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.

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

Background:The effect of proteasome inhibitors on atherosclerosis is known to vary depending on the atherosclerosis stage. Previous studies have shown that the highest proteasome expression in atherosclerotic lesions is at the progression stage. Adhesion molecules play a role in the progression stage of atherosclerosis, but no studies have analyzed the effect of proteasome inhibitors on the expression of adhesion molecules at this stage. Methods: This experimental study aimed to analyze the effect of a proteasome inhibitor, namely bortezomib, on the vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule1 (ICAM-1) expressions in blood vessels of rat model of atherosclerosis at the progression stage. This study used 18 male Wistar rats divided into three groups, i.e. group I that is the control group given standard feed, group II induced by atherosclerosis, and group III induced by atherosclerosis and given bortezomib. Atherosclerosis induction was performed using vitamin D3 (700,000 IU/kg) orally by gastric intubation on the 1 st day and atherogenic feed given for four days. Bortezomib 50 µg/kgBW/day was administered intra-peritoneally. The expression of VCAM-1 and ICAM-1 molecules was measured using immunohistochemistry and analyzed quantitatively using Adobe Photoshop software. Results: The statistical test showed differences in VCAM-1 expression between atherosclerosis + Bortezomib group and atherosclerosis group, but there were no differences in the expression of ICAM-1 and atherosclerotic lesions between the groups. Conclusions: Administration of bortezomib 50μg/kg for four days in progressive atherosclerosis model rats can inhibit VCAM-1 expression, although it does not affect ICAM-1 expression and cannot inhibit atherosclerotic lesion formation.

Background: Numerous studies have been performed to analyze the effect of proteasome inhibitors on atherosclerosis. However, there is still controversy and the mechanism of action of proteasome inhibitors is still not clearly understood. This study aimed to analyze the effect of proteasome inhibitor on 8-hydroxy-2′-deoxyguanosine (8-OHdG) level in the serum of atherosclerotic rats and the antioxidant expression of Superoxide Dismutase 2 (SOD2) in the aorta. Methods: The sample was 18 rats with the strain Wistar rats aged 2-3 months. The sample was grouped into normal (N) group got a standard feed, A1 induced by atherosclerosis, and A2 induced by atherosclerosis and given proteasome inhibitor. The proteasome inhibitor was a bortezomib dose of 50 µg/kg BW/day given on days one and three. After four days of treatment, rats were sacrificed, and the aorta removal was done for analyzing the tunica intima-media thickness (IMT) and SOD2 expression assessment using immunohistochemistry, and serum 8-OHdG measurement was done using the ELISA method. SOD2 expression assessment was carried out quantitatively using Adobe Photoshop. Results: We established a decrease in IMT in the A2 group compared to the A1 group and an enhancement of SOD2 expression and a decrease in 8-OHdG levels in the A2 group compared to the A1 group, although not statistically significant. Conclusion: In our findings showed bortezomib can prevent thickening tunica intima-media in the aorta, although does not reduce serum 8-OHdG levels and did not significantly increase SOD2 expression in the aorta.

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