Montilla P L, Vargas J F, Túnez I F, Muñoz de Agueda M C, Valdelvira M E, Cabrera E S
Departamento de Bioquímica y Biología Molecular, School of Medicine-The University of Córdoba, Spain.
J Pineal Res. 1998 Sep;25(2):94-100. doi: 10.1111/j.1600-079x.1998.tb00545.x.
We have studied the effect of the administration of two doses of melatonin (melatonin 100 and melatonin 200 microg/kg bw) on diabetes and oxidative stress experimentally induced by the injection of streptozotocin (STZ) in female Wistar rats. STZ was injected as a single dose (60 mg/kg i.p. in buffered citrate solution, pH 4.0) and melatonin (melatonin 100, 100 microg/kg/day i.p.; melatonin 200, 200 microg/kg/day i.p.) beginning 3 days before diabetes induction and continuing until the end of the study (8 weeks). The parameters analysed to evaluate oxidative stress and the diabetic state were a) for oxidative stress, changes of lipoperoxides (i.e., malondialdehyde, MDA) in plasma and erythrocytes and the changes in reduced glutathione (GSH) in erythrocytes and b) for diabetes, changes in glycemia, lipids (triglycerides: TG; total cholesterol: TC; HDL-cholesterol, HDL-c), percentage of glycosylated hemoglobin (Hb%), and plasma fructosamine. The injection of STZ caused significant increases in the levels of glycemia, percentage of glycosylated hemoglobin, fructosamine, cholesterol, triglycerides, and lipoperoxides in plasma and erythrocytes, whereas it decreased the levels of HDL-c and the GSH content in erythrocytes. The melatonin 100 dose reduced significantly all these increases, except the percentage of glycosylated hemoglobin. With regard to the decreases of plasma HDL-c and GSH content in erythrocytes, this melatonin dose returned them to normal levels. The melatonin 200 dose produced similar changes, though the effects were especially noticeable in the decrease of glycemia (55% vs. diabetes), percentage of hemoglobin (P < 0.001 vs diabetes), and fructosamine (31% vs. diabetes). This dose also reversed the decreases of HDL-c and GSH in erythrocytes. Both doses of melatonin caused significant reduction of the percentage of glycosylated hemoglobin in those groups that were non-diabetic. These illustrate the protective effect of melatonin against oxidative stress and the severity of diabetes induced by STZ. In particular, this study confirms two facts: 1) the powerful antioxidant action of this pineal indole and 2) the importance of the severity of oxidative stress to maintain hyperglycemia and protein glycosylation, two pathogenetic cornerstones indicative of diabetic complications. Melatonin reduces remarkably the degree of lipoperoxidation, hyperglycemia, and protein glycosylation, which gives hope to a promising perspective of this product, together with other biological antioxidants, in the treatment of diabetic complications where oxidative stress, either in a high or in a low degree, is present.
我们研究了给雌性Wistar大鼠注射两剂褪黑素（褪黑素100和褪黑素200微克/千克体重）对链脲佐菌素（STZ）诱导的实验性糖尿病和氧化应激的影响。STZ以单剂量（60毫克/千克，腹腔注射于pH 4.0的柠檬酸盐缓冲溶液中）注射，褪黑素（褪黑素100，100微克/千克/天，腹腔注射；褪黑素200，200微克/千克/天，腹腔注射）在糖尿病诱导前3天开始给药，并持续至研究结束（8周）。用于评估氧化应激和糖尿病状态的分析参数为：a）对于氧化应激，血浆和红细胞中脂质过氧化物（即丙二醛，MDA）的变化以及红细胞中还原型谷胱甘肽（GSH）的变化；b）对于糖尿病，血糖、脂质（甘油三酯：TG；总胆固醇：TC；高密度脂蛋白胆固醇：HDL-c）、糖化血红蛋白百分比（Hb%）和血浆果糖胺的变化。注射STZ导致血糖水平、糖化血红蛋白百分比、果糖胺、胆固醇、甘油三酯以及血浆和红细胞中脂质过氧化物水平显著升高，而红细胞中HDL-c水平和GSH含量降低。褪黑素100剂量显著降低了所有这些升高水平，但糖化血红蛋白百分比除外。对于血浆HDL-c降低和红细胞中GSH含量降低，该褪黑素剂量使其恢复到正常水平。褪黑素200剂量产生了类似的变化，尽管在降低血糖（与糖尿病组相比降低55%）、血红蛋白百分比（与糖尿病组相比P < 0.001）和果糖胺（与糖尿病组相比降低31%）方面效果尤为明显。该剂量还逆转了红细胞中HDL-c和GSH的降低。两剂褪黑素均使非糖尿病组的糖化血红蛋白百分比显著降低。这些结果说明了褪黑素对氧化应激和STZ诱导的糖尿病严重程度的保护作用。特别是，本研究证实了两个事实：1）这种松果体吲哚具有强大的抗氧化作用；2）氧化应激的严重程度对于维持高血糖和蛋白质糖基化的重要性，这是指示糖尿病并发症的两个发病机制基石。褪黑素显著降低了脂质过氧化程度、高血糖和蛋白质糖基化程度，这为该产品以及其他生物抗氧化剂在治疗存在不同程度氧化应激的糖尿病并发症方面带来了有前景的希望。
