Effect of Lipoic Acid on Serum Paraoxonase-1 and Paraoxonase-3 Protein Levels and Activities in Diabetic Rats

Abstract

The aim of the present study was to investigate the effect of streptozotocin-induced diabetes mellitus and lipoic acid treatment on serum paraoxonase-1 and paraoxonase-3 protein levels and paraoxonase, arylesterase and lactonase activities.

36 rats were equally and randomly divided into 4 groups as control, lipoic acid, diabetes and diabetes+lipoic acid. To induce diabetes, a single dose of streptozotocin (40 mg/kg) was injected intraperitoneally to diabetes and diabetes+lipoic acid groups. Lipoic acid (10 mg/kg/day) was injected intraperitoneally for 14 days to lipoic acid and diabetes+lipoic acid groups. Serum PON1 and PON3 protein levels were measured by western blotting. Serum paraoxonase, arylesterase and lactonase activities were determined by the measuring initial rate of substrate (paraoxon, phenylacetate and dihydrocoumarin) hydrolysis.

Streptozotocin-induced diabetes mellitus caused a significant decrease whereas lipoic acid treatment caused a significant increase in serum PON1 and PON3 protein levels and paraoxonase, arylesterase and lactonase activities. The increase percent of serum PON3 protein was higher than that of serum PON1 protein and the increase percent of serum lactonase activity was higher than that of serum paraoxonase and arylesterase activities in diabetes+lipoic acid group.

We can report that, like PON1 protein, PON3 protein and actually its lactonase activity may also have a role as an antioxidant in diabetes mellitus and lipoic acid treatment may be useful for the prevention of the atherosclerotic complications of diabetes by increasing serum PON1 and PON3 protein levels and serum enzyme activities.

Key words

streptozotocin-induced diabetes mellitus - lipoic acid - paraoxonase 1 - paraoxonase 3 - arylesterase - lactonase

