Interrogating stonefish venom: small molecules present in envenomation caused by Synanceia spp

Area of Science:

• Marine Biology
• Biochemistry
• Toxicology

Background:

• Stonefish (Synanceia spp.) are highly venomous, causing severe human stings globally.
• Previous research focused on venom proteins, neglecting small molecules.
• Understanding venom composition is crucial for treating stings and developing therapeutics.

Purpose of the Study:

• To identify and characterize small molecules in Synanceia verrucosa and Synanceia horrida venoms.
• To investigate the biological activity of these venoms on human receptors.
• To explore the cytotoxic effects and potential therapeutic applications of stonefish venom components.

Main Methods:

• Nuclear magnetic resonance (NMR) and mass spectrometry for molecule identification.
• Fractionation techniques to isolate venom components.
• Electrophysiological assays on human nicotinic acetylcholine receptors (nAChRs) and GABA_A receptors (GABA_AR).
• Cytotoxicity assays on human peripheral blood mononuclear cells (PBMCs).

Main Results:

• Discovered three novel small molecules in stonefish venom: gamma-aminobutyric acid (GABA), choline, and O-acetylcholine.
• Reported the first identification of GABA in fish venom.
• Demonstrated that S. horrida venom activates neuronal and muscle-type nAChRs.
• Showed both S. horrida and S. verrucosa venoms activate GABA_AR.
• Venoms exhibited cell-specific cytotoxicity against PBMCs.
• No activity was observed on Na⁺ channel subtypes involved in pain.

Conclusions:

• Stonefish venoms contain previously unidentified small molecules with significant biological activity.
• GABA, choline, and O-acetylcholine represent new targets for understanding venom's effects.
• Further investigation of small venom molecules is essential for developing effective treatments for stonefish stings and discovering drug leads.