Venoms and Toxins - Current Issue

Ecological and environmental management are key factors governing the sustainable development of society. For years, persistent and severe problems have occurred in many aspects that have greatly influenced the environment with the rise of economy and technology worldwide. Although efforts have been made to reduce the pollutants, it remains a substantial problem to be solved due to the lack of knowledge of ecological toxinology. In this review, we will begin with several ecological disasters happened in past decades, originated from toxic pollutants, human activity, venomous species and deadly virus. By exemplifying the long-lasting influence and cause of these biological events, extensive warning and social recognition will hopefully be promoted. Furthermore, from a more academic view, this review will also propose new thinking on some public concerns, such as the unexpected prevalence of severe acute respiratory syndrome (SARS), transgenic food and beyond this. Finally, by combining the ongoing advances in techniques, ways to make a reasonable use of these bio-toxins will be approached, which may help to balance the relationship of environment, human life and economic development.

The venoms of Tunisian wildlife snakes are complex mixtures containing proteins/peptides and non-protein molecules. Proteins and peptides are the most abundant compounds responsible for the biological effects of venoms. Snake venoms proteins have enzymatic or non-enzymatic activities, which are grouped into different families, including C-type lectin proteins, disintegrins (long, medium and short disintegrins), Kunitz-type serine protease inhibitors, natriuretic-like peptides, vascular endothelial growth factor-related proteins, L-amino acid oxidases, phospholipases A2 and serine proteinases. With technological advancements, the toxic effects of venoms were turned into potential benefits for clinical diagnosis, basic research and development of new research tools and drugs of potential clinical use. Our research team has shown that Macrovipera lebetina and Cerastes cerastes venom components of Tunisian wildlife snakes had great potential for the development of new drugs for the treatment of cancer, angiogenesis disorders or cardiovascular diseases. This review is an overview of snake venom proteins from Macrovipera lebetina and Cerastes cerastes and their biochemical, pharmacological and molecular characterization and their importance as protein resources with therapeutic potential.

The scorpion toxins are the largest potassium channel-blocking, peptide family. The understanding of toxin binding interfaces is usually restricted to two classical binding interfaces: one is the toxin α-helix motif, and the other is the antiparallel β-sheet motif. In this review, such traditional knowledge has been updated by another two different binding interfaces: one is BmKTX toxin using the turn motif between the α-helix and antiparallel β-sheet domains as the binding interface, while the other is Tsκ toxin using the turn motif between the β-sheet in the N-terminal and α-helix domains as the binding interface. Their interaction analysis indicated that the scarce, negatively charged residues in the scorpion toxins played a critical role in orientating the toxin binding interface. In view of the toxin, being negatively charged amino acids as a “binding interface regulator”, the law of scorpion toxin-potassium channel interaction was proposed, that is, the polymorphism of negatively charged residue distribution determines the diversity of toxin binding interfaces. Such a law was used to develop the scorpion toxin-potassium channel recognition control technique. According to this technique, three Kv1.3 channel-targeted peptides, using BmKTX as the template, were designed with the distinct binding interfaces from that of BmKTX by modulating the distribution of toxin, negatively charged residues. In view of the potassium channel as the common target of different animal toxins, the proposed law was also shown to adjust the binding interfaces of other animal toxins. The toxin-potassium channel interaction law would strongly accelerate the research and development of different potassium channel-blocking animal toxins in the future.

Parkinson’s disease (PD) has caused most economies to lose their active human capital. Due to poor understanding of the pathophysiology of PD, PD animal models were developed to aid the investigation of PD pathogenesis and therapy. Currently, the toxin-induced and the genetic animal models are being used for most PD research.

Most neurotoxin animal model studies on PD are focused on the motor features and economic importance associated with dopamine depletion; however, the molecular pathways for cell loss by these models and its usefulness in PD drug development have not been reported fully. In this review, we have provided a summary of the toxic mechanism and shortcomings of four neurotoxins (6-OHDA, MPTP, Rotenone and, Paraquat) that are frequently used to mimic PD in animal models. This review will give readers basic knowledge for selecting the best toxin for a specific PD experiment and also provide information that will help in the future development of toxins with fewer shortcomings. This review also summarizes the mechanism and features of some PD genetic models.

