Cindy Gabriela Rivera Tobar, Yisel Del Mar Morales Urmendiz, Marcela Alejandra Vallejo, Diego Felipe Manquillo, Victoria Eugenia Niño Castaño, Ana Isabel Ospina Caicedo, Leydy Lorena Mendoza Tobar, Jimmy Alexander Guerrero Vargas, Rosa Amalia Dueñas Cuellar
{"title":"Immunomodulatory effect of <i>Tityus</i> sp. in mononuclear cells extracted from the blood of rheumatoid arthritis patients.","authors":"Cindy Gabriela Rivera Tobar, Yisel Del Mar Morales Urmendiz, Marcela Alejandra Vallejo, Diego Felipe Manquillo, Victoria Eugenia Niño Castaño, Ana Isabel Ospina Caicedo, Leydy Lorena Mendoza Tobar, Jimmy Alexander Guerrero Vargas, Rosa Amalia Dueñas Cuellar","doi":"10.1590/1678-9199-JVATITD-2023-0064","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2023-0064","url":null,"abstract":"<p><strong>Background: </strong>Pathophysiological mechanisms of rheumatoid arthritis arise because of a proinflammatory environment, generated by the interaction of autoreactive lymphocytes and proinflammatory mediators. Current strategies to mitigate the progression of the disease produce adverse effects, so there is a need for new therapeutic strategies and molecular targets to treat this disease. In this context, evidence suggests that scorpion venoms could modulate the immune response and some important cellular mechanisms of pharmacological interest. To evaluate the immunomodulatory effect of the venom of <i>Tityus</i> sp. (a possible new species close to <i>Tityus metuendus</i>) peripheral blood mononuclear cells of women diagnosed with RA were compared to cells of a control group.</p><p><strong>Methods: </strong>A case-control study was conducted with a sample of 10 women with a confirmed diagnosis of RA and controls matched by sex and age. The cytotoxicity of the venom was evaluated to find sublethal concentrations of the venom, and subsequently, their immunomodulatory capacity in terms of percentage of proliferation, cell activation, and cytokines production.</p><p><strong>Results: </strong>the venom of <i>Tityus</i> sp. produced a decrease in the percentage of proliferation in the CD3<sup>+</sup>, CD3<sup>+</sup>CD4<sup>+</sup>, and CD3<sup>+</sup>CD8<sup>+</sup> cell subpopulations of RA patients and healthy controls, at concentrations of 252 and 126 µg/mL. However, the venom did not induce significant differences in the percentage of cell activation markers. The venom caused a decrease in IL-10 at a concentration of 252 µg/mL compared to untreated cells from patients and controls. The remaining cytokines did not show significant differences.</p><p><strong>Conclusion: </strong>the venom of <i>Tityus</i> sp. is a potential source of molecules with immunomodulatory ability in CD4 and CD8 T lymphocytes. This result directs venom characterization studies to identify pharmacological targets with immunomodulatory capacity in T lymphocytes to enhance research in the treatment of autoimmune disorders such as RA.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"30 ","pages":"e20230064"},"PeriodicalIF":1.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11498904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jessica Rojas-Palomino, Alejandro Gómez-Restrepo, Cristian Salinas-Restrepo, César Segura, Marco A Giraldo, Juan C Calderón
{"title":"Electrophysiological evaluation of the effect of peptide toxins on voltage-gated ion channels: a scoping review on theoretical and methodological aspects with focus on the Central and South American experience.","authors":"Jessica Rojas-Palomino, Alejandro Gómez-Restrepo, Cristian Salinas-Restrepo, César Segura, Marco A Giraldo, Juan C Calderón","doi":"10.1590/1678-9199-JVATITD-2023-0048","DOIUrl":"10.1590/1678-9199-JVATITD-2023-0048","url":null,"abstract":"<p><p>The effect of peptide toxins on voltage-gated ion channels can be reliably assessed using electrophysiological assays, such as the patch-clamp technique. However, much of the toxinological research done in Central and South America aims at purifying and characterizing biochemical properties of the toxins of vegetal or animal