Effects of vipoxin and its components on HepG2 cells

Area of Science:

• Biochemistry
• Toxicology
• Cell Biology

Background:

• Snake venom phospholipases A2 (svPLA2) are key toxins with diverse effects.
• Vipoxin, from Vipera ammodytes meridionalis venom, is a complex of a toxic PLA2 subunit and a non-toxic acidic component (VAC).
• The distinct roles of vipoxin and its subunits in cellular toxicity remain under investigation.

Purpose of the Study:

• To investigate the effects of vipoxin and its individual subunits on HepG2 cell integrity and viability.
• To differentiate the cytotoxic and genotoxic potential of the PLA2 subunit, VAC, and the intact vipoxin complex.
• To explore the role of subunit interactions in vipoxin's overall toxicity.

Main Methods:

• Exposure of HepG2 cells to purified vipoxin, its PLA2 subunit, and VAC.
• Assessment of cell viability, cytotoxicity, cytoskeletal integrity, apoptosis, and genotoxicity (DNA damage).
• Correlation of observed effects with enzymatic activity and subunit composition.

Main Results:

• The PLA2 subunit induced concentration-dependent cytotoxicity, cytoskeletal changes, and apoptosis, linked to its enzymatic activity.
• Vipoxin and VAC did not affect cell viability but exhibited significant genotoxicity.
• The PLA2 subunit caused moderate DNA damage, not directly related to its catalytic activity.

Conclusions:

• Vipoxin subunits exert distinct effects on HepG2 cells, with the PLA2 subunit being cytotoxic and VAC being genotoxic.
• The heterodimeric complex vipoxin shows both cytotoxic and genotoxic potential, influenced by subunit interactions.
• Subunit interplay is crucial in determining the specific cyto- and genotoxic outcomes of vipoxin.