Abstract
In the present paper, the extracellular antioxidant activity of N-acetyl-cysteine (NAC) is explained by considering its ability to regenerate the free form of albumin Cys34 by breaking the disulfide bond of the cysteinylated form (HSA-Cys). NAC’s capability to regenerate albumin Cys34 (HSA-SH) was studied by MS intact protein analysis in human plasma and in a concentration range of NAC easily achievable after oral and i.v. administration (5–50 µg/mL). NAC dose-dependently broke the HSA-Cys bond to form the dimer NAC-Cys thus regenerating Cys34, whose reduced state was maintained for at least 120 min. Cys was faster in restoring Cys34, according to the reaction constant determined with the glutathione disulfide (GSSG) reaction, but after 60 min the mixed disulfide HSA-Cys turned back due to the reaction of the dimer Cys-Cys with Cys34. The explanation for the different rate exchanges between Cys-Cys and Cys-NAC with Cys34 was given by molecular modeling studies. Finally, the Cys34 regenerating effect of NAC was related to its ability to improve the total antioxidant capacity of plasma (TRAP assay). The results well indicate that NAC greatly increases the plasma antioxidant activity and this effect is not reached by a direct effect but through the regenerating effect of Cys34.
Highlights
N-acetylcysteine (NAC), the N-acetyl derivative of the natural amino acid l-cysteine, is a reference antioxidant compound widely used in in vitro and ex vivo conditions
The present paper demonstrates that NAC enhances the plasma antioxidant activity by restoring Cys34 through a selective thiol-disulfide mechanism
The present paper demonstrates that NAC enhances the plasma antioxidant in patients with oxidative-based diseases and characterized by an impaired balance between Cys34 in activity by restoring Cys34 through a selective thiol-disulfide mechanism
Summary
N-acetylcysteine (NAC), the N-acetyl derivative of the natural amino acid l-cysteine, is a reference antioxidant compound widely used in in vitro and ex vivo conditions. A critical insight into the antioxidant property of NAC showed that the direct antioxidant activity of NAC is not really efficient, in particular when compared to other endogenous thiols such as Cys or GSH [1]. This is explained by the low acidity of the NAC thiol as a consequence of the amino group acetylation, making the equilibrium between the antioxidant form (thiolate) and the thiol, largely shift toward the latter, which is the inactive from. By considering the reaction rates of the endogenous antioxidants, of the substrates and of NAC toward the main radical and non-radical oxidants, it can be assumed that NAC acts as a direct antioxidant agent only toward some specific oxidants and when it is present in a high concentration as when it occurs in in vitro condition
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
