N-acetylcysteine reduces methemoglobin in an in-vitro model of glucose-6-phosphate dehydrogenase deficiency.
OBJECTIVE
To determine whether N-acetylcysteine (NAC) reduces methemoglobin (MHB) in an in-vitro model of glucose-6-phosphate dehydrogenase (G6PD) deficiency, given that methylene blue is an ineffective MHB antidote in G6PD deficiency.


METHODS
Five volunteers donated blood, which was divided equally into 2 test tubes, centrifuged, and washed with Tris-Mopps buffer (pH 7.4, 15 mmol/L glucose). Both tubes were incubated with epiandrosterone (EA) (400 micromol), a specific inhibitor of G6PD. After 75 microL of 0.18 mol hydroxylamine (HA) was added to induce MHB formation, 150 microL of NAC (20 mg/mL) was added to tube 1 and 150 microL of phosphate-buffered saline (PBS) was added to tube 2 as a volume control. Serial MHB levels are reported as a percentage of total hemoglobin (Hb). G6PD activity was measured at baseline, 15 minutes after EA, and at 5 hours.


RESULTS
Mean G6PD activity at baseline was 9.2+/-2.9 U/g Hb (normal >4.6 U/g Hb); 15 minutes after EA was 3.0+/-1.0 U/g Hb; and at experiment's end was 2.3+/-0.7 U/g Hb. The mean (+/-SD) areas under the concentration-time curves (AUCs) of NAC-EA-HA and PBS-EA-HA samples were compared using an unpaired t-test and were significantly different: PBS-EA-HA, 20,400+/-1,100 % min, vs NAC-EA-HA, 10,400+/-1,000 % min, respectively (p < 0.05).


CONCLUSIONS
In this in-vitro model of G6PD deficiency, NAC efficiently reduced MHB.
Wright
R O
RO
Department of Medicine, Harvard University Medical School, Children's Hospital, Boston, MA, USA.
Woolf
A D
AD
Shannon
M W
MW
Magnani
B
B
D000111:Acetylcysteine / Q000494:pharmacology*; D000738:Androsterone; D000931:Antidotes / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000378:metabolism*; D006801:Humans; D008706:Methemoglobin / Q000378:metabolism*; D008708:Methemoglobinemia / Q000188:drug therapy; D008751:Methylene Blue
D000931:Antidotes; D016166:Free Radical Scavengers; D008706:Methemoglobin; D000738:Androsterone; D008751:Methylene Blue; D000111:Acetylcysteine