origin, lacking electrophysiological approaches. This may happen due to technical and infrastructure limitations or because researchers are unfamiliar with the techniques and cellular models that can be used to gain information about the effect of a molecule on ion channels. Given the potential interest of many research groups in the highly biodiverse region of Central and South America, we reviewed the most relevant conceptual and methodological developments required to implement the evaluation of the effect of peptide toxins on mammalian voltage-gated ion channels using patch-clamp. For that, we searched MEDLINE/PubMed and SciELO databases with different combinations of these descriptors: \"electrophysiology\", \"patch-clamp techniques\", \"Ca<sup>2+</sup> channels\", \"K<sup>+</sup> channels\", \"cnidarian venoms\", \"cone snail venoms\", \"scorpion venoms\", \"spider venoms\", \"snake venoms\", \"cardiac myocytes\", \"dorsal root ganglia\", and summarized the literature as a scoping review. First, we present the basics and recent advances in mammalian voltage-gated ion channel's structure and function and update the most important animal sources of channel-modulating toxins (e.g. cnidarian and cone snails, scorpions, spiders, and snakes), highlighting the properties of toxins electrophysiologically characterized in Central and South America. Finally, we describe the local experience in implementing the patch-clamp technique using two models of excitable cells, as well as the participation in characterizing new modulators of ion channels derived from the venom of a local spider, a toxins' source less studied with electrophysiological techniques. Fostering the implementation of electrophysiological methods in more laboratories in the region will strengthen our capabilities in many fields, such as toxinology, toxicology, pharmacology, natural products, biophysics, biomedicine, and bioengineering.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"30 ","pages":"e20230048"},"PeriodicalIF":1.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11389830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yao Sun, Gen-Bao Zhang, Shu Li, Xiao-Yu Liu, Lei Chen, Peng-Ju Bao
{"title":"Identification and analgesic activity study of analgesic protein Ⅶ-2 from <i>Naja naja atra</i> venom.","authors":"Yao Sun, Gen-Bao Zhang, Shu Li, Xiao-Yu Liu, Lei Chen, Peng-Ju Bao","doi":"10.1590/1678-9199-JVATITD-2023-0099","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2023-0099","url":null,"abstract":"<p><strong>Background: </strong>Acid-sensing ion channel 1a (ASIC1a) plays a critical role in physiological and pathological processes. To further elucidate the biological functions of ASICs and their relationships with disease occurrence and development, it is advantageous to investigate and develop additional regulatory factors for ASICs.</p><p><strong>Methods: </strong>In this study, cation exchange chromatography was used to separate seven chromatographic components from <i>Naja naja atra</i> venom. Capillary electrophoresis was employed to detect that Ⅶ peak component containing a main protein Ⅶ-2, which could bind to ASIC1a. The analgesic effects of Ⅶ-2 protein were determined using hot plate methods, and ASIC1a expression in spinal cord tissue from rats with inflammatory pain was detected using western blot.</p><p><strong>Results: </strong>The purified Ⅶ-2 protein named <i>Naja naja atra</i> venom-Ⅶ-2 (NNAV-Ⅶ-2) was obtained by Sephadex G-50 gel filtration, which exhibited a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a molecular weight of 6.7 kD. Remarkably, the NNAV-Ⅶ-2 protein demonstrated a significant analgesic effect and downregulated ASIC1a expression in the spinal cord tissue of rats with inflammatory pain.</p><p><strong>Conclusions: </strong>The analgesic mechanism of the NNAV-Ⅶ-2 protein may be associated with its binding to ASIC1a, consequently downregulating ASIC1a expression in neural tissues.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"30 ","pages":"e20230099"},"PeriodicalIF":1.