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Abstract Background Scorpion envenomation, a prevalent medical emergency in rural areas, demands immediate attention due to its potential severity. While ocular manifestations are uncommon, they can lead to significant complications such as corneal ulceration. We present a unique case of corneal ulceration subsequent to a yellow scorpion (Hemiscorpius lepturus) sting near the eye, a scenario not previously documented. Case presentation A 34-year-old male sought medical care following a scorpion sting despite prior anti-venom treatment. Clinical examination revealed pronounced ocular inflammation, corneal stromal melting, and anterior chamber inflammation, with microbiological confirmation of Pseudomonas spp infection. Treatment comprised fortified ceftazidime and vancomycin eye drops, alongside topical corticosteroids, leading to visual and corneal healing. Conclusion This case highlights the urgency of addressing scorpion envenomation and its potential for severe ocular complications, including corneal ulceration. Prompt diagnosis and targeted therapy with antibiotics and corticosteroids are crucial for favorable outcomes. A comprehensive understanding and timely intervention in scorpion sting-induced ocular manifestations are essential for optimal patient management and outcomes in such cases.

Background: Scorpion envenomation, a prevalent medical emergency in rural areas, demands immediate attention due to its potential severity. While ocular manifestations are uncommon, they can lead to significant complications such as corneal ulceration. We present a unique case of corneal ulceration subsequent to a yellow scorpion (Hemiscorpius lepturus) sting near the eye, a scenario not previously documented. Case presentation: A 34-year-old male sought medical care following a scorpion sting despite prior anti-venom treatment. Clinical examination revealed pronounced ocular inflammation, corneal stromal melting, and anterior chamber inflammation, with microbiological confirmation of Pseudomonas spp infection. Treatment comprised fortified ceftazidime and vancomycin eye drops, alongside topical corticosteroids, leading to visual and corneal healing. Conclusion: This case highlights the urgency of addressing scorpion envenomation and its potential for severe ocular complications, including corneal ulceration. Prompt diagnosis and targeted therapy with antibiotics and corticosteroids are crucial for favorable outcomes. A comprehensive understanding and timely intervention in scorpion sting-induced ocular manifestations are essential for optimal patient management and outcomes in such cases. [ABSTRACT FROM AUTHOR]

In this study, the fraction of the Hemiscorpius lepturus scorpion venom was subjected. The two bioactive fractions (F2 and F4) were separated and collected by RP-HPLC. Next, the cytotoxicity of F2 and F4 against human red blood cells and MCF-7 cell line was investigated. The expression levels of Bax, Bcl-2, and p53 genes in cancer cells treated with fractions were determined. In order to evaluate the effects of the two extract fractions, breast cancer was induced in BALB-c mice developed by the injection of MCF-7 cells. Following the intraperitoneal injection of F2 and F4 into mice, the levels of IFN-γ and IL-4 were measured using ELISA. The effects of fractions on the survival of MCF-7 cancer cells were significant compared to normal cells (p < 0.001), while they had no significant hemolysis activity against red blood cells (p > 0.05). The results showed that the expression of Bax and p53 was increased in MCF-7 cells treated with fractions compared to control cells without treatment, while the expression of Bcl-2 was decreased. The results of the in vivo analysis showed that the level of IFN-γ was increased, whereas the level of IL-4 was significantly reduced in mice treated with F2 and F4 at the concentrations of 5 and 10 mg/kg compared to control animals (p < 0.0001). Based on the results, two extract fractions of H. lepturus scorpion venom exert anti-cancer properties, and they are able to modulate the immune system and induce apoptosis in cancer cells. [ABSTRACT FROM AUTHOR]

Scorpions are the oldest terrestrial fauna with an ancient evolutionary history. To study the origins of scorpions, we conducted a molecular phylogenetic study of the arthropod using slowly evolving enolase sequences. In this study, we used deep RNA-seq technology to identify the enolase sequences of Androctonus crassicauda and Hemiscorpius lepturus scorpions. The scorpion's enolase sequences were in silico analyzed to predict the protein structures, physicochemical characterization, and exon-intron organization. The enolase of the scorpion was found to be a protein of 433 amino acids with a molecular mass of ∼47 kDa and an acidic isoelectric point. Here, we reported the existence of 8 exons and an inner GC/AG intron for scorpion enolase. Using homology modeling, the enolase of the scorpions was found to be very conservative during the evolution process. Furthermore, our phylogenetic analysis indicated the independent evolution of the Buthidae family from other scorpions and also the sister group relationship of Hemiscorpionidae with the Caraboctonidae families. The scorpions' enolase sequences demonstrated a close fit to those of spiders, followed by mite counterparts. This strongly supports our phylogeny analysis, which indicates a sister-group relationship between scorpions and spiders and their common ancestors with mites. This study provided support for the pairing of scorpions with spiders, mites, etc. using enolase as a nuclear gene. Our molecular clock analyzes of the arthropod show that the most recent common ancestor of arachnids and insects were diversified in the Cryogenian period of Neoproterozoic era, earlier than dates reported from fossil records. [ABSTRACT FROM AUTHOR]

Acute kidney injury is a common complication of Hemiscorpius lepturus (HL) scorpion envenomation, via several mechanisms including pigment nephropathy, direct nephrotoxic effects of scorpion venom, hemolytic uremic syndrome (HUS), and acute interstitial nephritis. ADAMTS13 deficiency is highly prevalent in patients with severe HL scorpion envenomation and is effective in the development of HUS. Fresh frozen plasma (FFP), by replacing ADAMTS13, has proven effects on HL scorpion envenomated patients with HUS. This study evaluated the role of FFP in reducing of kidney injuries in complicated cases. In this open label randomized clinical trial, a total of 98 patients with massive hemoglobinuria following HL scorpion envenomation were included in the intervention and control groups (49 patients per group). The intervention group received FFP (10 cc/kg every 12 hours for three days) in addition to the anti-venom and other current therapies. Laboratory findings of renal activity, hemolysis, and urinalysis were evaluated in both groups, and maximum changes were compared. Comparison of maximum changes in laboratory findings between the two groups showed that administration of FFP can significantly reduce the deterioration of Blood Urea Nitrogen (BUN) and Creatinine (Cr) levels in the intervention group (p < 0.001 and p = 0.003, respectively). In comparison with the control group, the incidence of proteinuria was significantly lower (p = 0.012), reduction of platelet count was significantly less (p = 0.044), and increase of lactate dehydrogenase (LDH) and leukocytosis was lower in the intervention group (p = 0.037 and p = 0.007, respectively). The mean length of hospital stay was 5.44 days in the intervention group and 5.933 days in the control group (p = 0.149). According to the present findings, FFP can significantly reduce the development of kidney damage after HL scorpion envenomation and can be safely used against the fatal progression of venom complications in severe cases, along with other common treatments. [ABSTRACT FROM AUTHOR]

