Effect of proteasome inhibitor on serum 8-OHdG and aortic SOD2 in a rat model of atherosclerosis

Abstract

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.