{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:58:58Z","timestamp":1791575938651,"version":"4.3.4"},"reference-count":55,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"State of S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2023\/03608-1"],"award-info":[{"award-number":["2023\/03608-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"State of S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Coordination for the Improvement of Higher Education Personnel (CAPES)","award":["2023\/03608-1"],"award-info":[{"award-number":["2023\/03608-1"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel (CAPES)","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"UFABC Multiuser Central Facilities (CEM-UFABC)","award":["2023\/03608-1"],"award-info":[{"award-number":["2023\/03608-1"]}]},{"name":"UFABC Multiuser Central Facilities (CEM-UFABC)","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Introduction. The proline-rich decapeptide 10c (Bj-PRO-10c; ENWPHPQIPP) from the Bothrops jararaca snake modulates argininosuccinate synthetase (AsS) activity to stimulate L-arginine metabolite production and neuroprotection in the SH-SY5Y cell line. The relationships between structure, interactions with AsS, and neuroprotection are little known. We evaluated the neuroprotective effects of Bj-PRO-10c and three other PROs (Bn-PRO-10a, &lt;ENWPRPKIPP; Bn-PRO-10a-MK, &lt;ENWPRPKIPPMK; and, Bn-PRO-10c, &lt;ENWPRPKVPP) identified from Bitis nasicornis snake venom, with a high degree of similarity to Bj-PRO-10c, on oxidative stress-induced toxicity in neuronal PC12 cells and L-arginine metabolite generation via AsS activity regulation. Methods. Cell integrity, metabolic activity, reactive oxygen species (ROS) production, and arginase activity were examined after 4 h of PRO pre-treatment and 20 h of H2O2-induced damage. Results. Only Bn-PRO-10a-MK and Bn-PRO-10c restored cell integrity and arginase function under oxidative stress settings, but they did not reduce ROS or cell metabolism. The MK dipeptide in Bn-PRO-10a-MK and valine (V8) in Bn-PRO-10c are important to these effects when compared to Bn-PRO-10a. Bj-PRO-10c is not neuroprotective in PC12 cells, perhaps because of their limited NMDA-type glutamate receptor activity. The PROs interaction analysis on AsS activation can be rated as follows: Bj-PRO-10c &gt; Bn-PRO-10c &gt; Bn-PRO-10a-MK &gt; Bn-PRO-10a. The structure of PROs and their correlations with enzyme activity revealed that histidine (H5) and glutamine (Q7) in Bj-PRO-10c potentiated their affinity for AsS. Conclusions. Our investigation provides the first insights into the structure and molecular interactions of PROs with AsS, which could possibly further their neuropharmacological applications.<\/jats:p>","DOI":"10.3390\/ph17070931","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T16:23:41Z","timestamp":1720801421000},"page":"931","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Small Structural Differences in Proline-Rich Decapeptides Have Specific Effects on Oxidative Stress-Induced Neurotoxicity and L-Arginine Generation by Arginosuccinate Synthase"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4519-8930","authenticated-orcid":false,"given":"Carlos","family":"Alberto-Silva","sequence":"first","affiliation":[{"name":"Natural and Humanities Sciences Center (CCNH), Experimental Morphophysiology Laboratory, Federal University of ABC (UFABC), S\u00e3o Bernardo do Campo 09606-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1585-7066","authenticated-orcid":false,"given":"Brenda Rufino","family":"da Silva","sequence":"additional","affiliation":[{"name":"Natural and Humanities Sciences Center (CCNH), Experimental Morphophysiology Laboratory, Federal University of ABC (UFABC), S\u00e3o Bernardo do Campo 09606-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio Cezar Araujo","family":"da Silva","sequence":"additional","affiliation":[{"name":"Natural and Humanities Sciences Center (CCNH), Experimental Morphophysiology Laboratory, Federal University of ABC (UFABC), S\u00e3o Bernardo do Campo 09606-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe Assump\u00e7\u00e3o da","family":"Cunha e Silva","sequence":"additional","affiliation":[{"name":"Natural and Humanities Sciences Center (CCNH), Experimental Morphophysiology Laboratory, Federal University of ABC (UFABC), S\u00e3o Bernardo do Campo 09606-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0565-9018","authenticated-orcid":false,"given":"Roberto Tadashi","family":"Kodama","sequence":"additional","affiliation":[{"name":"Structure and Functions of Biomolecules Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilmar Dias","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Immunochemistry, Butantan Institute, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0141-7241","authenticated-orcid":false,"given":"Maricilia Silva","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa & Desenvolvimento\u2014IP&D, Universidade do Vale do Para\u00edba\u2014UNIVAP, Av. Shishima Hifumi, 2911, S\u00e3o Jos\u00e9 dos Campos 12244-390, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9582-4699","authenticated-orcid":false,"given":"Fernanda Calheta Vieira","family":"Portaro","sequence":"additional","affiliation":[{"name":"Structure and Functions of Biomolecules Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"de Souza, J.M., Goncalves, B.D.C., Gomez, M.v., Vieira, L.B., and Ribeiro, F.M. (2018). Animal Toxins as Therapeutic Tools to Treat Neurodegenerative Diseases. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00145"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41570-022-00393-7","article-title":"The Chemistry of Snake Venom and Its Medicinal Potential","volume":"6","author":"Oliveira","year":"2022","journal-title":"Nat. Rev. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"170528","DOI":"10.1016\/j.peptides.2021.170528","article-title":"Whether Short Peptides Are Good Candidates for Future Neuroprotective Therapeutics?","volume":"140","author":"Perlikowska","year":"2021","journal-title":"Peptides"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Alberto-Silva, C., and Portaro, F.C.V. (2024). Neuroprotection Mediated by Snake Venom. Natural Molecules in Neuroprotection and Neurotoxicity, Academic Press.","DOI":"10.1016\/B978-0-443-23763-8.00019-1"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.toxicon.2010.03.014","article-title":"Low-Molecular-Mass Peptides from the Venom of the Amazonian Viper Bothrops atrox Protect against Brain Mitochondrial Swelling in Rat: Potential for Neuroprotection","volume":"56","author":"Martins","year":"2010","journal-title":"Toxicon"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.toxicon.2017.02.015","article-title":"Neuroprotective Property of Low Molecular Weight Fraction from B. Jararaca Snake Venom in H2O2-Induced Cytotoxicity in Cultured Hippocampal Cells","volume":"129","author":"Querobino","year":"2017","journal-title":"Toxicon"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"107178","DOI":"10.1016\/j.toxicon.2023.107178","article-title":"Peptide Fraction from B. jararaca Snake Venom Protects against Oxidative Stress-Induced Changes in Neuronal PC12 Cell but Not in Astrocyte-like C6 Cell","volume":"231","author":"Echeverry","year":"2023","journal-title":"Toxicon"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1021\/acs.jnatprod.2c00304","article-title":"Antioxidant and Neuroprotective Effects of the First Tryptophyllin Found in Snake Venom (Bothrops moojeni)","volume":"85","author":"Dematei","year":"2022","journal-title":"J. Nat. Prod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.peptides.2018.03.017","article-title":"Bradykinin-Potentiating PEPTIDE-10C, an Argininosuccinate Synthetase Activator, Protects against H2O2-Induced Oxidative Stress in SH-SY5Y Neuroblastoma Cells","volume":"103","author":"Querobino","year":"2018","journal-title":"Peptides"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"El-Aziz, T.M.A., Soares, A.G., and Stockand, J.D. (2019). Snake Venoms in Drug Discovery: Valuable Therapeutic Tools for Life Saving. Toxins, 11.","DOI":"10.3390\/toxins11100564"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/ddr.21732","article-title":"Snake Venom-Derived Bradykinin-Potentiating Peptides: A Promising Therapy for COVID-19?","volume":"82","author":"Gouda","year":"2021","journal-title":"Drug Dev. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Diniz-Sousa, R., Caldeira, C.A.d.S., Pereira, S.S., Da Silva, S.L., Fernandes, P.A., Teixeira, L.M.C., Zuliani, J.P., and Soares, A.M. (2023). Therapeutic Applications of Snake Venoms: An Invaluable Potential of New Drug Candidates. Int. J. Biol. Macromol., 238.","DOI":"10.1016\/j.ijbiomac.2023.124357"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/j.toxicon.2005.02.017","article-title":"The Bradykinin-Potentiating Peptides from Venom Gland and Brain of Bothrops jararaca Contain Highly Site Specific Inhibitors of the Somatic Angiotensin-Converting Enzyme","volume":"45","author":"Hayashi","year":"2005","journal-title":"Toxicon"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s40409-017-0134-7","article-title":"The Modular Nature of Bradykinin-Potentiating Peptides Isolated from Snake Venoms","volume":"23","author":"Sciani","year":"2017","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1002\/rcm.2931","article-title":"Mass Spectrometric Analysis of the Individual Variability of Bothrops jararaca Venom Peptide Fraction. Evidence for Sex-Based Variation among the Bradykinin-Potentiating Peptides","volume":"21","author":"Pimenta","year":"2007","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1046\/j.1471-4159.2003.01743.x","article-title":"The C-Type Natriuretic Peptide Precursor of Snake Brain Contains Highly Specific Inhibitors of the Angiotensin-Converting Enzyme","volume":"85","author":"Hayashi","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.bbagen.2015.02.005","article-title":"New Proline-Rich Oligopeptides from the Venom of African Adders: Insights into the Hypotensive Effect of the Venoms","volume":"1850","author":"Kodama","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1111\/j.1742-4658.2008.06389.x","article-title":"A Novel Bradykinin Potentiating Peptide Isolated from Bothrops jararacussu Venom Using Catallytically Inactive Oligopeptidase EP24.15","volume":"275","author":"Rioli","year":"2008","journal-title":"FEBS J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.toxicon.2011.07.013","article-title":"Bradykinin-Potentiating Peptides: Beyond Captopril","volume":"59","author":"Camargo","year":"2012","journal-title":"Toxicon"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"20022","DOI":"10.1074\/jbc.M109.021089","article-title":"Argininosuccinate Synthetase Is a Functional Target for a Snake Venom Anti-Hypertensive Peptide: Role in Arginine and Nitric Oxide Production","volume":"284","author":"Guerreiro","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.peptides.2013.07.016","article-title":"Proline Rich-Oligopeptides: Diverse Mechanisms for Antihypertensive Action","volume":"48","author":"Morais","year":"2013","journal-title":"Peptides"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.brainres.2010.09.067","article-title":"Enhancement of the Citrulline-Nitric Oxide Cycle in Astroglioma Cells by the Proline-Rich Peptide-10c from Bothrops jararaca Venom","volume":"1363","author":"Guerreiro","year":"2010","journal-title":"Brain Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.bcp.2010.12.016","article-title":"Bj-PRO-5a, a Natural Angiotensin-Converting Enzyme Inhibitor, Promotes Vasodilatation Mediated by Both Bradykinin B2 and M1 Muscarinic Acetylcholine Receptors","volume":"81","author":"Morais","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/cyto.a.20963","article-title":"The Snake Venom Peptide Bj-PRO-7a Is a M1 Muscarinic Acetylcholine Receptor Agonist","volume":"79","author":"Negraes","year":"2011","journal-title":"Cytom. A"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e20230043","DOI":"10.1590\/1678-9199-jvatitd-2023-0043","article-title":"Activation of M1 Muscarinic Acetylcholine Receptors by Proline-Rich Oligopeptide 7a (<EDGPIPP) from Bothrops Jararaca Snake Venom Rescues Oxidative Stress-Induced Neurotoxicity in PC12 Cells","volume":"20","author":"Silva","year":"2024","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.toxicon.2019.06.012","article-title":"Protective