Intracellular glutathione and bronchoalveolar cells in fibrosing alveolitis:: effects of N-acetylcysteine
Intracellular glutathione and bronchoalveolar cells in fibrosing alveolitis:: effects of N-acetylcysteine
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DOI：
10.1183/09031936.02.00204902
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发表时间：
2002-05-01
影响因子：
24.3
通讯作者：
Vogelmeier, C
中科院分区：
文献类型：
--
作者：
Behr, J;Degenkolb, B;Vogelmeier, C
细胞外谷胱甘肽缺乏和过度氧化应激可能是纤维化肺泡炎的发病机制之一。高剂量n -乙酰半胱氨酸（NAC）补充部分逆转细胞外谷胱甘肽消耗和氧化损伤，但对细胞内谷胱甘肽的影响尚不清楚。对18例FA患者（9例男性，年龄52+/-2岁）在口服NAC (600mg t.i.d) 12周前后的细胞内总谷胱甘肽（GSH(t)）和支气管肺泡灌洗细胞（BAC）的活化进行了评估。8名健康非吸烟者（2名男性，年龄36+/-6岁）作为对照组。FA降低了细胞内GSH(t) （1.57+/-0.20 nmol）。1 × 10(6) BAC(-1) vs . 2.78+/-0.43 nmol。10 (6) BAC(1))。NAC处理后，细胞内GSH(t)含量增加（1.57+/-0.20 nmol vs 1.87+/-0.19 nmol）。1 x10 (6) BAC(1))。NAC处理后BAC的自发氧化活性降低(2.7+/-0.8与1.0+/-0.2 nmol-1 × 10(6) BAC（-1).h(-1)）。白细胞介素-8浓度（82.1+/-31.5 vs 80.0+/-22.6 pg.mL）和髓过氧化物酶活性（1.93+/-0.64 vs 1.55+/-0.47 mU）。mL(-1) BALF， NS)无显著变化，但与细胞内GSH(t)呈负相关。综上所述，高剂量n -乙酰半胱氨酸补充可轻微提高细胞内谷胱甘肽水平。在这些患者中，这种增加与氧化活性的轻度降低有关，但与支气管肺泡细胞活性的降低无关。
Extracellular glutathione deficiency and exaggerated oxidative stress may contribute to the pathogenesis of fibrosing alveolitis (FA). High-dose N-acetylcysteine (NAC) supplementation partially reverses extracellular glutathione depletion and oxidative damage, but effects on intracellular glutathione are unknown.Intracellular total glutathione (GSH(t)) and activation of bronchoalveolar lavage cells (BAC) obtained from 18 FA patients (9 males, aged 52+/-2 yrs), before and after 12 weeks of oral NAC (600 mg t.i.d.), were assessed. Eight healthy nonsmokers (2 males, aged 36+/-6 yrs) served as a control group.Intracelluar GSH(t) was decreased in FA (1.57+/-0.20 nmol.1x10(6) BAC(-1) versus 2.78+/-0.43 nmol.10(6) BAC(-1)). After NAC treatment, the intracellular GSH(t) content increased (1.57+/-0.20 versus 1.87+/-0.19 nmol.1x10(6) BAC(-1)). The spontaneous oxidative activity of BAC decreased after NAC treatment (2.7+/-0.8 versus 1.0+/-0.2 nmol-1x10(6) BAC(-1).h(-1)). Interleukin-8 concentration (82.1+/-31.5 versus 80.0+/-22.6 pg.mL bronchoalveolar fluid (BALF), nonsignificant (NS)) and myeloperoxidase activity (1.93+/-0.64 versus 1.55+/-0.47 mU.mL(-1) BALF, NS) did not change significantly, but were found to be inversely correlated to intracellular GSH(t).In conclusion, high-dose N-acetylcysteine supplementation increases intracellular glutathione levels slightly. This increase is associated with a mild reduction of oxidative activity but not with a reduction of bronchoalveolar cell activation in these patients.