Background: Blocking Kv 1.2 and Kv 1.3 potassium channels using scorpion venom- derived toxins holds potential therapeutic value. These channels are implicated in autoimmune diseases such as neurodegenerative diseases, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes., Objective: The present work aims at the discovery and in silico activity analysis of potassium channel blockers (KTxs) from the cDNA library derived from the venom gland of Iranian scorpion Hemiscorpius lepturus (H. lepturus)., Methods: The sequence regarding potassium channel blockers were extracted based on Gene Ontology for H. lepturus venom gland. Homology analyses, superfamily, family, and evolutionary signatures of H. lepturus KTxs (H.L KTxs) were determined by using BLASTP, COBALT, PROSITE, and InterPro servers. The predicted 3D structures of H.L KTxs were superimposed against their homologs to predict structure activity relationship. Molecular docking analysis was also performed to predict the binding affinity of H.L KTxs to Kv 1.2 and Kv 1.3 channels. Finally, the toxicity was predicted., Results: Seven H.L KTxs, designated as Leptukalin, were extracted from the cDNA library of H. lepturus venom gland. Homology analyses proved that they can act as potassium channel blockers and they belong to the superfamily and family of Scorpion Toxin-like and Short-chain scorpion toxins, respectively. Structural alignment results confirmed the activity of H.L KTxs. Binding affinity of all H.L KTxs to Kv 1.2 and Kv 1.3 channels ranged from -4.4 to -5.5 and -4 to -5.7 Kcal/mol, respectively. In silico toxicity assay showed that Leptukalin 3, Leptukalin 5, and Leptukalin 7 were non-toxic., Conclusion: Three non-toxic KTxs, Leptukalin 3, 5, and 7, were successfully discovered from the cDNA library of H. lepturus venom gland. Gathering all data together, the discovered peptides are promising potassium channel blockers. Accordingly, Leptukalin 3, 5, and 7 could be suggested for complementary in vitro studies and mouse model of autoimmune diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Hemiscorpius lepturus is one of the most dangerous scorpions in Iran and the world. Numerous studies have been conducted on phospholipases, especially phospholipase D, in this scorpion’s venom, and the results have shown this protein to be the main cause of death. Therefore, one of the most effective ways of preventing fatalities is to produce a toxoid vaccine from the deadly toxin of the venom. The present study was conducted to assess the non-toxicity of this toxoid and the safety of the vaccine candidate in BALB/c mice. Methods: The production of interferon-gamma and interleukin-4 cytokines in the spleen cells of the mice was measured using ELISpot assay 28 days following immunization with rPLD toxoid. Results: The unpaired t-test results showed a significant increase in the concentration of IFN-γ cytokine in the vaccinat­ed mice (P= 0.001), indicating that the immune system is directed toward the Th1 pattern, while no significant differ­ence was observed in the levels of IL-4 (P= 0.16) despite an increase in this cytokine. The in-vivo tests showed that the mice immunized with interval doses of 80µg of toxoid were completely protected against 10 × the LD100 of the venom. Moreover, the toxoid had no dermonecrotic effects and caused no necrotic and inflammatory complications in the rabbit skin. Conclusion: As a vaccine, the toxoid has the potential to increase the Th1 cytokine response and, subsequently, in­crease acquired cellular immunity. Thus, this toxoid appears to be able to provide an effective vaccine against the ven­om of Hemiscorpius lepturus.

Background: Hemiscorpius lepturus is one of the most dangerous scorpions in Iran and the world. Numerous studies have been conducted on phospholipases, especially phospholipase D, in this scorpion’s venom, and the results have shown this protein to be the main cause of death. Therefore, one of the most effective ways of preventing fatalities is to produce a toxoid vaccine from the deadly toxin of the venom. The present study was conducted to assess the nontoxicity of this toxoid and the safety of the vaccine candidate in BALB/c mice. Methods: The production of interferon-gamma and interleukin-4 cytokines in the spleen cells of the mice was measured using ELISpot assay 28 days following immunization with rPLD toxoid. Results: The unpaired t-test results showed a significant increase in the concentration of IFN-γ cytokine in the vaccinated mice (P= 0.001), indicating that the immune system is directed toward the Th1 pattern, while no significant difference was observed in the levels of IL-4 (P= 0.16) despite an increase in this cytokine. The in-vivo tests showed that the mice immunized with interval doses of 80µg of toxoid were completely protected against 10 × the LD100 of the venom. Moreover, the toxoid had no dermonecrotic effects and caused no necrotic and inflammatory complications in the rabbit skin. Conclusion: As a vaccine, the toxoid has the potential to increase the Th1 cytokine response and, subsequently, increase acquired cellular immunity. Thus, this toxoid appears to be able to provide an effective vaccine against the venom of Hemiscorpius lepturus. [ABSTRACT FROM AUTHOR]

Background: Scorpion stings are responsible for many deaths in humans; however, the toxicity mechanisms of the venoms from many species are not well studied. We investigated the cardiotoxicity of the crude venom from H. lepturus scorpion and its isolated fractions, F-I to F-VI. Methods: The scorpion’s venom was extracted into six fractions by chromotagraphy. Healthy male Wistar rats (N=72) were equally divided into eight groups of nine: G1: Controls (0.5ml. normal saline), G2: Crude venom (1000µg/kg), G3: F-I (120µg/kg), G4: F-II (430µg/kg), G5: F-III (80 µg/kg), G6: F-IV (180µg/kg), G7: F-V (60µg/kg), and G8: F-VI (130µg/kg). Blood samples were obtained by cardiac puncture at 1, 3 and 24 hours after the venom injection. The serum levels of AST, LDH, CPK, CK-MB and troponin-I were determined. Upon euthanasia, the hearts were removed from the rats and examined microscopically for histopathology. Results: In groups receiving crude venom and F-VI, we observed multifocal fragmentation of myocardial fibers, hemorrhage, degeneration and disappearance of striations in cardiac muscles as compared to the controls. The findings showed that AST and LDH activity in groups 2, 4 and 8, CPK activity in groups 2, 4, 6 and 8 and CK-MB activity and troponin-I levels in groups 2 and 8 increased significantly compared to those in the control group. Conclusion: There was evidence of significant cardiotoxicity in the group receiving crude venom and F-VI. Although alterations in the enzymatic and troponin-I levels were observed in other groups, the greatest cardiotoxicity of H. lepturus venom was caused by fraction VI.

Background: The present study determined the effect of the fractions obtained from Hemiscorpius lepturus scorpion venom on the tachyzoite of Toxoplasma gondii. Methods: The fractions of dried venom of He. lepturus scorpion of Khuzestan Province, southern Iran in 2019 were isolated through gel filtration chromatography, and then tachyzoites were exposed to fractions of venom at different concentrations. Trypan blue counting and MTT were applied to assay tachyzoite viability, and the inhibition of the cellular growth of fractions in Vero cells was evaluated. Results: The maximum effect on tachyzoite was observed in fraction 5 of venom. To further separate the protein, fraction 5 was used in high-performance liquid chromatography assay to purify its proteins. Based on the results of HPLC of fraction 5, among which the second peak, a peptide with

Background: The present study determined the effect of the fractions obtained from Hemiscorpius lepturus scorpion venom on the tachyzoite of Toxoplasma gondii. Methods: The fractions of dried venom of He. lepturus scorpion of Khuzestan Province, southern Iran in 2019 were isolated through gel filtration chromatography, and then tachyzoites were exposed to fractions of venom at different concentrations. Trypan blue counting and MTT were applied to assay tachyzoite viability, and the inhibition of the cellular growth of fractions in Vero cells was evaluated. Results: The maximum effect on tachyzoite was observed in fraction 5 of venom. To further separate the protein, fraction 5 was used in high-performance liquid chromatography assay to purify its proteins. Based on the results of HPLC of fraction 5, among which the second peak, a peptide with <10 IKDa representing a more potent effect in eliminating the tachyzoite of T. gondii. Conclusion: The scorpion venom-purified fractions possess anti-parasitic activity against the tachyzoite of T. gondii and can be used in parasite-controlling studies. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this research was to use environmental variables for predicting the probability of Hemiscorpius lepturus existence in the provinces where situated in the west of the Zagros Mountains. Materials and Methods: In this study, 64 occurrence records of the H. lepturus were extracted from the published documents available in electronic databases. MaxEnt model was used for predicting the ecological niches of this species. Normalized difference vegetation index (NDVI) and 19 climatic variables were used as the environmental variables affecting the distribution of this scorpion. The Jackknife test in the model was used to indicate the importance of variables to predict the probability of the presence of the studied species. The logistic threshold that was evaluated using a logistic regression algorithm showed the converting of the probability model into a binary model. The model was evaluated by area under the curve (AUC). The probability presence map of this scorpion was then prepared in ArcGIS 10.5 Software. Results: The results of the analysis showed that the most important environmental factor on the distribution of H. lepturus was the maximum temperature of the warmest month (Bio5) with a contribution rate of 43% and permutation importance of 8%. The Jackknife test revealed that NDVI did not gain any value when it used independently in the model. The logistic threshold was reported 0.255 for the maximum test sensitivity plus specificity. The AUC of the model was 0.7698, shows an acceptable value for model validity. Overall the hot spots for this toxic scorpion seem to be in Khuzestan, Lorestan, and Ilam Provinces of the studied area. Conclusion: Regarding our findings, MaxEnt algorithm, in combination with geographic information system contributed to revealing the effects of environmental variables on the probability of H. lepturus presence in the west of Zagros Mountains. These visualized maps as a warning alarm can be helpful to policymakers for managing, controlling, and monitoring the scorpionism in high-risk areas.