Effects of Distinct Proline-Rich Oligopeptides from B. jararaca Snake Venom against Oxidative Stress-Induced Neurotoxicity","volume":"167","author":"Querobino","year":"2019","journal-title":"Toxicon"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cbi.2015.04.004","article-title":"A Tripeptide Isolated from Bothrops atrox Venom Has Neuroprotective and Neurotrophic Effects on a Cellular Model of Parkinson\u2019s Disease","volume":"235","author":"Martins","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"ref_28","unstructured":"Haines, R.J., Pendleton, L.C., and Eichler, D.C. (2011). Argininosuccinate Synthase: At the Center of Arginine Metabolism. Int. J. Biochem. Mol. Biol., 2."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2579S","DOI":"10.3945\/jn.115.226621","article-title":"Arginine Metabolism Revisited","volume":"146","author":"Morris","year":"2016","journal-title":"J. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Cervelli, M., Averna, M., Vergani, L., Pedrazzi, M., Amato, S., Fiorucci, C., Rossi, M.N., Maura, G., Mariottini, P., and Cervetto, C. (2022). The Involvement of Polyamines Catabolism in the Crosstalk between Neurons and Astrocytes in Neurodegeneration. Biomedicines, 10.","DOI":"10.3390\/biomedicines10071756"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.mib.2015.10.005","article-title":"Dual Role of Arginine Metabolism in Establishing Pathogenesis","volume":"29","author":"Gogoi","year":"2016","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"102429","DOI":"10.1016\/j.npep.2024.102429","article-title":"Pharmacological Profile of Agmatine: An in-Depth Overview","volume":"105","author":"Rafi","year":"2024","journal-title":"Neuropeptides"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Calabrese, E., Hayes, A.W., Pressman, P., Kapoor, R., Dhawan, G., Calabrese, V., and Agathokleous, E. (2023). Polyamines and Hormesis: Making Sense of a Dose Response Dichotomy. Chem. Biol. Interact., 386.","DOI":"10.1016\/j.cbi.2023.110748"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"428010","DOI":"10.1155\/2012\/428010","article-title":"Mechanism of Oxidative Stress in Neurodegeneration","volume":"2012","author":"Gandhi","year":"2012","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.biochi.2020.11.022","article-title":"Reactive Oxygen and Nitrogen Species and Innate Immune Response","volume":"181","year":"2021","journal-title":"Biochimie"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e20200171","DOI":"10.1590\/1678-9199-jvatitd-2020-0171","article-title":"Novel Neuroprotective Peptides in the Venom of the Solitary Scoliid Wasp Scolia decorata ventralis","volume":"27","author":"Portaro","year":"2021","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1007\/s11011-022-00948-z","article-title":"Captopril Exhibits Protective Effects through Anti-Inflammatory and Anti-Apoptotic Pathways against Hydrogen Peroxide-Induced Oxidative Stress in C6 Glioma Cells","volume":"37","author":"Sahin","year":"2022","journal-title":"Metab. Brain Dis."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Quincozes-Santos, A., Bobermin, L.D., Latini, A., Wajner, M., Souza, D.O., Gon\u00e7alves, C.A., and Gottfried, C. (2013). Resveratrol Protects C6 Astrocyte Cell Line against Hydrogen Peroxide-Induced Oxidative Stress through Heme Oxygenase 1. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064372"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Alberto-Silva, C., Portaro, F.C.V., Kodama, R.T., Pantale\u00e3o, H.Q., Inagaki, H., Nihei, K.I., and Konno, K. (2021). Comprehensive Analysis and Biological Characterization of Venom Components from Solitary Scoliid Wasp Campsomeriella annulata annulata. Toxins, 13.","DOI":"10.3390\/toxins13120885"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/978-1-0716-1437-2_2","article-title":"Considerations for the Use of SH-SY5Y Neuroblastoma Cells in Neurobiology","volume":"2311","author":"Kovalevich","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"20","DOI":"10.31083\/j.jin2201020","article-title":"SH-SY5Y Cell Line In Vitro Models for Parkinson Disease Research-Old Practice for New Trends","volume":"22","author":"Ioghen","year":"2023","journal-title":"J. Integr. