Snake Venom Peptide Fractions from Bothrops jararaca and Daboia siamensis Exhibit Differential Neuroprotective Effects in Oxidative Stress-Induced Zebrafish Models

<b>Introduction:</b> Snake venoms are rich sources of bioactive peptides with therapeutic potential, particularly against neurodegenerative diseases linked to oxidative stress. While the peptide fraction (<10 kDa) from <i>Bothrops jararaca</i> venom has shown in vitro neuroprotection, analogous fractions from related species remain unexplored in vivo. <b>Methods:</b> This study comparatively evaluated the neuroprotective effects of two peptide fractions (pf) from <i>Daboia siamensis</i> (pf-<i>Ds</i>) and <i>B. jararaca</i> (pf-<i>Bj</i>) against H₂O₂-induced oxidative stress using in vitro (PC12 cells) and in vivo (zebrafish, <i>Danio rerio</i>) models. <b>Results:</b> In vitro, pf-<i>Ds</i> (1 µg mL^-1) did not protect PC12 cells against H₂O₂-induced cytotoxicity, unlike previously reported effects of pf-<i>Bj</i>. In vivo, neither pf-<i>Ds</i> nor pf-<i>Bj</i> (1-20 µg mL^-1) 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-<i>Ds</i> or pf-<i>Bj</i> (10 µg mL^-1) for 4 h, followed by co-exposure to H₂O₂ (0.2 mmol L^-1) for an additional 10 h to induce oxidative stress (4-20 h model); (II) Embryos at 4 hpf were treated with pf-<i>D</i>s or pf-<i>Bj</i> (10 µg mL^-1) continuously until 96 hpf, after which they were exposed to H₂O₂ (0.2 mmol L^-1) for another 24 h (96-120 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-<i>Bj</i> significantly reversed the H₂O₂-induced locomotor impairment, whereas pf-<i>Ds</i> did not confer protection. <b>Conclusions:</b> These findings demonstrate, for the first time, the in vivo neuroprotective potential of pf-<i>Bj</i> against oxidative stress-induced behavioral deficits in zebrafish, contingent on the treatment regimen. The differential effects between pf-<i>Ds</i> and pf-<i>Bj</i> highlight species-specific venom composition and underscore the value of zebrafish for evaluating venom-derived peptides.