{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:00:34Z","timestamp":1791576034751,"version":"4.3.4"},"reference-count":68,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State of S\u00e3o Paulo Research Foundation","award":["2023\/03608-1"],"award-info":[{"award-number":["2023\/03608-1"]}]},{"name":"State of S\u00e3o Paulo Research Foundation","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"the Improvement of Higher Education Personnel (CAPES)","award":["2023\/03608-1"],"award-info":[{"award-number":["2023\/03608-1"]}]},{"name":"the Improvement of Higher Education Personnel (CAPES)","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Introduction: Snake venoms are rich sources of bioactive peptides with therapeutic potential, particularly against neurodegenerative diseases linked to oxidative stress. While the peptide fraction (&lt;10 kDa) from Bothrops\u00a0jararaca venom has shown in vitro neuroprotection, analogous fractions from related species remain unexplored in vivo. Methods: This study comparatively evaluated the neuroprotective effects of two peptide fractions (pf) from Daboia\u00a0siamensis (pf-Ds) and B.\u00a0jararaca (pf-Bj) against H2O2-induced oxidative stress using in vitro (PC12 cells) and in vivo (zebrafish, Danio\u00a0rerio) models. Results: In vitro, pf-Ds (1 \u00b5g mL\u22121) did not protect PC12 cells against H2O2-induced cytotoxicity, unlike previously reported effects of pf-Bj. In vivo, neither pf-Ds nor pf-Bj (1\u201320 \u00b5g mL\u22121) induced significant developmental toxicity in zebrafish larvae up to 120 h post-fertilization (hpf). The neuroprotective effects of both pf were evaluated using two experimental models: (I) Larvae at 96 hpf were exposed to either pf-Ds or pf-Bj (10 \u00b5g mL\u22121) for 4 h, followed by co-exposure to H2O2 (0.2 mmol L\u22121) for an additional 10 h to induce oxidative stress (4\u201320 h model); (II) Embryos at 4 hpf were treated with pf-Ds or pf-Bj (10 \u00b5g mL\u22121) continuously until 96 hpf, after which they were exposed to H2O2 (0.2 mmol L\u22121) for another 24 h (96\u2013120 h model). In a short-term treatment model, neither fraction reversed H2O2-induced deficits in metabolism or locomotor activity. However, in a prolonged treatment model, pf-Bj significantly reversed the H2O2-induced locomotor impairment, whereas pf-Ds did not confer protection. Conclusions: These findings demonstrate, for the first time, the in vivo neuroprotective potential of pf-Bj against oxidative stress-induced behavioral deficits in zebrafish, contingent on the treatment regimen. The differential effects between pf-Ds and pf-Bj highlight species-specific venom composition and underscore the value of zebrafish for evaluating venom-derived peptides.<\/jats:p>","DOI":"10.3390\/ph18050678","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T11:35:13Z","timestamp":1746185713000},"page":"678","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Snake Venom Peptide Fractions from Bothrops\u00a0jararaca and Daboia\u00a0siamensis Exhibit Differential Neuroprotective Effects in Oxidative Stress-Induced Zebrafish Models"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3658-6505","authenticated-orcid":false,"given":"Felipe Assump\u00e7\u00e3o","family":"da Cunha e Silva","sequence":"first","affiliation":[{"name":"Experimental Morphophysiology Laboratory, Natural and Humanities Sciences Center (CCNH), Universidade Federal do ABC (UFABC), S\u00e3o Bernardo do Campo 09606-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda Rufino da","family":"Silva","sequence":"additional","affiliation":[{"name":"Experimental Morphophysiology Laboratory, Natural and Humanities Sciences Center (CCNH), Universidade Federal do ABC (UFABC), S\u00e3o Bernardo do Campo 09606-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9011-9159","authenticated-orcid":false,"given":"Leticia Ribeiro de","family":"Barros","sequence":"additional","affiliation":[{"name":"Experimental Morphophysiology Laboratory, Natural and Humanities Sciences Center (CCNH), Universidade Federal do ABC (UFABC), S\u00e3o Bernardo do Campo 09606-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emidio","family":"Beraldo-Neto","sequence":"additional","affiliation":[{"name":"Biochemistry Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4430-0905","authenticated-orcid":false,"given":"Adolfo Luis Almeida","family":"Maleski","sequence":"additional","affiliation":[{"name":"Experimental Morphophysiology Laboratory, Natural and Humanities Sciences Center (CCNH), Universidade Federal do ABC (UFABC), S\u00e3o Bernardo do Campo 09606-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4519-8930","authenticated-orcid":false,"given":"Carlos","family":"Alberto-Silva","sequence":"additional","affiliation":[{"name":"Experimental Morphophysiology Laboratory, Natural and Humanities Sciences Center (CCNH), Universidade Federal do ABC (UFABC), S\u00e3o Bernardo do Campo 09606-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13291","DOI":"10.1074\/jbc.R900010200","article-title":"The Nrf2-Antioxidant Response Element Signaling Pathway and Its Activation by Oxidative Stress","volume":"284","author":"Nguyen","year":"2009","journal-title":"J. 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