CoQ10 and Carnitine Prevented Mitochondrial Dysfunction Elicited by Fluoxetine and Alprazolam in Chicken Embryos

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Many of psycholeptic and psychotrophic drugs have been implicated with mitochondrial dysfunction. FXT and APZ have been reported to disrupt mitochondrial oxidative phosphorylation, respiration, membrane permeability, resulting in mitochondrial dysfunction. To perform a wider spectrum of survey, we selected two representative top 5 rank psychotrophic drugs, Fluoxetine (FXT) and Alprazolam (APZ), to examine the etiology of mitochondrial dysfunction induced by these drugs and the preventive effect of Coenzyme Q10 (CoQ 10) and L-carnitine. FXT and APZ at 0.1, 1.0, and 10 M were applied to HH stage-10 (day 1.5) chick embryos, co-treated with CoQ 10 and L-carnitine, each at 0.2 M and, 2.0 M. Results indicated FXT at 10 M and APZ at 1 M induced maximum malformation rates, reaching 53% and 80%, respectively. The major types of malformation included liposis of cervical muscles, myofiber fragmentation, inflammation, and edema. Transmission Electron Microscopic (TEM) examination revealed severe mitochondrial damage, in particular, by APZ. In addition, reduction in body weight and ATP production, and downregulation of carnitine acyl transferase 1 (CPT1) gene, as well as upregulation of ACC gene were apparently observed, implicating severe inhibition of -oxidation. Other features included upregulation of SOD, hydrogen peroxide and NO, and GSH depletion. CoQ10 and L-carnitine effectively suppressed the malformation rate, the mortality rates, and the upregulation of ACC gene, and at the same time these two medications were effective for amelioration of the downregulated CPT1. On the other hand, the parameters associated with oxidative stress like SOD, hydrogen peroxide, NO, and GSH were all effectively alleviated. More importantly, the ATP production was also effeciently restored. Conclusively, CoQ and carnitine are able to elicit satisfactory prevention on the adverse effects provoked by FXT and/or APZ. We suggest the use these nutraceutics along with the FXT and/or APZ for clinical appliance. The optimum dose of CoQ and L-carnitine is 2.0 M.