Mechanisms of Drug Toxicity Group, Department of Pharmaceutical Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
Environ Toxicol Pharmacol. 2001 Sep;10(4):207-13. doi: 10.1016/s1382-6689(01)00084-9.
Diabetes leads to premature organ and system failure and considerably shortens lifespan. Careful control of glucose levels may not be enough to prevent the onset of complications in most diabetics. Compared with non-diabetics, diabetic tissues must not only resist a much greater long-term threat from hyperglycaemia-mediated reactive species but also defend themselves with compromised antioxidant systems. Although antioxidant therapy is a logical step in the prevention of oxidant and carbonyl stresses in the face of intermittent hyperglycaemia, this approach is not yet universally accepted to be effective in preventing complications. Although there are many biochemical indices of oxidant stress, piecemeal elevations of individual markers may not necessarily reflect true diabetic cellular antioxidant status. A dynamic process such as in vitro methaemoglobin generation may provide an opportunity to compare the response of a diabetic erythrocyte with that of a non-diabetic before and after corrective antioxidant therapy. Due to compromised cellular antioxidant capacity, diabetic cells generate less methaemoglobin in the presence of aromatic amine hydroxylamines, 4-aminophenol and nitrite compared with non-diabetics. Agents such as dihydrolipoic acid have been shown to correct methaemoglobin formation-mediated thiol deficits during in vitro studies. It is hoped that the progress of antioxidant supplementation studies in diabetics can be monitored with the aid of in vitro methaemoglobin generation using agents such as hydroxylamines, 4-aminophenol and nitrite. The most appropriate antioxidants and dosages can thus be recommended to diabetics worldwide to attenuate the development of complications.
糖尿病会导致器官和系统提前衰竭，大大缩短寿命。尽管严格控制血糖水平可能不足以预防大多数糖尿病患者并发症的发生，但与非糖尿病患者相比，糖尿病患者的组织不仅必须抵抗高血糖介导的活性物质带来的长期威胁，还必须在抗氧化系统受损的情况下进行自我防御。尽管抗氧化疗法是在面对间歇性高血糖时预防氧化剂和羰基应激的合理步骤，但这种方法在预防并发症方面尚未被普遍认为是有效的。虽然有许多氧化剂应激的生化指标，但个别标志物的零星升高不一定反映真正的糖尿病细胞抗氧化状态。体外高铁血红蛋白生成等动态过程可能为比较糖尿病红细胞和非糖尿病红细胞在抗氧化治疗前后的反应提供机会。由于细胞抗氧化能力受损，与非糖尿病患者相比，糖尿病细胞在存在芳香胺羟胺、4-氨基酚和亚硝酸盐时生成的高铁血红蛋白较少。在体外研究中，已证明二氢硫辛酸等药物可以纠正高铁血红蛋白形成介导的巯基缺陷。希望通过使用羟胺、4-氨基酚和亚硝酸盐等药物进行体外高铁血红蛋白生成来监测糖尿病患者抗氧化补充剂研究的进展。这样就可以向全世界的糖尿病患者推荐最合适的抗氧化剂和剂量，以减轻并发症的发展。
