Hicdonmez Tufan, Kanter Mehmet, Tiryaki Mehmet, Parsak Turgay, Cobanoglu Sebahattin
Faculty of Medicine, Department of Neurosurgery, Trakya University, Edirne, Turkey.
Neurochem Res. 2006 Apr;31(4):473-81. doi: 10.1007/s11064-006-9040-z. Epub 2006 May 9.
N-acetylcysteine (NAC) is a precursor of glutathione, a potent antioxidant, and a free radical scavenger. The beneficial effect of NAC on nervous system ischemia and ischemia/reperfusion models has been well documented. However, the effect of NAC on nervous system trauma remains less understood. Therefore, we aimed to investigate the therapeutic efficacy of NAC with an experimental closed head trauma model in rats. Thirty-six adult male Sprague-Dawley rats were randomly divided into three groups of 12 rats each: Group I (control), Group II (trauma-alone), and Group III (trauma+NAC treatment). In Groups II and III, a cranial impact was delivered to the skull from a height of 7 cm at a point just in front of the coronal suture and over the right hemisphere. Rats were sacrificed at 2 h (Subgroups I-A, II-A, and III-A) and 12 h (Subgroups I-B, II-B, and III-B) after the onset of injury. Brain tissues were removed for biochemical and histopathological investigation. The closed head trauma significantly increased tissue malondialdehyde (MDA) levels (P < 0.05), and significantly decreased tissue superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities (P < 0.05), but not tissue catalase (CAT) activity, when compared with controls. The administration of a single dose of NAC (150 mg/kg) 15 min after the trauma has shown protective effect via decreasing significantly the elevated MDA levels (P < 0.05) and also significantly (P < 0.05) increasing the reduced antioxidant enzyme (SOD and GPx) activities, except CAT activity. In the trauma-alone group, the neurons became extensively dark and degenerated into picnotic nuclei. The morphology of neurons in the NAC treatment group was well protected. The number of neurons in the trauma-alone group was significantly less than that of both the control and trauma+NAC treatment groups. In conclusion, the NAC treatment might be beneficial in preventing trauma-induced oxidative brain tissue damage, thus showing potential for clinical implications.
N-乙酰半胱氨酸（NAC）是谷胱甘肽的前体，谷胱甘肽是一种强效抗氧化剂和自由基清除剂。NAC对神经系统缺血及缺血/再灌注模型的有益作用已有充分记录。然而，NAC对神经系统创伤的影响仍了解较少。因此，我们旨在通过大鼠实验性闭合性颅脑创伤模型研究NAC的治疗效果。36只成年雄性Sprague-Dawley大鼠随机分为三组，每组12只：第一组（对照组）、第二组（单纯创伤组）和第三组（创伤+NAC治疗组）。在第二组和第三组中，从冠状缝前方、右半球上方7厘米高度对颅骨进行撞击。在损伤发生后2小时（亚组I-A、II-A和III-A）和12小时（亚组I-B、II-B和III-B）处死大鼠。取出脑组织进行生化和组织病理学研究。与对照组相比，闭合性颅脑创伤显著增加组织丙二醛（MDA）水平（P<0.05），显著降低组织超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）活性（P<0.05），但不影响组织过氧化氢酶（CAT）活性。创伤后15分钟给予单剂量NAC（150mg/kg）显示出保护作用，可显著降低升高的MDA水平（P<0.05），并显著（P<0.05）提高降低的抗氧化酶（SOD和GPx）活性，但不影响CAT活性。在单纯创伤组中，神经元广泛变黑并退化为固缩核。NAC治疗组神经元的形态得到良好保护。单纯创伤组的神经元数量显著少于对照组和创伤+NAC治疗组。总之，NAC治疗可能有助于预防创伤诱导的氧化脑组织损伤，因此具有临床应用潜力。
