Ohkuwa T, Sato Y, Naoi M
Department of Biosciences, Nagoya Institute of Technology, Japan.
Life Sci. 1995;56(21):1789-98. doi: 10.1016/0024-3205(95)00150-5.
Production of hydroxyl radicals was examined in the diabetic rats induced by streptozotocin to prove its involvement to the pathogenesis of diabetes. Hydroxyl radicals generated in plasma, heart muscle, liver and brain of the hyperglycemic rats were quantitatively assayed by trapping hydroxyl radicals with salicylic acid as 2,3- and 2,5-dihydroxybenzoic acid. The concentrations of 2,3- and 2,5-dihydroxybenzoic acid were significantly increased in all the tissues of the diabetic rats. In the brain and heart muscle of the diabetic rats, the increase of 2,3-dihydroxybenzoic acid was more manifest than that of 2,5-dihydroxybenzoic acid, while in liver 2,5-dihydroxybenzoic acid increased markedly. All the values of 2,3-dihydroxybenzoic acid detected in the tissues of the diabetic rats were quite higher than those in control. Hydroxyl radical production and blood glucose concentration were depended almost linearly on the amount of streptozotocin injected to rats up to 60 mg/kg body weight. It was suggested that 2,3-dihydroxybenzoic acid was produced from hydroxyl radicals themselves, while 2,5-dihydroxybenzoic acid was produced by hydroxylation of salicylic acid not only with hydroxyl radicals, but also by enzymatic reaction of microsomal cytochrome-P450. Hydroxyl radical formation may account for some pathological process especially in the heart muscle and brain.
研究了链脲佐菌素诱导的糖尿病大鼠体内羟基自由基的产生情况，以证明其与糖尿病发病机制有关。通过用2,3 - 二羟基苯甲酸和2,5 - 二羟基苯甲酸作为水杨酸捕获羟基自由基，对高血糖大鼠血浆、心肌、肝脏和大脑中产生的羟基自由基进行了定量测定。糖尿病大鼠所有组织中2,3 - 二羟基苯甲酸和2,5 - 二羟基苯甲酸的浓度均显著升高。在糖尿病大鼠的大脑和心肌中，2,3 - 二羟基苯甲酸的增加比2,5 - 二羟基苯甲酸更明显，而在肝脏中2,5 - 二羟基苯甲酸显著增加。糖尿病大鼠组织中检测到的所有2,3 - 二羟基苯甲酸的值均远高于对照组。羟基自由基的产生和血糖浓度几乎与注射到大鼠体内的链脲佐菌素量呈线性关系，直至60 mg/kg体重。提示2,3 -二羟基苯甲酸由羟基自由基自身产生，而2,5 - 二羟基苯甲酸不仅由羟基自由基使水杨酸羟基化产生，还可通过微粒体细胞色素P450的酶促反应产生。羟基自由基的形成可能是某些病理过程的原因，尤其是在心肌和大脑中。
