Scorpion Venom and the Inflammatory Response

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

Balance Between Pro- and Anti-Inflammatory Cytokines in Mice Treated With Centruroides noxius Scorpion Venom

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 (LD(50)) 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 LD(50) 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 LD(50) 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

The dynamics of cytokine d nitric oxide secretion in mice injected with Tityus serrulatus scorpion venom.

AIMS: The effects of Tityus serrulatus venom (TSV) were analysed with respect to the susceptibility of four isogenic mouse, the symptoms following injection of venom and the inflammatory mediators in an experimental model of severe envenomation induced in mice. METHODS: The susceptibility was analysed by lethal dose (LD50) determination, including the symptoms observed during envenomating and glucose levels. The detection of cytokines in serum from mice were analysed using enzyme-linked immunosorbent assay, and nitric oxide (NO) was analysed using nitrite determination. RESULTS: The estimated LD50 values were in micrograms per 100 microliters, and the susceptibility of mice to TSV varies with: (a) mouse strain and route of injection (A/J < BALB/c < C57Bl/6 = DBA); (b) mouse strain and sex (A/J female and male < BALB/c female and male); and (c) body weight (all groups of A/J < BALB/c groups). Among the mouse strains studied, BALB/c mice presented moderate sensibility to TSV, with changes in specific signs and serum levels of glucose, several cytokines and NO, when injected intraperitoneally (i.p.) with 1 LD50 of venom. Sweating, salivation and tremor were the specific signs that preceded death. The maximum levels of glucose in sera from mice injected i.p. with 1 LD50 of TSV were observed 60-90 min post-injection. Significant differences were observed in the time-course of cytokine levels, and the venom induced marked elevations of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-10 and interferon gamma (IFN-gamma). The maximum levels of IL-1alpha and IL-1beta were observed 2 h post-injection. The more pronounced levels of IL-6 were observed 4 h post-injection. There was an early increase in IFN-gamma followed by an even higher level after 4 h. IL-10 levels peaked between 6 and 8 h, and this cytokine probably modulates the secretion of IFN-gamma. Tumor necrosis factor release was not detected in BALB/c mice injected with TSV. NO levels attained maximal release after 2 h, following venom injection, while a second peak for NO was at 6 h. CONCLUSIONS: These findings indicate that the susceptibility to the systemic effects of the venom varies among mice of different haplotypes, and that the cytokines such as IL-1, IL-6, IFN-gamma and NO are strongly involved in the pathogenesis caused by this venom and are correlated with the severity of envenomation

EVALUATION OF ANTI-ARTHRITIC POTENTIAL OF PARTITIONED EXTRACTS OF BOUGAINVILLEA X BUTTIANA (VAR. ROSE) HOLTTUM AND STANDL

Objective: Bougainvillea is a natural source with potential for clinical use, and this plant is routinely employed in traditional Medicine in Mexico. This study planned to evaluate the effect of ethanolic extract partitioned of Bougainvillea x buttiana on acute and chronic inflammation.Methods: The extract from Bougainvillea x buttiana partitioned originated two phases the aqueous (BxbREaq) and organic (BxbREop) phases were employed in anti-inflammatory activity. Acute inflammation was evaluated using the carrageenan model, whereas the chronic inflammation with anti-arthritic potential was explored with complete Freund´s adjuvant (CFA). Arthritis was caused by intradermal inoculation of CFA, and the extract was administered orally at different doses for 21 d. Paw oedema was determined at 7, 14 and 21 d, and serum from the mice were obtained to detect cytokine levels by ELISA and for biological assays.Results: Phytochemistry studies revealed that these extracts contain alkaloids, carbohydrates, fatty acids, and tannins. The results demonstrated that these extracts significantly inhibited mouse paw oedema for acute and chronic inflammation in a dose-dependent manner. Additionally, BxbREop extracts markedly inhibited the production of TNF-α, IL-1β, and IL-6 and remarkably increased IL-10 in serum from mice with control or arthritic groups.Conclusion: The combined results suggest that BxbREop extract shows a potent effect in mice against CFA-induced arthritis for its ability to inhibit paw oedema and arthritic symptoms

Effect of Tityus serrulatus venom on cytokine production and the activity of murine macrophages