Objective(s): Scorpion venom has toxic effects on mammals, insects and crustaceans. Toxicogenic peptides are major contributors to the scorpion venom, which make it toxic. The Hemiscorpius lepturus (H. lepturus) is one of the most common scorpion bites agent, and responsible for 95% of scorpion bite deaths cases in Iran.Materials and Methods: In this project, we fractionated the H. lepturus scorpion venom and analyzed toxic fractions of the venom. The crude venom of H. lepturus was dialyzed against distilled water and then the soluble part of the venom was isolated from the non-soluble (mucoproteins) part of the venom and loaded onto the Sephadex G-50 gel filtration column, then after determining the toxicity of the obtained fractions (fractions toxicity were detected in mice by IV injection), the resulting toxic fraction was purified with three stages of ion-exchange chromatography (anion and cationic) and RP-HPLC. The purity of the fractions was verified by SDS-PAGE electrophoreses.Results: The LD50 of H. lepturus venom was 177.01 µg/mouse. The crude venom had 7 detectable bands with molecular weights of 10-100 KDa and one band less than 10 KDa. Finally, after the different stages of chromatography, two HL2153 and HL2155 peaks were obtained from the RP-HPLC, which were depicted single bands and high purity. The electrophoretic analysis showed molecular weight 4874 Da for HL2153 and 5107 Da for HL2155 toxins.Conclusion: It is concluded that H. lepturus venom contains two HL2153 and HL2155 toxins with a relatively similar molecular weight and similar electrical charge 4874 and 5107 Da, respectively.

Background: Breast cancer is now the most important type of cancer in women around the globe and accounts for 25% of all types of cancer. Prevention and treatment of cancer are essential. Method: The main methods for treating cancer include chemotherapy, surgery, radiotherapy, gene therapy, and hormone therapy. Chemopreventive test programmes began in 1987, when over 1,000 agents and agent combinations were selected and evaluated in preclinical studies of chemopreventive activity against various types of cancers. Results: An important feature of anticancer drugs is a cytotoxic effect on cancer cells; these drugs have some cytotoxic agents found in animal venom. The ICD-85 is a combination of three peptides, ranging from 10,000 to 30,000 Da, and derived from the venom of the Iranian brown snake (Gloydius halys) and the yellow scorpion (Hemiscorpius lepturus). Conclusion: ICD-85 has an anti-proliferative effect and anti-angiogenesis activity on cancer cells. The side effects of chemotherapy are multiple drug resistance and effects on natural tissues, among others. Therefore, cytotoxic anticancer drugs are useful in treating cancer. The present work investigates the effects of ICD-85 on in vivo and in vitro studies.

Objective(s): In this study, the neutralizing abilities of the equine and the recently introduced camelid antivenoms on the hemodynamic parameters (inotropism, chronotropism, and arrhythmogenicity) were assessed following envenomation by Hemiscorpius lepturus venom in rats. Materials and Methods: At first, the electrophoretic profiles of both products were obtained by using the SDS-PAGE method (12.5%) and stained with Coomassie blue and silver nitrate. Secondly, different doses of the camelid antivenom (10, 50, and 100 µl) were given intravenously in 10 min before venom injection (400 µg/rat). The neutralizing potencies of camelid and equine antivenoms were measured by preincubation (100 µl) with H. lepturus venom for 30 min at room temperature. Finally, equal amounts of the antivenoms were injected intravenously to observe the hemodynamic changes.Results: Based on the electrophoretic profile, it was evident that undesired proteins significantly decreased in equine antivenom, owing to impurities. Pretreatment with the camelid antivenom (100 µl), neutralized the elevation of the mean arterial pressure evoked with scorpion venom injection (88.15±4.56 versus 10.2±1.23 percent at the 8th min). The Incubation of the venom and the camelid antivenom counteracted the hemodynamic changes, but the equine product had no effect. The intravascular injection of the equine antivenom transiently increased the mean arterial pressure as compared to the control (108.67±8.63 mmHg versus 52.67±1.93 mmHg at the 10th min).Conclusion: The most obvious finding emerging from this study was that the camelid antivenom neutralized the hemodynamic changes in rats significantly, but in comparison, the equine antivenom had just a minor ability.

Background: The Disintegrin and Metalloproteinase (ADAM) family, also known as the metalloproteinase/disintegrin/cysteine-rich (MDC) proteins, includes both secreted and transmembrane molecules involved in critical biological processes, such as cell migration, adhesion, and signaling. This study aimed to investigate the evolutionary relationships and structural characteristics of disintegrin and metalloproteinase proteins identified in the venom gland transcriptome of the scorpion Hemiscorpius lepturus., Methods: Using bioinformatics tools, we analyzed the open reading frame, conserved motifs, and primary, secondary, and tertiary structures of these proteins. Five proteins, named HLDis- Met1, HLDisMet2, HLDisMet3, HLDisMet4, and HLDisMet5, were identified. Their predicted 3- D structures were within normal ranges (Z-score between -4 to -9)., Results: Phylogenetic analysis revealed that HLDisMet1 shares similarities with proteins from various spider species (Nephila pilipes, Argiope bruennichi, Araneus ventricosus, and Trichonephila inaurata madagascariensis), HLDisMet2 with the scorpion Centruroides sculpturatus, HLDis- Met4 with the scorpion Tityus serrulatus, and HLDisMet5 with several snake species (Python bivittatus, Vipera anatolica senliki, Protobothrops mucrosquamatus, and Naja naja)., Conclusion: These findings highlight the significant similarities between HLDisMet proteins and those found in other venomous species, suggesting a complex and diverse evolutionary pathway for venom components. The cross-species conservation observed may indicate a convergent evolutionary strategy, where different species independently develop similar venom components to adapt to similar ecological niches or prey types. This study highlights the evolutionary significance of venom diversification and its potential applications in understanding venom biology across different species., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Abstract: Background: Hemiscorpius lepturus is a medically important scorpion found along the Iranian borders, especially near to Khuzestan Province in the south-west of Iran. This is the only non-buthid scorpion which is potentially lethal in southern Iran and is responsible for severe dermonecrotic scorpionism. OBJECTIVES: In this study, DNA fragment of the mitochondrial cytochrome c oxidase subunit I (COXI) gene of H. Lepturus for the molecular phylogenetic analysis was amplified. METHODS: We amplified a 624 bp gene fragment of cytochrome C oxidase subunit I (COXI) from H. lepturus collected from Khuzestan, Ahvaz by PCR. After sequencing of the PCR products, the phylogenetic analysis was performed using the neighbor-joining method with 1000 replicates of bootstrapping using the MEGA7 software. RESULTS: The results of phylogenetic analysis revealed four distinct clusters (A1, A2, B and C) belonging to the family of Hemiscorpionidae that were grouped together with bootstrap score between 77-96%. The gene fragment of Hl-Kh formed a cluster relative to the only scorpion of H. Lepturus (Hl) from Izeh, Iran with a good bootstrap score of 96. These two samples isolated from the Khuzestan province of Iran are closely related, as they clustered together as Cluster B. The genetic distances of Hl-Kh among the cluster A1, A2 and C ranged from 16 to19% and the lowest interspecific distance was in cluster B between Hl-Kh and Hl (6%). CONCLUSIONS: Hl-Kh isolated from the Khuzestan province of Iran are closely related to Hl, as they showed the greatest interspecific variation observed in Hemisccorpius genus in this study. Although the sample size in Cluster B is not large enough to draw a final conclusion, the percentage of sequence divergence was high enough for interspecific comparisons to provide separation of species.

