• Eman R Youness Department of Medical Biochemistry, National Research Centre, Dokki, Giza, P.O.12622, Egypt.
  • Hanan Farouk Aly Department of Therapeutic Chemistry, National Research Centre, Dokki, Giza, P.O.12622, Egypt.
  • M El Nemr Department of Internal Medicines, 6 October University, Cairo, Egypt.


Objective: The objective of this study is to investigate blood nuclear factor κB (NF-κB), apelin, Lipid peroxide product ; thiobarbituric acid (TBA) malonaldehyde (MDA), monocyte chemoattractant protein-1 (MCP-1), B-cell lymphoma 2 (Bcl2), and paraoxonase (PON1) levels in patients with non -alcoholic fatty liver disease (NAFLD) in a trail to correlate the significance of these biomarkers in the diagnosis and initiation of NAFLD patients.

Methods: A total of 32 patients with NAFLD and 45 healthy controls were enrolled in the study. Apelin levels were measured along with, NF-κB, MCP1, MDA, Bcl2, and PON1 were detected.

Results: Significant increase in serum NF-κB, MDA, MCP1, and apelin levels in NAFLD patients with percentages increase 1031.23, 293.02, 165.93, and 120 %, respectively, while significant reduction in PON1 and BCl2 with percentages decrease 54.58 and 79.03 %, respectively, were detected as compared to controls. A significant correlation was found between serum concentration of the measured biomarkers with the incidence of NAFLD.

Conclusions: It could be concluded that the patients with NAFLD have significantly increased circulating apelin, NF-κB, and MDA levels as compared to healthy control subjects while significant reduction in BCl2 and PON1 levels were recorded. Besides, the NAFLD status is tightly attributed to the existence of insulin resistance and oxidative stress.

Keywords: Apelin, Adiponectin, Non-alcoholic fatty liver disease, Nil, Monocyte chemoattractant protein-1, Bcl2, Paraoxanse1.


