Protective effects of CoQ10 and L-carnitine against antidepressant-induced mitochondrial dysfunction and teratogenicity in chicken embryos

Abstract

Fluoxetine (FXT) and alprazolam (APZ), widely used for mental disorders, have poorly studied adverse effects on mitochondrial function, including oxidative phosphorylation, electron transport, and membrane permeability. This study represents the first investigation using a chick embryo model (HH-stage 10, day 1.5) to analyze the teratogenic effects of FXT and APZ and explore the protective potential of coenzyme Q10 (CoQ10) and L-carnitine (CNT). Administration of FXT (10 μM) and APZ (1 μM) resulted in high teratogenic rates of 53 % and 80 %, respectively, predominantly manifesting as lipid myopathy in hatching muscles, characterized by lipid accumulation, myofibril disruption, inflammation, and edema. Gene expression analysis revealed upregulation of acetyl-CoA carboxylase (ACC) and downregulation of carnitine palmitoyltransferase 1 (CPT1), leading to impaired lipid peroxidation and excessive reactive oxygen species (ROS) production. Markers of oxidative stress, including superoxide dismutase (SOD), hydrogen peroxide (H₂O₂), and nitric oxide (NO), were significantly elevated, correlating with glutathione (GSH) depletion and mitochondrial ultrastructural damage, resulting in reduced ATP production. Notably, co-administration of CoQ10 and CNT with FXT or APZ significantly improved teratogenic and mortality rates and reduced oxidative stress levels. Specifically, CoQ10 (2 μM) in the FXT group significantly reduced SOD, H₂O₂, and NO levels, while co-treatment with CNT and CoQ10 (2 μM) in the APZ group significantly alleviated NO levels. This pioneering study highlights the novel and crucial potential of CoQ10 and CNT as nutritional supplements to mitigate mitochondrial damage and antioxidant system imbalance caused by FXT and APZ, providing an innovative strategy for clinical application.