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N-Acetylcysteine Reduces Methemoglobin in an In-vitro Model of Glucose-6-phosphate Dehydrogenase Deficiency

  1. Robert O. Wright MD1,3,6,7,*,
  2. Alan D. Woolf MD, MPH1,3,6,
  3. Michael W. Shannon MD, MPH2,3,6,
  4. Barbarajean Magnani MD, PhD4,5,6

Article first published online: 28 JUN 2008

DOI: 10.1111/j.1553-2712.1998.tb02617.x

Issue

Academic Emergency Medicine

Academic Emergency Medicine

Volume 5, Issue 3, pages 225–229, March 1998

Additional Information

How to Cite

Wright, R. O., Woolf, A. D., Shannon, M. W. and Magnani, B. (1998), N-Acetylcysteine Reduces Methemoglobin in an In-vitro Model of Glucose-6-phosphate Dehydrogenase Deficiency. Academic Emergency Medicine, 5: 225–229. doi: 10.1111/j.1553-2712.1998.tb02617.x

Author Information

  1. 1

    Harvard University Medical School, Children s Hospital, Boston, MA, Divisions of General Pediatrics

  2. 2

    Harvard University Medical School, Children s Hospital, Boston, MA, Divisions of General Pediatrics and Emergency Medicine

  3. 3

    Program in Clinical Pharmacology/Toxicology and Departments of Medicine

  4. 4

    Laboratory Medicine/Pathology

  5. 5

    Brigham and Women's Hospital, Boston, MA, Department of Anesthesia, Center for Experimental Therapeutics and Reperfusion Injury

  6. 6

    Massachusetts Poison Control System, Boston, MA

  7. 7

    Brown University School of Medicine, Hasbro Children's Hospital/Rhode Island Hospital, Providence, RI, Department of Pediatrics, Division of Emergency Medicine

* Rhode Island Hospital, Department of Emergency Medicine, Davol Building, 593 Eddy Street, Providence, RI 02903. Fax: 401–444–4307.

Publication History

  1. Issue published online: 28 JUN 2008
  2. Article first published online: 28 JUN 2008
  3. Received: May 28, 1997; revision received: July 30, 1997; accepted: August 6, 1997; updated: November 2, 1997.

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Keywords:

  • N-acetylcysteine;
  • methemoglobin;
  • glucose-6-phosphate dehydrogenase deficiency;
  • G6PD deficiency;
  • toxicology;
  • poisoning;
  • antidote

ABSTRACT

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 μmol), a specific inhibitor of G6PD. After 75 μL of 0.18 mol hydroxylamine (HA) was added to induce MHB formation, 150 μL of NAC (20 mg/mL) was added to tube 1 and 150 μL 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).

Conclusion: In this in-vitro model of G6PD deficiency, NAC efficiently reduced MHB.

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