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1.
J Ophthalmic Inflamm Infect ; 14(1): 30, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918257

RESUMO

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.

2.
Curr Pharm Des ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38757320

RESUMO

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.

3.
Protein Sci ; 33(3): e4901, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38358130

RESUMO

Broadly-neutralizing monoclonal antibodies are becoming increasingly important tools for treating infectious diseases and animal envenomings. However, designing and developing broadly-neutralizing antibodies can be cumbersome using traditional low-throughput iterative protein engineering methods. Here, we present a new high-throughput approach for the standardized discovery of broadly-neutralizing monoclonal antibodies relying on phage display technology and consensus antigens representing average sequences of related proteins. We showcase the utility of this approach by applying it to toxic sphingomyelinases from the venoms of species from very distant orders of the animal kingdom, the recluse spider and Gadim scorpion. First, we designed a consensus sphingomyelinase and performed three rounds of phage display selection, followed by DELFIA-based screening and ranking, and benchmarked this to a similar campaign involving cross-panning against recombinant versions of the native toxins. Second, we identified two scFvs that not only bind the consensus toxins, but which can also neutralize sphingomyelinase activity of native whole venom in vitro. Finally, we conclude that the phage display campaign involving the use of the consensus toxin was more successful in yielding cross-neutralizing scFvs than the phage display campaign involving cross-panning.


Assuntos
Esfingomielina Fosfodiesterase , Venenos de Aranha , Animais , Aranha Marrom Reclusa , Escorpiões , Anticorpos Amplamente Neutralizantes , Consenso , Anticorpos Monoclonais
4.
Arch Razi Inst ; 78(5): 1542-1554, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38590678

RESUMO

Hemiscorpius species are distributed in Africa and Asia. Seven species of this genus have been identified in Iran of which six species have been reported from Hormozgan province. Members of this genus are the most dangerous scorpions in Iran. corpions were collected by moving stones during the day and searching at night using portable UV lights from 2011 to 2022 from different areas in Hormozgan province. Three species were identified from Hormozgan province including Hemiscorpius acanthocercus, H.enischnocela and H. shahii which are endemic to Iran. These species have limited distribution and were reported only from the south of Iran. The number of trichobothria are 3, 10-12 and 15-17 in H. acanthocercus, H. enischnochela and H. shahii, respectively. The measured values showed that H. Shahii is larger than H. enischnochela and H. acanthocercus. Specimens of H. acanthocercus are brown to dark brown samples with dark metasomal segment V. There have been reports of death from biting this species. Members of H. enischnochela are light brown to yellow samples. Members of H. Shahii are large brown samples. All three species have sexual dimorphism. Although these three species can be distinguished based on their morphological characters, the molecular investigation is needed to confirm the validity of all species of this genus. Identifying species and determining their distribution range is very useful in facilitating education and treatment management.


Assuntos
Animais Peçonhentos , Escorpiões , Animais , Irã (Geográfico)
5.
Iran J Parasitol ; 17(1): 79-89, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046559

RESUMO

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 KDa 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.

6.
J Arthropod Borne Dis ; 16(1): 1-12, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36636239

RESUMO

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.

7.
Molecules ; 26(9)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33925223

RESUMO

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.


Assuntos
Analgésicos/farmacologia , Peptídeos/farmacologia , Escorpiões/química , Sequência de Aminoácidos , Analgésicos/química , Animais , Sequência de Bases , Cromatografia Líquida de Alta Pressão , Biologia Computacional/métodos , Hemólise/efeitos dos fármacos , Irã (Geográfico) , Dose Máxima Tolerável , Fases de Leitura Aberta , Peptídeos/química , Peptídeos/genética , Conformação Proteica , Picadas de Escorpião , Análise Espectral
9.
Toxins (Basel) ; 12(10)2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33019554

