Haloperidol cytotoxicity and its relation to oxidative stress

Area of Science:

• Pharmacology
• Toxicology
• Neuroscience

Background:

• Haloperidol (HP) is a widely used antipsychotic medication.
• Long-term HP use is associated with severe adverse effects, including extrapyramidal symptoms and cardiac arrhythmias.
• HP's cytotoxicity is implicated in both neurotoxicity and cardiotoxicity.

Purpose of the Study:

• To review the cytotoxicity of haloperidol.
• To explore the role of reactive oxygen species and oxidative stress in HP-induced toxicity.
• To summarize the multi-modal mechanisms by which HP induces oxidative stress.

Main Methods:

• Literature review of studies on haloperidol's mechanisms of action and toxicity.
• Analysis of evidence linking HP to oxidative stress, lipid peroxidation, and cellular damage.
• Examination of studies investigating the effects of antioxidants on HP-induced side effects.

Main Results:

• Haloperidol induces cytotoxicity via oxidative stress, affecting both neuronal and cardiac cells.
• HP-induced oxidative stress involves mechanisms such as dopamine metabolism, glutathione depletion, NF-κB activation, and mitochondrial dysfunction.
• Evidence suggests that antioxidants, like vitamin E, can reduce HP-related adverse effects, particularly extrapyramidal symptoms.

Conclusions:

• Oxidative stress is a key mechanism underlying haloperidol's neurotoxic and cardiotoxic effects.
• Targeting HP-induced oxidative stress with antioxidants presents a promising strategy for managing its adverse effects.