N‑acetylcysteine inhibits atherosclerosis by correcting glutathione‑dependent methylglyoxal elimination and dicarbonyl/oxidative stress in the aorta of diabetic mice
| Autor: | Shaoqiong Zhou, Lihua Liu, Bin Wang, Meng’en Zhu, Xin Fang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine dicarbonyl stress Cancer Research medicine.medical_specialty Mice Knockout ApoE medicine.disease_cause Biochemistry Diabetes Mellitus Experimental Nitric oxide Diabetes Complications Acetylcysteine Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine methylglyoxal Genetics medicine Animals Molecular Biology Aorta chemistry.chemical_classification Reactive oxygen species diabetes biology Methylglyoxal Articles Glutathione Atherosclerosis Pyruvaldehyde Malondialdehyde N-acetylcysteine Nitric oxide synthase Oxidative Stress 030104 developmental biology Endocrinology Oncology chemistry 030220 oncology & carcinogenesis biology.protein Molecular Medicine Oxidative stress medicine.drug |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2021.11840 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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