Snake venom-induced tissue damage as a paradigm of redox imbalance, ferroptosis, and inflammaging

Area of Science:

• Toxicology
• Cellular Biology
• Pathophysiology

Background:

• Snakebite envenomation is a significant global health issue with complex local and systemic effects.
• While venom toxins are studied, the cellular mechanisms of tissue damage and organ dysfunction are less understood.
• Oxidative stress is increasingly implicated in venom-induced pathology.

Purpose of the Study:

• To review current mechanistic evidence linking snake venom toxins to oxidative stress and cellular damage.
• To explore the role of mitochondrial dysfunction, iron release, and lipid peroxidation in venom-induced redox imbalance.
• To compare ferroptosis with other cell death pathways in the context of venom-induced disease.

Main Methods:

• Literature review of contemporary mechanistic studies on snake venom toxins.
• Analysis of evidence associating phospholipase A₂, snake venom metalloproteinases, and three-finger toxins with cellular damage.
• Examination of interactions between oxidative mechanisms, immune activation, and endothelial dysfunction.

Main Results:

• Oxidative stress, driven by mitochondrial dysfunction and iron release, is central to venom toxicity.
• Ferroptotic cell death, an iron-dependent process, contributes to progressive tissue damage.
• Oxidative mechanisms interact with immune and vascular responses to cause organ-specific toxicity (liver, kidney, heart, nervous system).

Conclusions:

• Snake venom-induced injury involves complex interactions between toxins, oxidative stress, and cellular death pathways like ferroptosis.
• Understanding these mechanisms, including redox imbalance and organ-specific toxicity, is crucial for improving treatment.
• Further research into these pathways may lead to enhanced antivenom strategies.