Study of the Acute Toxicity of Scorpion Leiurus macroctenus Venom in Rats.

Background: The expansion of the territory of human habitation leads to inevitable interference in the natural range of distribution of one or another species of animals, some of which may be dangerous for human life. Scorpions-the Arachnida class and order Scorpiones-can be considered as such typical representatives. Scorpions of the Buthidae family pose a particular danger to humans. However, LD50 has not yet been defined for many species of this family, in particular, new representatives of the genus Leiurus. Leiurus macroctenus is a newly described species of scorpion distributed in Oman, and the toxicity of its venom is still unknown. Estimating the LD50 of the venom is the first and most important step in creating the antivenom and understanding the medical significance of the researched animal species. The purpose of this study was to determine the lethal dose (LD100), the maximum tolerated dose (LD0), and the average lethal dose (LD50) in rats when using Leiurus macroctenus scorpion venom. Methods and Results: 15 sexually mature scorpions were used in the study, which were kept in the same conditions and milked by a common method (electric milking). For the study, 60 male rats were used, which were injected intramuscularly with 0.5 ml of venom solution with a gradual increase in the dose (5 groups, 10 rats in each), and 10 rats were injected intramuscularly with physiological solution as control group. LD calculations were done using probit analysis method in the modification of the method by V.B. Prozorovsky. The LD0 of Leiurus macroctenus scorpion venom under the conditions of intramuscular injection was 0.02 mg/kg, LD100 was 0.13 mg/kg, and LD50 was 0.08 ± 0.01 mg/kg. Conclusions: The analysis of scientific publications and other sources of information gives reason to believe that Leiurus macroctenus has one of the highest values of LD50 not only among scorpions but also among all arthropods in the world. All these point to the significant clinical importance of this species of scorpion and require further research that will concern the toxic effect of its venom on various organ systems. Determining the LD50 of the venom for new scorpion species is crucial for creating effective antivenoms and understanding the medical implications of envenomation by this species.

Cytokines and their regulators in rat lung following scorpion envenomation.

Nowadays, more than two billion inhabitants of underdeveloped tropical and subtropical countries are at risk of being stung by scorpions. Scorpion stings annually cause 2000-3000 deaths as they can lead to the respiratory and/or cardiovascular complications. Pathogenesis of lung damage under scorpion envenomation is often comprehensive. Respiratory failure can have a cardiogenic origin, associated with venom neurotoxin action. However, some venom components can stimulate pro-inflammatory signaling cascades followed by cytokines synthesis, recruit and activate immune cells, participating in the inflammatory response in lung injury. Scorpions of the Leiurus genus ("deathstalker") are one of the most dangerous Arthropoda. To date, 22 species of this genus have been described, but the venom composition and the mechanisms of tissues damage under envenomation have been studied to some extent only for L. quinquestriatus, L. hebraeus, and L. abdullahbayrami. Scorpions of L. macroctenus species are expected to be very hazardous, but the possibility of their venom cause inflammation in the lung tissue has not been investigated to date. Therefore, in this study, we focused on evaluating the levels of cytokines and their regulators - transcription factors (HIF-1α and NF-κB) and growth factors (FGF-2, VEGF, and EGF) - in rat lung homogenates after L. macroctenus envenomation. The results revealed a decrease in the levels of most pro-inflammatory cytokines (IL-6, IL-8, IL-1ß and TNF-α) with simultaneous rise in the content of both anti-inflammatory cytokines (IL-4 and IL-10) and interferon-γ. Furthermore, the levels of all researched transcription factors and growth factors were shown to be increased too. The detected changes peak occurred at 24 h, whereas a tendency towards all indicators values normalization was observed in 72 h after venom injection. Thus, our results did not reveal signs of a classic inflammatory process in the lungs of rats injected with L. macroctenus venom. However, the obtained data indicate venom influence both on cytokine profile and on their regulators content in the rat lungs, which is a feature of certain alterations in the innate immune response, caused by studied venom components. But, the mechanisms of the changes we found require additional researches.

Protein and peptide profiles of rats' organs in scorpion envenomation.

