Simvastatin reduces high uric acid-induced oxidative stress and inflammatory response in vascular endothelial cells via nuclear factor E2-related factor 2 (Nrf2) signaling

Document Type : Original Article

Authors

1 Department of Traditional Chinese Medicine and Rheumatism Immunology, The First Affiliated Hospital of Army Medical University, Chongqing 400038, P.R.China

2 Traditional Chinese Medicine Department, The People’s Hospital of Dadukou District Chongqing, Chongqing, 400084, P.R. China

Abstract

Objective(s): Increased oxidative stress and inflammatory response are risk factors for kidney and cardiovascular diseases in patients with hyperuricemia. Uric acid (UA) has been reported to cause inflammation and oxidative damage in cells by inhibiting the nuclear factor E2-related factor 2 (Nrf2) pathway. Notably, Simvastatin (SIM) can regulate the Nrf2 pathway, but whether SIM can regulate inflammatory response and oxidative stress in vascular endothelial cells induced by high UA via this pathway has not been clarified.
Materials and Methods: To demonstrate this speculation, cell activity, as well as apoptosis, was estimated employing CCK-8 and TUNEL, respectively. Indicators of oxidative stress and inflammation were assessed by related kits and western blotting. Subsequently, the effects of SIM on signaling pathways were examined using western blotting.
Results: The result showed that after UA exposure, oxidative stress was activated and inflammation was increased, and SIM could reverse this trend. Meanwhile, SIM could inhibit high UA-induced apoptosis. In addition, western blotting results showed that SIM reversed the down-regulation of the expression of Nrf2 pathway-related proteins caused by high UA.
Conclusion: SIM alleviated the inflammatory response as well as inhibiting oxidative stress through the Nrf2 pathway, thereby attenuating high UA-induced vascular endothelial cell injury.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 26, Issue 8
August 2023
Pages 927-933

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