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"102056","DOI":"10.1016\/j.arr.2023.102056","article-title":"Neuroprotection by Agmatine: Possible Involvement of the Gut Microbiome?","volume":"91","author":"Saha","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.neuro.2019.05.001","article-title":"Neuroprotective Offerings by Agmatine","volume":"73","author":"Kotagale","year":"2019","journal-title":"Neurotoxicology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"17448069211029171","DOI":"10.1177\/17448069211029171","article-title":"Agmatine Requires GluN2B-Containing NMDA Receptors to Inhibit the Development of Neuropathic Pain","volume":"17","author":"Peterson","year":"2021","journal-title":"Mol. Pain"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Kritis, A.A., Stamoula, E.G., Paniskaki, K.A., and Vavilis, T.D. (2015). Researching Glutamate-Induced Cytotoxicity in Different Cell Lines: A Comparative\/Collective Analysis\/Study. Front. Cell. Neurosci., 9.","DOI":"10.3389\/fncel.2015.00091"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/0197-0186(94)90096-5","article-title":"Cytotoxic Effects of Glutamic Acid on PC12 Cells","volume":"24","author":"Froissard","year":"1994","journal-title":"Neurochem. Int."},{"key":"ref_47","first-page":"131","article-title":"Role of Cytotoxicity Experiments in Pharmaceutical Development","volume":"8","author":"Nemes","year":"2018","journal-title":"Cytotoxicity"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/cyto.a.20860","article-title":"The Central Nervous System as Target for Antihypertensive Actions of a Proline-Rich Peptide from Bothrops jararaca Venom","volume":"77","author":"Lameu","year":"2010","journal-title":"Cytom. A"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1038\/hr.2010.208","article-title":"Brain Nitric Oxide Production by a Proline-Rich Decapeptide from Bothrops jararaca Venom Improves Baroreflex Sensitivity of Spontaneously Hypertensive Rats","volume":"33","author":"Lameu","year":"2010","journal-title":"Hypertens. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.peptides.2018.10.005","article-title":"BJ-PRO-7A and BJ-PRO-10C Induce Vasodilatation and Inotropic Effects in Normotensive and Hypertensive Rats: Role of Nitric Oxide and Muscarinic Receptors","volume":"110","author":"Nunes","year":"2018","journal-title":"Peptides"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.toxicon.2007.11.003","article-title":"Tissue Distribution in Mice of BPP 10c, a Potent Proline-Rich Anti-Hypertensive Peptide of Bothrops jararaca","volume":"51","author":"Silva","year":"2008","journal-title":"Toxicon"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1101\/pdb.prot087379","article-title":"Crystal Violet Assay for Determining Viability of Cultured Cells","volume":"2016","author":"Feoktistova","year":"2016","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.jtemb.2014.08.001","article-title":"Diphenyl Diselenide (PhSe)2 Inhibits Biofilm Formation by Candida albicans, Increasing Both ROS Production and Membrane Permeability","volume":"29","author":"Rosseti","year":"2015","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/0471142735.im1422s93","article-title":"Quantitative Assessment of Macrophage Functions in Repair and Fibrosis","volume":"93","author":"Wynn","year":"2011","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_55","first-page":"e2704","article-title":"Determination of Mitochondrial Membrane Potential and Reactive Oxygen Species in Live Rat Cortical Neurons","volume":"51","author":"Joshi","year":"2011","journal-title":"J. Vis. Exp."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/7\/931\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:13:20Z","timestamp":1760109200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/7\/931"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,11]]},"references-count":55,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ph17070931"],"URL":"https:\/\/doi.org\/10.3390\/ph17070931","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,11]]}}}