Coenzyme Q10 and alpha-tocopherol protect against amitriptyline toxicity

Area of Science:

• Biochemistry
• Toxicology
• Cell Biology

Background:

• Amitriptyline is a widely prescribed antidepressant.
• Amitriptyline toxicity affects cardiovascular, autonomic, and central nervous systems.
• Understanding the mechanisms of amitriptyline toxicity is crucial.

Purpose of the Study:

• To investigate the cytotoxic effects of amitriptyline on human fibroblasts and zebrafish embryos.
• To evaluate the protective role of coenzyme Q(10) and alpha-tocopherol against amitriptyline toxicity.

Main Methods:

• Primary human fibroblasts and zebrafish embryos were treated with amitriptyline.
• Oxidative stress, mitochondrial function, and cell death were assessed.
• The effects of coenzyme Q(10) and alpha-tocopherol supplementation were analyzed.

Main Results:

• Amitriptyline induced oxidative stress and mitochondrial dysfunction in human fibroblasts, characterized by reduced mitochondrial protein expression, decreased enzyme activity, and lower membrane potential.
• Amitriptyline treatment increased apoptotic cell death and activated mitochondrial permeability transition.
• Coenzyme Q(10) and alpha-tocopherol attenuated reactive oxygen species (ROS) production, lipid peroxidation, mitochondrial dysfunction, and cell death.
• In zebrafish embryos, amitriptyline increased embryonic cell death and apoptosis, with both antioxidants providing significant protection.

Conclusions:

• Oxidative stress and mitochondrial dysfunction are key mechanisms underlying amitriptyline cytotoxicity.
• Cell membrane integrity and mitochondrial function are critical targets of amitriptyline toxicity.
• Coenzyme Q(10) and alpha-tocopherol demonstrate significant protective effects against amitriptyline-induced toxicity in both cellular and embryonic models.