Evaluation of Oxidative Protein Damage in Patients with Hypercholesterolemia
Hypercholesterolemia, Protein thiols, Reactive oxygen species, LDL cholesterol.
DOI:
https://doi.org/10.70284/njirm.v4i4.2208Keywords:
Hypercholesterolemia, Protein thiols, Reactive oxygen species, LDL cholesterolAbstract
Background: Hypercholesterolemia is highly prevalent in Indian population and known to contribute towards increased mortality and morbidity related to cardiovascular and cerebrovascular disorders. An antioxidant defence system consisting of enzymatic and non-enzymatic compounds prevents oxidative damage of lipoproteins in the plasma. When the activity of this system decreases or the reactive oxygen species (ROS) production increases, oxidative stress may occur.The –SH group (reduced thiols) bound to proteins (protein thiols) play a major role in maintaining the antioxidant status of the body. Protein thiols acts as major extracellular antioxidant, they react with reactive oxygen species (ROS) and prevent LDL oxidation. Such thiols have been studied in different disease conditions and found to be decreased compared to healthy control samples. Reduced concentration of protein thiol found to have positive correlation with increase serum level of LDL cholesterol. In the current work we have measured the level of serum protein thiols along with lipid profile in newly diagnosed hyperlipidemic patients and we tried to establish the relationship between serum protein thiols and lipid profile parameters. Objective: To study the level of protein thiols as a potent antioxidant in patient with an increased level of cholesterol. Materials: After obtaining prior consent, blood (2 ml) was taken using aseptic precautions from hypercholesterolemic patients (n = 25) and age and sex matched healthy controls (n = 25) in plain vacutainers. Serum protein thiols were measured by spectrophotometric method using 5, 5′ dithio-bis (2-nitrobenzoic acid) (DTNB). Triglyceride levels were measured by Cobas 6000 using a GPO Trinder method and HDL levels by Cobas 6000 using a direct- homogenous method. LDL levels were calculated. Results: There was a significant decrease in the levels of protein thiols p< 0.001 in hypercholesterolemic patients when compared to healthy controls and a corresponding correlatable increase in the level of LDL cholesterol due to oxidative damage. Conclusion: There may be a role for protein thiols as a biomarker in pathophysiology of cardiovascular and cerebrovascular disorders in patients with hyperlipidemia.
References
2. Ramakrishna V, Jaikhani R. Oxidative stress in non-insulin-dependent diabetes mellitus (NIDDM) patients. Acta Diabetol 2008;45:41–6.
3. Prakash M, Upadhya S, Prabhu R. Protein thiolsoxidation and lipid peroxidation in patients with uremia. Scand J Clin Lab Invest 2004;64: 599–604.
4. Mallikarjunappa S, Prakash M. Urine protein thiols in chronic renal failure patients. Indian Journal of Nephrology 2007;17:7–9.
5. Telci A, Cakatay U, Salman S, Satman I, Sivas A. Oxidative protein damage in early stage type I diabetic patients. Diabetes Res Clin Pract 2000;50:213–23.
6. Hatice P, Banu S, Neslihan B. Lipid peroxidation and resistance tooxidation in patients with type 2 diabetes mellitus. Tohoku J Exp Med 2004;203:211–18.
7. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70–7.
8. Hu ML. Measurement of protein thiol groups and glutathione in plasma. In: Parker L. Ed. Methods of enzymology, California: Academic Press. 1994; 233:380-85.
9. Meister A, Anderson ME. Glutathione. Annu Rev Biochem 1983;52:711-60.
10. Himmelfarb J, McMonagle E, McMenamin E. Plasma protein thiol oxidation and carbonyl formation in chronic renal failure. Kidney Int 2000;58:2571–8.
11. Beckman K. B., Ames B. N. The free radical theory of aging matures. Physiol. Rev 1998;78:547–81.
12. Basci A., Wallin J. D., Shah S. V. Effect of stimulated neutrophils on cyclic nucleotide content in isolated rat glomeruli. Am. J. Physiol 1987;252:F429–F436
13. Baud L., Ardaillou R. Reactive oxygen species: production and role in the kidney. Am. J. Physiol 1986;251:F765–F776.
14. Riedle B., Kerjaschki D. Reactive oxygen species cause direct damage of Engelbreth-Holm-Swarm matrix. Am. J. Pathol.1997;151:215–31.
15. Sharma P., Reddy K., Franki N., Samwal V., Sankaran R., Ahuja T. S., Gibbons N., Mattana J., Singhal P. C. Native and oxidized low density lipoproteins modulate mesangial cell apoptosis. Kidney Int 1996;50:1604–11.
16. Stenvinkel P, Alvestrand A. Inflammation in end-stage renal disease: sources, consequences, and therapy. Semin Dial 2002;15:329–37.
17. Kunsch C, Medford RM. Oxidative stress as a regulator of gene expression in the vasculature. Circ Res 1999;85:753–66.
18. Stenvinkel P, Pecoits-Filho R, Lindholm B. Coronary artery disease in end-stage renal disease: no longer a simple plumbing problem. J Am Soc Nephrol 2003;14:1927–39.
19. Quyyumi AA, Mulcahy D, Andrews NP, Husain S, Panza JA, Cannon III RO. Coronary vascular nitric oxide activity in hypertension and hypercholesterolemia. Circulation 1997;95:104 –10.
20. Chowienczyk PJ, Watts GF, Cockcroft JR, Ritter JM. Impaired endothelium- dependent vasodilation of forearm resistance vessels in hypercholesterolaemia. Lancet 1992;340:1430-2.
21. Mu¨gge A, Brandes RP, Bo¨ger RH, Dwenger A, Bode-Bo¨ger S, Kienke S, Frolich JC, Lichtlen PR. Vascular release of superoxide radicals is enhanced in hypercholesterolemic rabbits. J Cardiovasc Pharmacol 1994;24:994 –8.22. Shaul PW. Regulation of endothelial nitric oxide synthase: Annu Rev Physiol 2002;64:749–74.
23. Vergnani L, Hatrik S, Ricci F, Passaro A, Manzoli N, Zuliani G, Brovkovych V, Fellin R, Malinski T. Effect of native and oxidized low-density lipoprotein on endothelial nitric oxide and superoxide production: key role of L-arginine availability. Circulation 2000;101: 126–6.
24. Rueckschloss U, Galle J, Holtz J, Zerkowski HR, Morawietz H. Induction of NAD(P)H oxidase by oxidized low-density lipoprotein in human endothelial cells: antioxidative potential of hydroxymethylglutaryl coenzyme A reductase inhibitor therapy. Circulation 2001;104:1767–72.
25. John S, Schlaich M, Langenfeld M, Weihprecht H, Schmitz G, Weidinger G, Schmieder RE. Increased bioavailability of nitric oxide after lipid lowering therapy in hypercholesterolemic patients: a randomized, placebo-controlled, double-blind study. Circulation 1998;98:211–6.
26. Herman AG, Moncada S. Therapeutic potential of nitric oxide donors in the prevention and treatment of atherosclerosis. Eur Heart J 2005;26:1945–5.
27. Touyz RM, Schiffrin EL. Reactive oxygen species in vascular biology: implications in hypertension. Histochem Cell Biol 2004;122:339-52.
28. Berry C, Hamilton CA, Brosnan MJ, Magill FG, Berg GA, McMurray JJ, Dominiczak AF. Investigation into the sources of superoxide in human blood vessels: angiotensin II increases superoxide production in human internal mammary arteries. Circulation 2000;101:2206-12.
29. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 2000;86:494 –501.