Background: Hemiscorpius lepturus envenomation is one of the most important medical issues in tropical regions of Iran, especially Khuzestan Province. Due to lack of reliable data about scorpion sting in Khuzestan Province, this investigation was performed to study the clinical presentation, prognosis factors, complications and mortality rates of Hemiscorpius lepturus sting. Methods: this study was a cross-sectional study performed at Sina Hospital, Karoon, Iran during 2011-2013. Required data such as demographic data, complications and outcomes were collected from medical records of all admitted victims of envenomation in this period and then were registered in a propriate checklist. Data were analyzed using SPSS version 16. Results: a total of 311 victims were studied. The highest frequency of sting was in the age range of 15-24 years. Most areas of the sting were the lower extremity. Forty-two patients delayed more than 24 hours to refer to the emergency room. The most common initial symptom in victims was pain in the sting location. Complications such as hematuria, hemoglobinuria, and coagulation disorders were most morbidity occurred in patients. 6 cases died. Conclusion: delay in referring to the hospital, the existence of hemoglobinuria, coagulation disorders and kidney failure were associated with poor prognosis in patients. It seems that patients who refer with delays and with symptoms such as hematuria, need for more medical health care.

Objective(s): Hemiscorpius lepturus is one of the dangerous scorpions of Iran leading to acute kidney injury (AKI) especially in infants. The purpose of this animal study was to compare the serological, pathological and scintigraphic data to quickly predict the occurrence of this disorder.Materials and Methods: In two groups of animals, each contained five rats, H. lepturus venom (1200 µg/Kg) were injected intravenously via the tail vein. At three hours and one week later, 99m Tc-DMSA (3 mCi) was intravenously injected and renal scintigraphy was performed after an hour. Moreover, plasma levels of creatinine, sodium, potassium, and blood urea nitrogen (BUN) were measured. At the end of the study, renal tissues were excised and prepared to perform pathological evaluation after Hematoxylin and Eosin staining.Results: All serological indices were remained unchanged compared to control. A large number of glomerular fibrin thrombi with entrapped red blood cells and simplified tubular epithelium in dilated and ectatic tubules were observed in high power field (×100) four hours after envenomation, which reduced significantly one week later. In our scintigraphic study, there was a statistically significant difference (P

Background: Scorpion stings are responsible for many deaths in humans; however, the toxicity mechanisms of the venoms from many species are not well studied. We investigated the cardiotoxicity of the crude venom from H. lepturus scorpion and its isolated fractions, F-I to F-VI. Methods: The scorpion's venom was extracted into six fractions by chromotagraphy. Healthy male Wistar rats (N=72) were equally divided into eight groups of nine: G1: Controls (0.5ml. normal saline), G2: Crude venom (1000μg/kg), G3: F-I (120μg/kg), G4: F-II (430μg/kg), G5: F-III (80 μg/kg), G6: F-IV (180μg/kg), G7: F-V (60μg/kg), and G8: F-VI (130μg/kg). Blood samples were obtained by cardiac puncture at 1, 3 and 24 hours after the venom injection. The serum levels of AST, LDH, CPK, CK-MB and troponin-I were determined. Upon euthanasia, the hearts were removed from the rats and examined microscopically for histopathology. Results: In groups receiving crude venom and F-VI, we observed multifocal fragmentation of myocardial fibers, hemorrhage, degeneration and disappearance of striations in cardiac muscles as compared to the controls. The findings showed that AST and LDH activity in groups 2, 4 and 8, CPK activity in groups 2, 4, 6 and 8 and CK-MB activity and troponin-I levels in groups 2 and 8 increased significantly compared to those in the control group. Conclusion: There was evidence of significant cardiotoxicity in the group receiving crude venom and F-VI. Although alterations in the enzymatic and troponin-I levels were observed in other groups, the greatest cardiotoxicity of H. lepturus venom was caused by fraction VI. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this research was to use environmental variables for predicting the probability of Hemiscorpius lepturus existence in the provinces where situated in the west of the Zagros Mountains. Materials and Methods: In this study, 64 occurrence records of the H. lepturus were extracted from the published documents available in electronic databases. MaxEnt model was used for predicting the ecological niches of this species. Normalized difference vegetation index (NDVI) and 19 climatic variables were used as the environmental variables affecting the distribution of this scorpion. The Jackknife test in the model was used to indicate the importance of variables to predict the probability of the presence of the studied species. The logistic threshold that was evaluated using a logistic regression algorithm showed the converting of the probability model into a binary model. The model was evaluated by area under the curve (AUC). The probability presence map of this scorpion was then prepared in ArcGIS 10.5 Software. Results: The results of the analysis showed that the most important environmental factor on the distribution of H. lepturus was the maximum temperature of the warmest month (Bio5) with a contribution rate of 43% and permutation importance of 8%. The Jackknife test revealed that NDVI did not gain any value when it used independently in the model. The logistic threshold was reported 0.255 for the maximum test sensitivity plus specificity. The AUC of the model was 0.7698, shows an acceptable value for model validity. Overall the hot spots for this toxic scorpion seem to be in Khuzestan, Lorestan, and Ilam Provinces of the studied area. Conclusion: Regarding our findings, MaxEnt algorithm, in combination with geographic information system contributed to revealing the effects of environmental variables on the probability of H. lepturus presence in the west of Zagros Mountains. These visualized maps as a warning alarm can be helpful to policymakers for managing, controlling, and monitoring the scorpionism in high-risk areas. [ABSTRACT FROM AUTHOR]

Objective(s): Scorpion venom has toxic effects on mammals, insects and crustaceans. Toxicogenic peptides are major contributors to the scorpion venom, which make it toxic. The Hemiscorpius lepturus (H. lepturus) is one of the most common scorpion bites agent, and responsible for 95% of scorpion bite deaths cases in Iran. Materials and Methods: In this project, we fractionated the H. lepturus scorpion venom and analyzed toxic fractions of the venom. The crude venom of H. lepturus was dialyzed against distilled water and then the soluble part of the venom was isolated from the non-soluble (mucoproteins) part of the venom and loaded onto the Sephadex G-50 gel filtration column, then after determining the toxicity of the obtained fractions (fractions toxicity were detected in mice by IV injection), the resulting toxic fraction was purified with three stages of ion-exchange chromatography (anion and cationic) and RPHPLC. The purity of the fractions was verified by SDS-PAGE electrophoreses. Results: The LD50 of H. lepturus venom was 177.01 µg/mouse. The crude venom had 7 detectable bands with molecular weights of 10-100 KDa and one band less than 10 KDa. Finally, after the different stages of chromatography, two HL2153 and HL2155 peaks were obtained from the RP-HPLC, which were depicted single bands and high purity. The electrophoretic analysis showed molecular weight 4874 Da for HL2153 and 5107 Da for HL2155 toxins. Conclusion: It is concluded that H. lepturus venom contains two HL2153 and HL2155 toxins with a relatively similar molecular weight and similar electrical charge 4874 and 5107 Da, respectively. [ABSTRACT FROM AUTHOR]

