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

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 H2O2-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 H2O2-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 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-Ds or pf-Bj (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-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.