Comparison of methylene blue, riboflavin, and N-acetylcysteine for the reduction of nitric oxide-induced methemoglobinemia.
OBJECTIVE
To investigate the treatment of nitric oxide (NO)-induced methemoglobinemia by methylene blue (MB), riboflavin, and N-acetylcysteine (NAC) in vitro.


METHODS
Prospective, controlled in vitro study.


METHODS
Research laboratory in a university hospital.


METHODS
Five healthy volunteers.


METHODS
Generation of 16% to 18% of methemoglobin in red blood cells by NO and subsequent addition of MB, riboflavin, or NAC. Simultaneous NO (32 ppm) and MB or riboflavin exposure of red blood cells. Induction of 14% to 18% of methemoglobin in red blood cells by NO, subsequent addition of MB or riboflavin, and further incubation with NO (80 ppm).


RESULTS
After discontinuation of NO, mean half-life for methemoglobin was significantly reduced by MB from 356 mins (controls) to 5 mins (10 microM) in a dose-dependent manner (p < .001). NAC did not alter the half-life for methemoglobin, and a reduction from 356 to 168 mins was seen for 120 microM riboflavin (p < .001). Methemoglobin formation after 3 hrs of NO exposure was 4.3%+/-0.7% in controls and 0.3%+/-0.1% with 10 microM MB (p < .001); 1 microM MB attenuated methemoglobin formation to 1.9%+/-0.1% (p < .01). With riboflavin (120 microM), methemoglobin was 2.2%+/-0.5% vs. 3.2%+/-0.6% in controls (p < .001). In the presence of high methemoglobin concentrations, further methemoglobin formation was inhibited by 1 and 10 microM MB (p < .001) and attenuated by 0.1 microM MB (p < .001) but not by riboflavin.


CONCLUSIONS
In vitro, NO-induced methemoglobin formation is significantly decreased by medium (1 microM) and high (10 microM) concentrations of MB and partially by high riboflavin concentrations (120 microM). NAC and low concentrations of riboflavin do not alter methemoglobin formation.
Dötsch
J
J
Department of Pediatrics, Friedrich-Alexander-University of Erlangen-Nürnberg, Germany.
Demirakça
S
S
Kratz
M
M
Repp
R
R
Knerr
I
I
Rascher
W
W
D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006801:Humans; D008706:Methemoglobin / Q000032:analysis / Q000187:drug effects; D008708:Methemoglobinemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D008751:Methylene Blue / Q000627:therapeutic use*; D009569:Nitric Oxide; D012256:Riboflavin / Q000627:therapeutic use*
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D009569:Nitric Oxide; D008706:Methemoglobin; D008751:Methylene Blue; D012256:Riboflavin; D000111:Acetylcysteine