A C-type lectin from Bothrops jararacussu venom reprograms endothelial cell biology.

Snake venoms are intricate mixtures of enzymes and bioactive factors that induce a range of detrimental effects in afflicted hosts. Certain Viperids, including Bothrops jararacussu, harbor C-type lectins (CTLs) known for their modulation of a variety of host cellular responses. In this study, we isolated and purified BjcuL, a CTL from B. jararacussu venom and investigated its impact on endothelial cell behavior, contrasting it with human galectin-1 (Gal-1), a prototype member of the galectin family with shared ß-galactoside-binding activity. We found that BjcuL binds to human dermal microvascular endothelial cells (HMECs) in a concentration- and carbohydrate-dependent fashion and reprograms the function of these cells, favoring a pro-inflammatory and pro-coagulant endothelial phenotype. In light of the quest for universal antagonists capable of mitigating the harmful consequences of snake venoms, BjcuL emerges as a promising target to be blocked in order to regulate pathological endothelial cell responses.

Immune response to neurotoxic South American snake venoms.

South American rattlesnakes (Crotalus durissus spp) and coral snakes (Micrurus sp) venoms are characterized by inducing a limited inflammatory innate immune response, in contrast to Bothrops sp snake venoms which exert a prominent inflammatory activity. Some Crotalus durissus spp venoms, in addition, exert immunosuppressive activities that hamper the development of neutralizing antibodies in animals immunized for antivenom production. Micrurus sp venoms are rich in low molecular mass neurotoxins that elicit a limited immune response. These characteristics make it difficult to generate antivenoms of high neutralizing activity. Therefore, the study of the mechanisms operating behind this limited immune response to venoms is relevant from both fundamental and practical perspectives. This review summarizes key aspects of the immune response to these venoms and discusses some pending challenges to further understand these phenomena and to improve antivenom production.

South American snake venoms with abundant neurotoxic components. Composition and toxicological properties. A literature review.

In South America there are three snake genera with predominantly neurotoxic venoms: Crotalus, Micrurus and Hydrophis, which include nine species/subspecies, 97 species and a single marine species, respectively. Although accidents with neurotoxic venoms are less frequent than those with anticoagulant, cytotoxic or necrotic venoms (e.g. from Bothrops), they are of major public health importance. Venoms from genus Crotalus have been extensively studied, while data on the venoms from the other two genera are very limited, especially for Hydrophis. The venoms of North and South American Crotalus species show biochemical and physiopathological differences. The former species cause bothrops-like envenomation symptoms, while the latter mainly have neurotoxic and myotoxic effects, leading to respiratory paralysis and, occasionally, renal failure by myoglobinuria and death, often with no local lesions. Micrurus and Hydrophis also cause neurotoxic envenomations. Many studies have isolated, identified and characterized new enzymes and toxins, thus expanding the knowledge of snake venom composition. The present review summarizes the currently available information on neurotoxic venoms from South American snakes, with a focus on protein composition and toxicological properties. It also includes some comments concerning potential medical applications of elapid and crotalic toxins.

First baseline for bioenergetic biomarkers in Cnesterodon decemmaculatus as test organism in ecotoxicological studies.

Cnesterodon decemmaculatus is a Neotropical teleost fish frequently used in ecotoxicological evaluations, whose biology has been thoroughly studied. Although there is considerable information on its response to different toxicants, no range of reference values has been so far established for the different biological parameters proposed as biomarkers of effect or exposure. Moreover, no study has yet examined the possible influence of the metabolic status of the exposed animals on their response to toxic stress. Therefore, the aim of this work was to provide a first baseline for a set of bioenergetic biomarkers in C. decemmaculatus adults exposed to a control medium under previously standardized conditions, and to assess their possible intrinsic seasonal variability. The responses of the biomarkers obtained from the controls were contrasted with those from the reference toxicant (Cadmio-Cd) and receiving waters (surface waters of the Reconquista River RR, Buenos Aires Province, Argentina). We conducted four 12-day assays (one in each season) of exposure to control media, (reconstituted moderate hard water, MHW) and two assays of exposure to Cd in MHW and surface river water (RR) in both summer and autumn. The variables recorded were: Food intake (In), fecal production (F), specific assimilation (A) and cumulative mortality, oxygen extraction efficiency (OEE), specific metabolic rate (SMR), ammonia excretion (N), ammonia quotient (AQ) and scope for growth (SFG). The seasonal variation shown by some physiological parameters, points to the need for establishing a baseline obtained from standardized media, preferably on a seasonal basis. Moreover, SFG and A appeared as the most sensitive biomarkers, emphasizing the importance to consider the metabolic status of the test organisms for the appropriate interpretation of results from ecotoxicological studies performed under controlled experimental conditions. The obtained results provide useful information on C. decemmaculatus as model species in ecotoxicological bioassays involving biomarkers of early effect.