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11398835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>Cupiennius</i> spiders (Trechaleidae) from southern Mexico: DNA barcoding, venomics, and biological effect.","authors":"Montserrat Padilla-Villavicencio, Gerardo Corzo, Karina Guillén-Navarro, Guillermo Ibarra-Núñez, Iván Arenas, Fernando Zamudio, Elia Diego-García","doi":"10.1590/1678-9199-JVATITD-2023-0098","DOIUrl":"10.1590/1678-9199-JVATITD-2023-0098","url":null,"abstract":"<p><strong>Background: </strong>Members of the genus <i>Cupiennius</i> Simon, 1891 are categorized as wandering spiders and are part of the family Trechaleidae. The genomics and proteomics of <i>Cupiennius</i> spiders from North America remain uncharacterized. The present study explores for the first time molecular data from the endemic species <i>Cupiennius chiapanensis</i> Medina, 2006, and also presents new data for <i>Cupiennius salei</i> (Keyserling, 1878), both collected in southern Mexico.</p><p><strong>Methods: </strong>In total, 88 <i>Cupiennius</i> specimens were collected from southern Mexico and morphologically identified. DNA was extracted and the mitochondrial COI fragment was amplified. COI sequences were analyzed, and a phylogenetic tree was inferred for species from the Americas. Genetic diversity was analyzed using haplotype networks and gene distances. Venom was obtained from <i>C. chiapanensis</i> and <i>C. salei</i> by electrostimulation. The venom was separated by HPLC, visualized using SDS-PAGE, and quantified for use in toxicity bioassays in mice and insects.</p><p><strong>Results: </strong>Analysis of COI sequences from <i>C. chiapanensis</i> showed 94% identity with <i>C. salei</i>, while <i>C. salei</i> exhibited 94-97% identity with sequences from Central and South American conspecifics. The venom from <i>C. chiapanensis</i> exhibited toxic activity against crickets. Venoms from <i>C. chiapanensis</i> and <i>C. salei</i> caused death in <i>Anastrepha obliqua</i> flies. Analysis of venom fractions from <i>C. salei</i> and <i>C. chiapanensis</i> revealed molecular masses of a similar size as some previously reported toxins and neurotoxic components. We determined the amino acid sequences of ChiaTx1 and ChiaTx2, toxins that are reported here for the first time and which showed toxicity against mice and insects.</p><p><strong>Conclusion: </strong>Our work is the first to report COI-based DNA barcoding sequences from southern Mexican <i>Cupiennius</i> spiders. Compounds with toxic activity were identified in venom from both species.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"30 ","pages":"e20230098"},"PeriodicalIF":1.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriela Marques Rodrigues, Mara Elvira de Almeida, Sóstenes Apolo Correia Marcelino, Paula Bretas Ullmann Fernandes, Jessica Oliveira Pereira da Cruz, Françoise Louanne Araújo, Raquel da Silva Ferreira, Ana Flávia Machado Botelho, Francisco Javier Bedoya, Gladys Margot Cahuana, Ana Belén Hitos, Bernat Soria, Fernanda Costal-Oliveira, Clara Guerra Duarte, Juan R Tejedo, Carlos Chávez-Olórtegui, Marília Martins Melo
{"title":"Protective effects of mesenchymal stromal cell-derived secretome on dermonecrosis induced in rabbits by <i>Loxosceles intermedia</i> spider venom.","authors":"Gabriela Marques Rodrigues, Mara Elvira de Almeida, Sóstenes Apolo Correia Marcelino, Paula Bretas Ullmann Fernandes, Jessica Oliveira Pereira da Cruz, Françoise Louanne Araújo, Raquel da Silva Ferreira, Ana Flávia Machado Botelho, Francisco Javier Bedoya, Gladys Margot Cahuana, Ana Belén Hitos, Bernat Soria, Fernanda Costal-Oliveira, Clara Guerra Duarte, Juan R Tejedo, Carlos Chávez-Olórtegui, Marília Martins Melo","doi":"10.1590/1678-9199-JVATITD-2024-0004","DOIUrl":"10.1590/1678-9199-JVATITD-2024-0004","url":null,"abstract":"<p><strong>Background: </strong>Loxoscelism refers to a set of clinical manifestations caused by the bite of spiders from the <i>Loxosceles</i> genus. The classic clinical symptoms are characterized by an intense inflammatory reaction at the bite site followed by local necrosis and can be classified as cutaneous loxoscelism. This cutaneous form presents difficult healing, and the proposed treatments are not specific or effective. This study aimed to evaluate the protective effect of mesenchymal stromal cells-derived secretome on dermonecrosis induced by <i>Loxosceles intermedia</i> spider venom in rabbits.