Anat Cell Biol.  2019 Jun;52(2):176-182. 10.5115/acb.2019.52.2.176.

The effect of alpha-lipoic acid on expression of VCAM-1 in type 2 diabetic rat

• Ismawati
• Mukhyarjon
• Asni E
• Romus I

• KMID: 2451221
• DOI: http://doi.org/10.5115/acb.2019.52.2.176

Abstract

Macrovascular diabetes complications are generally caused by a process called atherosclerosis. Evidences suggest that to initiate atherosclerosis, oxidated low-density lipoprotein (oxLDL) has to promote the expression of adhesion molecule. Several studies have evidenced the relevance of oxidative stress and atherosclerosis. However, the protective effect of alpha-lipoic acid (ALA) at atherosclerosis still needs to be explored. This study is aimed at investigating the concentration of plasma oxLDL and the expression of adhesion molecule of type 2 diabetes mellitus (DM) using rat model. Eighteen male rats were segregated into three groups labeled as control group, DM group and DM+ALA group. Type 2 diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg) followed by nicotinamide (110 mg/kg). ALA was administered at a dose of 60 mg/kg body weight/day throughout the feeding period of 3 weeks. Plasma oxLDL concentration was measured by enzyme-linked immunosorbent assays and expression of vascular cell adhesion molecule-1 (VCAM-1) was measured by immunohistochemistry. Expression of abdominal aortic adhesion molecule was assessed by calculation with Adobe Photoshop CS3. Analysis of variance test was used to compare the concentration of plasma oxLDL and expression of adhesion molecule. A P-value of 0.05 was considered statistically significant. Plasma oxLDL was lower in diabetic rat+ALA compared with the diabetic rat. Percentage of area VCAM-1 in DM+ALA group was lower than DM group. There were no significant differences between groups in intensity of VCAM-1. In conclusion, ALA showed protective effects against early atherosclerosis in diabetic rats.

Keyword

Atherosclerosis; Vascular cell adhesion molecule-1; Diabetes mellitus

MeSH Terms

Animals
Atherosclerosis
Diabetes Complications
Diabetes Mellitus
Diabetes Mellitus, Type 2
Enzyme-Linked Immunosorbent Assay
Humans
Immunohistochemistry
Injections, Intraperitoneal
Lipoproteins
Male
Models, Animal
Niacinamide
Oxidative Stress
Plasma
Rats*
Streptozocin
Thioctic Acid*
Vascular Cell Adhesion Molecule-1*
Lipoproteins
Niacinamide
Streptozocin
Thioctic Acid
Vascular Cell Adhesion Molecule-1

Figure

• 

  Fig. 1 Blood glucose level in the three groups after 72 hours. Diabetes was induced by a single intraperitoneal injection streptozotocin followed by intraperitoneal administration of nicotinamide in the group II and III. After 72 hours, blood glucose concentration was measured. ALA, alpha-lipoic acid. a)P<0.05 vs. control.

• 

  Fig. 2 Microscopic photography of aorta abdominal of rats (H&E staining; A and B, ×100; C, ×400). (A) Normal. (B, C) Atherosclerosis lesion induced by diabetes. 1, increased intimal wall thickness; 2, foam cell.

• 

  Fig. 3 The effect of alpha-lipoic acid on the concentration of plasma oxidated low-density lipoprotein (oxLDL). The animals were organized into the following groups: I, negative control group without diabetes induction; II, positive control group with diabetes induction; and III, treatment group received alpha-lipoic acid (ALA) orally. DM, diabetes mellitus. a)P<0.05 vs. control. b)P<0.05 vs. DM.

• 

  Fig. 4 Immunoreactivity of VCAM-1 in abdominal aortic from rats. Diaminobenzidine stains the VCAM-1 brown. Slides were counterstained with H&E, ×400 original magnification. Showing the expression of VCAM-1 (black arrows) was significantly lower in DM+ALA (C) than in DM (B). Expression of abdominal aortic adhesion molecule was assessed by calculation with Adobe Photoshop CS3 for percentage of area and intensity. (A) Normal: histogram present intensity, 28.71; area percent=8.02%. (B) DM: histogram present intensity, 58.26; area percent, 21.26%. (C) DM+ALA: histograms present intensity, 43.53; area percent,13.46%. L, lumen side; VACM-1, vascular cell adhesion molecule-1; DM, group with streptozotocin/nicotinamide-induced diabetes; DM+ALA, group with streptozotocin/nicotinamide/alpha-lipoic acid-induced diabetes.

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