Hemiscorpius lepturus envenomation induces acute kidney injury (AKI) through hemoglubinoria and mitochondrial dysfunction. Mitochondria supports ATP production to promote the regulation of fluid and electrolyte balance. Mitochondrial homeostasis in different metabolic environments can be adjusted by overexpression of PGC-1α. High reactive oxygen species (ROS) production after H. lepturus envenomation and heme oxygenase-1 (HO-1) overexpression causes ATP depletion as well as mitochondrial homeostasis disruption, which lead to progression in renal diseases. The present study aims to evaluate the role of venom induced-AKI in modulating mitochondrial function in cell death and metabolic signaling associated with PPAR-α, PGC-1α, and Nrf-2 as the main transcription factors involved in metabolism. Based on the data, two significant events occurred after envenomation: reduction of gl glutathione level and overexpression of the cytoprotective enzyme HO-1. Apaoptosis induction is associated with a significant decrease in the transcription of PPAR-α, PGC-1α and Nrf-2 after administrating lethal dose of venom (10 mg/kg). Furthermore, at the lower doses of venom (1 and 5 mg/kg), with a significant recovery accompanied with PGC-1α upregulation occurs after AKI. As the findings indicate, PGC-1α has a key role in restoring the mitochondrial function at the recovery phase of mouse model of AKI, which highlights the PGC-1α as a therapeutic target for venom induced-AKI prevention and treatment. • Mitochondrial homeostasis following AKI condition is related to PGC-1α overexpression in response to glutathion depletion. • PGC-1α as a therapeutic target for H. lepturus induced-AKI prevention is involved in restoring of mitochondrial mass. • In sever envenomation condition, transcript level of Nrf2 is significantly suppressed preposition to HO-1 upregulation. • Nrf-2 is not the main transcription factors in HO-1 signaling. [ABSTRACT FROM AUTHOR]

Objective(s): In this study, the neutralizing abilities of the equine and the recently introduced camelid antivenoms on the hemodynamic parameters (inotropism, chronotropism, and arrhythmogenicity) were assessed following envenomation by Hemiscorpius lepturus venom in rats. Materials and Methods: At first, the electrophoretic profiles of both products were obtained by using the SDS-PAGE method (12.5%) and stained with Coomassie blue and silver nitrate. Secondly, different doses of the camelid antivenom (10, 50, and 100 μl) were given intravenously in 10 min before venom injection (400 μg/rat). The neutralizing potencies of camelid and equine antivenoms were measured by preincubation (100 μl) with H. lepturus venom for 30 min at room temperature. Finally, equal amounts of the antivenoms were injected intravenously to observe the hemodynamic changes. Results: Based on the electrophoretic profile, it was evident that undesired proteins significantly decreased in equine antivenom, owing to impurities. Pretreatment with the camelid antivenom (100 μl), neutralized the elevation of the mean arterial pressure evoked with scorpion venom injection (88.15±4.56 versus 10.2±1.23 percent at the 8th min). The Incubation of the venom and the camelid antivenom counteracted the hemodynamic changes, but the equine product had no effect. The intravascular injection of the equine antivenom transiently increased the mean arterial pressure as compared to the control (108.67±8.63 mmHg versus 52.67±1.93 mmHg at the 10th min). Conclusion: The most obvious finding emerging from this study was that the camelid antivenom neutralized the hemodynamic changes in rats significantly, but in comparison, the equine antivenom had just a minor ability. [ABSTRACT FROM AUTHOR]

Introduction: Hemiscorpius lepturus envenomation is a serious health problem in the southern provinces of Iran. The antiserum produced in Iran to counteract this scorpion venom is not entirely effective due to the risk of anaphylactic shock and other adverse effects., Methods: Therefore, more efficient alternatives to treat patients deserve attention, and plants are extensively good candidates to be studied. This study aimed to assess the potential of the aqueous fraction of Malva sylvestris in inhibiting the toxic effects of H. lepturus venom. Injection of sub-lethal dose of H. lepturus venom leads to severe tissue damage in vital organs including the kidney, liver, heart and intestine, after 24 hours., Results: By injecting 80 mg of the aqueous extract of M. sylvestris into the peritoneum helped treat the damaged tissues caused by H. lepturus venom in mice., Conclusion: Thus, Malva sylvestris could serve as an alternative treatment for scorpion sting envenomation and may be used as a drug to neutralize relevant toxic effects in patients stung by H. lepturus ., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Hemiscorpius lepturus scorpion stings do not induce considerable pain based on epidemiological surveys conducted in the southwest part of Iran. Accordingly, this study was aimed to identify the analgesic molecule in H. lepturus venom by analyzing a cDNA library of the scorpion venom gland looking for sequences having homology with known animal venom analgesic peptides. The analgesic molecule is a cysteine rich peptide of 55 amino acids. the synthetic peptide was deprotected and refolded. RP-HPLC, Ellman’s, and DLS assays confirmed the refolding accuracy. Circular dichroism (CD) showed helix and beta sheet contents. This peptide, called leptucin, demonstrated 95% analgesic activity at the dose of 0.48 mg/kg in hot plate assay. Leptucin at the doses of 0.32, 0.48, and 0.64 mg/kg showed 100% activity in thermal tail flick test. No hemolysis or cytotoxicity was observed at 8 and 16 μg. Histopathology evaluations indicated no hepatotoxicity, nephrotoxicity, and cardiotoxicity. We thus report that leptucin is the analgesic agent of H. lepturus venom. Regarding the high in vivo efficacy of leptucin and the fact it shows no observable toxicity, it could be suggested as a drug lead in a preclinical study of acute pain as well as the study of its mechanism of action.

Objective: Scorpion venom, considered as a treasure trove of various bioactive molecules, is a new approach to induce cancer cell death via apoptosis pathways. In the present study, we evaluated for first time the anti-proliferative efficacy of Hemiscorpius lepturus scorpion venom and its pathway on a colon carcinoma cell. Materials and methods: The CT26 and VERO cell lines were treated with various concentrations of the venom. The IC50 values were estimated by MTT assay test, and the apoptosis was evaluated by flow cytometry. Moreover, RT-PCR analysis was used to investigate the levels of Bax, Bcl2, Trp53, and Casp3 mRNA expression. The mice xenograft model was established to evaluate the therapy efficiency of venom. Some valuable exponential growth parameters were evaluated in treated mice. Result: The scorpion venom inhibited the growth of CT26 cells with an IC50 value about 120 μg/ml. However, VERO cells increased to 896 μg/ml under the same condition. A remarkable apoptotic cells in CT26 cells were revealed by flow cytometry assay. A significant over-expression was observed in Bax, Casp3, and Trp53 and downregulated in Bcl2 mRNA level in tumor tissue after treatment with scorpion venom (p < 0.05). All changes of valuable exponential growth parameters showed a shrinking tumor size. Conclusion: Our findings indicated that Hemiscorpius lepturus venom has a special anti-proliferative effect on CT26 cells via Trp53/Bcl2/Casp3 pathway. Considering its powerful cytotoxic vigor against a colon cancer cell (CT26) and low toxicity to non-tumorigenic cell (VERO), we propose that this venom probably has a specific effect on other colon cancer cells and may turn out to be a novel therapeutic strategy in treating colon cancer. [ABSTRACT FROM AUTHOR]