The purpose of this study was to investigate the effects of Tityus serrulatus venom (TSV) on murine peritoneal macrophages evaluated in terms of activation. The effects of crude TSV were analysed by detection of cytokines, oxygen intermediate metabolites (H2O2) and nitric oxide (NO) in supernatants of peritoneal macrophages. Several functional bioassays were employed including an in vitro model for envenomating: cytotoxicity of TSV was assessed using the lyses percentage. Tumor necrosis factor (TNF) activity was assayed by measuring its cytotoxic activity on L-929 cells, and interleukin-6 (IL-6) and interferon-γ (IFN-γ) were assayed by enzyme-linked immunosorbent assay, whereas NO levels were detected by Griess colorimetric reactions in culture supernatant of macrophages incubated with TSV and subsequently exposed to either lipopolysaccharide or IFN-γ. Incubation of macrophages with TSV increased production of IL-6 and IFN-γ in a dose-dependent manner. TNF production was not detected in supernatants treated with TSV at any concentration. The increase in IL-6 secretion was not associated with concentration-dependent cytoxicity of TSV on these cells. These data suggest that the cytotoxicity does not appear to be the main cause of an increased cytokine production by these cells. Although NO is an important effector molecule in macrophage microbicidal activity, the inducing potential of the test compounds for its release was found to be very moderate, ranging from 125 to 800 mM. Interestingly, NO levels of peritoneal macrophages were increased after IFN-γ. Moreover, NO production had an apparent effect on macrophage activity. The results obtained here also shown that the TSV induces an important elevation in H2O2 release. These results combined with NO production suggest that TSV possesses significant immunomodulatory activities capable of stimulating immune functions in vitro

Immunomodulatory Effects of the Tityus serrulatus Venom on Murine Macrophage Functions in Vitro

Tityus serrulatus scorpion venom (TSV) consists of a very complex mixture of molecules and demonstrates significant immunomodulatory activities capable of stimulating immune functions in vivo. The purpose of this study was to compare the crude TSV with fractionated toxins extracted from this venom in order to determine which toxin(s) presented immunomodulatory effects on peritoneal macrophages. TSV was fractionated using gel filtration chromatography resulting in 5 heterogeneous fractions. The effects of these different fractions were analysed in vitro using detection by means of cytokines, oxygen intermediate metabolites (H2O2), and nitric oxide (NO) in supernatants of peritoneal macrophages. Several functional bioassays were employed: tumor necrosis factor (TNF) activity was assayed by measuring its cytotoxic activity in L929 cells, and other cytokines were assayed by enzyme-linked immunosorbent assay, whereas NO levels were detected by Griess colorimetric reactions in culture supernatant of macrophages exposed to different fractions. In vitro studies revealed that all fractions studied here presented an increment in H2O2, NO, and cytokines levels. The more pronounced increments were observed in macrophage cultures exposed to fraction FII which demonstrated that (a) the highest levels of IL-1α, IL-β, and TNF were observed after 12 hours and that (b) the maximum levels of IFN-γ and NO were observed after 72 hours. Taken together, these data indicate that fractions have a differential immunomodulating effect on macrophage secretion, and that FII is a potent activator of TNF production of macrophages

Allamanda cathartica: A Review of the Phytochemistry, Pharmacology, Toxicology, and Biotechnology

In this work, we explore the current knowledge about the phytochemistry and in vitro and in vivo evaluations of the extracts and, where appropriate, the main active components characterized and isolated from the Allamanda cathartica. Of the 15 Allamanda species, most phytochemical, pharmacological, and toxicological studies have focused on A. cathartica. These plants are used for the treatment of various health disorders. Numerous phytochemical investigations of plants from the A. cathartica have shown the presence of hydrocarbons, alcohols, esters, ethers, aldehydes, ketones, fatty acids, phospholipids, volatile compounds, phenolic compounds, flavonoids, alkaloids, steroids, terpenes, lactones, and carbohydrates. Various studies have confirmed that extracts and active substances isolated from the A. cathartica have multiple pharmacological activities. The species A. cathartica has emerged as a source of traditional medicine used for human health. Further studies on the phytochemical, pharmacological, and toxicological properties and their mechanisms of action, safety, and efficacy in the species of A. cathartica is recommended