The metabolism of N-acetylcysteine by human endothelial cells.
When human umbilical endothelial cells were depleted of their glutathione by incubation in a sulfur amino acid-free medium, subsequent incubation of the cells with this deficient medium supplemented with N-acetylcysteine resulted in a dose-dependent stimulation of the synthesis of cellular glutathione. Similarly, the inclusion of N-acetylcysteine in the medium during the period of depletion of glutathione caused a dose-dependent retardation of the depletion kinetics. In contrast, the incubation of control cells in normal medium supplemented with N-acetylcysteine did not increase cellular glutathione levels above controls. These observations indicate the presence of an N-deacetylase in/on the cells with specificity for N-acetylcysteine. Due to the large surface area of the endothelium in the vasculature it seems likely that endothelial cell N-deacetylation plays a role in the metabolic disposition of N-acetylcysteine, particularly when administered intravenously. N-Acetylcysteine is, however, a relatively poor precursor to glutathione biosynthesis in comparison to cystine. Thus, any cytoprotective, antioxidant effect exerted by N-acetylcysteine on the human endothelium is likely to be due to direct scavenging of reactive intermediates rather than by stimulated glutathione synthesis in the endothelial cells themselves.
Cotgreave
I
I
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Moldéus
P
P
Schuppe
I
I
D000111:Acetylcysteine / Q000493:pharmacokinetics / Q000494:pharmacology*; D000581:Amidohydrolases / Q000378:metabolism; D000975:Antioxidants; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism*; D005978:Glutathione / Q000096:biosynthesis*; D006801:Humans; D014470:Umbilical Cord
D000975:Antioxidants; D000581:Amidohydrolases; D005978:Glutathione; D000111:Acetylcysteine