Mechanisms of Drug Toxicity Group, Pharmaceutical Sciences Institute, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
Environ Toxicol Pharmacol. 2003 Sep;14(3):121-7. doi: 10.1016/S1382-6689(03)00048-6.
α-Lipoic acid, dihydrolipoic acid (DHLA), N-acetyl cysteine and ascorbate were compared with methylene blue for their ability to attenuate and/or reduce methaemoglobin formation induced by sodium nitrite, 4-aminophenol and dapsone hydroxylamine in human erythrocytes. Neither α-lipoic acid, DHLA, N-acetyl cysteine nor ascorbate had any significant effects on methaemoglobin formed by nitrite, either from pre-treatment, simultaneous addition or post 30 min addition of the agents up to the 60 min time point, although N-acetyl cysteine did reduce methaemoglobin formation at 120 min (P<0.05). In all three treatment groups at 30, 60 and 120 min, there were no significant effects mediated by DHLA or N-acetyl cysteine on 4-aminophenol (1 mM)-mediated haemoglobin oxidation. Ascorbate caused marked significant reductions in 4-aminophenol methaemoglobin in all treatment groups at 30-120 min except at 30 min in the simultaneous addition group (P<0.0001). Neither α-lipoic acid, nor N-acetyl cysteine showed any effects on hydroxylamine-mediated methaemoglobin formation at 30 and 60 in all treatment groups. In contrast, DHLA significantly reduced hydroxylamine-mediated methaemoglobin formation at all three time points after pre-incubation and simultaneous addition (P<0.001), while ascorbate was ineffective. Compared with methylene blue, which was effective in reducing methaemoglobin formation by all three toxins (P<0.01), ascorbate was only highly effective against 4-aminophenol mediated methaemoglobin, whilst the DHLA-mediated attenuation of dapsone hydroxylamine-mediated methaemoglobin formation indicates a possible clinical application in high-dose dapsone therapy.
α-硫辛酸、二氢硫辛酸（DHLA）、N-乙酰半胱氨酸和抗坏血酸与亚甲蓝进行了比较，以评估它们对亚硝酸钠、4-氨基酚和对氨苯砜羟胺诱导的人红细胞中高铁血红蛋白形成的抑制和/或减少作用。α-硫辛酸、DHLA、N-乙酰半胱氨酸和抗坏血酸对亚硝酸钠形成的高铁血红蛋白均无显著影响，无论是预处理、同时添加还是在 30 分钟后添加至 60 分钟时间点，尽管 N-乙酰半胱氨酸确实减少了 120 分钟时的高铁血红蛋白形成（P<0.05）。在所有三个治疗组中，在 30、60 和 120 分钟时，DHLA 或 N-乙酰半胱氨酸对 4-氨基酚（1mM）介导的血红蛋白氧化均无显著影响。抗坏血酸在所有治疗组中都显著减少了 4-氨基酚高铁血红蛋白，除了在同时添加组的 30 分钟时（P<0.0001）。在所有治疗组中，α-硫辛酸和 N-乙酰半胱氨酸在 30 和 60 分钟时均未显示对羟胺介导的高铁血红蛋白形成有任何影响。相比之下，DHLA 在预孵育和同时添加后所有三个时间点都显著降低了羟胺介导的高铁血红蛋白形成（P<0.001），而抗坏血酸则无效。与对三种毒素（P<0.01）诱导的高铁血红蛋白形成均有效的亚甲蓝相比，抗坏血酸仅对 4-氨基酚介导的高铁血红蛋白非常有效，而 DHLA 介导的对氨苯砜羟胺介导的高铁血红蛋白形成的抑制作用表明其可能在大剂量对氨苯砜治疗中有临床应用。