Problem of scorpion envenomation becomes more alarming each year. Main effects of scorpion venom are commonly believed to be related to its neurotoxic properties, yet severe symptoms may also be developed due to the uncontrolled enzymatic activity and formation of various bioactive molecules, including middle-mass molecules (MMMs). MMMs are considered as endogenous intoxication markers, their presence may indicate multiple organ failure. Scorpions, belong to the Leiurus macroctenus species, are very dangerous, nevertheless, effects of their venom on protein and peptide composition within the tissues remains unclear. In this work we have focused the attention on changes in protein and MMM levels and peptide composition in various organs during Leiurus macroctenus envenomation. The results revealed a decrease in protein level during envenomation as well as a significant increment of MMM210 and MMM254 levels in all assessed organs. Quantitative and qualitative compositions of various protein and peptide factions were continually changing. All of this may suggest that Leiurus macroctenus sting causes considerable destruction of cell microenvironment across all essential organs, providing systemic envenomation. In addition, MMM level increment may indicate endogenous intoxication development. Peptides, formed during envenomation, may possess various bioactive properties, analysis of which constitutes an area of further studies.

The Activity of Metalloproteases and Serine Proteases in Various Organs after Leiurus macroctenus Envenomation.

Background: Scorpion stings may be life-threatening since their venoms are comprised of a wide range of toxins and other bioactive molecules, such as enzymes. At the same time, scorpion envenomation may increase matrix metalloproteases (MMPs) levels, which enhance proteolytic tissue destruction by venom. However, investigations on the impact of many scorpions' venoms, such as those of Leiurus macroctenus, on tissue proteolytic activity and MMP levels have not yet been conducted. Methods and Results: The present study aimed to examine the total proteolysis levels in various organs after Leiurus macroctenus envenomation and evaluate the metalloproteases and serine proteases' contributions to the total proteolytic activity. Changes in MMPs and TIMP-1 levels were tested as well. Envenomation led to a significant increase in proteolytic activity levels in all assessed organs, mostly in the heart (by 3.34 times) and lungs (by 2.25 times). Conclusions: Since EDTA presence showed a noticeable decrease in total proteolytic activity level, metalloproteases appeared to play a prominent role in total proteolytic activity. At the same time, MMPs and TIMP-1 levels were increased in all assessed organs, suggesting that Leiurus macroctenus envenomation causes systemic envenomation, which may induce multiple organ abnormalities, mostly because of the uncontrolled metalloprotease activity.

MATHEMATICAL MODELING OF TELEROENTGENOGRAPHIC PARAMETERS ACCORDING TO THE METHOD OF SCHWARZ A. M. DEPENDING ON THE BASIC CEPHALOMETRIC PARAMETERS IN UKRAINIAN YOUNG MEN AND YOUNG WOMEN WITH DIFFERENT FACE TYPES.

OBJECTIVE: The aim: Is development and analysis of regression models of teleroentgenographic indices according to Schwarz A. M., which can be adjusted during surgery depending on the parameters that usually do not change in Ukrainian young men and young women with with normal occlusion close to orthognathic occlusion and different facial types. PATIENTS AND METHODS: Materials and methods: Teleroentgenographic indices were obtained using a dental cone-beam tomograph Veraviewepocs 3D Morita and studied in 49 young men and 76 young women with normal occlusion close to orthognathic. Persons were divided into groups with different face types according to the recommendations of Schwarz A. M. In the license package "Statistica 6.0", regression models of teleroentgenographic indices were built according to Schwarz A. M. RESULTS: Results: For young men with orthognathic occlusion and with different types of faces according to Schwarz A. M. constructed 10 of 27 possible reliable regression models of the group of teleroentgenographic indicators, which can be corrected during surgical, orthopedic interventions in dentistry depending on the group of basic, invariable cephalometric indicators greater than 0.6 (R2 = from 0.609 to 0.996); and in young women with different face types, 8 of the 27 possible reliable regression models in which the coefficient of determination is greater than 0.6 (R2 = from 0.642 to 0.986). CONCLUSION: Conclusions: The developed regression models provide the most individualized approach in determining the method and scope of the required dental intervention.