Journal of Venomous Animals and Toxins Including Tropical Diseases最新文献

Background: In Colombia, several species of Buthidae scorpions belonging to the genera Centruroides and Tityus coexist, and their stings are considered life-threatening to humans because of their venom neurotoxins. Despite previous studies focusing on neurotoxins from these scorpion genera, little is known about the enzymes present in their venoms and their relationship with whole venom toxicity.

Methods: Here, using proteomic and biochemical protocols the enzymatic activities of the venoms of three Colombian scorpion species, C. margaritatus, T. pachyurus, and T. n. sp. aff. metuendus, were compared to establish the presence and absence of enzymes such as phospholipases, hyaluronidases, and proteases that could be related to venom toxicity. Results: C. margaritatus was positive for hyaluronidases, T. n. sp. aff. metuendus for proteases, and T. pachyurus exhibited activity for all three mentioned enzymes.

Conclusion: This information provides valuable insights into the specific enzyme diversity of each species' venom and their potential role in venom toxicity, which could contribute to the development of better treatments and prevention strategies for scorpion envenomation.

The skin of anuran species is a protective barrier against predators and pathogens, showing also chemical defense by substances that represent a potential source for bioactive substances. This review describes the current chemical and biological knowledge from the skin secretions of Leptodactylidae species, one of the most diverse neotropical frog families. These skin secretions reveal a variety of substances such as amines (12), neuropeptides (16), and antimicrobial peptides (72). The amines include histamine and its methylated derivatives, tryptamine derivatives and quaternary amines. The peptides of Leptodactylidae species show molecular weight up to 3364 Da and ocellatins are the most reported. The peptides exhibit commonly glycine (G) or glycine-valine (GV) as C-terminal amino acids, and the most common N-terminal amino acids are glutamic acid (E), lysine (K), and valine (V). The substances from Leptodactylidae species have been evaluated against pathogenic microorganisms, particularly Escherichia coli and Staphylococcus aureus, and the most active peptides showed MIC of 1-15 µM. Furthermore, some compounds showed also pharmacological properties such as immunomodulation, treatment of degenerative diseases, anticancer, and antioxidant. Currently, only 9% of the species in this family have been properly studied, highlighting a large number of unstudied species such as an entire subfamily (Paratelmatobiinae). The ecological context, functions, and evolution of peptides and amines in this family are poorly understood and represent a large field for further exploration.

Background: The bioactive peptides derived from snake venoms of the Viperidae family species have been promising as therapeutic candidates for neuroprotection due to their ability to prevent neuronal cell loss, injury, and death. Therefore, this study aimed to evaluate the cytoprotective effects of a synthetic proline-rich oligopeptide 7a (PRO-7a; Bothrops jararaca snake, on oxidative stress-induced toxicity in neuronal PC12 cells and astrocyte-like C6 cells.

Methods: Both cells were pre-treated for four hours with different concentrations of PRO-7a, submitted to H₂O₂-induced damage for 20 h, and then the oxidative stress markers were analyzed. Also, two independent neuroprotective mechanisms were investigated: a) L-arginine metabolite generation via argininosuccinate synthetase (AsS) activity regulation to produce agmatine or polyamines with neuroprotective properties; b) M1 mAChR receptor subtype activation pathway to reduce oxidative stress and neuron injury.

Results: PRO-7a was not cytoprotective in C6 cells, but potentiated the H₂O₂-induced damage to cell integrity at a concentration lower than 0.38 μM. However, PRO-7a at 1.56 µM, on the other hand, modified H₂O₂-induced toxicity in PC12 cells by restoring cell integrity, mitochondrial metabolism, ROS generation, and arginase indirect activity. The α-Methyl-DL-aspartic acid (MDLA) and L-N^Ω-Nitroarginine methyl ester (L-Name), specific inhibitors of AsS and nitric oxide synthase (NOS), which catalyzes the synthesis of polyamines and NO from L-arginine, did not suppress PRO-7a-mediated cytoprotection against oxidative stress. It suggested that its mechanism is independent of the production of L-arginine metabolites with neuroprotective properties by increased AsS activity. On the other hand, the neuroprotective effect of PRO-7a was blocked in the presence of dicyclomine hydrochloride (DCH), an M1 mAChR antagonist.

Conclusions: For the first time, this work provides evidence that PRO-7a-induced neuroprotection seems to be mediated through M1 mAChR activation in PC12 cells, which reduces oxidative stress independently of AsS activity and L-arginine bioavailability.

