D'Almeida V, Camarini R, Azzalis L A, Junqueira V B, Carlini E A
Departamento de Bioquímica, Universidade de São Paulo, Brasil.
J Biochem Toxicol. 1996;11(4):197-201. doi: 10.1002/(SICI)1522-7146(1996)11:4<197::AID-JBT5>3.0.CO;2-F.
Fenfluramine is an anorectic drug widely used for the regulation of food intake that presents some adverse effects at the central and peripheral levels. d-Fenfluramine, an isomer of dl-fenfluramine, is postulated to be more effective and to induce less side effects than the racemic compound. These drugs act preferentially on the serotonergic system. Some authors have suggested that fenfluramine causes a degeneration of serotonergic neurons. Alterations of the serotonergic system are also observed during the aging process, and in this case, a relationship with reactive oxygen species has been already established. In view of these data, the present study was conducted to investigate the relationship between fenfluramine and brain antioxidant defense system in mature and aged animals. Rats aged 4 and 17 months were chronically treated with dl-fenfluramine, d-fenfluramine, or saline. Brain activity of superoxide dismutase and glutathione peroxidase was significantly affected by aging. Catalase activity was altered by the treatment. Total glutathione content and chemiluminescence in the brains were also altered by aging. Glutathione levels were altered as a function of the interaction between age and treatment. These findings suggest that treatment with d- or dl-fenfluramine results in alteration of the anti-oxidant system that could be exacerbated when associated with the aging process.
芬氟拉明是一种广泛用于调节食物摄入量的食欲抑制剂，它在中枢和外周水平均会产生一些不良反应。d - 芬氟拉明是dl - 芬氟拉明的一种异构体，据推测其比外消旋化合物更有效且副作用更少。这些药物主要作用于血清素能系统。一些作者认为芬氟拉明会导致血清素能神经元变性。在衰老过程中也观察到血清素能系统的改变，并且在这种情况下，已经确定了其与活性氧的关系。鉴于这些数据，本研究旨在探讨芬氟拉明与成熟和老年动物脑抗氧化防御系统之间的关系。对4个月和17个月大的大鼠长期给予dl - 芬氟拉明、d - 芬氟拉明或生理盐水。超氧化物歧化酶和谷胱甘肽过氧化物酶的脑活性受衰老影响显著。过氧化氢酶活性因治疗而改变。脑中总谷胱甘肽含量和化学发光也因衰老而改变。谷胱甘肽水平因年龄和治疗之间的相互作用而改变。这些发现表明，d - 或dl - 芬氟拉明治疗会导致抗氧化系统改变，当与衰老过程相关时可能会加剧这种改变。
