Ferreira Ana Paula Oliveira, Rodrigues Fernanda Silva, Della-Pace Iuri Domingues, Mota Bibiana Castagna, Oliveira Sara Marchesan, Velho Gewehr Camila de Campos, Bobinski Franciane, de Oliveira Clarissa Vasconcelos, Brum Juliana Sperotto, Oliveira Mauro Schneider, Furian Ana Flavia, de Barros Claudio Severo Lombardo, Ferreira Juliano, Santos Adair Roberto Soares Dos, Fighera Michele Rechia, Royes Luiz Fernando Freire
Laboratório de Bioquímica do Exercício, Departamento de Métodos e Técnicas Desportivas, Centro de Educação Física e Desportos, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil; Programa de Pós - Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Programa de Pós - Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Neurochem Int. 2013 Nov;63(6):583-93. doi: 10.1016/j.neuint.2013.09.012. Epub 2013 Sep 25.
Traumatic brain injury (TBI) is a devastating disease that commonly causes persistent mental disturbances and cognitive deficits. Although studies have indicated that overproduction of free radicals, especially superoxide (O2(-)) derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a common underlying mechanism of pathophysiology of TBI, little information is available regarding the role of apocynin, an NADPH oxidase inhibitor, in neurological consequences of TBI. Therefore, the present study evaluated the therapeutic potential of apocynin for treatment of inflammatory and oxidative damage, in addition to determining its action on neuromotor and memory impairments caused by moderate fluid percussion injury in mice (mLFPI). Statistical analysis revealed that apocynin (5mg/kg), when injected subcutaneously (s.c.) 30min and 24h after injury, had no effect on neuromotor deficit and brain edema, however it provided protection against mLFPI-induced object recognition memory impairment 7days after neuronal injury. The same treatment protected against mLFPI-induced IL-1β, TNF-α, nitric oxide metabolite content (NOx) 3 and 24h after neuronal injury. Moreover, apocynin treatment reduced oxidative damage (protein carbonyl, lipoperoxidation) and was effective against mLFPI-induced Na(+), K(+)-ATPase activity inhibition. The present results were accompanied by effective reduction in lesion volume when analyzed 7days after neuronal injury. These data suggest that superoxide (O2(-)) derived from NADPH oxidase can contribute significantly to cognitive impairment, and that the post injury treatment with specific NADPH oxidase inhibitors, such as apocynin, may provide a new therapeutic approach to the control of neurological disabilities induced by TBI.
创伤性脑损伤（TBI）是一种破坏性疾病，通常会导致持续性精神障碍和认知缺陷。尽管研究表明自由基的过度产生，尤其是源自烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶的超氧化物（O2(-)）是TBI病理生理学的常见潜在机制，但关于NADPH氧化酶抑制剂阿朴吗啡在TBI神经后果中的作用，目前可用信息较少。因此，本研究评估了阿朴吗啡治疗炎症和氧化损伤的治疗潜力，此外还确定了其对小鼠中度液压冲击损伤（mLFPI）引起的神经运动和记忆障碍的作用。统计分析显示，阿朴吗啡（5mg/kg）在损伤后30分钟和24小时皮下注射时，对神经运动缺陷和脑水肿没有影响，然而它能在神经元损伤7天后保护小鼠免受mLFPI诱导的物体识别记忆损伤。相同的治疗方法在神经元损伤后3小时和24小时可保护小鼠免受mLFPI诱导的白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、一氧化氮代谢产物含量（NOx）升高的影响。此外，阿朴吗啡治疗可减少氧化损伤（蛋白质羰基化、脂质过氧化），并有效对抗mLFPI诱导的钠钾-ATP酶活性抑制。当在神经元损伤7天后进行分析时，本研究结果还伴随着损伤体积的有效减小。这些数据表明，源自NADPH氧化酶的超氧化物（O2(-)）可能对认知障碍有显著影响，并且用特定的NADPH氧化酶抑制剂（如阿朴吗啡）进行损伤后治疗，可能为控制TBI引起的神经功能障碍提供一种新的治疗方法。
