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

Academic Emergency Medicine - Tập 5 Số 3 - Trang 225-229 - 1998
Robert O. Wright1,2,3,4, Alan D. Woolf2,3,4, Michael W. Shannon5,3,4, B Magnani6,7,3
1Brown University School of Medicine, Hasbro Children's Hospital/Rhode Island Hospital, Providence, RI, Department of Pediatrics, Division of Emergency Medicine
2Harvard University Medical School, Children s Hospital, Boston, MA, Divisions of General Pediatrics
3Massachusetts Poison Control System, Boston, MA
4Program in Clinical Pharmacology/Toxicology and Departments of Medicine
5Harvard University Medical School, Children s Hospital, Boston, MA, Divisions of General Pediatrics and Emergency Medicine
6Brigham and Women's Hospital, Boston, MA, Department of Anesthesia, Center for Experimental Therapeutics and Reperfusion Injury
7Laboratory Medicine/Pathology

Tóm tắt

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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