1. Bodakhe SH, Gupta SK. Diagnostic methods for non-alcoholic fatty liver diseases alternative to liver biopsy: A review. Asian J Pharm Clin Res 2015;8:54-9.
2. Singh G, Dhadwa N, Harikumar S. Experimental models for hepatotoxicity. Asian J Pharm Clin Res 2015;8:70-4.
3. Wincent MM, Potrilingam D, Anagha V, Jacob SC, Andhuvan G. Assessment of drug related problems in patients with chronic diseases in the general medicine units of a tertiary care hospital. Int J Pharm Pharm Sci 2017;9:194-200.
4. Yamaguchi H, Chen J, Bhalla K, Wang HG. Regulation of bax activation and apoptotic response to microtubule-damaging agents by p53 transcription-dependent and -independent pathways. J Biol Chem 2004;279:39431-7.
5. Lomonaco R, Sunny NE, Bril F, Cusi K. Nonalcoholic fatty liver disease: Current issues and noveltreatment approaches. Drugs 2013;73:1-14.
6. Zhu C, Xie P, Zhao F, Zhang L, An W, Zhan Y. Mechanism of the promotion of steatotic HepG2 cellapoptosis by cholesterol. Int J Clin Exp Pathol 2014;7:6807-13.
7. Eccleston HB, Andringa KA, Betancourt AM, Betancourt AL, Mantena SK, Swain TM, et al. Chronic exposure to a high-fat diet induces hepatic steatosis, impairs nitric oxide bioavailability, and modifies the mitochondrial proteome in mice. Antioxid Redox Signal 2011;15:447-59.
8. Bhardwaj A, Modi KP. Antidiabetic and antihyperlipidaemic activity of Nelumbo nucifera gaertnethanol seed extract in streptozotocin induced diabetic rats. Int J Pharm Pharm 2017;9:197-204.
9. Anderson N, Borlak J. Molecular mechanisms and therapeutic targets insteatosis and steatohepatitis. Pharmacol Rev 2008;60:311-57.
10. Al Sharif M, Alov P, Vitcheva V, Pajeva I, Tsakovska I. Modes of action related to repeated dose toxicity: Tissue-specific biological roles of PPAR ligand-dependent dysregulation in nonalcoholic fatty liver disease. PPAR Res 2014;2014:432647.
11. Nuño-Lámbarri N, Barbero-Becerra VJ, Uribe M, Chávez-Tapia NC. Mitochondrial molecular pathophysiology of nonalcoholic fatty liver disease: A proteomics Approach. Int J Mol Sci 2016;17:281, 1-12.
12. Abdel-Salam OM, Youness E, Adia A, Mohammed N, Abu Elhamed WA. Nuclear factor-kappa B and other oxidative stress biomarkers in serum of autistic children. Open J Mol Integ Physiol 2015;5:18-27.
13. Haddad JJ. Redox regulation of pro-inflammatory cytokines and iκb-α/nf-κb nuclear translocation and activation. Biochem Biophy Res Commun 2002;296:847-56.
14. Meral C, Tascilar E, Karademir F, Tanju IA, Cekmez F, Ipcioglu OM, et al. Elevated plasma levels of apelin in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metabol 2010;23:497-502.
15. Aviram M, Rosenblat M, Billecke S. Human serum paraoxonase (PON1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic Biol Med 1999;26:892-904.
16. Watson AD, Berliner JA, Hama SY. Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low-density lipoprotein. J Clin Invest 1995;96:2882-91.
17. Canales A, Sanchez-Muniz FJ. Paraoxanase something more than an enzyme? Med Clin (Barc) 2003;121:537-48.
18. Mackness MI, Arrol S, Abbott C, Durrington PN. Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase. Atherosclerosis 1993a;104:129-35.
19. Mackness MI, Abbott C, Arrol S. The role of high density lipoprotein and lipid-soluble antioxidant vitamins in inhibiting low-density lipoprotein oxidation. Biochem J 1993b;294:829-34.
20. Ayub A, Mackness MI, Arrol S. Serum paraoxonase after myocardial infarction. Arterioscler Thromb Vasc Biol 1999;19:330-5.
21. Mackness MI, Harty D, Bhatnagar D. Serum paraoxonase activity in familial hypercholesterolemia and insulin-dependent diabetes mellitus. Atherosclerosis 1991;186:193-6.
22. Abbott CA, Mackness MI, Kumar S. Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins. Arterioscler Thromb Vasc Biol 1995;15:1812-8.
23. Sutherland WH, de Jong SA, Walker RJ. Hypochlorous acid and low serum paraoxonase activity in haemodialysis patients: An in vitro study. Nephrol Dial Transplant 2004;19:75-82.
24. Pasqualini L, Cortese C, Marchesi S. Paraoxonase 1 activity modulates endothelial function in patients with peripheral arterial disease. Atherosclerosis 2005;183:349-54.
25. Selek S, Aslan M, Nazlıgul Y. Serum PON1 activity and oxidative stress in non-alcoholic fatty liver disease. J Harran Univ Med Fac 2012;9:86 90.
26. Bafikol M, Bafikol G, Denz K, Ozbakir O, Yucesoy MA. New marker for lipid peroxidation: Serum paraoxonase activity in non-alcoholic steatohepatitis. Turk J Gastroenterol 2005;16:119-23.
27. Ruiz-Larrea MB, Leal AM, Liza M, Lacort M, de Groot H. Antioxidant effects of estradiol and2-Hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes. Steroids 1994;59:383-8.
28. Fossati P, Prencipe L. Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem 1982;28:2077-80.
29. Trinder P. Determination of glucose in blood using glucose oxidase with an alternative oxygen receptor. Ann Clin Biochem 1969;6:24-7.
