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

Cui Y, Narasimhulu CA, Liu L, Zhang Q, Liu PZ, Li X, Xiao Y, Zhang J, Hao H, Xie X, He G, Cui L, Parthasarathy S, Liu Z - Sci Rep (2015)

Bottom Line: NAC treatment also significantly decreased serum ox-LDL level in patients with coronary artery diseases and hyperlipidemia without effect on LDL level.NAC also significantly reduced atherosclerotic plaque formation in hyperlipidemic LDLR(-/-) mice.NAC attenuated in vivo oxidation of native LDL and ROS formation from ox-LDL associated with decreased atherosclerotic plaque formation in hyperlipidemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.

ABSTRACT
Low-density lipoprotein (LDL) is non-atherogenic, while oxidized LDL (ox-LDL) is critical to atherosclerosis. N-acetylcysteine (NAC) has anti-atherosclerotic effect with largely unknown mechanisms. The present study aimed to determine if NAC could attenuate in vivo LDL oxidation and inhibit atherosclerosis. A single dose of human native LDL was injected intravenously into male C57BL/6 mice with and without NAC treatment. Serum human ox-LDL was detected 30 min after injection, reached the peak in 3 hours, and became undetectable in 12 hours. NAC treatment significantly reduced serum ox-LDL level without detectable serum ox-LDL 6 hours after LDL injection. No difference in ox-LDL clearance was observed in NAC-treated animals. NAC treatment also significantly decreased serum ox-LDL level in patients with coronary artery diseases and hyperlipidemia without effect on LDL level. Intracellular and extracellular reactive oxidative species (ROS) production was significantly increased in the animals treated with native LDL, or ox-LDL and in hyperlipidemic LDL receptor knockout (LDLR(-/-)) mice that was effectively prevented with NAC treatment. NAC also significantly reduced atherosclerotic plaque formation in hyperlipidemic LDLR(-/-) mice. NAC attenuated in vivo oxidation of native LDL and ROS formation from ox-LDL associated with decreased atherosclerotic plaque formation in hyperlipidemia.

No MeSH data available.


Related in: MedlinePlus

Native LDL conversion to ox-LDL in vivo.After a single injection of human native LDL to C57BL/6 mouse, the serum levels of native LDL and ox-LDL were determined at different time points. The native LDL level reached the peak in 5 min and stayed at a significantly elevated level for 1 hour, then gradually decreased to undetectable level in 10 hours. A measurable level of ox-LDL was detected 30 min after intravenous administration of native LDL. The serum ox-LDL level reached the peak in 3 hours, then started to decline, but stayed at detectable level until shortly after the disappearance of native LDL (A). The peak serum ox-LDL level at 3 hours after native LDL injection was dramatically decreased in the animals with NAC treatment (B). *P < 0.01, n = 5; **P < 0.001, #P < 0.001, n = 5.
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f2: Native LDL conversion to ox-LDL in vivo.After a single injection of human native LDL to C57BL/6 mouse, the serum levels of native LDL and ox-LDL were determined at different time points. The native LDL level reached the peak in 5 min and stayed at a significantly elevated level for 1 hour, then gradually decreased to undetectable level in 10 hours. A measurable level of ox-LDL was detected 30 min after intravenous administration of native LDL. The serum ox-LDL level reached the peak in 3 hours, then started to decline, but stayed at detectable level until shortly after the disappearance of native LDL (A). The peak serum ox-LDL level at 3 hours after native LDL injection was dramatically decreased in the animals with NAC treatment (B). *P < 0.01, n = 5; **P < 0.001, #P < 0.001, n = 5.

Mentions: Native LDL was rapidly converted to ox-LDL with significant increase in serum ox-LDL by 30 min after injection. The maximal ox-LDL level was observed by 3 hours, then started to decline gradually afterwards with no detectable serum ox-LDL 12 hours after native LDL administration (Fig. 2A). A detectable level of both intracellular and extracellular ROS was generated in the animals after intravenous native LDL administration. Similar results on intracellular and extracellular ROS production were observed in the mice treated with ox-LDL injection. No in vivo ROS production was detected in the animals received Sat-LDL (Fig. 3A).


