Limits...
N-acetylcysteine reduces oxidative stress in sickle cell patients.

Nur E, Brandjes DP, Teerlink T, Otten HM, Oude Elferink RP, Muskiet F, Evers LM, ten Cate H, Biemond BJ, Duits AJ, Schnog JJ, CURAMA study gro - Ann. Hematol. (2012)

Bottom Line: One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose.During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications.These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands.

ABSTRACT
Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbSβ(0)-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress.

Show MeSH

Related in: MedlinePlus

Plasma levels of AGEs (pentosidine and Nε-(carboxy-methyl)lysine (CML)) in controls (CTRL; white bar) and sickle cell patients (SCD) at baseline (black bar) and after 6 weeks (gray bar) N-acetylcysteine (NAC) treatment. a Baseline pentosidine levels were higher in sickle cell patients than in controls (P < 0.0001). Pentosidine decreased after 6 weeks NAC treatment in both 1,200 and 2,400 mg groups, though the differences were not statistically significant. b CML levels at baseline were also higher in sickle cell patients than in controls (P = 0.019) and decreased after 6 weeks NAC treatment in both groups. Means ± SEM
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3368118&req=5

Fig4: Plasma levels of AGEs (pentosidine and Nε-(carboxy-methyl)lysine (CML)) in controls (CTRL; white bar) and sickle cell patients (SCD) at baseline (black bar) and after 6 weeks (gray bar) N-acetylcysteine (NAC) treatment. a Baseline pentosidine levels were higher in sickle cell patients than in controls (P < 0.0001). Pentosidine decreased after 6 weeks NAC treatment in both 1,200 and 2,400 mg groups, though the differences were not statistically significant. b CML levels at baseline were also higher in sickle cell patients than in controls (P = 0.019) and decreased after 6 weeks NAC treatment in both groups. Means ± SEM

Mentions: Plasma levels of cell-free hemoglobin decreased after NAC treatment and returned towards baseline levels after cessation of the treatment in patients of both 1,200 (from 5.0 (1.4–16.7) to 2.7 (2.1–8.5) μmol/l) and 2,400 mg (from 6.5 (4.5–10.4) μmol/l to 6.5 (3.4–7.8) μmol/l) groups, though the differences were not statistically significant (Fig. 3, panels g and h). Both pentosidine and CML were significantly higher in sickle cell patients at baseline as compared to healthy controls, and CML decreased significantly after 6 weeks of treatment when analyzing the two dose groups together (Fig. 4). None of the other measured parameters changed during the treatment period (Table 1).Fig. 4


N-acetylcysteine reduces oxidative stress in sickle cell patients.

Nur E, Brandjes DP, Teerlink T, Otten HM, Oude Elferink RP, Muskiet F, Evers LM, ten Cate H, Biemond BJ, Duits AJ, Schnog JJ, CURAMA study gro - Ann. Hematol. (2012)

Plasma levels of AGEs (pentosidine and Nε-(carboxy-methyl)lysine (CML)) in controls (CTRL; white bar) and sickle cell patients (SCD) at baseline (black bar) and after 6 weeks (gray bar) N-acetylcysteine (NAC) treatment. a Baseline pentosidine levels were higher in sickle cell patients than in controls (P < 0.0001). Pentosidine decreased after 6 weeks NAC treatment in both 1,200 and 2,400 mg groups, though the differences were not statistically significant. b CML levels at baseline were also higher in sickle cell patients than in controls (P = 0.019) and decreased after 6 weeks NAC treatment in both groups. Means ± SEM
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368118&req=5

Fig4: Plasma levels of AGEs (pentosidine and Nε-(carboxy-methyl)lysine (CML)) in controls (CTRL; white bar) and sickle cell patients (SCD) at baseline (black bar) and after 6 weeks (gray bar) N-acetylcysteine (NAC) treatment. a Baseline pentosidine levels were higher in sickle cell patients than in controls (P < 0.0001). Pentosidine decreased after 6 weeks NAC treatment in both 1,200 and 2,400 mg groups, though the differences were not statistically significant. b CML levels at baseline were also higher in sickle cell patients than in controls (P = 0.019) and decreased after 6 weeks NAC treatment in both groups. Means ± SEM
Mentions: Plasma levels of cell-free hemoglobin decreased after NAC treatment and returned towards baseline levels after cessation of the treatment in patients of both 1,200 (from 5.0 (1.4–16.7) to 2.7 (2.1–8.5) μmol/l) and 2,400 mg (from 6.5 (4.5–10.4) μmol/l to 6.5 (3.4–7.8) μmol/l) groups, though the differences were not statistically significant (Fig. 3, panels g and h). Both pentosidine and CML were significantly higher in sickle cell patients at baseline as compared to healthy controls, and CML decreased significantly after 6 weeks of treatment when analyzing the two dose groups together (Fig. 4). None of the other measured parameters changed during the treatment period (Table 1).Fig. 4

Bottom Line: One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose.During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications.These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands.

ABSTRACT
Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbSβ(0)-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress.

Show MeSH
Related in: MedlinePlus