</p><p><strong>Methods: </strong>Sixteen rabbits were distributed into four groups (n = 4). Except for group 1 (G1), which received only PBS, the other three groups (G2, G3, and G4) were initially challenged with 10 μg of <i>L. intermedia</i> venom, diluted in 100 μL of NaCl 0.9%, by intradermic injection in the interscapular region. Thirty minutes after the challenge all groups were treated with secretome, except for group 2. Group 1 (G1-control group) received intradermal injection (ID) of 60 μg of secretome in 0.15 M PBS; Group 2 (G2) received 0.9% NaCl via ID; Group 3 (G3) received 60 μg of secretome, via ID and Group 4 (G4), received 60 μg of secretome by intravenous route. Rabbits were evaluated daily and after 15 days were euthanized, necropsied and skin samples around the necrotic lesions were collected for histological analysis.</p><p><strong>Results: </strong>Rabbits of G1 did not present edema, erythema, hemorrhagic halo, or necrosis. In animals from G2, G3, and G4, edema appeared after 6h. However, minor edema was observed in the animals of G2 and G3. Hemorrhagic halo was observed in animals, six hours and three days after, on G2, G3, and G4. Macroscopically, in G4, only one animal out of four had a lesion that evolved into a dermonecrotic wound. No changes were observed in the skin of the animals of G1, by microscopic evaluation. All animals challenged with <i>L. intermedia</i> venom showed similar alterations, such as necrosis and heterophilic infiltration. However, animals from G4 showed fibroblast activation, early development of connective tissue, neovascularization, and tissue re-epithelialization, indicating a more prominent healing process.</p><p><strong>Conclusion: </strong>These results suggest that secretome from mesenchymal stromal cells cultured in a xeno-free and human component-free culture media can be promising to treat dermonecrosis caused after <i>Loxosceles</i> spiders bite envenoming.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"30 ","pages":"e20240004"},"PeriodicalIF":1.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11276892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Magnus Ake Gidlund, Raphael Fagnani Sanchez Molina, Eva Burger
{"title":"An improved high-performance liquid chromatography (HPLC) method for detection of variations in the hydroxyproline content of tissue homogenates from <i>Paracoccidioides brasiliensis</i>-infected mice.","authors":"Magnus Ake Gidlund, Raphael Fagnani Sanchez Molina, Eva Burger","doi":"10.1590/1678-9199-JVATITD-2023-0068","DOIUrl":"10.1590/1678-9199-JVATITD-2023-0068","url":null,"abstract":"<p><strong>Background: </strong>Paracoccidioidomycosis (PCM) is a severe granulomatous disease<i>.</i> The hallmark of this mycosis is fibrin degradation and granuloma formation as a result of a wound-healing process in the context of excessive inflammation. Therefore, as the content of collagen can be assessed by the methodology described in this manuscript, we propose that the content of hydroxyproline (HYP) be employed as a new and efficient measurement of granulomatous lesions developed. To estimate the level of HYP the major byproduct of the degradation process, we hypothesized that this simple and efficient technique could serve as a marker of disease severity.</p><p><strong>Methods: </strong>Five B10.A female mice were infected with <i>P</i>. <i>brasiliensis</i> and, after 15 days, the omentum was removed, subjected to histopathological analysis or processed (i.e. deproteinized and derivatized), and further analyzed on a reverse phase HPLC using a C-18 column. The omentum of five uninfected controls was also collected and similarly analyzed.