[Snake venom Kunitz/BPTI family: Structure, classification and pharmacological potential]. / LA FAMILE KUNITZ/BPTI DES VENINS DE SERPENTS: STRUCTURE, CIASSIFICATION ET POTENTIEL PHARMACOLOGIQUE.

Snake venoms are rich sources of serine proteinase inhibitors that are members of the KunitzBPTI (bovine pancreatic trypsin inhibitor) family. Generally, these inhibitors are formed by 60 amino acids approximately. Their folding is characterised by a canonical loop that binds in a complementary manner to the active site of serine protease. Some variants from snake venoms show only weak inhibitory activity against proteases while others are neurotoxic. Moreover, proteases inhibitors are involved in various physiological prdcesses, such as blood coagulation, fibrinolysis, and inflammation. Also, these molecules showed an anti-tumoralpotent and anti-metastatic effect. Interestingly, KunitzBPTI peptides can have exquisite binding specificities and possess high potency for their targets making them excellent therapeutic candidates.

[Snake Venom L-Amino Acid Oxidases potential biomedical applications]. / LES L-AMINO ACIDES OXYDASES DES VENINS DE SERPENTS ET LEURS POTENTIELLES APPLICATIONS BIOMEDICALES.

L-amino acid oxidases (LAAOs) are flavoenzymes widely found in several organisms, including venoms snakes, where they contribute to the toxicity of ophidian envenomation. Their toxicity is primarily due to enzymatic activity, but other mechanisms have been proposed recently which require further investigation. LAAOs exert biological and pharmacological effects, including actions on platelet aggregation and the induction of apoptosis, hemorrhage and cytotoxicity. These proteins present a high biotechnological potentialfor the development of antimicrobial, antitumor and antiprotozoan agents. This review summarizes the biochemical properties, structural characteristics and various biological functions of snake venoms' LAAO. Furthermore, the putative mechanisms of action, were well detailed.

[Use of medicinal plants against scorpionic and ophidian venoms]. / Utilisation des plantes médicinales contre l'envenimation scorpionique et ophidienne.

The scorpionic and ophidian envenomations are a serious public health problem in Tunisia especially in Southeastern regions. In these regions Artemisia campestris L is a plant well known which has a very important place in traditional medicine for its effectiveness against alleged venom of scorpions and snakes. In this work, we tested for the first time, the anti-venomous activity of Artemisia campestris L against the scorpion Androctonus australis garzonii and the viper Macrovipera lebetina venoms. Assays were conducted by fixing the dose of extract to3 mg/mouse while doses of venom are variable. The leaves of Artemisia campestris L were extracted by various organic solvents (Ether of oil, ethyl acetate, methanol and ethanol) and each extract was tested for its venom neutralizing capacity. For the ethanolic extract, a significant activity with respect to the venoms of scorpion Androctonus australis garzonii (Aag), was detected. Similarly, a significant neutralizing activity against the venom of a viper Macrovipera lebetina (Ml), was obtained with the dichloromethane extract. These results suggest the presence of two different type of chemical components in this plant: those neutralizing the venom of scorpion are soluble in ethanol whereas those neutralizing the venom of viper are soluble in dichloromethane.

Identification of second lipolysis activating protein from scorpion Buthus occitanus tunetanus.

Besides the previously described LVP1, a second protein, LVP2, inducing a lipolytic response in adipose cells, was purified from scorpion Buthus occitanus tunetanus venom. It represented 2% of crude venom proteins, with pHi = 6 and molecular mass of 16889 Da. The reduction and the alkylation of LVP2 revealed an heterodimeric structure. Isolated alpha and beta chains of LVP2 have a molecular weight (MW) of 8822 Da and 8902, respectively. This protein was not toxic to mice and stimulated lipolysis on freshly dissociated rat adipocytes in a dose-dependent manner with EC50 = 2 +/- 0.75 microg/ml. LVP2 subunits did not display any lipolytic activity. As previously described for venom and LVP1, beta adrenergic receptor (beta AR) antagonists interfere with LVP2 activity. Furthermore, it is shown that LVP2 competes with [3H] CGP 12177 (beta1/beta2 AR antagonist) for binding to adipocyte plasma membrane with an IC50 of about 10(-7)M. Thus, these results bring original information on the existence of proteins that are present in scorpion venoms and can exert a distinct biological activity on adipocyte lipolysis through a beta-type adreno-receptor pathway.

Purification, characterization and molecular modelling of two toxin-like proteins from the Androctonus australis Hector venom.

Two toxin-like proteins (AahTL1 and AahTL3) were purified from the venom of the scorpion Androctonus australis Hector (Aah). AahTL1 and AahTL3 are the first non toxic proteins cross-reacting with AahI toxins group which indicates that these proteins can be used as a model of vaccins. In order to study structure-function relationships, their complete amino-acid sequences (66 residues) were determined, by automated Edman degradation. They show more than 50% of similarity with both AahI and AahIII antimammal toxins. Three-dimensional structural models of AahTL1 and AahTL3 constructed by homology suggest that the two proteins are structurally similar to antimammal scorpion alpha-toxins specific to voltage dependent Na+ channels. The models showed also that amino-acid changes between potent Aah toxins and both AahTL1 and AahTL3 disrupt the electrostatic potential gradient at their surface preventing their interaction with the receptor, which may explain their non toxicity.