Hemiscorpius lepturus (H. lepturus) is the most venomous scorpion in Iran. Its venom can damage vital body organs and cause fatal consequences. This study aimed to evaluate the effects of this scorpion venom on the mortality rates of mice. This experimental study was conducted on two groups of mice (treatment and control) weighing between 27 and 30 grams of the same age and race. In the treatment group, 1 micro liter of diluted crude venom of H. lepturus scorpion in 0.1 ml of normal saline was injected with suitable syringe. The control group received 0.1 ml of sterile normal saline. Data obtained from the groups were recorded and analyzed with Chi square and Fisher's exact tests. The results showed that H.lepturus venom could cause death by as much as 82 percent over 6 to 240 hours. The initial major symptoms of poisoning in mice after injection of venom included humping, lack of nutrition, immobilization, and piloerection. In final stages of life, contractions, severe shaking of legs and occasional moanings were observed, which continued until an hour before death. Not all injections of H.lepturus venom are fatal, in cases where mice had local wounds due to venom injection, they survived. It can be concluded that the injection-induced ulcers in mice are appropriate immune responses against this venom. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hemiscorpius lepturus is a medically important scorpion found along the Iranian borders, especially near to Khuzestan Province in the south-west of Iran. This is the only non-buthid scorpion which is potentially lethal in southern Iran and is responsible for severe dermonecrotic scorpionism. OBJECTIVES: In this study, DNA fragment of the mitochondrial cytochrome c oxidase subunit I (COXI) gene of H. Lepturus for the molecular phylogenetic analysis was amplified. METHODS: We amplified a 624 bp gene fragment of cytochrome C oxidase subunit I (COXI) from H. lepturus collected from Khuzestan, Ahvaz by PCR. After sequencing of the PCR products, the phylogenetic analysis was performed using the neighbor-joining method with 1000 replicates of bootstrapping using the MEGA7 software. RESULTS: The results of phylogenetic analysis revealed four distinct clusters (A1, A2, B and C) belonging to the family of Hemiscorpionidae that were grouped together with bootstrap score between 77-96%. The gene fragment of Hl-Kh formed a cluster relative to the only scorpion of H. Lepturus (Hl) from Izeh, Iran with a good bootstrap score of 96. These two samples isolated from the Khuzestan province of Iran are closely related, as they clustered together as Cluster B. The genetic distances of Hl- Kh among the cluster A1, A2 and C ranged from 16 to19% and the lowest interspecific distance was in cluster B between Hl-Kh and Hl (6%). CONCLUSIONS: Hl-Kh isolated from the Khuzestan province of Iran are closely related to Hl, as they showed the greatest interspecific variation observed in Hemisccorpius genus in this study. Although the sample size in Cluster B is not large enough to draw a final conclusion, the percentage of sequence divergence was high enough for interspecific comparisons to provide separation of species. [ABSTRACT FROM AUTHOR]

Objective(s): Hemiscorpius lepturus is one of the dangerous scorpions of Iran leading to acute kidney injury (AKI) especially in infants. The purpose of this animal study was to compare the serological, pathological and scintigraphic data to quickly predict the occurrence of this disorder. Materials and Methods: In two groups of animals, each contained five rats, H. lepturus venom (1200 µg/Kg) were injected intravenously via the tail vein. At three hours and one week later, 99m Tc-DMSA (3 mCi) was intravenously injected and renal scintigraphy was performed after an hour. Moreover, plasma levels of creatinine, sodium, potassium, and blood urea nitrogen (BUN) were measured. At the end of the study, renal tissues were excised and prepared to perform pathological evaluation after Hematoxylin and Eosin staining. Results: All serological indices were remained unchanged compared to control. A large number of glomerular fibrin thrombi with entrapped red blood cells and simplified tubular epithelium in dilated and ectatic tubules were observed in high power field (×100) four hours after envenomation, which reduced significantly one week later. In our scintigraphic study, there was a statistically significant difference (P<0.05) in kidney count rate per pixels (CRPP) in both acute and chronic phases compared to the sham group that received normal saline (0.84±0.05 and 1.36±0.07 versus 1.7±0.05). Conclusion: The results of this preliminary animal study suggest renal scintigraphy is a non-invasive method to predict the occurrence of the AKI in H. lepturus envenomation. It leads the way for more investigation to counteract the renal failure induced by this venom. [ABSTRACT FROM AUTHOR]

Background: Hemiscorpius lepturus envenomation is one of the most important medical issues in tropical regions of Iran, especially Khuzestan Province. Due to lack of reliable data about scorpion sting in Khuzestan Province, this investigation was performed to study the clinical presentation, prognosis factors, complications and mortality rates of Hemiscorpius lepturus sting. Methods: this study was a cross-sectional study performed at Sina Hospital, Karoon, Iran during 2011-2013. Required data such as demographic data, complications and outcomes were collected from medical records of all admitted victims of envenomation in this period and then were registered in a propriate checklist. Data were analyzed using SPSS version 16. Results: a total of 311 victims were studied. The highest frequency of sting was in the age range of 15-24 years. Most areas of the sting were the lower extremity. Forty-two patients delayed more than 24 hours to refer to the emergency room. The most common initial symptom in victims was pain in the sting location. Complications such as hematuria, hemoglobinuria, and coagulation disorders were most morbidity occurred in patients. 6 cases died. Conclusion: delay in referring to the hospital, the existence of hemoglobinuria, coagulation disorders and kidney failure were associated with poor prognosis in patients. It seems that patients who refer with delays and with symptoms such as hematuria, need for more medical health care. [ABSTRACT FROM AUTHOR]

Background: We investigated the hemodynamic changes (Inotropic, chronotropic and arrhythmogenic) in intrave­nously envenomed anesthetized rats with Hemiscorpius lepturus venom. The neutralizing potencies of different drugs and commercial antivenom were assessed simultaneously. Methods: Different doses of the crude venom (100, 200 and 400μg/rat) were injected during five minutes via the femoral vein and cardiovascular changes were recorded in rats in Razi Institute Corporation, Karaj, Iran in 2017. The drugs (Atropine, lidocaine, propranolol and prazosin) were injected before the venom for determination of the coun­teracting effects. Different volumes (100, 500 and 1000µl) of the antivenom were pre envenomed to neutralize cardi­ovascular changes. Results: Temporary hypertension and bradycardia with no arrhythmogenic effects were depicted within twenty minutes. There was a difference in arterial pressure between the venom (400μg/rat) and the vehicle at 8 minutes (114.68±5.1mmHg versus 70.2±4.3mmHg). Elevation of the mean arterial pressure was inhibited by propranolol (2 mg/kg) and neutralized by prazosin (1mg/kg) while lidocaine (4mg/kg) and atropine (1mg/kg) had no effects. Pre­medication with Iranian commercial antivenom (1000μl) produced surprisingly temporary hypertension compared to the vehicle (140.84±4.5 versus 84.3±3.2). It had no neutralizing properties on blood pressure variation before the venom injection. Volume-expanded hypertension phenomenon was ruled out in a parallel study. Conclusion: This venom has vasoconstrictive effects in rats probably due to the presence of norepinephrine like ma­terials in its content or liberated from adrenal gland inhibited by prazosin premedication. The neutralizing effects of antivenom on venom-induced hypertension are questionable.

In this study, the scorpion venom of H. lepturus was fractionized by reversed phase high-pressure liquid chromatography (RP-HPLC). The sequences of two peptide fractions were identified by tandem mass spectrometry and named as HL-10 (AFPYYGHHLG) and HL-7 (YLYELAR), respectively. Antioxidant activity and cellular effect of synthetic peptides on A549 cell line were investigated. Results showed that the two peptides had high activities in radical scavenging and inhibition of lipid peroxidation in a concentration-dependent manner. The HL-10 and HL-7 peptides demonstrated cytotoxicity on A549 without any hemolytic effect. By increasing of peptide concentrations induced significantly (P ≤ 0.01) activities of catalase and glutathione peroxidase. Our results showed that HL-7 peptide had higher antioxidant potency, whereas the HL-10 peptide revealed a great cytotoxicity on A549 cell line by MTT assay. Our results suggested that the peptides of H. lepturus, possessed free radicals scavenging likewise increased antioxidant enzyme activities in A549 cells. [ABSTRACT FROM AUTHOR]