30. Richmond W. Preparation and properties of a cholesterol oxidase from Nocardia sp. and its application to the enzymatic assay of total cholesterol in serum. Clin Chem 1974;19:1350-6.
31. Belfield A, Goldberg D. Colorimetric determination of alkaline phosphatase activity. Enzyme 1971;12:561-6.
32. Reitman S, Frankel S. A colourimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957;28:56-62.
33. Persijn JP, van der Slik W. A new method for the determination of gamma-glutamyltransferase in serum. Clin Chem Lab Med 1976;14:421-7.
34. Kumon Y, Nakauchi Y, Suehiro T. Proinflammatory cytokines but not acute phase serum amyloid A or reactive protein, down-regulates paraoxonase 1 (PON1) expression by HepG2. Amyloid 2002;9:160-4.
35. Ferre N, Camps J, Cabre M. Hepatic paraoxonase activity alterations and free radical production in rats with experimental cirrhosis. Metabolism 2001;50:997-1000.
36. Andjelkovic AV, Kerkovich D, Pachter JS. Monocyte: Astrocyte interactions regulate MCP-1 expression in both cell types. J Leukoc Biol 2000;68:545-52.
37. Semple BD, Bye N, Rancan M, Ziebell JM, Morganti-Kossmann MC. Role of CCL2 (MCP-1) in traumatic brain injury (TBI): Evidence from severe TBI patients and CCL2- mice. J Cereb Blood Flow Metab 2010;30:769-82.
38. Tuaillon N, Shen DF, Berger RB, Lu B, Rollins BJ, Chan CC. MCP 1 expression in endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 2002;43:1493-8.
39. Mandrekar P, Ambade A, Lim A, Szabo G, Catalano D. An essential role for monocyte chemoattractant protein-1 in alcoholic liver injury: Regulation of proinflammatory cytokines and hepaticsteatosis in mice. Hepatology 2011;54:2185-97.
40. Abdel-Salam OM, Youness ER, Omara EA, Sleem AA. Effect of adipose tissue-derived mesenchymal stem cell treatment on oxidative stress and inflammatory response following Escherichia coli lipopolysaccharide. Comput Clin Pathol 2014;23:65-80.
41. Kitade H, Chen G, Ni Y, Ota T. Nonalcoholic fatty liver disease and insulin resistance: New insights and potential new treatments. Nutrients 2017;9:387-400.
42. Miura K, Yang L, van Rooijen N, Ohnishi H,Seki E. Hepatic recruitment of macrophages promotesnonal coholicsteatohepatitis through CCR2. Am J Physiol Gastrointest 2012;302:G1310-21.
43. Chen F, Castranova V, Shi X, Demers LM. New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases. Clin Chem 1999;45:7-17.
44. Koo JW, Russo SJ, Ferguson D, Nestler EJ, Duman RS. Nuclear factor-kappaB is a critical mediator of stress-impaired neurogenesis and depressive behavior. Proc Natl Acad Sci 2010;107:2669-74.
45. Cerpa-Cruz S, González-Díaz V, Martínez-Bonilla G, Gutiérrez- Ureña S, Rodríguez-Cortés E, et al. Non-Alcoholic fatty steatohepatitis an inflammatory disorder beyond the Liver. J Clin Cell Immunol 2013;4:2-8.
46. Baranova A, Younossi ZM. Fantuzzi G, Mazzone T, editor. Adipokines in Non-Alcoholic Fatty Liver Disease. Nutrition and Health: Adipose Tissue and Adipokines in Health and Disease. Totowa, NJ: Humana Press Inc.; 2007. p. 291-305.
47. Lavallard VJ, Gual P. Autophagy and non-alcoholic fatty liver disease. Biomed Res Int 2014;2014: Article ID: 120179, 13.
48. Lavallard VJ, Bonnafous S, Patouraux S. Serum markers of hepatocyte death and apoptosis are noninvasive biomarkers of severe fibrosis in patients with alcoholic liver disease. PLoS One 2011;6:e17599.
49. Lu Y, Zhu X, Liang GX, Cui RR, Liu Y, Wu SS. Apelin-APJ induces ICAM-1, VCAM-1 and MCP-1 expression via NF-kB/JNK signal pathway in human umbilical vein endothelial cells. Amino Acids 2012;43:2125-36.
50. Yasuzaki H, Yoshida S, Hashimoto T, Shibata W, Inamori M, Toya Y. Involvement of the apelin receptor APJ in Fas-induced liver injury. Liver Int 2013;33:118-26.
51. Wang YL, Liu LJ, Zhao WJ, Li JX. Intervening TNF-_via PPAR with gegenqinlian decoction in experimental nonalcoholic fatty liver disease. Evid Based Complement Altern Med 2015;2015:715638.
52. Koroğlu E, Canbakan B, Atay K, Hatemi İ, Tuncer M, Dobrucalı A, et al. Role of oxidative stress and insulin resistance in disease severity of non-alcoholic fatty liver disease. Turk J Gastroenterol 2016;27:361 6.
53. Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: Old questions and new insights. Science 2011;332:1519-23.
54. Leach NV, Dronca E, Vesa SC. Serum homocysteine levels oxidative stress and cardiovascular risk in non-alcoholic steatohepatitis. Eur J Int Med 2014;25:762-7.
55. Diez-Rodriquez R. Insulin resistance and metabolic syndrome are related to non-alcoholic fatty liver disease, but not visceral adiposity index, in severely obese patients. Rev Esp Enferm Dig 2014;106:522-8.
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How to Cite
Youness, E. R., H. F. Aly, and M. E. Nemr. “ROLE OF APELIN/MONOCYTE CHEMOATTRACTANT PROTEIN-1, INFLAMMATORY, APOPTOTIC MARKERS IN THE REGULATION OF PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 11, no. 8, Aug. 2018, pp. 138-42, doi:10.22159/ajpcr.2018.v11i8.25281.
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