Differential effect of antioxidant treatment on plasma and tissue paraoxonase activity in hyperleptinemic rats

• Published in: Pharmacological research 2005-06, Vol.51 (6), p.523-532
• Main Authors: Beltowski, Jerzy, Jamroz-Wiśniewska, Anna, Borkowska, Ewelina, Wójcicka, Grażyna
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Antioxidants - pharmacology; Aryldialkylphosphatase - antagonists & inhibitors; Aryldialkylphosphatase - blood; Aryldialkylphosphatase - metabolism; Atherosclerosis; Enzyme Activation - drug effects; Enzyme Activation - physiology; Humans; Leptin; Leptin - antagonists & inhibitors; Leptin - biosynthesis; Male; Obesity; Oxidative Stress - drug effects; Oxidative Stress - physiology; Paraoxonase; Rats; Rats, Wistar; Tissue Distribution - drug effects; Tissue Distribution - physiology
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2005.01.007

Recent studies suggest that adipose tissue hormone, leptin, is involved in atherogenesis, especially in obese subjects. Previously, we have demonstrated that experimentally induced hyperleptinemia decreases plasma paraoxonase 1 (PON1) activity. The aim of this study was to investigate whether treatment with synthetic antioxidant, Tempol, modulates the effect of leptin on plasma and tissue PON1 in the rat. Leptin was administered at a dose of 0.25 mg kg −1 s.c. twice daily for 7 days and Tempol was added to the drinking water at a concentration of 2 mM. Leptin reduced plasma PON1 activity toward paraoxon, phenyl acetate and γ-decanolactone to 71.1, 72.3 and 57.1% of control, respectively. In addition, leptin decreased PON1 activity toward paraoxon in aorta, renal cortex and medulla to 78.6, 49.2 and 48.0% of control, respectively, but had no effect on PON1 in heart, lung and liver. PON1 activity toward phenyl acetate was lower following leptin treatment only in aorta. Leptin increased plasma concentration and urinary excretion of isoprostanes as well as malonyldialdehyde + 4-hydroxyalkenals level in aorta, renal cortex and renal medulla. Coadministration of Tempol prevented leptin-induced oxidative stress and normalized PON1 activity in aorta and kidney. However, Tempol had no effect on plasma PON1 in leptin-treated rats. These data indicate that hyperleptinemia decreases tissue PON1 activity through oxidative stress-dependent mechanism. In contrast, leptin-induced downregulation of plasma PON1 is not mediated by oxidative stress.