Background: We investigated the hemodynamic changes (Inotropic, chronotropic and arrhythmogenic) in intravenously envenomed anesthetized rats with Hemiscorpius lepturus venom. The neutralizing potencies of different drugs and commercial antivenom were assessed simultaneously. Methods: Different doses of the crude venom (100, 200 and 400μg/rat) were injected during five minutes via the femoral vein and cardiovascular changes were recorded in rats in Razi Institute Corporation, Karaj, Iran in 2017. The drugs (Atropine, lidocaine, propranolol and prazosin) were injected before the venom for determination of the counteracting effects. Different volumes (100, 500 and 1000µl) of the antivenom were pre envenomed to neutralize cardiovascular changes. Results: Temporary hypertension and bradycardia with no arrhythmogenic effects were depicted within twenty minutes. There was a difference in arterial pressure between the venom (400μg/rat) and the vehicle at 8 minutes (114.68±5.1mmHg versus 70.2±4.3mmHg). Elevation of the mean arterial pressure was inhibited by propranolol (2 mg/kg) and neutralized by prazosin (1mg/kg) while lidocaine (4mg/kg) and atropine (1mg/kg) had no effects. Premedication with Iranian commercial antivenom (1000μl) produced surprisingly temporary hypertension compared to the vehicle (140.84±4.5 versus 84.3±3.2). It had no neutralizing properties on blood pressure variation before the venom injection. Volume-expanded hypertension phenomenon was ruled out in a parallel study. Conclusion: This venom has vasoconstrictive effects in rats probably due to the presence of norepinephrine like materials in its content or liberated from adrenal gland inhibited by prazosin premedication. The neutralizing effects of antivenom on venom-induced hypertension are questionable. [ABSTRACT FROM AUTHOR]

Hemiscorpius lepturus belonging to Hemiscorpiidae family is the most venomous of all types of scorpion existing in south west of Iran causing hemoglobinuria and dermal lesions by envenomation. We compare the hemolytic pattern upon time in different domestic animals upon time according to their different sphingomyelin contents. In addition other in vitro hematologic parameters, platelet lysis, coagulation changes and finally preservative factors (temperature, pH, protases) are discussed. The hemolytic activity was inhibited significantly by heating at 100 °C for 60 minutes (26%) and reached 38% via incubation with papain (10U/ml) while retained over a pH range of 4-11. Horses and sheep have the lower (61%) and upper (100%) rate of hemolysis. Calcium and magnesium ions could increase rate of hemolysis and EDTA solution had significantly decresing effect. The venom significantly changed in vitro coagulation factors (PT and APTT) from base line levels and had no effect on platelet lysis. It seems that our venom belongs to metalloproteinases due to potentiation effects of bivalent cations (calcium and magnesium) and ghost cell formation in our study indicatiing hemoglobin efflux.

Background and aim: Continuous appearance of antibiotic resistance bacteria can cause significant complications and mortality. In this regard, tracing for new antimicrobial agents is of great significance. During the past decades, many studies have documented isolation of Antimicrobial Peptides (AMPs) from different sources. These peptides which are responsible for hinnate immunity were purified from human, vertebrates, invertebrates, insects, venomous animals, and plants. This study aimed to extract antibacterial peptides from Iranian scorpion Hemiscorpius lepturus. Material and Methods: Venom was obtained by electric stimulation and its quality examined by protein electrophoresis. The venom peptides were purified using Gel filtration chromatography and subsequently with Reverse Phase- High Performance Liquid Chromatography (RP-HPLC). The peptide fractions were evaluated for antibacterial activity against Pseudomonas aeruginosa ATCC 27853. Inhibitory activity was determined by disk diffusion method. Result: Seven protein fractions were obtained from Sephadex-G50, among them only two fractions had peptides with less than 10 kDa. One FPLC purified fraction had anti-pseudomonas activity by disk diffusion method and was selected for further purification. Four major fractions were obtained by RP-HPLC ranging from 4 to 7 kDa. Subsequent tests showed that two fractions had bactericidal activity against pseudomonas. Conclusion: Natural compounds like antimicrobial peptides derived from venomous animals could be an effective solution to deal with multidrug-resistant pathogens. The results demonstrated that two peptide fractions of the scorpion venom had bactericidal activity against pseudomonas. This is the first report for isolation of antibacterial peptides from the Iranian scorpion Hemiscorpius lepturus.

Scorpionism is a known significant problem of medical and social importance in many tropical and subtropical regions including the Middle East. In Iran, highest prevalence of scorpion sting about 60% of all the stings has been reported from Khuzestan province. Among the 21,000 cases of reported scorpion stung patients, 12% were caused by H. lepturus, but contributed to 95% of all moralities in scorpion stung patients. The sting of H. lepturus does not produce an immediate pain as does the sting of other scorpions, rather cause delayed swelling that may diffuse and is often accompanied by late necrosis at the sting site suggestive of less significant role of the nervous system stimulation. Since the venom from H. lepturus is cytotoxic in nature and the renal response and blood toxicity are normally simultaneously manifested, it is suggested that the toxin binds to kidney tissue and potentially induce acute renal failure in stung patients. Pharmacokinetic analysis revealed that Intramuscular) i.m) injection of antivenoms is ineffective in neutralizing the action of venoms. Although some reports mention the slow distribution rate of H. lepturus venom following sting, but since the cytotoxic effect of venom from this scorpion is irreversible by antivenom once it occurs, it is recommended to use antivenom through intravascular (i.v) route. Antivenoms of F(ab)2 fraction are the best choice of treatment for their fast extravasation, their ample distribution into the extracellular space, and their prolonged retention time.

Introduction:The highest mortality from scorpion stings in Iran is due to the stings of a particular type of scorpion known asHemiscorpius lepturus(H. lepturus, Gadim in local language). The present study aimed at investigating the use of plasmapheresis to treat severe cases ofH. lepturusstings. Method:This pilot study was a randomized clinical trial conducted from June 2015 to June 2016 in Razi hospital of Ahvaz, Iran. Twenty-nine patients who had been stung byH. lepturusand admitted to ICU because of disseminated intravascular coagulation (DIC) were randomly assigned into control (15 patients, supportive treatments) and plasmapheresis (14 patients, supportive treatments + plasmapheresis) groups, and the patient outcomes were compared between the two groups. Findings:Eighteen patients were female (62%), and the mean of patient age was 24 ± 7. Most of the sting cases had occurred in the torso (15 patients, 52%). Only 10 patients (34%) arrived in the hospital within 12 h of being stung. There was no significant difference between the two groups in terms of the demographic and sting features. In the plasmapheresis group, hemoglobin level was significantly lower, while the PT and INR were measurably higher. In total, the plasmapheresis group experienced 29 sessions of treatment (an average of two sessions for each patient). Overall, 19 patients (66%) expired, whereas 10 patients (34%) experienced recovery with or without complications. The rate of recovery was significantly higher in the plasmapheresis group compared with controls, with eight patients (57%) in the plasmapheresis group surviving compared with two (14%) in the control group (p=.045). The duration of hospitalization was higher in the plasmaphersis group (p < .001). A comparison of the dead and recovered patients’ features indicated that the dead patients arrived in the hospital significantly later than the recovered ones, and they also had lower platelet counts. Conclusions:The findings of this small-scale pilot study show that using plasmapheresis in treating DIC in patients stung byH. lepturuscan prevent death and encourage recovery. However, prior to using plasmapheresis as a routine treatment for severe cases of people stung by this scorpion or other similar ones, further controlled studies with a larger sample size are needed. [ABSTRACT FROM AUTHOR]

Objective Scorpion ( Hemiscorpius lepturus ) stings are a public health concern in Iran, particularly in south and southwestern regions of Iran. The gold standard for the treatment of a scorpion sting is anti-venom therapy. However, immunotherapy can have serious side effects, such as anaphylactic shock (which can sometimes even lead to death). The aim of the current study was to demonstrate the protective effect of ozone against toxicity induced by Hemiscorpius lepturus ( H. lepturus ) venom in mice. Methods Eight hours after the injection of ozone to the experimental design groups, the male mice were decapitated and mitochondria were isolated from five different tissues (liver, kidney, heart, brain, and spinal cord) using differential ultracentrifugation. Then, assessment of mitochondrial parameters including mitochondrial reactive oxidative species (ROS) production, mitochondrial membrane potential (MMP), ATP level, and the release of cytochrome c from the mitochondria was performed. Results Our results showed that H. lepturus venom-induced oxidative stress is related to ROS production and MMP collapse, which is correlated with cytochrome c release and ATP depletion, indicating the predisposition to the cell death signaling. Conclusion In general, ozone therapy in moderate dose can be considered as clinically effective for the treatment of H. lepturus sting as a protective and antioxidant agent. [ABSTRACT FROM AUTHOR]

