Antidepressant and antipsychotic drugs differentially affect PON1 enzyme activity

Abstract

Human serum paraoxonase (PON1, EC 3.1.8.1.) is a high-density lipid (HDL)-associated, calciumdependent enzyme. In this study, the effects of Haloperidol, Fluoxetine hydrochloride, Diazepam and Acepromazine drugs used for the therapy of antidepressant and antipsychotic diseases, on paraoxonase enzyme activity was studied in in vitro inhibition studies on purified human serum PON1. PON1 enzyme was purified from human blood using two-step procedures, namely, ammonium sulfate precipitation and sepharose-4B-l-tyrosine-1-napthylamine hydrophobic interaction chromatography. The overall purification of human serum PON1 was obtained in a activity of 109.29 U/mL and this enzyme was purified 125-fold. The SDSpolyacrylamide gel electrophoresis of the enzyme indicates a single band with an apparent MW of 43 kDa. Inhibition studies indicated that haloperidol and fluoxetine hydrocloride were effective inhibitors on purified human serum PON1 activity with IC 50 of 0.187 and 3.08 mM values, respectively. The kinetics of interaction of haloperidol and fluoxetine hydrocloride with the purified human serum PON1 indicated uncompetitive inhibiton pattern with K i of 4.15 and 0.007 mM, respectively.

Oxidative stress in drug naïve first episode psychosis and antioxidant effects of risperidone

“…fluoxetine) agents, but not benzodiazepines (e.g. diazepam), reduce PON1 activity (Avcikurt et al, 2014). There is also growing evidence that strategies to mitigate OS are associated with clinical improvement in schizophrenia, e.g.…”

Modulatory Effect of Lifestyle-Related, Environmental and Genetic Factors on Paraoxonase-1 Activity: A Review

“…Kati et al [187], in their study on eleven SSRI-intoxicated patients, found significantly lower PON1 AREase activity and total antioxidant capacity with higher levels of oxidative stress markers in comparison to healthy controls. Contradictory information was obtained for fluoxetine, a major inhibitor of P 450 system isozymes, which was determined by Avcikurt et al [188] to inhibit PON1 activity in a noncompetitive manner, while Saadaoui et al [189] had not observed any effect on PON1 within the therapeutic doses range. Remarkably, a pleiotropic substance, mirtazapine, which, apart from antagonizing serotoninergic and noradrenergic receptors, exerts cytoprotective effects and is involved in several antioxidant mechanisms' activation, was found to have an inhibitory effect on PON1 in vitro.…”

Glyphosate Suppresses the Ability of PON1 to Hydrolyse Oxidized-LDL in the Exposed Farm Workers in Pahang, Malaysia

“…11 Several factors/conditions have been reported to affect the activities of PON1. These include drugs such as antidepressants, 12 smoking, 13 renal failure, 14 diabetes, 15 and exposure to pesticides. 16 Owing to the growing use of pesticides as a result of increase agricultural activities, the present study was undertaken to evaluate the levels of PON1 activities and lipid parameters in farm workers exposed to glyphosate pesticide and relate it to the possibility of being a risk to the development of atherosclerosis and coronary artery disease.…”