</p><p><strong>Results: </strong>Infected mice showed numerous, disseminated paracoccidioidomycotic lesions, as well as marked collagen deposits, as observed in histopathologic analysis, and high levels of HYP. Normal uninfected mice showed no granulomas, little or no deposits of collagen fibers, and very low levels of HYP, as evaluated by HPLC. Our results show that the disease intensity as evaluated number and the morphology of the granulomatous lesions were correlated to the HYP levels using small tissue samples from the omentum, the main target organ of <i>P. brasiliensis</i>.</p><p><strong>Conclusions: </strong>Here we propose an alternative methodology to follow disease evolution and, to some extent, fungal load in experimental <i>P. brasiliensis</i> infection and suggest its usefulness to other diseases with pronounced fibrin degradation.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"30 ","pages":"e20230068"},"PeriodicalIF":1.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11270750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carolina Petri Bernardes, Ernesto Lopes Pinheiro, Isabela Gobbo Ferreira, Isadora Sousa de Oliveira, Neife Aparecida Guinaim Dos Santos, Suely Vilela Sampaio, Eliane Candiani Arantes, Antonio Cardozo Dos Santos
{"title":"Fraction of <i>C. d. collilineatus</i> venom containing crotapotin protects PC12 cells against MPP <sup>+</sup> toxicity by activating the NGF-signaling pathway.","authors":"Carolina Petri Bernardes, Ernesto Lopes Pinheiro, Isabela Gobbo Ferreira, Isadora Sousa de Oliveira, Neife Aparecida Guinaim Dos Santos, Suely Vilela Sampaio, Eliane Candiani Arantes, Antonio Cardozo Dos Santos","doi":"10.1590/1678-9199-JVATITD-2023-0056","DOIUrl":"10.1590/1678-9199-JVATITD-2023-0056","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. There is no effective treatment for neurodegenerative diseases. Snake venoms are a cocktail of proteins and peptides with great therapeutic potential and might be useful in the treatment of neurodegenerative diseases. Crotapotin is the acid chain of crotoxin, the major component of <i>Crotalus durissus collilineatus</i> venom. PD is characterized by low levels of neurotrophins, and synaptic and axonal degeneration; therefore, neurotrophic compounds might delay the progression of PD. The neurotrophic potential of crotapotin has not been studied yet.</p><p><strong>Methods: </strong>We evaluated the neurotrophic potential of crotapotin in untreated PC12 cells, by assessing the induction of neurite outgrowth. The activation of the NGF signaling pathway was investigated through pharmacological inhibition of its main modulators. Additionally, its neuroprotective and neurorestorative effects were evaluated by assessing neurite outgrowth and cell viability in PC12 cells treated with the dopaminergic neurotoxin MPP<sup>+</sup> (1-methyl-4-phenylpyridinium), known to induce Parkinsonism in humans and animal models.</p><p><strong>Results: </strong>Crotapotin induced neuritogenesis in PC12 cells through the NGF-signaling pathway, more specifically, by activating the NGF-selective receptor trkA, and the PI3K/Akt and the MAPK/ERK cascades, which are involved in neuronal survival and differentiation. In addition, crotapotin had no cytotoxic effect and protected PC12 cells against the inhibitory effects of MPP<sup>+</sup> on cell viability and differentiation.</p><p><strong>Conclusion: </strong>These findings show, for the first time, that crotapotin has neurotrophic/neuroprotective/neurorestorative potential and might be beneficial in Parkinson's disease. Additional studies are necessary to evaluate the toxicity of crotapotin in other cell models.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"30 ","pages":"e20230056"},"PeriodicalIF":1.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cleuber Rodrigo de Souza Bueno, Daniela Vieira Buchaim, Benedito Barraviera, Rui Seabra Ferreira, Paulo Sérgio da Silva Santos, Carlos Henrique Bertoni Reis, Marcelo Augusto Cini, Milton Carlos Kuga, Geraldo Marco Rosa, Rogerio Leone Buchaim
