Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul - UFRGS, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil.
Metab Brain Dis. 2012 Dec;27(4):605-12. doi: 10.1007/s11011-012-9335-5. Epub 2012 Sep 12.
The use of psychostimulant methylphenidate has increased in recent years for the treatment of attention-deficit hyperactivity disorder in children and adolescents. However, the behavioral and neurochemical changes promoted by its use are not yet fully understood, particularly when used for a prolonged period during stages of brain development. Thus, the aim of this study was to determine some parameters of oxidative stress in encephalic structures of juvenile rats subjected to chronic methylphenidate treatment. Wistar rats received intraperitoneal injections of methylphenidate (2.0 mg/kg) once a day, from the 15th to the 45th day of age or an equivalent volume of 0.9% saline solution (controls). Two hours after the last injection, animals were euthanized and the encephalic structures obtained for determination of oxidative stress parameters. Results showed that methylphenidate administration increased the activities of superoxide dismutase and catalase, but did not alter the levels of reactive species, thiobarbituric acid reactive substances levels and sulfhydryl group in cerebellum of rats. In striatum and hippocampus, the methylphenidate-treated rats presented a decrease in the levels of reactive species and thiobarbituric acid reactive substances, but did not present changes in the sulfhydryl groups levels. In prefrontal cortex, methylphenidate promoted an increase in reactive species formation, SOD/CAT ratio, and increased the lipid peroxidation and protein damage. These findings suggest that the encephalic structures respond differently to methylphenidate treatment, at least, when administered chronically to young rats. Notably, the prefrontal cortex of juvenile rats showed greater sensitivity to oxidative effects promoted by methylphenidate in relation to other encephalic structures analyzed.
近年来，哌醋甲酯作为一种治疗儿童和青少年注意力缺陷多动障碍的药物被广泛使用。然而，其使用所带来的行为和神经化学变化尚未被完全理解，尤其是在大脑发育阶段长期使用时。因此，本研究旨在确定慢性哌醋甲酯处理的幼年大鼠脑内结构的一些氧化应激参数。Wistar 大鼠从第 15 天到第 45 天每天接受腹腔注射哌醋甲酯（2.0mg/kg）或等量的 0.9%生理盐水（对照组）。最后一次注射后 2 小时，处死动物并获取脑内结构以测定氧化应激参数。结果表明，哌醋甲酯给药增加了超氧化物歧化酶和过氧化氢酶的活性，但没有改变小脑内活性物质、硫代巴比妥酸反应物质水平和巯基的水平。在纹状体和海马中，接受哌醋甲酯治疗的大鼠的活性物质和硫代巴比妥酸反应物质水平降低，但巯基水平没有变化。在前额叶皮质中，哌醋甲酯促进了活性物质的形成、SOD/CAT 比值的增加，并增加了脂质过氧化和蛋白质损伤。这些发现表明，脑内结构对哌醋甲酯治疗的反应不同，至少在对幼年大鼠进行慢性给药时是这样。值得注意的是，与分析的其他脑内结构相比，幼年大鼠的前额叶皮质对哌醋甲酯引起的氧化作用更为敏感。