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

Cui Y, Narasimhulu CA, Liu L, Zhang Q, Liu PZ, Li X, Xiao Y, Zhang J, Hao H, Xie X, He G, Cui L, Parthasarathy S, Liu Z - Sci Rep (2015)

Native LDL conversion to ox-LDL in vivo.After a single injection of human native LDL to C57BL/6 mouse, the serum levels of native LDL and ox-LDL were determined at different time points. The native LDL level reached the peak in 5 min and stayed at a significantly elevated level for 1 hour, then gradually decreased to undetectable level in 10 hours. A measurable level of ox-LDL was detected 30 min after intravenous administration of native LDL. The serum ox-LDL level reached the peak in 3 hours, then started to decline, but stayed at detectable level until shortly after the disappearance of native LDL (A). The peak serum ox-LDL level at 3 hours after native LDL injection was dramatically decreased in the animals with NAC treatment (B). *P < 0.01, n = 5; **P < 0.001, #P < 0.001, n = 5.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4633729&req=5

f2: Native LDL conversion to ox-LDL in vivo.After a single injection of human native LDL to C57BL/6 mouse, the serum levels of native LDL and ox-LDL were determined at different time points. The native LDL level reached the peak in 5 min and stayed at a significantly elevated level for 1 hour, then gradually decreased to undetectable level in 10 hours. A measurable level of ox-LDL was detected 30 min after intravenous administration of native LDL. The serum ox-LDL level reached the peak in 3 hours, then started to decline, but stayed at detectable level until shortly after the disappearance of native LDL (A). The peak serum ox-LDL level at 3 hours after native LDL injection was dramatically decreased in the animals with NAC treatment (B). *P < 0.01, n = 5; **P < 0.001, #P < 0.001, n = 5.
Mentions: Native LDL was rapidly converted to ox-LDL with significant increase in serum ox-LDL by 30 min after injection. The maximal ox-LDL level was observed by 3 hours, then started to decline gradually afterwards with no detectable serum ox-LDL 12 hours after native LDL administration (Fig. 2A). A detectable level of both intracellular and extracellular ROS was generated in the animals after intravenous native LDL administration. Similar results on intracellular and extracellular ROS production were observed in the mice treated with ox-LDL injection. No in vivo ROS production was detected in the animals received Sat-LDL (Fig. 3A).

Bottom Line: NAC treatment also significantly decreased serum ox-LDL level in patients with coronary artery diseases and hyperlipidemia without effect on LDL level.NAC also significantly reduced atherosclerotic plaque formation in hyperlipidemic LDLR(-/-) mice.NAC attenuated in vivo oxidation of native LDL and ROS formation from ox-LDL associated with decreased atherosclerotic plaque formation in hyperlipidemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.

ABSTRACT
Low-density lipoprotein (LDL) is non-atherogenic, while oxidized LDL (ox-LDL) is critical to atherosclerosis. N-acetylcysteine (NAC) has anti-atherosclerotic effect with largely unknown mechanisms. The present study aimed to determine if NAC could attenuate in vivo LDL oxidation and inhibit atherosclerosis. A single dose of human native LDL was injected intravenously into male C57BL/6 mice with and without NAC treatment. Serum human ox-LDL was detected 30 min after injection, reached the peak in 3 hours, and became undetectable in 12 hours. NAC treatment significantly reduced serum ox-LDL level without detectable serum ox-LDL 6 hours after LDL injection. No difference in ox-LDL clearance was observed in NAC-treated animals. NAC treatment also significantly decreased serum ox-LDL level in patients with coronary artery diseases and hyperlipidemia without effect on LDL level. Intracellular and extracellular reactive oxidative species (ROS) production was significantly increased in the animals treated with native LDL, or ox-LDL and in hyperlipidemic LDL receptor knockout (LDLR(-/-)) mice that was effectively prevented with NAC treatment. NAC also significantly reduced atherosclerotic plaque formation in hyperlipidemic LDLR(-/-) mice. NAC attenuated in vivo oxidation of native LDL and ROS formation from ox-LDL associated with decreased atherosclerotic plaque formation in hyperlipidemia.

No MeSH data available.


Related in: MedlinePlus