Tahirovic I, Sofic E, Sapcanin A, Gavrankapetanovic I, Bach-Rojecky L, Salkovic-Petrisic M, Lackovic Z, Hoyer S, Riederer P
Department of Chemistry, Faculty of Science, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
J Neural Transm Suppl. 2007(72):235-40. doi: 10.1007/978-3-211-73574-9_29.
It is believed that oxidative stress plays a central role in the pathogenesis of metabolic diseases like diabetes mellitus (DM) and its complications (like peripheral neuropathy) as well as in neurodegenerative disorders like sporadic Alzheimer's disease (sAD). Representative experimental models of these diseases are streptozotocin (STZ)-induced diabetic rats and STZ-intracerebroventricularly (STZ-icv) treated rats, in which antioxidant capacity against peroxyl (ORAC(-ROO)) and hydroxyl (ORAC(-OH)) free radical was measured in three different brain regions (hippocampus, cerebellum, and brain stem) by means of oxygen radical absorbance capacity (ORAC) assay. In the brain of both STZ-induced diabetic and STZ-icv treated rats decreased antioxidant capacity has been found demonstrating regionally specific distribution. In the diabetic rats these abnormalities were not associated with the development of peripheral diabetic neuropathy. Also, these abnormalities were not prevented by the icv pretreatment of glucose transport inhibitor 5-thio-D-glucose in the STZ-icv treated rats, suggesting different mechanism for STZ-induced central effects from those at the periphery. Similarities in the oxidative stress alterations in the brain of STZ-icv rats and humans with sAD could be useful in the search for new drugs in the treatment of sAD that have antioxidant activity.
人们认为，氧化应激在糖尿病（DM）及其并发症（如周围神经病变）等代谢性疾病以及散发性阿尔茨海默病（sAD）等神经退行性疾病的发病机制中起着核心作用。这些疾病的代表性实验模型是链脲佐菌素（STZ）诱导的糖尿病大鼠和经脑室注射STZ（STZ-icv）处理的大鼠，通过氧自由基吸收能力（ORAC）测定法在三个不同脑区（海马体、小脑和脑干）测量其对过氧自由基（ORAC(-ROO)）和羟基自由基（ORAC(-OH)）的抗氧化能力。在STZ诱导的糖尿病大鼠和经STZ-icv处理的大鼠脑中，均发现抗氧化能力下降，且呈现区域特异性分布。在糖尿病大鼠中，这些异常与周围糖尿病神经病变的发展无关。此外，在经STZ-icv处理的大鼠中，脑室注射葡萄糖转运抑制剂5-硫代-D-葡萄糖进行预处理并不能预防这些异常，这表明STZ诱导的中枢效应与外周效应的机制不同。STZ-icv大鼠脑内氧化应激改变与sAD患者的相似性，可能有助于寻找具有抗氧化活性的新型药物来治疗sAD。