{"title":"Delayed repair of the facial nerve and its negative impacts on nerve and muscle regeneration.","authors":"Cleuber Rodrigo de Souza Bueno, Daniela Vieira Buchaim, Benedito Barraviera, Rui Seabra Ferreira, Paulo Sérgio da Silva Santos, Carlos Henrique Bertoni Reis, Marcelo Augusto Cini, Milton Carlos Kuga, Geraldo Marco Rosa, Rogerio Leone Buchaim","doi":"10.1590/1678-9199-JVATITD-2023-0093","DOIUrl":"10.1590/1678-9199-JVATITD-2023-0093","url":null,"abstract":"<p><strong>Background: </strong>In this experimental protocol, we evaluated the immediate and delayed repair of the buccal branch of the facial nerve (BBFN) with heterologous fibrin biopolymer (HFB) as a coaptation medium and the use of photobiomodulation (PBM), performing functional and histomorphometric analysis of the BBFN and perioral muscles.</p><p><strong>Methods: </strong>Twenty-eight rats were divided into eight groups using the BBFN bilaterally (the left nerve was used for PBM), namely: G1 - control group, right BBFN (without injury); G2 - control group, left BBFN (without injury + PBM); G3 - Denervated right BBFN (neurotmesis); G4 - Denervated left BBFN (neurotmesis + PBM); G5 - Immediate repair of right BBFN (neurotmesis + HFB); G6 - Immediate repair of left BBFN (neurotmesis + HFB + PBM); G7 - Delayed repair of right BBFN (neurotmesis + HFB); G8 - Delayed repair of left BBFN (neurotmesis + HFB + PBM). Delayed repair occurred after two weeks of denervation. All animals were sacrificed after six weeks postoperatively.</p><p><strong>Results: </strong>In the parameters of the BBFN, we observed inferior results in the groups with delayed repair, in relation to the groups with immediate repair, with a significant difference (<i>p</i> < 0.05) in the diameter of the nerve fiber, the axon, and the thickness of the myelin sheath of the group with immediate repair with PBM compared to the other experimental groups. In measuring the muscle fiber area, groups G7 (826.4 ± 69.90) and G8 (836.7 ± 96.44) were similar to G5 (882.8 ± 70.51). In the functional analysis, the G7 (4.10 ± 0.07) and G8 (4.12 ± 0.08) groups presented normal parameters.</p><p><strong>Conclusion: </strong>We demonstrated that delayed repair of BBFN is possible with HFB, but with worse results compared to immediate repair, and that PBM has a positive influence on nerve regeneration results in immediate repair.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"30 ","pages":"e20230093"},"PeriodicalIF":2.4,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11132725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natalia Scanavachia da Silva, Julia Lombardi, Frank Kirchhoff, Rui Seabra Ferreira, Benedito Barraviera, Alexandre Leite Rodrigues de Oliveira, Luciana Politti Cartarozzi
{"title":"Effects of local and systemic treatment with human natural killer-1 mimetic peptide (HNK-1) after ventral root avulsion and reimplantation in mice.","authors":"Natalia Scanavachia da Silva, Julia Lombardi, Frank Kirchhoff, Rui Seabra Ferreira, Benedito Barraviera, Alexandre Leite Rodrigues de Oliveira, Luciana Politti Cartarozzi","doi":"10.1590/1678-9199-JVATITD-2023-0065","DOIUrl":"10.1590/1678-9199-JVATITD-2023-0065","url":null,"abstract":"<p><strong>Background: </strong>Spinal ventral root injuries generate significant motoneuron degeneration, which hinders full functional recovery. The poor prognosis of functional recovery can be attributed to the use or combination of different therapeutic approaches. Several molecules have been screened as potential treatments in combination with surgical reimplantation of the avulsed roots, the gold standard approach for such injuries. Among the studied molecules, human natural killer-1 (HNK-1) stands out as it is related to the stimulation of motor axon outgrowth. Therefore, we aimed to comparatively investigate the effects of local administration of an HNK-1 mimetic peptide (mp-HNK-1) and systemic treatment with ursolic acid (UA), another HNK-1 mimetic, after ventral root avulsion and reimplantation with heterologous fibrin biopolymer (HFB).