RESUMO

The Hemiscorpius lepturus scorpion and brown spider Loxosceles intermedia represent a public health problem in Asia and America, respectively. Although distinct, these organisms contain similar toxins responsible for the principal clinical signs of envenomation. To better understand the properties of these toxins, we designed a study to compare recombinant Heminecrolysin (rHNC) and rLiD1, the major phospholipase D toxins of scorpion and spider venom, respectively. Using a competitive ELISA and a hemolytic inhibition test, we come to spot a cross reaction between scorpion and spider venoms along with an epitopic similarity between rHNC and rLiD1 associated with neutralizing antibodies. Results show that the ability of the rHNC to hydrolyze lysophosphatidylcholine (LPC) is equivalent to that of rLiD1 to hydrolyze sphingomyelin and vice-versa. rHNC exclusively catalyze transphosphatidylation of LPC producing cyclic phosphatidic acid (cPA). The in-silico analysis of hydrogen bonds between LPC and toxins provides a possible explanation for the higher transphosphatidylase activity of rHNC. Interestingly, for the first time, we reveal that lysophosphatidic acid (LPA) can be a substrate for both enzymes using cellular and enzymatic assays. The finding of the usage of LPA as a substrate as well as the formation of cPA as an end product could shed more light on the molecular basis of Hemiscorpius lepturus envenomation as well as on loxoscelism.


Assuntos
Antivenenos/farmacologia , Aranha Marrom Reclusa , Fosfolipase D/toxicidade , Diester Fosfórico Hidrolases/toxicidade , Venenos de Escorpião/toxicidade , Escorpiões , Pele/efeitos dos fármacos , Venenos de Aranha/toxicidade , Animais , Antivenenos/imunologia , Aranha Marrom Reclusa/enzimologia , Aranha Marrom Reclusa/imunologia , Reações Cruzadas , Epitopos , Hemólise/efeitos dos fármacos , Mordeduras e Picadas de Insetos/enzimologia , Lisofosfatidilcolinas/metabolismo , Necrose , Fosfolipase D/imunologia , Fosfolipase D/metabolismo , Diester Fosfórico Hidrolases/imunologia , Venenos de Escorpião/enzimologia , Venenos de Escorpião/imunologia , Escorpiões/enzimologia , Escorpiões/imunologia , Pele/enzimologia , Pele/patologia , Esfingomielinas/metabolismo , Venenos de Aranha/enzimologia , Venenos de Aranha/imunologia , Especificidade por Substrato
10.
Iran J Basic Med Sci ; 23(2): 195-201, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32405362

RESUMO

OBJECTIVES: 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.

11.
Toxicon ; 183: 36-43, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32445840

RESUMO

Treatment of scorpion envenomation is a challenging issue since serotherapy is implemented by administration of polyvalent equine antisera. In our previous study we discovered that recombinant phospholipase D1 (Hl-RecPLD1) is responsible for the lethality of Hemiscorpius lepturus (H. lepturus) venom in mice. Accordingly, this study was aimed to investigate the protectivity of purified anti-Hl-RecPLD1 IgG against the lethality or major complications of H. lepturus venom. The neutralization efficiency of purified anti-Hl-RecPLD1 IgGs against sphingomyelinase activities of the crude venom and Hl-RecPLD1 was also assessed. Anti-Hl-RecPLD1 IgGs at optimum amount of 3.7 mg completely neutralized one Lethal Dose 100 (LD100) of crude venom in mice. The anti-Hl-RecPLD1 IgGs remarkably reduced the necrosis area from 6.5 to 1 cm2 in rabbit derma, induced by the crude venom. The anti-Hl-RecPLD1 IgGs remarkably reduced the sphingomyelinase and hemolytic activities of crude venom as well. In conclusion, a novel rabbit monovalent IgG against Hl-RecPLD1 was able to completely protect the mice against the lethality of H. lepturus crude venom and reduced its toxicity as well. Such monovalent anti-Hl-RecPLD1 IgGs may have potential applications in serotherapy of H. lepturus envenomation.


