TY - JOUR AB - In diabetic animal models, high plasma/tissue levels of methylglyoxal (MG) are implicated in atherosclerosis. N‑acetylcysteine (NAC) is a cysteine prodrug that replenishes intracellular glutathione (GSH) levels, which can increase the elimination of MG in diabetes mellitus (DM). The present study investigated the anti‑atherosclerotic role of NAC in DM and aimed to determine whether the mechanism involved GSH‑dependent MG elimination in the aorta. Apolipoprotein‑E knockdown (ApoE‑/‑) mice injected with streptozotocin for 5 days exhibited enhanced atherosclerotic plaque size in the aortic root; notably, a high‑lipid diet aggravated this alteration. NAC treatment in the drinking water for 12 weeks decreased the size of the atherosclerotic lesion, which was associated with a reduction in MG‑dicarbonyl stress and oxidative stress, as indicated by decreased serum malondialdehyde levels, and increased superoxide dismutase‑1 and glutathione peroxidase‑1 levels in the diabetic aorta. Endothelial damage was also corrected by NAC, as indicated by an increase in the expression levels of phosphorylated (p‑)Akt and p‑endothelial nitric oxide synthase (eNOS) in the aorta, as well as nitric oxide (NO) in the serum. In addition, MG‑treated human umbilical vein endothelial cells (HUVECs) exhibited increased reactive oxygen species and decreased antioxidant enzyme expression levels. NAC treatment corrected the alteration in HUVECs induced by MG, whereas the protective role of NAC was blocked via inhibition of GSH. These findings indicated that the diabetic aorta was more susceptible to atherosclerotic lesions compared with non‑diabetic ApoE‑/‑ mice. Furthermore, NAC may offer protection against atherosclerotic development in DM by altering aortic and systemic responses via correcting GSH‑dependent MG elimination, leading to decreased oxidative stress and restoration of the p‑Akt/p‑eNOS pathway in the aorta. AD - Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China AU - Fang,Xin AU - Liu,Lihua AU - Zhou,Shaoqiong AU - Zhu,Mengen AU - Wang,Bin DA - 2021/03/01 DO - 10.3892/mmr.2021.11840 IS - 3 JO - Mol Med Rep KW - N‑acetylcysteine diabetes glutathione methylglyoxal dicarbonyl stress atherosclerosis PY - 2021 SN - 1791-2997 1791-3004 SP - 201 ST - N‑acetylcysteine inhibits atherosclerosis by correcting glutathione‑dependent methylglyoxal elimination and dicarbonyl/oxidative stress in the aorta of diabetic mice T2 - Molecular Medicine Reports TI - N‑acetylcysteine inhibits atherosclerosis by correcting glutathione‑dependent methylglyoxal elimination and dicarbonyl/oxidative stress in the aorta of diabetic mice UR - https://doi.org/10.3892/mmr.2021.11840 VL - 23 ER -