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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

NAC treatment decreased serum ox-LDL Level in hyperlipidemic patients.Serum ox-LDL levels were measured using ELISA in the patients with documented coronary artery disease (CAD) and hyperlipidemia after one week of NAC treatment. The serum ox-LDL level was significantly elevated in the patients with hyperlipidemia as compared with the healthy volunteers. NAC treatment significantly decreased the serum ox-LDL level in the patients. The serum ox-LDL remained decreased in the patients one week after discontinuation of NAC. *P < 0.001, NAC treatment vs placebo (n = 5); **p < 0.01, n = 5.
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f5: NAC treatment decreased serum ox-LDL Level in hyperlipidemic patients.Serum ox-LDL levels were measured using ELISA in the patients with documented coronary artery disease (CAD) and hyperlipidemia after one week of NAC treatment. The serum ox-LDL level was significantly elevated in the patients with hyperlipidemia as compared with the healthy volunteers. NAC treatment significantly decreased the serum ox-LDL level in the patients. The serum ox-LDL remained decreased in the patients one week after discontinuation of NAC. *P < 0.001, NAC treatment vs placebo (n = 5); **p < 0.01, n = 5.

Mentions: Serum LDL, non-HDL lipoprotein level, and ox-LDL were all significantly increased in the patients with hyperlipidemia over the age- and sex-matched healthy individuals as expected (Supplemental Table 2). There were no significant differences in lipid profile and serum ox-LDL level in the patients of the two groups at baseline. After one week of NAC treatment, there were no significant changes in serum LDL, non-HDL lipoprotein levels, blood glucose, TSH, kidney and liver functions in the patients. However, the serum ox-LDL was significantly decreased in the patients with NAC treatment as compared with the placebo group (Fig. 5). Of note, decreased level of serum ox-LDL was still present in the patients one week after NAC discontinuation. Moreover, decreased level of serum ox-LDL was still present in the patients one week after NAC discontinuation. These data demonstrated that NAC treatment selectively decreased serum ox-LDL level, indicating that NAC might decrease in vivo oxidation of LDL in the patients.


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)

NAC treatment decreased serum ox-LDL Level in hyperlipidemic patients.Serum ox-LDL levels were measured using ELISA in the patients with documented coronary artery disease (CAD) and hyperlipidemia after one week of NAC treatment. The serum ox-LDL level was significantly elevated in the patients with hyperlipidemia as compared with the healthy volunteers. NAC treatment significantly decreased the serum ox-LDL level in the patients. The serum ox-LDL remained decreased in the patients one week after discontinuation of NAC. *P < 0.001, NAC treatment vs placebo (n = 5); **p < 0.01, n = 5.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: NAC treatment decreased serum ox-LDL Level in hyperlipidemic patients.Serum ox-LDL levels were measured using ELISA in the patients with documented coronary artery disease (CAD) and hyperlipidemia after one week of NAC treatment. The serum ox-LDL level was significantly elevated in the patients with hyperlipidemia as compared with the healthy volunteers. NAC treatment significantly decreased the serum ox-LDL level in the patients. The serum ox-LDL remained decreased in the patients one week after discontinuation of NAC. *P < 0.001, NAC treatment vs placebo (n = 5); **p < 0.01, n = 5.
Mentions: Serum LDL, non-HDL lipoprotein level, and ox-LDL were all significantly increased in the patients with hyperlipidemia over the age- and sex-matched healthy individuals as expected (Supplemental Table 2). There were no significant differences in lipid profile and serum ox-LDL level in the patients of the two groups at baseline. After one week of NAC treatment, there were no significant changes in serum LDL, non-HDL lipoprotein levels, blood glucose, TSH, kidney and liver functions in the patients. However, the serum ox-LDL was significantly decreased in the patients with NAC treatment as compared with the placebo group (Fig. 5). Of note, decreased level of serum ox-LDL was still present in the patients one week after NAC discontinuation. Moreover, decreased level of serum ox-LDL was still present in the patients one week after NAC discontinuation. These data demonstrated that NAC treatment selectively decreased serum ox-LDL level, indicating that NAC might decrease in vivo oxidation of LDL in the patients.

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