N-acetylcysteine inhibits in vivo oxidation of native low-density lipoprotein

Cui, Yuqi; Narasimhulu, Chandrakala Aluganti; Liu, Lingjuan; Zhang, Qingbin; Liu, Patrick Z.; Li, Xin; Xiao, Yuan; Zhang, Jia; Hao, Hong; Xie, Xiaoyun; He, Guanglong; Cui, Lianqun; Parthasarathy, S.; Liu, Zhenguo

doi:10.1038/srep16339

Cited by 24 publications

(29 citation statements)

References 43 publications

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“…Our study is in keeping with previous studies showing that NAC inhibits atherosclerosis in apoE-/-mice [41,42]. A more recent study in LDLR-/-mice has shown that NAC effectively inhibits in vivo oxidation of LDL [43]. Furthermore, the study showed that NAC was capable of significantly decreasing the level of oxLDL in hyperlipidaemic patients [43].…”

Section: Discussionsupporting

confidence: 91%

“…A more recent study in LDLR-/-mice has shown that NAC effectively inhibits in vivo oxidation of LDL [43]. Furthermore, the study showed that NAC was capable of significantly decreasing the level of oxLDL in hyperlipidaemic patients [43]. One effect we established in the ribose-cysteine treated apoE-/-mice, which was not reported for NAC, was that of a significant LDL-lowering effect.…”

Section: Discussionmentioning

confidence: 79%

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Ribose-cysteine protects against the development of atherosclerosis in apoE-deficient mice

et al. 2020

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Ribose-cysteine is a synthetic compound designed to increase glutathione (GSH) synthesis. Low levels of GSH and the GSH-dependent enzyme, glutathione peroxidase (GPx), is associated with cardiovascular disease (CVD) in both mice and humans. Here we investigate the effect of ribose-cysteine on GSH, GPx, oxidised lipids and atherosclerosis development in apolipoprotein E-deficient (apoE-/-) mice. Female 12-week old apoE-/-mice (n = 15) were treated with 4-5 mg/day ribose-cysteine in drinking water for 8 weeks or left untreated. Blood and livers were assessed for GSH, GPx activity and 8-isoprostanes. Plasma alanine transferase (ALT) and lipid levels were measured. Aortae were quantified for atherosclerotic lesion area in the aortic sinus and brachiocephalic arch and 8-isoprostanes measured. Ribose-cysteine treatment significantly reduced ALT levels (p<0.0005) in the apoE-/-mice. Treatment promoted a significant increase in GSH concentrations in the liver (p<0.05) and significantly increased GPx activity in the liver and erythrocytes of apoE-/-mice (p<0.005). The level of 8-isoprostanes were significantly reduced in the livers and arteries of apoE-/mice (p<0.05 and p<0.0005, respectively). Ribose-cysteine treatment showed a significant decrease in total and low density lipoprotein (LDL) cholesterol (p<0.05) with no effect on other plasma lipids with the LDL reduction likely through upregulation of scavenger receptor-B1 (SR-B1). Ribose-cysteine treatment significantly reduced atherosclerotic lesion area by >50% in both the aortic sinus and brachiocephalic branch (p<0.05). Ribose-cysteine promotes a significant GSH-based antioxidant effect in multiple tissues as well as an LDL-lowering response. These effects are accompanied by a marked reduction in atherosclerosis suggesting that ribose-cysteine might increase protection against CVD.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 79%

Ribose-cysteine protects against the development of atherosclerosis in apoE-deficient mice

et al. 2020

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“…It was reported that a significant amount of ROS was produced spontaneously from ox-LDL in vitro and in vivo [53,63]. ROS and oxidative Fig.…”

Section: Discussionmentioning

confidence: 99%

Probucol Protects Endothelial Progenitor Cells Against Oxidized Low-Density Lipoprotein via Suppression of Reactive Oxygen Species Formation In Vivo

