Alpha Lipoic Acid Inhibits Expression of Intercellular Adhesion Molecule-1 (ICAM-1) in Type 2 Diabetic Mellitus Rat Models

Ismawati Ismawati, Enikarmila Asni, Mukhyarjon Mukhyarjon, Ilhami Romus

Abstract


BACKGROUND: Diabetes mellitus (DM) is associated with an accelerated atherosclerotic macrovascular disease affecting medium-sized arteries. Several evidences support the role of oxidative stress in atherogenesis. However, the role of alpha lipoic acid (ALA) to prevent atherosclerosis is still debatable. This study was conducted to determine the effect of 60 mg/kg/day ALA for 21 days toward the expression of intercellular adhesion molecule-1 (ICAM-1) in rat model.

METHODS: Eighteen male rats were divided into three groups labelled as control group, type 2 DM (T2DM) group, and T2DM+ALA group. The T2DM rat models were created by intraperitoneally injecting 50 mg/kg streptozotocin, followed by 110 mg/kg nicotinamide. Immunohistochemistry was used to evaluate the ICAM- 1 expression in rats. Quantitative image analysis of immunohistochemical stains was done on the abdominal aorta using Adobe Photoshop CS3 to find the area percentage and intensity. Kruskal-Wallis and Mann-Whitney tests were used to compare the mean value of area percentage and intensity.

RESULTS: There was an increase in area percentage and intensity of ICAM-1 expression. The highest area percentage of ICAM-1 expression was found in the DM group, while the lowest was found in the control group. There were significant differences in the area percentage and intensity between DM+ALA group and DM group, where the area percentage and intensity of ICAM-I in DM group was higher than the DM+ALA group.

CONCLUSION: In conclusion, our results demonstrate that ALA inhibits the expression of ICAM-1 in T2DM rat models.

KEYWORDS: atherosclerosis, ICAM-1, alpha lipoic acid


Full Text:

PDF

References


American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014; 37(Supplement 1): S81-90, CrossRef.

International Diabetes Federation. IDF Diabetes Atlas. 8th edition. Brussels: International Diabetes Federation; 2017, article.

Manrique CM, Rosenzweig JL, Umpierrez GE. Patient information page from the hormone foundation: diabetes, dyslipidemia and heart protection. J Clin Endocrinol Metab. 2009; 94: 1-2, CrossRef.

Pyle AL, Young PP. Atheromas feel the pressure: biomechanical stress and atherosclerosis. Am J Pathol. 2010; 177: 4-9, CrossRef.

Wu JT, Wu LL. Association of soluble markers with various stages and major events of atherosclerosis. Ann Clin Lab Sci. 2005; 35: 240-50, PMID.

Herrmann J, Lerman LO, Lerman A. On to the road to degradation: atherosclerosis and the proteasome. Cardiovasc Res. 2010; 85: 291-302, CrossRef.

Golbidi S, Badran M, Laher I. Diabetes and alpha lipoic acid. Front Pharmacol. 2011; 2: 69, CrossRef.

Yi X, Maeda N. a-Lipoic acid prevents the increase in atherosclerosis induced by diabetes in apolipoprotein E-deficient mice fed high-fat/low-cholesterol diet. Diabetes. 2006; 55: 2238-44, CrossRef.

Park S, Karunakaran U, Jeoung NH, Jeon JH LI. Physiological effect and therapeutic application of alpha lipoic acid. Curr Med Chem. 2014; 21: 3636-45, CrossRef.

Lee SR, Jeong MH, Lim SY, Hong SN. The effect of alpha lipoic acid (thioctacid hr ®) on endothelial function in diabetic and hypertensive patients. Korean Circulation J. 2006; 36: 559-64, CrossRef.

Heinisch BB, Francesconi M, Mittermayer F, Schaller G, Gouya G, Wolzt M, 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: 148-54, CrossRef.

Ismawati, Mukhyarjon, Asni E, Romus I. The effect of alpha-lipoic acid on expression of VCAM-1 in type 2 diabetic rat. Anat Cell Biol. 2019; 52: 176-82, CrossRef.

Skovsø S. Modeling type 2 diabetes in rats using high fat diet and streptozotocin. J Diabetes Invest 2014; 5: 349-58, CrossRef.

Ismawati I, Winarto W, Sari RP. Pencegahan lesi aterosklerosis oleh asam alfa lipoat pada aorta mencit jantan (mus musculus) yang diberi diet tinggi kolesterol. Jurnal Ilmu Kedokteran. 2017; 5: 19- 25, CrossRef.

Ismawati, Oenzil F, Yanwirasti, Yerizel E. Changes in expression of proteasome in rats at different stages of atherosclerosis. Anat Cell Biol. 2016; 49(2): 99-106, CrossRef.

Lehr HA, Mankoff DA, Corwin D, Santeusanio G, Gown AM. Application of photoshop-based image analysis to quantification of hormone receptor expression in breast cancer. J Histochem Cytochem. 1997; 45: 1559-65, CrossRef.

Förstermann U, Münzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation. 2006; 113: 1708-14, CrossRef.

Mearini G, Schlossarek S, Willis MS, Carrier L. The ubiquitin-proteasome system in cardiac dysfunction. Biochim Biophys Acta - Mol Basis Dis. 2008; 1782: 749-63, CrossRef.

Budin SB, Othman F, Louis SR, Abu Bakar M, Radzi M, Osman K, et al. Effect of alpha lipoic acid on oxidative stress and vascular wall of diabetic rats. Rom J Morphol Embryol. 2008; 50: 23-30, PMID.

Sena CM, Nunes E, Louro T, Proença T, Fernandes R, Boarder MR, et al. Effects of α-lipoic acid on endothelial function in aged diabetic and high-fat fed rats. Br J Pharmacol. 2008; 153: 894-90, CrossRef.




DOI: https://doi.org/10.18585/inabj.v12i1.906

Indexed by:

                 

                  

               

     

 

The Prodia Education and Research Institute