• References

• 1 Duckworth WC. Hyperglycemia and cardiovascular disease. Curr Atheroscler Rep 2001; 3: 383-391
• 2 Bashan N, Kovsan J, Kachko I. et al. Positive and negative regulation of insulin signaling by reactive oxygen and nitrogen species. Physiol Rev 2009; 89: 27-71
• 3 Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol 2014; 24: R453-R462
• 4 Del Rio D, Stewart AJ, Pellegrini N. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 2005; 15: 316-328
• 5 Ng CJ, Shih DM, Hama SY. et al. The paraoxonase gene family and atherosclerosis. Free Radic Biol Med 2005; 38: 153-163
• 6 Draganov DI, Stetson PL, Watson CE. et al Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation. J Biol Chem 2000; 275: 33435-33442
• 7 Harel M, Aharoni A, Gaidukov L. et al. Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat Struct Mol Biol 2004; 11: 412-419
• 8 Rodríguez Esparragón F, Hernández Trujillo Y, Macías Reyes A. et al. Concerning the significance of paraoxonase-1 and SR-B1 genes in atherosclerosis. Rev Esp Cardiol 2006; 59: 154-164
• 9 Précourt LP, Amre D, Denis MC. et al. The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis 2011; 214: 20-36
• 10 Aviram M, Rosenblat M. Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. Free Radic Biol Med 2004; 37: 1304-1316
• 11 Wójcicka G, Jamroz-Wiśniewska A, Marciniak A. et al. The differentiating effect of glimepiride and glibenclamide on paraoxonase 1 and platelet-activating factor acetylohydrolase activity. Life Sci 2010; 87: 126-132
• 12 Mackness B, Mackness MI, Arrol S. et al. Serum paraoxonase (PON1) 55 and 192 polymorphism and paraoxonase activity and concentration in non-insulin dependent diabetes mellitus. Atherosclerosis 1998; 139: 341-349
• 13 Boemi M, Leviev I, Sirolla C. et al. Serum paraoxonase is reduced in type 1 diabetic patients compared to non-diabetic, first degree relatives; influence on the ability of HDL to protect LDL from oxidation. Atherosclerosis 2001; 155: 229-235
• 14 Tas S, Sarandol E, Ayvalik SZ. et al. Vanadyl sulfate, taurine, and combined vanadyl sulfate and taurine treatments in diabetic rats: effects on the oxidative and antioxidative systems. Arch Med Res 2007; 38: 276-283
• 15 Gavrovskaia LK, Ryzhova OV, Safonova AF. et al. Effect of taurine and thioctacide on carbohydrate metabolism and the antioxydant system in rats with experimental diabetes. Eksp Klin Farmakol 2008; 71: 34-35
• 16 Nair SP, Shah NC, Taggarsi A. et al. PONI and its association with oxidative stress in type I and type II diabetes mellitus. Diabetes Metab Syndr 2011; 5: 126-129
• 17 Rosenblat M, Karry R, Aviram M. Paraoxonase 1 (PON1) is a more potent antioxidant and stimulant of macrophage cholesterol efflux, when present in HDL than in lipoprotein-deficient serum: relevance to diabetes. Atherosclerosis 2006; 187: 74-81
• 18 Savu O, Serafinceanu C, Grajdeanu IV. et al. Paraoxonase lactonase activity, inflammation and antioxidant status in plasma of patients with type 1 diabetes mellitus. J Int Med Res 2014; 42: 523-529
• 19 Patra SK, Singh K, Singh R. Paraoxonase 1: A better atherosclerotic risk predictor than HDL in type 2 diabetes mellitus. Diabetes Metab Syndr 2013; 7: 108-111
• 20 Rosenblat M, Draganov D, Watson CE. et al Mouse macrophage paraoxonase 2 activity is increased whereas cellular paraoxonase 3 activity is decreased under oxidative stress. Arterioscler Thromb Vasc Biol 2003; 23: 468-474
• 21 Reddy ST, Wadleigh DJ, Grijalva V. et al. Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids. Arterioscler Thromb Vasc Biol 2001; 21: 542-547
• 22 Aviram M, Rosenblat M, Billecke S. et al. Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic Biol Med 1999; 26: 892-904
• 23 Golbidi S, Badran M, Laher I. Diabetes and alpha lipoic acid. Front Pharmacol 2011; 2: 69
• 24 Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001; 17: 888-895
• 25 Rochette L, Ghibu S, Richard C. et al. Direct and indirect antioxidant properties of α-lipoic acid and therapeutic potential. Mol Nutr Food Res 2013; 57: 114-125
• 26 Ramakrishnan N, Wolfe WW, Catravas GN. Radioprotection of hematopoietic tissues in mice by lipoic acid. Radiat Res 1992; 130: 360-365
• 27 Maritim AC, Sanders RA, Watkins 3rd JB. Effects of alpha-lipoic acid on biomarkers of oxidative stress in streptozotocin-induced diabetic rats. J Nutr Biochem 2003; 14: 288-294
• 28 Lowry OH, Rosebrough NJ, Farr AL. et al. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-275
• 29 Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-358
• 30 Abbott CA, Mackness MI, Kumar S. et al. Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins. Arterioscler Thromb Vasc Biol 1995; 15: 1812-1818
• 31 Gan KN, Smolen A, Eckerson HW. et al Purification of human serum paraoxonase/arylesterase. Evidence for one esterase catalyzing both activities. Drug Metab Dispos 1991; 19: 100-106
• 32 Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 2012; 9: 671-675
• 33 Romani R, De Medio GE, di Tullio S. et al. Modulation of paraoxonase 1 and 3 expression after moderate exercise training in the rat. J Lipid Res 2009; 50: 2036-2045
• 34 Ng CJ, Bourquard N, Hama SY. et al. Adenovirus-mediated expression of human paraoxonase 3 protects against the progression of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2007; 27: 1368-1374
• 35 Heinisch BB, Francesconi M, Mittermayer F. et al. Alpha lipoic acid improves vascular endothelial function in patients with type 2 diabetes: a placebo controlled randomized trial. Eur J Clin Invest 2010; 40: 148-154
• 36 Xiang GD, Sun HL, Zhao LS. et al. The antioxidant alpha-lipoic acid improves endothelial dysfunction induced by acute hyperglycaemia during OGTT in impaired glucose tolerance. Clin Endocrinol (Oxf) 2008; 68: 716-723
• 37 Yi X, Maeda N. alpha-Lipoic acid prevents the increase in atherosclerosis induced by diabetes in apolipoprotein E-deficient mice fed high-fat/low-cholesterol diet. Diabetes 2006; 55: 2238-2244
• 38 Khamaisi M, Rudich A, Potashnik R. et al. Lipoic acid acutely induces hypoglycemia in fasting nondiabetic and diabetic rats. Metabolism 1999; 48: 504-510
• 39 Mirjana M, Jelena A, Aleksandra U. et al. Alpha-lipoic acid preserves the structural and functional integrity of red blood cells by adjusting the redox disturbance and decreasing O-GlcNAc modifications of antioxidant enzymes and heat shock proteins in diabetic rats. Eur J Nutr 2012; 51: 975-986
• 40 Wang GG, Li W, Lu XH. et al. Taurine attenuates oxidative stress and alleviates cardiac failure in type I diabetic rats. Croat Med J 2013; 54: 171-179
• 41 Li W, Wang G, Lu X. et al. Lycopene ameliorates renal function in rats with streptozotocin-induced diabetes. Int J Clin Exp Pathol 2014; 7: 5008-5015
• 42 Tappia PS, Thliveris J, Xu YJ. et al. Effects of amino acid supplementation on myocardial cell damage and cardiac function in diabetes. Exp Clin Cardiol 2011; 16: e17-e22
• 43 Xu J, Lee ES, Baek SH. et al. Effect of bilirubin on triglyceride synthesis in streptozotocin-induced diabetic nephropathy. J Korean Med Sci 2014; 29: S155-S163
• 44 Asker SA, Mazroa SA, Abdel-Malek H. Influence of alpha-lipoic acid on streptozotocin induced diabetic cardiomyopathy in adult male albino rats: A biochemical and microscopical study. Egypt J Histol 2010; 33: 92-102
• 45 Wang L, Wu CG, Fang CQ. et al. The protective effect of α-Lipoic acid on mitochondria in the kidney of diabetic rats. Int J Clin Exp Med 2013; 6: 90-97
• 46 Draganov DI, La Du BN. Pharmacogenetics of paraoxonases: a brief review. Naunyn Schmiedebergs Arch Pharmacol 2004; 369: 78-88
• 47 Trudel K, Sinnett D, James RW. et al. Iron-ascorbic acid-induced oxidant stress and its quenching by paraoxonase 1 in HDL and the liver: comparison between humans and rats. J Cell Biochem 2005; 96: 404-411
• 48 Shih DM, Xia YR, Yu JM. et al. Temporal and tissue-specific patterns of Pon3 expression in mouse: in situ hybridization analysis. Adv Exp Med Biol 2010; 660: 73-87