Zhang

Chen

et al. 2016

Cell Physiol Biochem

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Background/Aims: Oxidized low-density lipoprotein (ox-LDL) is a major component of hyperlipidemia and contributes to atherosclerosis. Endothelial progenitor cells (EPCs) play an important role in preventing atherosclerosis and notably decreased in hyperlipidemia. Ox-LDL and ox-LDL-related reactive oxygen species (ROS) have deleterious effects on EPCs. Probucol as an antioxidant and anti-inflammatory drug reduces ROS production. The present study was to determine if probucol could protect EPCs from ox-LDL in vivo and to investigate the potential mechanisms. Methods: ox-LDL was injected into male C57BL/6 mice for 3 days with or without probucol treatment with PBS as control. Bone marrow (BM) fluid, serum, circulating mononuclear cells (MNCs) and EPCs were collected for analysis. Results: the increased extracellular ROS in BM, serum and blood intracellular ROS production in the mice with ox-LDL treatment in association with a significant reduction of circulating MNCs and EPCs were restored with Probucol treatment. A significant increase in the serum ox-LDL and C-reactive protein and decrease in superoxide dismutase and circulating MNCs and EPCs were observed in hyperlipidemic patients that were effectively reversed with probucol treatment. Conclusion: these data suggested that probucol could protect EPCs from ox-LDL through inhibition of ROS production in vivo.

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“…In turn, oxidative stress promotes oxidation of cell phospholipids and generation of Tr-OxPLs [ 30 ]. Suppression of oxidative stress by ROS scavengers like NAC has been shown to attenuate in vivo oxidation of circulating lipoproteins in patients [ 44 ]. WR-1065, a bioactive thiol metabolite of amifostine, acts as free-radical scavenger and, similarly to NAC, protects cells and tissues from oxidative damage.…”

Section: Discussionmentioning

confidence: 99%

Role of truncated oxidized phospholipids in acute endothelial barrier dysfunction caused by particulate matter

et al. 2018

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Particulate matter (PM) air pollution is a global environmental health problem contributing to more severe lung inflammation and injury. However, the molecular and cellular mechanisms of PM-induced exacerbation of lung barrier dysfunction and injury are not well understood. In the current study, we tested a hypothesis that PM exacerbates vascular barrier dysfunction via ROS-induced generation of truncated oxidized phospholipids (Tr-OxPLs). Treatment of human pulmonary endothelial cells with PM caused endothelial cell barrier disruption in a dose-dependent fashion. Biochemical analysis showed destabilization of cell junctions by PM via tyrosine phosphorylation and internalization of VE-cadherin. These events were accompanied by PM-induced generation of Tr-OxPLs, detected by mass spectrometry analysis. Furthermore, purified Tr-OxPLs: POVPC, PGPC and lyso-PC alone, caused a rapid increase in endothelial permeability and augmented pulmonary endothelial barrier dysfunction induced by submaximal doses of PM. In support of a role of TR-OxPLs-dependent mechanism in mediation of PM effects, ectopic expression of intracellular type 2 platelet-activating factor acetylhydrolase (PAFAH2), which specifically hydrolyzes Tr-OxPLs, significantly attenuated PM-induced endothelial hyperpermeability. In summary, this study uncovered a novel mechanism of PM-induced sustained dysfunction of pulmonary endothelial cell barrier which is driven by PM-induced generation of truncated products of phospholipid oxidation causing destabilization of cell junctions.

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N-acetylcysteine inhibits in vivo oxidation of native low-density lipoprotein

Cited by 24 publications

References 43 publications

Ribose-cysteine protects against the development of atherosclerosis in apoE-deficient mice

Ribose-cysteine protects against the development of atherosclerosis in apoE-deficient mice

Probucol Protects Endothelial Progenitor Cells Against Oxidized Low-Density Lipoprotein via Suppression of Reactive Oxygen Species Formation In Vivo

Role of truncated oxidized phospholipids in acute endothelial barrier dysfunction caused by particulate matter

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