Development of a new drug molecule is costly and requires a long time. Many attempts have been made to improve the safety of the effective level of “old” drugs, utilizing various ways like individualizing drug therapy, curative drug control, and dose titration. But, recently, important efforts have been made to discover the novel drug releasing systems, which can be supplied to a target system in the human body, while controlling the level and time of delivery. Polymers, whether synthetic or natural, have great importance in pharmaceutical applications, especially in the field of drug delivery. The use of polymers in pharmaceutical applications ranges from their use as binders in tablets to viscosity and flow controlling factors in liquids, and they can be used in suspensions and emulsions; also, in some cases, they can be used as film coatings. Moreover, they may be used as membranes implanted within the living body. Current work highlights the importance of drug delivery systems and the role of polymers in them.

Background: Natural products are characterized by a complex chemical composition and are capable of concurrently modulate several signalling pathways. Considering the biological complexity of carcinogenesis, natural products represent key components of the therapeutic armamentarium for oncological diseases. The bark of Terminalia arjuna is used in traditional Ayurvedic medicine for its astringent, expectorant, cardiotonic, styptic, and antidysenteric properties. Alongside its traditional uses, Terminalia arjuna exhibits different biological activities including antimutagenic and anticarcinogenic.

Objective: This study was designed to evaluate the toxic effects of an alcoholic extract obtained from the bark of T. arjuna on a human T-lymphoblastic cell line (Jurkat). We explored the phytochemical composition and investigated the cytotoxic, cytostatic, genotoxic, and anti-genotoxic effects.

Methods: The phytochemical composition was analyzed using spectrophotometric methods; all the biological endpoints were assessed through flow cytometry.

Results: The phytochemical screening showed that polyphenols represent about 64% of the extract. Moreover, the extract was cytotoxic on Jurkat cells by inducing both apoptosis and necrosis, and blocked the cell cycle in the G2/M phase. Additionally, it was found that the extract lacks any genotoxic effect, but was not effective in protecting Jurkat cells from the DNA damage induced by H2O2 and etoposide.

Conclusion: The results of our study show the toxic effects of Terminalia arjuna on Jurkat cells and confirm the pivotal role played by natural compounds in the oncological field. Further studies should be performed to better understand its clinical potential and deepen its toxicological profile.

Background: The World Health Organization added snakebite envenoming to its priority list of neglected tropical diseases. Snakebite envenoming is a particularly important public health problem in rural areas of tropical and sub-tropical countries. In 2017, more than 30 thousand cases of snakebites were reported in Brazil, with the North and Northeast regions being the most affected and Bothrops sp snakes causing most of these cases.

Objective: The objective of this study was to evaluate, in vitro, the coagulating, cytotoxic, oxidizing and antioxidant effects caused by Bothrops jararacussu and B. moojeni crude venoms.

Methods: The crude venoms protein profiles were characterized, and the biological effects were evaluated and compared between the species.

Results: The crude venoms composition showed similar protein profiles. The B. jararacussu and B. moojeni crude venoms showed coagulant activity and were capable of causing indirect hemolysis on the erythrocyte membrane, but did not protect the erythrocyte membrane from damage against hypotonic solutions. The B. jararacussu crude venom promoted hemagglutination.

Conclusion: The crude venoms were not able to promote an oxidizing effect on hemoglobin and could not prevent the phenylhydrazine oxidizing effect; however, the crude venoms presence caused increase in the methemoglobin formation by phenylhydrazine oxidation.

Background: Carissa spinarum Linn has been used as a traditional medicine to treat various ailments, including snakebite. It is found in India, Ceylon and Thailand.

Objective: The study was performed to determine the inhibiting potential of Carissa spinarum methanolic leaf extract on the pharmacological effects of Viper venom.

Methods: The dose-dependent enzymatic studies, pharmacological and in vivo studies were conducted using standard methods.

Results: It neutralized toxic enzymes in a dose-dependent manner with concentrations ranging from 53.3 –1190.4 μg/mL, inhibited lysis of fibrinogen at 1:8 (venom: extract, w/w), and increased the procoagulant activity and lecithin lysis at 1:25 (venom: extract, w/w). The extract neutralized the LD50 of venom in mice and embryos, reduced haemorrhage, myotoxicity and edema induced by the venom in mice.

Conclusion: The observed results confirm that the leaf extract possesses adequate phytochemicals that could neutralize the toxic properties of the venom.