Efek N-Asetil-L- Sistein (NAC) terhadap Kadar Adma Plasma dan Ekspresi Protein Vcam-l pada Disfungsi Endotel Tikus Diabetes

Irma Santi, Budi Suprapti, Imam Susilo, Junaidi Khotib



Endothelial dysfunction is an early state of symptoms in a cardiovascular disease. An elevated oxidative stress plays a key role in the pathogenesis of macrovascular diabetic complication. The present study was design to evaluate the effect of NAC on plasma ADMA level and the expression of VCAM-1 protein on endothelial dysfunction in diabetic rats. Thirty male Sprague–Dawley rats were divided into 5 groups i.e. normal rats, diabetic rats, treatment with NAC 30 mg/kgBW, NAC 56 mg/ kgBW and NAC 100 mg/kgBW. Diabetic rats model was induced by intraperitonial administration of alloxan monohydrate at dose of 150 mg/kgBW, diabetes occurred on 3nd day after alloxan injection and then started treatment of N-acetyl-L-cystein for 28 days. ADMA plasma level was analyzed with Elisa Reader and the expression of VCAM-1 protein was evaluated by immunohistochemistry. Conclusion of this research is that treatment with NAC 30 mg/kgBW, NAC 56 mg/kgBW and NAC 100 mg/kgBW for 28 days may prevent oxidative stress indicated by the decreasing of plasma ADMA level by 45.8%: 55.75% and 65.92%, respectively and the decreasing of the expression of VCAM-1 protein on endothelial dysfunction in diabetic rat by 24%: 31.75% and 58.92%, respectively.

Key words : (NAC), Endothelial dysfunction, ADMA, VCAM-1


Disfungsi endotel merupakan tahap awal pada penyakit kardiovaskular. Peningkatan stres oksidatif berperan penting dalam patogenesis komplikasi makrovaskular pada penyakit diabetes. Penelitian ini bertujuan untuk mengevaluasi efek N-asetil sistein (NAC) dalam menurunkan kadar ADMA plasma dan ekspresi protein VCAM-1 pada disfungsi endotel tikus diabetes. 30 tikus jantan strain sprague- Dawley dibagi menjadi 5 kelompok yaitu kelompok normal, kelompok diabetes, kelompok perlakuan NAC pada dosis 30, 56 dan 100 mg/kgBB. Model tikus diabetes diperoleh dengan diinduksi aloksan monohidrat 150 mg/kgBB secara intraperitonial, kondisi diabetes terjadi pada hari ke-3 setelah induksi aloksan selanjutnya dilakukan pemberian N-asetil sistein selama 28 hari. Kadar ADMA plasma dianalisis dengan metode ELISA dan ekspresi protein VCAM-1 dianalisis secara imunohistokimia. Kesimpulan dari penelitian ini bahwa pemberian NAC pada dosis 30, 56 dan 100 mg/kgBB selama 28 hari dapat mencegah peningkatan stres oksidatif yang ditandai dengan menurunnya kadar ADMA plasma berturut-turut 45,80%; 55,75% dan 65,92% serta menurunnya ekspresi dari protein VCAM-1 pada disfungsi endotel tikus diabetes berturut-turut 24,00% ;31,75% dan 58,92%.

Kata kunci : ADMA, Endothelial dysfunction, NAC, VCAM-1


(NAC), Endothelial dysfunction, ADMA, VCAM-1


Rochette L, Zeller M, Cottin Y, Vergely C. Diabetes, oxidative stress and therapeutic strategies. Biochim. Biophys. Acta. 2014; 17(2795) : 2-18,30.

PERKENI. The consensus of Management and prevention in diabetes mellitus Type 2 in Indonesia. Ist Ed. Surabaya : Airlangga University Press; 2011.

Triplitt CL., Reasner C.A, Isley WC. Pharmacotherapy A pathophysiologic Approach: Diabetes mellitus. 7th Ed. New york: McGraw-Hill companies ; 2008.

Forbes JM, Cooper M E. Mechanism of diabetic complications. Physiol. Rev. 2013; 93: 139-66.

Caterina RD, Basta G, Schmidt A.M. Endothelial Dysfunctions and Vascular Disease : Advanced glycation endproducts and the accelerated atherosclerosis in Diabetes. 1stb Ed. Australia: Blackwell Publishing; 2007

Sibal L, Agarwa SC, Home PD, Boger RH. The role of asymmetric dimethylarginine (ADMA) in endothelial dysfunction and cardiovascular disease (Review). Curr Cardiol Rep. 2010;6 (2) : 82-90.

Rodrigo R,editor. Oxidative stress and antioxidants : their role in human disease. 1st Ed. New. York: Nova Science Publishers ; 2009.

Samuni Y, Goldstein S, Dean OM, Berk M. The chemistry and biological activities of N-acetylcysteine. Biochim. Biophys. Acta. 2013 ; 18 (3): 1830,4117.

Schulze F, Wesemann R, Schwedhelm E, Sydow K, Albsmeier J, Cooke JP, et al. Determination of asymmetric dimethylarginine (ADMA) using a novel ELISA assay. Clin. Chem. Lab. Med. 2004 ; 42:1377-78.

Sun SY. N-acetylcysteine, reactive oxygen species and beyond. Cancer Biol. Ther. 2010 ;9 (2) :109.

Ivanouski O, Szumilak D, Khoa TN, Ruellan N. The antioxidant NAC prevents accelerated atherosclerosis in uremic apolipoprotein E knocout mice. Kidney Int. 2005; 67(3): 2289. 12. Sadowska A, Keenoy M, Backer W. Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD: Discordant in vitro and in vivo dose-effects. Pulm. Pharmacol. Ther. 2007;11 (8): 20.

Zainuddin M.The research method: Pharmacy and health. 1st Ed. Surabaya: Airlangga University Press; 2011.

Lequin RM. Enzyme immunoassay (IEA) / enzyme - linked Immunosorbent assay (ELISA). Clin. Chem. 2005;51(12): 2415-16. 15. Allred DC. Assessment of prognostic and predictive factors in breast cancer by immunohistochemistry. Connect. 2005; 4 (1):9.

Nassar T, Kadery B, Lotan C, Da as, N. Effects of the superoxide dismutase-mimetic compound tempol on endothelial dysfunction in streptozotocin-induced diabetic rats. Eur. J. Pharmacol. 2002;115,436.

Sena CM, Pereira AM, Saica R. Endothelial dysfunction : A major mediator of diabetic vascular disease. Biochim. Biophys. Acta. 2013;12 (2): 1832, 2227.

Frode TS, Medeiros YS. Animal models to test drugs with potential antidiabetic activity. J. Ethnopharmacol. 2007; (4):115:173-75.

Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of rat pancreas. Physiol Res. 2001;50(4):536-38.

Full Text: PDF


  • There are currently no refbacks.

Buletin Penelitian Kesehatan (Bulletin of Health Research, p-ISSN: 0125-9695. e-ISSN: 2338-3453) is published by Badan Penelitian dan Pengembangan Kesehatan, Ministry of Health of Republic of Indonesia
Main Indexing :

Visitor Number : View BPK Statistics
Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.