Physicochemical and biological characterization of nanovenoms, a new tool formed by silica nanoparticles and Crotalus durissus terrificus venom.

Nanoparticles (NPs) are being studied due to their potential use as therapeutic and immunomodulatory tools, including their ability to transport antigens with the aim to induce a specific immune response. The production of snake antivenoms (AV) involves several inoculations of venom (V) in the presence of adjuvants (ADJ) to improve the immune response of inoculated animals, causing a decrease in its quality and shelf life. Therefore, it is interesting to develop new strategies for reduce these side effects. For that reason, associating V to NPs to replace conventional ADJ could be a useful tool for future AV production. In this work, nanovenoms (NVs) were generated by the adsorption of Crotalus durissus terrificus (Cdt) V proteins over silica NPs (SiNPs) synthesized according to the Stöber method. Microphotographies obtained under Transmission Electron Microscopy (TEM) displayed a protein crown over NPs and Fourier Transform Infrared (FT-IR) presented the expected spectra for NVs resulting from the sum of those exhibited by Cdt V and SiNPs separately. SDS PAGE and immunoblotting assays confirmed the presence of proteins over SiNPs. Furthermore, the different enzymatic activities detected demonstrated that SiNPs were capable of binding V proteins preserving its activity and therefore would keep its native structure. In the same way, the NVs conserve the potential cytotoxic effects present in the V as we observed when culturing THP-1 cells with these complexes. This evidence allows us to infer that developed NVs could be used as a new platform for the production of antisera or for immunomodulatory therapies.

Use of integrated biomarker indexes for assessing the impact of receiving waters on a native neotropical teleost fish.

In the field of aquatic ecotoxicology, indexes obtained from a battery of biomarkers have proved to be a useful tool for assessing quantifiable and integrated health responses of organisms exposed to pollutants. The objective of this work was to evaluate the effects of exposure to the Reconquista River water (RR) on adults of Cnesterodon decemmaculatus using different integrated indexes. We conducted a 12-d laboratory assay involving the exposure of fish to RR, a negative control (moderately hard water - MHW medium), and a positive control (for genotoxicity with MHW + Cyclophosphamide, CP). There were measured metabolic (food intake and specific assimilation, specific metabolic rate, oxygen extraction efficiency, ammonia excretion, and ammonia quotient), genotoxic (comet assay, micronucleus test, and nuclear abnormalities), morphological variables (total length, body and liver weight) and biochemical variables (Electron Transport System - ETS, Acetylcholinesterase activity - AChE, Catalase - CAT, Glutathione-S-transferase - GST, Glutathione content - GSH and tissue proteins). These variables were grouped into different indexes: morphological (Condition Factor - K and Liver Somatic Index-LSI), metabolic (Scope for Growth-SFG), genetic damage (GDI) and integrated biomarker response - IBR (AChE brain, CAT, GST and GSH liver, GSH gills, ETS muscle) indexes. Results indicated that RR water induced metabolic, biochemical and genetic damages. The SFG, GDI and IBR were suitable to assess the effects of exposure to an environmental sample in an integrated approach, reducing uncertainty due to inherent biomarker variability. These indexes have emerged as promising tools for environmental monitoring studies.

Cadmium effects on some energy metabolism variables in Cnesterodon decemmaculatus adults.

This work is focused on the responses of some energy metabolism variables in Cnesterodon decemmaculatus adults exposed to cadmium under controlled laboratory conditions. This species has been used as bioindicator for evaluating the effects of different chemicals on diverse biological processes and is frequently used as test organism in ecotoxicity studies that include cadmium as reference toxicant. Animals were exposed for 12 days to the following concentrations: 0, 0.45, and 0.8 mg Cd/L. Food intake, fecal production, specific assimilation, condition factor, mortality percentage, oxygen consumption, oxygen extraction efficiency, specific metabolic rate, ammonia excretion, and ammonia quotient were measured. The overall balance was expressed as scope for growth (SFG). Cadmium-exposed groups showed a significant decrease in food assimilation and condition factor at the end of the exposure. There was an increase in specific metabolic rate and a decrease in SFG in the group exposed to 0.8 mg Cd/L. The condition factor and the SFG appeared as sensitive biomarkers of health status and growth of the animals, respectively. Cadmium-exposed fish reduced food intake, which was reflected in a decreased assimilation with concomitant decline in the external energy supply from feeding. Our results highlight the importance of considering the metabolic status of the test organisms when analyzing the responses of the biomarkers usually used as effect parameters in ecotoxicological evaluations under experimental conditions.