Ophidian envenomation is an important health problem in Brazil and other South American countries. In folk medicine, especially in developing countries, several vegetal species are employed for the treatment of snakebites in communities that lack prompt access to serum therapy. However, the identification and characterization of the effects of several new plants or their isolated compounds, which are able to inhibit the activities of snake venom, are extremely important and such studies are imperative. Snake venom contains several organic and inorganic compounds; phospholipases A2 (PLA2s) are one of the principal toxic components of venom. PLA2s display a wide variety of pharmacological activities, such as neurotoxicity, myotoxicity, cardiotoxicity, anticoagulant, hemorrhagic, and edema-inducing effects. PLA2 inhibition is of pharmacological and therapeutic interests as these enzymes are involved in several inflammatory diseases. This review describes the results of several studies of plant extracts and their isolated active principles, when used against crude snake venoms or their toxic fractions. Isolated inhibitors, such as steroids, terpenoids, and phenolic compounds, are able to inhibit PLA2s from different snake venoms. The design of specific inhibitors of PLA2s might help in the development of new pharmaceutical drugs, more specific antivenom, or even as alternative approaches for treating snakebites.

Snake venoms are natural sources of biologically active molecules that are able to act selectively and specifically on different cellular targets, modulating physiological functions. Thus, these mixtures, composed mainly of proteins and peptides, provide ample and challenging opportunities and a diversified molecular architecture to design and develop tools and agents of scientific and therapeutic interest. Among these components, peptides and small proteins play diverse roles in numerous physiological processes, exerting a wide range of pharmacological activities, such as antimicrobial, antihypertensive, analgesic, antitumor, analgesic, among others. The pharmaceutical and cosmetic industries have recognized the huge potential of these privileged frameworks and believe them to be a promising alternative to contemporary drugs. A number of natural or synthetic peptides from snake venoms have already found preclinical or clinical applications for the treatment of pain, hypertension, cardiovascular diseases and aging skin. A well-known example is captopril, whose natural peptide precursor was isolated from Bothrops jararaca snake venom, which is a peptide-based drug that inhibits the angiotensin-converting enzyme, producing an anti-hypertensive effect. The present review looks at the main peptides (natriuretic peptides, bradykinin-potentiating peptides and sarafotoxins) and low mass proteins (crotamine, disintegrins and three-Finger toxins) from snake venoms, as well as synthetic peptides inspired by them, describing their biochemical, structural and physiological features, as well as their applications as research tools and therapeutic agents.

Obstruction of the portal vein may be related to constriction by malignant tumors or thrombosis associated with liver disease. We herein have reported our experience with patients undergoing liver transplantation with portal vein thrombosis (PVT) whose diagnosis was made intraoperatively. From September 1991 to May 2009, we studied 27/419 (6.4%) patients with PVT who were evaluated according to the presence of esophagogastric varices, underlying disease, malignancy, and if there was previous surgery, review of medical records on data collected prospectively. We observed 24 (88.9%) patients with PVT grade 1, 2 (7.4%) with grade 2, and 1 (3.7%) with grade 3. The average age of the PVT patients was 47.5 years; the average model for End-Stage Liver Discase score was 18.3, and the predominant diagnosis, hepatitis C cirrhosis. Eighteen underwent a sclerotherapy/ligature. The sensitivity of ultrasound for grade 1 thrombosis was 39.1%; for grade 2, 50%; and for grade 3, 100%. Portal vein thrombectomy was performed in 24 patients. In other patients (grade 2), we performed an anastomosis of the donor portal vein to the recipient gastric vein or to a greater splanchnic collateral vein. In only 1 patient was the graft performed using the donor portal vein-donor iliac vein-recipient superior mesenteric vein. None of the patients displayed PVT in the immediate postoperative period. Actuarial survivals at the years 1, 3, and 5 were 85%, 74%, and 63%, respectively. We concluded that PVT cannot be considered to be a contraindication for liver transplantation.