Assuntos
Anticorpos Anti-Idiotípicos , Soros Imunes , Fosfolipase D , Venenos de Escorpião/toxicidade , Escorpiões , Animais , Antivenenos , Cavalos , Camundongos , Coelhos , Esfingomielina Fosfodiesterase
12.
Molecules ; 25(7)2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32260428

RESUMO

Hemiscorpius lepturus (H. lepturus) which belongs to the Scorpionidae family, is the deadliest scorpion in Iran. It causes pathological manifestations like dermonecrosis, hemolysis, renal failure, necrotic ulcers, and in some cases, even death. The venom of this scorpion is well-known for its cytotoxic effects in comparison with the other venomous scorpions which show significant neurotoxic effects. Due to the painless nature of the sting of this scorpion, the clinical symptoms occur in victims 24 to 72 h post-sting. In our previous studies during the last decade, we demonstrated that the medical complications are attributable to the presence of phospholipase D (PLD) as a major toxin in the venom. With the purpose of designing and constructing a vaccine against H. lepturus for humans, animal model experiments were performed. To achieve this goal, non-toxic PLD was developed by mutation of two critical catalytic residues-His12 and His48-into alanines and the product was then denominated mut-rPLD1. The in-vivo tests showed that the mice immunized with interval doses of 10 µg of mut-rPLD1, were completely protected against 10× the LD100 of the venom. In conclusion, this mutant may be an effective vaccine candidate against scorpion envenomation by H. lepturus in future clinical studies.


Assuntos
Substituição de Aminoácidos , Fosfolipase D/administração & dosagem , Venenos de Escorpião/imunologia , Escorpiões/enzimologia , Alanina/metabolismo , Animais , Proteínas de Artrópodes/administração & dosagem , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Modelos Animais de Doenças , Histidina/metabolismo , Imunização , Masculino , Camundongos , Fosfolipase D/genética , Fosfolipase D/imunologia , Coelhos , Venenos de Escorpião/efeitos adversos , Escorpiões/genética
13.
Vet World ; 13(2): 296-303, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32255972

RESUMO

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 byarea 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.

14.
Toxicon ; 174: 57-63, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31887316

RESUMO

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.


Assuntos
Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Venenos de Escorpião/toxicidade , Escorpiões/fisiologia , Injúria Renal Aguda/induzido quimicamente , Animais , Expressão Gênica , Camundongos , Testes de Toxicidade Aguda
15.
Curr Radiopharm ; 13(2): 99-106, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31456528

RESUMO

BACKGROUND: The Hemiscorpius lepturus (H. lepturus) is a deadly scorpion species living in the southern Iran. OBJECTIVE: H. lepturus induces delayed toxicity symptoms and understanding the long term biodistribution/ biokinetic of the venom is of great interest in toxicology. METHODS: A Ga-67 labeled venom was prepared using a DOTA -conjugated venom followed by radiolabeling using 67GaCl3 at 40°C for 90 min. The purification of the radiolabeled venom was performed using size exclusion-chromatography (radiochemical purity 71%). The radiolabeled venom was stable in the final solution in the presence of human serum at 37°C for 72 hours. The tissue distribution was studied in blood, heart, liver, spleen, muscle, brain, kidney, intestine and skin tissues at the intervals of 1, 4, 24, 48 and 72 hours using tissue counting and SPECT imaging. RESULTS: The radiolabeled venom mixture obtained with an estimated molar activity of 0.52 MBq/µg. The main accumulation tissues during the first 72 hours were kidneys, blood, liver, intestines, stomach and skin, respectively. Therefore, it is likely that H. lepturus' clinical effects and renal toxicity are primary and caused by direct effects of the H. lepturus venom. CONCLUSION: The results have largely shown the direct clinical effects on the studied tissues during the 72-hour period and antivenom administration can strongly alleviate the toxicity effects as early as 72 hours in the management of the patients.