</p><p><strong>Methods: </strong>Female mice of the isogenic strain C57BL/6JUnib were divided into five experimental groups: Avulsion, Reimplantation, mp-HNK-1 (in situ), and UA (systemic treatment). Mice were evaluated 2 and 12 weeks after surgery. Functional assessment was performed every four days using the Catwalk platform. Neuronal survival was analyzed by cytochemistry, and glial reactions and synaptic coverage were evaluated by immunofluorescence.</p><p><strong>Results: </strong>Treatment with UA elicited long-term neuroprotection, accompanied by a decrease in microglial reactions, and reactive astrogliosis. The neuroprotective effects of UA were preceded by increased glutamatergic and GABAergic inputs in the ventral spinal cord two weeks after injury. However, a single application of mp-HNK-1 had no significant effects. Functional analysis showed that UA treatment led to an improvement in motor and sensory recovery.</p><p><strong>Conclusion: </strong>Overall, the results indicate that UA is neuroprotective, acting on glial cells and synaptic maintenance, and the combination of these findings led to a better functional recovery.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"30 ","pages":"e20230065"},"PeriodicalIF":2.4,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11105159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acute phase reactions in <i>Daboia siamensis</i> venom and fraction-induced acute kidney injury: the role of oxidative stress and inflammatory pathways in <i>in vivo</i> rabbit and <i>ex vivo</i> rabbit kidney models.","authors":"Narongsak Chaiyabutr, Jureeporn Noiprom, Kanyanat Promruangreang, Taksa Vasaruchapong, Panithi Laoungbua, Orawan Khow, Lawan Chanhome, Visith Sitprija","doi":"10.1590/1678-9199-JVATITD-2023-0070","DOIUrl":"10.1590/1678-9199-JVATITD-2023-0070","url":null,"abstract":"<p><strong>Background: </strong>This study examines the direct nephrotoxic effects of <i>Daboia siamensis</i> venom (RVV) and venom fractions in <i>in vivo</i> and isolated perfused kidneys (IPK) to understand the role of inflammation pathways and susceptibility to oxidative stress in venom or fraction-induced acute renal failure.</p><p><strong>Methods: </strong>We administered RVV and its venom fractions (PLA<sub>2</sub>, MP, LAAO, and PDE) to rabbits <i>in vivo</i> and in the IPK model. We measured oxidative stress biomarkers (SOD, CAT, GSH, and MDA) in kidney tissue, as well as inflammatory cytokines (TNF-α, IL-1β, IFN-γ, IL-4, IL-5, and IL-10), MDA and GSH levels in plasma and urine. We also calculated fractional excretion (FE) for pro-/anti-inflammatory cytokines and oxidative stress biomarkers, including the ratios of pro-/anti-inflammatory cytokines in urine after envenomation.</p><p><strong>Results: </strong>In both kidney models, significant increases in MDA, SOD, CAT, and GSH levels were observed in kidney tissues, along with elevated concentrations of MDA and GSH in plasma and urine after injecting RVV and venom fractions. Moreover, RVV injections led to progressive increases in FE<sub>MDA</sub> and decreases in FE<sub>GSH.</sub> The concentrations of IL-4, IL-5, IL-10, IFN-γ, and TNF-α in plasma increased <i>in vivo</i>, as well as in the urine of the IPK model, but not for IL-1β in both plasma and urine after RVV administrations. Urinary fractional excretion of TNF-α, IL-1β, IFN-γ, IL-4, IL-5, and IL-10 tended to decrease <i>in vivo</i> but showed elevated levels in the IPK model. A single RVV injection <i>in vivo</i> disrupted the balance of urinary cytokines, significantly reducing either the TNF-α/IL-10 ratio or the IFN-γ/IL-10 ratio.</p><p><strong>Conclusion: </strong>RVV induces renal tubular toxicity by increasing oxidative stress production and elevating inflammatory cytokines in urine. During the acute phase of acute kidney injury, the balance of urine cytokines shifts toward anti-inflammatory dominance within the first two hours post-RVV and venom fractions.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"30 ","pages":"e20230070"},"PeriodicalIF":2.4,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11131233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}