Tityus serrulatus scorpion is responsible for a significant number of envenomings in Brazil, ranging from mild to severe, and in some cases, leading to fatalities. While supportive care is the primary treatment modality, moderate and severe cases require antivenom administration despite potential limitations and adverse effects. The remarkable proliferation of T. serrulatus scorpions, attributed to their biology and asexual reproduction, contributes to a high incidence of envenomation. T. serrulatus scorpion venom predominantly consists of short proteins acting as neurotoxins (α and β), that primarily target ion channels. Nevertheless, high molecular weight compounds, including metalloproteases, serine proteases, phospholipases, and hyaluronidases, are also present in the venom. These compounds play a crucial role in envenomation, influencing the severity of symptoms and the spread of venom. This review endeavors to comprehensively understand the T. serrulatus scorpion venom by elucidating the primary high molecular weight compounds and exploring their potential contributions to envenomation. Understanding these compounds' mechanisms of action can aid in developing more effective treatments and prevention strategies, ultimately mitigating the impact of scorpion envenomation on public health in Brazil.

Background: The relationship between viral infections and host factors holds high hopes for identifying the role of Interferon Lambda 3 (IFNL3) and Interleukin 6 (IL-6) polymorphisms in the development of Chronic Liver Disease (CLD) in patients infected with hepatitis Delta virus (HDV) in the Western Brazilian Amazon.

Methods: Cross-sectional study conducted with a cohort of 40 chronic HDV patients, 27 with CLD and 13 without evident liver damage. Biological samples from the participants were analyzed using the polymerase chain reaction (PCR) technique, followed by sequencing by the automated Sanger method.

Results: The rs8099917 T allele, from the IFNL3 gene, showed a higher frequency in both groups; however, it was not possible to establish an association with HDV infection [OR = 1.42 (0.42 - 4.75; p = 0.556 (95% CI). For IL-6, the rs1800795 G allele was superior to rs1800795 C. Analyzing both distributions in the studied groups, any association with HDV was absent (p > 0.05).

Conclusion: The results suggest that the rs8099917 T/G (IFNL3) and rs1800795 G/C (IL-6) polymorphisms are not associated with the evolution of HDV in the studied population.

Snakebite envenoming is a significant global health challenge, and for over a century, traditional plasma-derived antivenoms from hyperimmunized animals have been the primary treatment against this infliction. However, these antivenoms have several inherent limitations, including the risk of causing adverse reactions when administered to patients, batch-to-batch variation, and high production costs. To address these issues and improve treatment outcomes, the development of new types of antivenoms is crucial. During this development, key aspects such as improved clinical efficacy, enhanced safety profiles, and greater affordability should be in focus. To achieve these goals, modern biotechnological methods can be applied to the discovery and development of therapeutic agents that can neutralize medically important toxins from multiple snake species. This review highlights some of these agents, including monoclonal antibodies, nanobodies, and selected small molecules, that can achieve broad toxin neutralization, have favorable safety profiles, and can be produced on a large scale with standardized manufacturing processes. Considering the inherent strengths and limitations related to the pharmacokinetics of these different agents, a combination of them might be beneficial in the development of new types of antivenom products with improved therapeutic properties. While the implementation of new therapies requires time, it is foreseeable that the application of biotechnological advancements represents a promising trajectory toward the development of improved therapies for snakebite envenoming. As research and development continue to advance, these new products could emerge as the mainstay treatment in the future.

Background: Diabetic kidney disease (DKD) is a serious microvascular complication of diabetes that affects both type 1 and type 2 diabetes patients at a high incidence rate. Naja Naja atra venom (NNAV) has been shown to have protective effects and improved renal function in diabetic rats. However, its mechanism of action is still unclear. This study aims to unravel the effectiveness and mechanisms of NNAV on DKD.

Methods: We conducted in vitro experiments in which Human Kidney-2 (HK-2) cells were stimulated with high glucose, and exposed to varying concentrations of NNAV. Cell morphology, as well as α-SMA, TGF-β1, and E-cadherin levels, were analyzed using immunofluorescence and western blot. In vivo experiments involved a diabetic rat model, where varying concentrations of cobra α-neurotoxin (CTX) were administrated via gastric treatment. We observed and noted pathomorphological changes, measured biochemical and oxidative stress indices, and used western blot to assess podocin and nephrin levels.

