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.