Snake venom is a complex mixture of active compounds consisting of 80-90% proteins and peptides that exhibit a variety of biological actions that are not completely clarified or identified. Of these, phospholipase A2 is one of the molecules that has shown great biotechnological potential. The objectives of this study were to isolate, biochemically and biologically characterize a Lys49 phospholipase A2 homologue from the venom of Bothrops neuwiedi urutu. The protein was purified after two chromatographic steps, anion exchange and reverse phase. The purity and relative molecular mass were assessed by SDS-PAGE, observing a molecular weight typical of PLA2s, subsequently confirmed by mass spectrometry obtaining a mass of 13,733 Da. As for phospholipase activity, the PLA2 proved to be enzymatically inactive. The analyses by Edman degradation and sequencing of the peptide fragments allowed for the identification of 108 amino acid residues; this sequence showed high identity with other phospholipases A2 from Bothrops snake venoms, and identified this molecule as a novel PLA2 isoform from B. neuwiedi urutu venom, called BnuTX-I. In murine models, both BnuTX-I as well as the venom induced edema and myotoxic responses. The cytotoxic effect of BnuTX-I in murine macrophages was observed at concentrations above 12 μg/mL. BnuTX-I also presented antimicrobial activity against gram-positive and negative bacterial strains, having the greatest inhibitory effect on Pseudomonas aeruginosa. The results allowed for the identification of a new myotoxin isoform with PLA2 structure with promising biotechnological applications.

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The emergence of antibiotic resistance drives an essential race against time to reveal new molecular structures capable of addressing this alarming global health problem. Snake venoms are natural catalogs of multifunctional toxins and privileged frameworks, which serve as potential templates for the inspiration of novel treatment strategies for combating antibiotic resistant bacteria. Phospholipases A2 (PLA2s) are one of the main classes of antibacterial biomolecules, with recognized therapeutic value, found in these valuable secretions. Recently, a number of biomimetic oligopeptides based on small fragments of primary structure from PLA2 toxins has emerged as a meaningful opportunity to overcome multidrug‐resistant clinical isolates. Thus, this review will highlight the biochemical and structural properties of antibacterial PLA2s and peptides thereof, as well as their possible molecular mechanisms of action and key roles in development of effective therapeutic strategies. Chemical strategies possibly useful to convert antibacterial peptides from PLA2s to efficient drugs will be equally addressed.

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Phospholipases A (PLAs) constitute a class of extensively studied toxins, isolated from snake venoms. Basic PLA isoforms mediate various toxicological effects, while the acidic isoforms generally have higher enzymatic activities, but do not promote evident toxic effects. The functions of these acidic isoforms in snake venoms are still not completely understood and more studies are needed to characterize the biological functions and diversification of acidic toxins in order to justify their abundant presence in these secretions. Recently, Lomonte and collaborators demonstrated, in a proteomic and toxicological study, high concentrations of PLAs in the venom of Agkistrodon piscivorus leucostoma. We have, herein, purified and characterized an acidic PLA from this snake venom, denominated AplTx-I, in order to better understand its biochemical and structural characteristics, as well as its biological effects. AplTx-I was purified using two chromatographic steps, in association with enzymatic and biological assays. The acidic toxin was found to be one of the most abundant proteins in the venom of A. p. leucostoma; the protein was monomeric with a molecular mass of 13,885.8 Da, as identified by mass spectrometry ESI-TOF and electrophoresis. The toxin has similar primary and tridimensional structures to those of other acidic PLAs, a theoretical and experimental isoelectric point of ≈5.12, and a calcium-dependent enzyme activity of 25.8985 nM/min/mg, with maximum values at 37 °C and pH 8.0. Despite its high enzymatic activity on synthetic substrate, AplTx-I did not induce high or significant myotoxic, coagulant, anticoagulant, edema, neuromuscular toxicity in mouse phrenic nerve-diaphragm preparations or antibacterial activities. Interestingly, AplTx-I triggered a high and selective neuromuscular toxicity in chick biventer cervicis preparations. These findings are relevant to provide a deeper understanding of the pharmacology, role and diversification of acidic phospholipase A isoforms in snake venoms.