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

Author(s)

da Cunha e Silva, Felipe Assumpcao ; da Silva, Brenda Rufino ; de Barros, Leticia Ribeiro ; Beraldo-Neto, Emidio ; Maleski, Adolfo Luis Almeida ; Alberto-Silva, Carlos

• Document type: Journal article
• Source: PHARMACEUTICALS; v. 18, n. 5, p. 18-pg., 2025-05-02.

Abstract

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 <mu>g 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 mu g 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 mu g 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 mu g 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. (AU)

• FAPESP's process: 23/03608-1 - Bioprospection of neuroprotective peptides from snake venoms in vitro and in vivo experimental models for the study of neurodegenerative diseases
• Grantee: Carlos Alberto da Silva
• Support Opportunities: Regular Research Grants