Hemoscorpius lepturus is the most medically important scorpion in Iran. The clinical signs of H. lepturus envenomation are remarkably similar to those reported for brown spiders, including dermonecrosis, hematuria, renal failure and even death. The lethality and toxicity of brown spiders' venom have been attributed to its phospholipase D activity. This study aims to identify a phospholipase D with possible lethality and dermonecrotic activity in H. lepturus venom. In this study, a cDNA library of the venom glands was generated by Illumina RNA sequencing. Phospholipase D (PLD) from H. lepturus was characterized according to its significant similarity with PLDs from brown spiders. The main chain designated as Hl-RecPLD1 (the first recombinant isoform of H. lepturus PLD) was cloned, expressed and purified. Sphingomyelinase, dermonecrotic and lethal activities were examined. Hl-PLD1 showed remarkable sequence similarity and structural homology with PLDs of brown spiders. The conformation of Hl-PLD1 was predicted as a "TIM beta/alpha-barrel". The lethal dose 50 (LD50) and dermonecrotic activities of Hl-RecPLD1 were determined as 3.1 μg/mouse and 0.7 cm2 at 1 μg respectively. It is the first report indicating that a similar molecular evolutionary mechanism has occurred in both American brown spiders and this Iranian scorpion. In conclusion, Hl-RecPLD1 is a highly active phospholipase D, which would be considered as the lethal dermonecrotic toxin in H. lepturus venom. [ABSTRACT FROM AUTHOR]

Scorpion sting is one of the most important problems in public health practice in many countries. Khuzestan yellow scorpion, scientifically known asHemiscorpius lepturus, belongs to the familyHemiscorpidae, and is one of the most common and dangerous scorpions in Iran.Hemiscorpius lepturusscorpion has potentially cytotoxic venom. The first treatment for scorpion envenoming is horse antisera. Due to their unique characteristics, camels have been considered as an important source for antiserum and monoclonal antibody (Nanobody) production. In the previous study, we reported a specific nanobody against the hemolytic fraction (heminecrolysin) ofHemiscorpius lepturusvenom. In the present study, a recombinant diabody was constructed and produced by fusion of two nanobodies. Results fromin vitroandin vivoassays showed that the diabody has a promising ability to neutralize venom activity. [ABSTRACT FROM AUTHOR]

Hemiscorpius lepturus scorpion is one of the most venomous members of the Hemiscorpiidae family. H. lepturus is distributed in Iran, Iraq and Yemen. The prevalence and severity of scorpionism is high and health services are not able to control it. Scorpionism in Iran especially in the southern regions (Khuzestan, Sistan and Baluchestan, Hormozgan, Ilam) is one of the main health challenges. Due to the medical and health importance of scorpionism, the focus of various studies has been on the identification of H. lepturus venom components. Nevertheless, until now, only a few percent of H. lepturus venom components have been identified and there is no complete information about the venom components of H. lepturus . The current study reports transcriptome analysis of the venom gland of H. lepturus scorpion. Illumina Next Generation Sequencing results identified venom components of H. lepturus . When compared with other scorpion's venom, the venom of H. lepturus consists of mixtures of peptides, proteins and enzymes such as; phospholipases, metalloproteases, hyaluronidases, potassium channel toxins, calcium channel toxins, antimicrobial peptides (AMPs), venom proteins, venom toxins, allergens, La1-like peptides, proteases and scorpine-like peptides. Comparison of identified components of H. lepturus venom was carried out with venom components of reported scorpions and various identities and similarities between them were observed. With transcriptome analysis of H. lepturus venom unique sequences, coding venom components were investigated. Moreover, our study confirmed transcript expression of previously reported peptides; Hemitoxin, Hemicalcin and Hemilipin. The gene sequences of venom components were investigated employing transcriptome analysis of venom gland of H. lepturus. In summary, new bioactive molecules identified in this study, provide basis for venomics studies of scorpions of Hemiscorpiidae family and promises development of novel biotherapeutics. [ABSTRACT FROM AUTHOR]

The venom of the Hemiscorpius lepturus scorpion contains mixtures of bioactive compounds that disturb biochemical and physiological functions of the victims. Hemiscorpius lepturus envenomation is recognized as a serious health concern in tropical regions. So far, there is no preventive procedure, and the main focus is on treatment of victims with an antiserum purified from hyper-immunized horses. Although antisera can neutralize the venom, they, in some cases, lead to anaphylactic shock and even death. Selection of peptides mimicking antigenic and immunogenic epitopes of toxins from random peptide libraries is a novel approach for the development of recombinant toxins and poly-epitopic vaccine. To achieve this aim, a phage display peptide library and three rounds of biopanning were performed on immobilized antibodies (IgGs) purified from the sera of hyper-immunized horses. The results show that the highest binding of the phage to immobilized horse antibodies occurred in the third round of biopanning. Over 125 individual clones carrying mimotopes of Hemiscorpius lepturus toxins were selected and subjected for sequencing. The sequencing results identified unique peptides mimicking the antigenic and immunogenic epitopes of Hemiscorpius lepturus toxins. The results of this study provide a basis for further studies and the development of a putative epitopic vaccine and a recombinant toxin. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the effect of Hemiscorpius lepturus venom on leukocytes and the leukocyte subgroups in peripheral blood of rat. Methods: In this experimental study, sixty N-Mari rats were divided into three groups of 20 rats. Then the rats in each group were divided into four subgroups based on the blood sampling time that was 2, 6, 24 and 48 hours after the venom injection, respectively. The control group did not receive anything, however, the first and the second ex­perimental groups received 0.1 and 0.01mg/kg of venom, subcutaneously. In accordance with a designated four sam­pling times, the blood sampling was carried out in three groups. After RBC lysis, the leukocytes and leukocyte sub­populations were determined and counted using appropriate hematological standard methods. Results: The leukocyte and the neutrophil count at two (P

Background: Scorpion sting is a public health problem in Khuzestan, South-West Iran. The aims of the current study were to monitor the hospitalized children, due to scorpion sting, and releasing more clinical and epidemiologic data related to scorpionism in this Province.Methods: In this retrospective study, the data of scorpion sting victims, among the hospitalized children in Abuzar Children Hospital of Ahvaz Jundi Shapur University of Medical Sciences, was analyzed from the points of epidemi­ological and clinical aspects in 2006.Results: The scorpion species of 18 files out of 57 were recognized accurately, using Farzanpay key of Iranian scor­pions, as Androctonus crassicauda (Scorpionida: Buthidae) and Hemiscorpious lepturus (Scorpionida: Hemiscorpii­dae).Conclusion: The most scorpionism emergencies among the children in the Khuzestan should be paid to those spe­cies. However, H. lepturus sting emergencies are in the top of attention among the children.

Hemiscorpius lepturus is the most dangerous scorpion species, endemic in Khuzestan province and other southwestern areas of Iran, causing morbidity and mortality in children and adults. The efficacy of the antivenom for reversal of manifestation caused by venom of this scorpion is a controversial issue. In the present work, H.lepturus venom (1500 μg/kg) was subcutaneously injected into two separate groups of rabbits. Groups 1 and 2 of rabbits received antivenom through i.v route, at 1 and 3 hours after venom injection respectively. Electrocardiograms of all the rabbits recorded during the experiment. In group 1 rabbits blood collection carriedout, before and 1 hr after venom injection as well as 3 and 24 hours after antivenom injection.In group2 animals, blood collection was carried out before and 3 hours after venom injection as well as 3 and 24 hours after antivenom injection. Separated serum used for determination of alanine aminotransferase (ALT), aspartateaminotransferase (AST), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), creatine kinase isoenzyme, MB (CK-MB), urea ، creatinine and Blood Urea Nitrogen (BUN). In group 1 rabbits highlysignificant (P