Assuntos
Radioisótopos de Gálio , Compostos Radiofarmacêuticos , Venenos de Escorpião/farmacocinética , Distribuição Tecidual , Animais , Humanos , Irã (Geográfico) , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Escorpiões , Tomografia Computadorizada de Emissão de Fóton Único/métodos
16.
J Parasit Dis ; 43(3): 472-478, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31406413

RESUMO

Pyrimethamine which is a main anti-Toxoplasma gondii drug has a serious side and toxic effects on the host. Accordingly, the development of new treatment options for toxoplasmosis with less toxic effects, low teratogenicity and parasiticidal effect against the various stage of T. gondii are dramatically crucial. Currently, natural molecules from scorpion and snake venoms are widely used as an alternative treatment against human disease, these compounds considered to be safe and to have low toxicity in comparison with synthetic drugs. Therefore, the goal of our study was to investigate the anti-Toxoplasma gondii activities of Hemiscorpius lepturus venom. We measured cytotoxicity of H. lepturus whole venom on Vero cells as well as effectiveness of this compound on viability of T. gondii applying colorimetric assay, according to mitochondrial oxidation of the MTT reagent (Methylthiazol tetrazolium 98%). The results of this study indicated that the H. lepturus whole venom has an anti-Toxoplasma effects with less toxic effect on Vero cells. Also, the T. gondii tachyzoites were treated with H. lepturus venom reached better results in comparison with Pyrimethamine-treated group. This research will serve as a base for future studies on toxoplasmosis and suggest a role for scorpion venom in promoting natural drugs.

17.
Toxicon ; 163: 23-31, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30890325

RESUMO

The main important clinical signs in acute kidney injury (AKI) after sever Hemiscorpius lepturus envenomation in patients is associated with proteinuria, hemolysis and hemoglobinuria. Unfortunately, our limited knowledge of molecular cell death mechanism in H. lepturus induced AKI restricts the development of desirable therapeutics. So, in the present study, the potential role of necroptosis and ferroptosis in H. lepturus induced AKI were investigated in male albino mice. The animals were administrated by SC injection of venom (1, 2.5, 5 and 10 mg/kg) based on LD50 determination. After 1 and 7 days, urinalysis, stereological assessments and gene expression of Ngal, Tnf-α, Tlr-4, Ripk3, Mlkl and Acsl4 were evaluated by real time PCR. Our data revealed that upregulation of renal Ngal expression is associated with the gene over expression of Tnf-α, Tlr-4, Ripk3 and Mlkl in venom treated kidneys. We observed that the Malondialdehyde (MDA) level was increased in dose-dependent manner similar to Acsl4 gene over expression suggesting a main role of ferroptosis in hemoglobinuria mediated AKI following envenomation. Moreover, transcriptional enhancement of Tlr-4and Tnf-α receptor can cause phosphorylation of Ripk3-Mlkl complex, collapse of membrane potential and DAMPs release which intensified the inflammation cytokines in kidney. Taken together, it supposes co-existence of two separate pathways of regulated necrosis and inflammatory environment provides a promising outlook in prevention and management of hemoglobinuria induced AKI following envenomation in clinical practice.


Assuntos
Injúria Renal Aguda/etiologia , Morte Celular/imunologia , Hemoglobinúria/induzido quimicamente , Venenos de Escorpião/toxicidade , Injúria Renal Aguda/induzido quimicamente , Animais , Expressão Gênica/efeitos dos fármacos , Hemoglobinúria/patologia , Hemoglobinúria/urina , Inflamação , Rim/patologia , Masculino , Malondialdeído/urina , Camundongos Endogâmicos BALB C , Proteinúria , Venenos de Escorpião/imunologia , Escorpiões , Transdução de Sinais
18.
Cell Biol Toxicol ; 35(4): 373-385, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30617443

RESUMO

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.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Venenos de Escorpião/uso terapêutico , Animais , Caspase 3/metabolismo , Linhagem Celular Tumoral , Chlorocebus aethiops , Neoplasias do Colo/tratamento farmacológico , Feminino , Concentração Inibidora 50 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Venenos de Escorpião/metabolismo , Escorpiões , Proteína Supressora de Tumor p53/metabolismo , Células Vero , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Proteína X Associada a bcl-2/metabolismo
19.
Iran J Basic Med Sci ; 22(12): 1440-1444, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32133062

RESUMO

OBJECTIVES: 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.

20.
J Arthropod Borne Dis ; 12(1): 31-40, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30018992

RESUMO

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.

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