive compounds present in the B. x buttiana extracts included the application of common phytochemical screening assays, GC-MS analysis, and cytotoxicity and antioxidant assays. The results show that the highest extraction yield was observed with water and methanol. The maximum total phenolic content amount and highest antioxidant potential were obtained when extraction with methanol was used. With the exceptions of water and ethanol extractions, all other extracts showed cytotoxicity ranging between 31% and 50%. The prevailing compounds in water, methanol, ethanol, and acetone solvents were as follows: 4H-pyran-4-one, 2,3-dihydro-3, 5-dihydroxy-6-methyl (2), 2-propenoic acid, 3-(2-hydrophenyl)-(E)- (3), and 3-O-methyl-d-glucose (6). By contrast, the major components in the experiments using solvents such as EtOH, DMK, EtOAc, DCM, and Hex were n-hexadecanoic acid (8), 9,12-octadecadienoic acid (Z,Z) (12); 9-octadecenoic acid (E)- (13), and stigmasta-5,22-dien-3-ol (28).

We have provided evidence that: (a) lethality of mice to crude Bothrops venom varies according the isogenic strain (A/J > C57Bl/6 > A/Sn > BALB/c > C3H/HePas > DBA/2 > C3H/He); (b)BALB/c mice (LD50=100.0 microg) were injected i.p. with 50 microg of venom produced IL-6, IL-10, INF-gamma, TNF-alpha and NO in the serum. In vitro the cells from the mice injected and challenged with the venom only released IL-10 while peritoneal macrophages released IL-10, INF-gamma and less amounts of IL-6; (c) establishment of local inflammation and necrosis induced by the venom, coincides with the peaks of TNF-alpha, IFN-gamma and NO and the damage was neutralized when the venom was incubated with a monoclonal antibody against a 60 kDa haemorrhagic factor. These results suggest that susceptibility to Bothrops atrox venom is genetically dependent but MHC independent; that IL-6, IL-10, TNF-alpha, IFN-gamma and NO can be involved in the mediation of tissue damage; and that the major venom component inducers of the lesions are haemorrhagins.

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Venom is a complex mixture of many substances such as toxins, enzymes, growth factor activators, and inhibitors are particularly responsible for the deleterious effects of cells. These constituents interact in the body with a large number of proteins and receptors, and this interaction determines the eventual inflammatory effect of the compounds. Envenomation by bees, scorpions, snakes, spiders and wasps involves the activation of the inflammatory response with the release and activation of pro-inflammatory cytokines and other mediators, such as nitric oxide. Recently, a battery of cytokines produced by activated T cells or macrophages have been added to in envenomations. Cytokines are important for the interactions between cells in the immune and inflammatory responses. Although the pathophysiology of envenomation is not fully understood, venom and immune responses are known to trigger the release of cytokines and nitric oxide. The cytokines initiate a cascade of events that lead to illness behaviors such as fever, anorexia, and, as well as a host of physiologic events such as activation of vasodilation, hypotension and increased nitric oxide production. Accumulating evidence indicates that these cytokines play important roles in mediating cell recruitment and activation necessary for inflammation and the repair of tissue damage. A better understanding of the involvement of the inflammatory system in different envenoming syndromes may have future therapeutic benefits.

CSV consists of a very complex of molecules and demonstrates significant cellular activities capable of stimulating immune functions in vivo. The purpose of this study was to analyze the effects of CSV on sex, weight, route of injection and the balance of pro- and anti-inflammatory cytokines in mice. The susceptibility and route of injection were analyzed by lethal (LD50) determination. The effects of CSV were also analyzed in blood from immunized mice using detection by means of antibodies and mediators production. Several functional bioassays were employed: TNF activity was assayed by measuring its cytotoxic activity in L929 cells, and other cytokines were assayed by enzyme-linked immunosorbent assay, whereas nitric oxide levels were detected by Griess colorimetric reactions in sera from BALB/c mice. After injecting subcutaneously, the LD50 presented an increase of the CSV correlation and similar levels of susceptibility were obtained for female and male from BALB/c mice. Significant differences were observed in the time-course of cytokine levels. The balance of pro- and anti-inflammatory cytokines TNF/IL-10 and IL-6/IL-10 ratios were significantly higher in injected mice group when compared with those obtained for non-injected group. The CSV is poor in antigenic composition and it is difficult to get antibodies specific to neutralizing the lethal factor. The effect of immunization with 0.5 LD50 of CSV on the balance of pro- and anti-inflammatory cytokines was measured. The maximum levels of TNF and IL-6, IFN-γ and NO were observed on days 7 and 21 after immunization, respectively. IL-10 levels peaked between days 21 and 28 after immunization with CSV. With respect to balance of pro- and anti-inflammatory cytokines it was possible to observe that negative correlation between serum levels of IL-6/IL-10 and TNF/IL-10 exists. These ratios may possibly reflect the balance of pro- and anti-inflammatory cytokines in serum, which may by manifested in the inflammatory status during the envenoming processes. In conclusion, an increase in the serum levels of TNF and IL-6 may be a useful marker for scorpion envenomation.