Results: High glucose levels can induce a decrease in E-cadherin expression and an increase in α-SMA and transforming growth factor-β1 (TGF-β1) expression in HK-2 cells. NNAV can inhibit the transdifferentiation of HK-2 cells to myofibroblast (MyoF) in a high glucose environment and reduce the expression of TGF-β1. Cobra α-neurotoxin (CTX) can reduce urine protein in diabetes model rats at an early stage, which is dose-independent and has a time application range. CTX can regulate the expression of nephrin and podocin.

Conclusion: The present study indicates that CTX and NNAV attenuate STZ and high glucose-induced DKD. Its mechanisms of action are associated with inhibiting oxidative stress and TEMT. The study suggests that NNAV and CTX might be a potential therapeutic drug for treating DKD.

Background: Echinometra lucunter is a sea urchin commonly found on America's rocky shores. Its coelomic fluid contains molecules used for defense and biological processes, which may have therapeutic potential for the treatment of amyloid-based neurodegenerative diseases, such as Alzheimer's, that currently have few drug options available.

Methods: In this study, we incubated E. lucunter coelomic fluid (ELCF) and fractions obtained by solid phase extraction in SH-SY5Y neuron-like cells to evaluate their effect on cell viability caused by the oligomerized amyloid peptide 42 (Aβ42o). Moreover, the Aβ42o was quantified after the incubation with ELCF fractions in the presence or not of cells, to evaluate if samples could cause amyloid peptide disaggregation. Antioxidant activity was determined in ELCF fractions, and cells were evaluated to check the oxidative stress after incubation with samples. The most relevant fraction was analyzed by mass spectrometry for identification of molecules.

Results: ELCF and certain fractions could prevent and treat the reduction of cell viability caused by Aβ42o in SH-SY5Y neuron-like cells. We found that one fraction (El50) reduced the oligomerized Aβ42 and the oxidative stress caused by the amyloid peptide through its antioxidant molecules, which in turn reduced cell death. Mass spectrometry analysis revealed that El50 comprises small molecules containing flavonoid antioxidants, such as phenylpyridazine and dihydroquercetin, and two peptides.

Conclusion: Our results suggest that sea urchin molecules may interact with Aβ42o and oxidative stress, preventing or treating neurotoxicity, which may be useful in treating dementia.

Background: The composition of the venom from solitary wasps is poorly known, although these animals are considered sources of bioactive substances. Until the present moment, there is only one proteomic characterization of the venom of wasps of the family Pompilidae and this is the first proteomic characterization for the genus Pepsis.

Methods: To elucidate the components of Pepsis decorata venom, the present work sought to identify proteins using four different experimental conditions, namely: (A) crude venom; (B) reduced and alkylated venom; (C) trypsin-digested reduced and alkylated venom, and; (D) chymotrypsin-digested reduced and alkylated venom. Furthermore, three different mass spectrometers were used (Ion Trap-Time of Flight, Quadrupole-Time of Flight, and Linear Triple Quadruple).

Results: Proteomics analysis revealed the existence of different enzymes related to the insect's physiology in the venom composition. Besides toxins, angiotensin-converting enzyme (ACE), hyaluronidase, and Kunitz-type inhibitors were also identified.

Conclusion: The data showed that the venom of Pepsis decorata is mostly composed of proteins involved in the metabolism of arthropods, as occurs in parasitic wasps, although some classical toxins were recorded, and among them, for the first time, ACE was found in the venom of solitary wasps. This integrative approach expanded the range of compounds identified in protein analyses, proving to be efficient in the proteomic characterization of little-known species. It is our understanding that the current work will provide a solid base for future studies dealing with other Hymenoptera venoms.

Aflatoxins are toxic secondary metabolites that often contaminate food and animal feed, causing huge economic losses and serious health hazards. Aflatoxin contamination has become a major concern worldwide. Biological methods have been used to reduce aflatoxins in food and feed by inhibiting toxin production and detoxification. Among biological methods, lactic acid bacteria are of significant interest because of their safety, efficiency, and environmental friendliness. This study aimed to review the mechanisms by which lactic acid bacteria degrade aflatoxins and the factors that influence their degradation efficiency, including the action of the lactic acid bacteria themselves (cell wall adsorption) and the antifungal metabolites produced by the lactic acid bacteria. The current applications of lactic acid bacteria to food and feed were also reviewed. This comprehensive analysis provided insight into the binding mechanisms between lactic acid bacteria and aflatoxins, facilitating the practical applications of lactic acid bacteria to food and agriculture.