Introduction: 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
Bothrops jararaca 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 siamensis (pf-
Ds) and
B. jararaca (pf-
Bj) against H
2O
2-induced oxidative stress using in vitro (PC12 cells) and in vivo (zebrafish,
Danio rerio) models.
Results: In vitro, pf-
Ds (1 µg mL
−1) did not protect PC12 cells against H
2O
2-induced cytotoxicity, unlike previously reported effects of pf-
Bj. In vivo, neither pf-
Ds nor pf-
Bj (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-
Ds or pf-
Bj (10 µg mL
−1) for 4 h, followed by co-exposure to H
2O
2 (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-
Ds or pf-
Bj (10 µg mL
−1) continuously until 96 hpf, after which they were exposed to H
2O
2 (0.2 mmol L
−1) for another 24 h (96–120 h model). In a short-term treatment model, neither fraction reversed H
2O
2-induced deficits in metabolism or locomotor activity. However, in a prolonged treatment model, pf-
Bj significantly reversed the H
2O
2-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.
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