title: Effects of N-acetylcysteine on dense cell formation in sickle cell disease.
abstract: The extent to which dense and irreversible sickle cells (ISCs) contribute to vaso-occlusive episodes in sickle cell disease remains unclear. N-Acetylcysteine (NAC) inhibits dense cell and ISC formation in sickle erythrocytes in vitro and restores glutathione levels toward normal. A phase II double-blind randomized clinical trial was completed to determine the efficacy of NAC in decreasing dense cell and ISC formation, and vaso-occlusive episodes in sickle cell disease. Twenty-one subjects with a history of at least two vaso-occlusive episodes per year and 6% dense cells were enrolled. Four treatment groups were analyzed; NAC at a dose of 2,400 mg per day decreased the percent dense cells from 20.1 +/- 2.9 to 12.6 +/- 2.1 (P < 0.05) and increased red cell glutathione levels from 292.8 +/- 74.5 to 576.7 +/- 155.1 (P < 0.05). In addition, we observed a decrease in vaso-occlusive episodes from 0.03 to 0.006 episodes per person-days and a decreased in relative risk to R = 0.39. Although NAC did not significantly decrease the number of ISCs, there was a downward trend at all doses tested. In summary, NAC inhibited dense cell formation, restored glutathione levels toward normal, and decreased vaso-occlusive episodes at a well-tolerated dose of 2,400 mg per day. To determine the long-term efficacy and safety of NAC, a multicenter phase III clinical trial is required.
authors.affiliation: Department of Molecular and Cell Biology, University of Texas at Dallas, 2601 Floyd Road, Mail Station FO 3.1, Richardson, TX 75083, USA. bpace@utdallas.edu
authors.forename: Betty S
authors.initials: BS
authors.lastname: Pace
authors.forename: Archil
authors.initials: A
authors.lastname: Shartava
authors.forename: Ardie
authors.initials: A
authors.lastname: Pack-Mabien
authors.forename: Mudhari
authors.initials: M
authors.lastname: Mulekar
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ardia
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goodman
mesh_terms: D000111:Acetylcysteine / Q000097:blood / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004913:Erythrocytes, Abnormal / Q000737:chemistry / Q000473:pathology*; D005260:Female; D005978:Glutathione / Q000097:blood; D006801:Humans; D008297:Male; D010919:Placebos; D014652:Vascular Diseases / Q000209:etiology / Q000517:prevention & control
chemical_list: D010919:Placebos; D005978:Glutathione; D000111:Acetylcysteine