{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:30:24Z","timestamp":1790645424634,"version":"4.1.0"},"reference-count":33,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2010,9]]},"abstract":"<jats:p> Chronic kidney disease (CKD) is associated with accelerated atherosclerosis and cardiovascular disease, which is largely mediated by oxidative stress. We investigated the effect of three glutathione (GSH) precursors: N-acetyl-cysteine (NAC), cystine as the physiological carrier of cysteine in GSH with added selenomethionine (F1), and NAC fortified with selenomethionine (F2) on oxidative stress induced by spermine (a uremic toxin) in cultured human aortic vascular smooth muscle cells (VSMC). VSMC were exposed to spermine (15 \u03bcM) with or without the given antioxidants (dose 50, 100, 200, and 500 \u03bcg\/ml) or vehicle (control) and assessed for intracellular GSH levels, 4-hydroxy-trans-2-nonenal (4-HNE), and incorporation of <jats:sup>13<\/jats:sup>C from glucose into alanine and protein. Spermine exposure reduced intracellular GSH levels, increased 4-HNE, and impaired glucose metabolism through reduction in pyruvate generation and\/or transamination. Treatment with NAC had no effect on intracellular glutathione level. In contrast, F1 maintained intracellular GSH at control levels at all four doses. Subsequent studies performed with 200 \u03bcg\/ml of F1, F2, or NAC (optimal dose) revealed normalization of 4-HNE, whereas restoration of <jats:sup>13<\/jats:sup>C from glucose to alanine or protein to control values was only noted in the F1 group. Spermine-induced alterations in VSMC ultrastructure were prevented in \u223c90% of cells treated with F1 but only \u223c50% of cells treated with either NAC or F2. In conclusion, F1 was more effective than NAC or F2 in ameliorating spermine-induced reduction in intracellular GSH levels and cellular alterations in VSMC. The cystine-based GSH precursor (F1) is a promising antioxidant, and further studies are needed to examine the effect of this compound in preventing CKD-associated vascular disease. <\/jats:p>","DOI":"10.1152\/ajpcell.00434.2009","type":"journal-article","created":{"date-parts":[[2010,7,12]],"date-time":"2010-07-12T10:20:35Z","timestamp":1278930035000},"page":"C638-C642","source":"Crossref","is-referenced-by-count":21,"title":["Effects of a novel cystine-based glutathione precursor on oxidative stress in vascular smooth muscle cells"],"prefix":"10.1152","volume":"299","author":[{"given":"Indrani","family":"Sinha-Hikim","sequence":"first","affiliation":[{"name":"Department of Medicine, Charles Drew University, Los Angeles;"},{"name":"David Geffen School of Medicine at University of California, Los Angeles;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoqing","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Charles Drew University, Los Angeles;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai-Nang N.","family":"Paul Lee","sequence":"additional","affiliation":[{"name":"Los Angeles Biomedical Research Institute, Torrance;"},{"name":"David Geffen School of Medicine at University of California, Los Angeles;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Crum","sequence":"additional","affiliation":[{"name":"Proimmune, Rhinebeck, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nosratola D.","family":"Vaziri","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, University of California Irvine, California; 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