N-acetylcysteine reduces methemoglobin in an in-vitro model of glucose-6-phosphate dehydrogenase deficiency

被引:15
|
作者
Wright, RO
Woolf, AD
Shannon, MW
Magnani, B
机构
[1] Harvard Univ, Childrens Hosp, Sch Med, Div Gen Pediat, Boston, MA 02115 USA
[2] Harvard Univ, Childrens Hosp, Sch Med, Div Emergency Med, Boston, MA 02115 USA
[3] Harvard Univ, Childrens Hosp, Sch Med, Program Clin Pharmacol Toxicol, Boston, MA 02115 USA
[4] Harvard Univ, Childrens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA
[5] Harvard Univ, Childrens Hosp, Sch Med, Dept Lab Med Pathol, Boston, MA 02115 USA
[6] Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesia, Boston, MA 02115 USA
[7] Massachusetts Poison Control Syst, Boston, MA USA
关键词
N-acetylcysteine; methemoglobin; glucose-6-phosphate dehydrogenase deficiency; G6PD deficiency; toxicology; poisoning; antidote;
D O I
10.1111/j.1553-2712.1998.tb02617.x
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Objective: To determine whether N-acetylcysteine (NAG) 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 mu mol), a specific inhibitor of G6PD. After 75 mu L of 0.18 mol hydroxylamine (HA) was added to induce MHB formation, 150 mu L of NAC (20 mg/mL) was added to tube 1 and 150 mu L 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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页码:225 / 229
页数:5
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