Dulundu Ender, Ozel Yahya, Topaloglu Umit, Sehirli Ozer, Ercan Feriha, Gedik Nursal, Sener Goksel
Department of 5th Surgery, Haydarpasa Numune Educational and Research Hospital, Istanbul, Turkey.
Pharmacology. 2007;79(3):163-70. doi: 10.1159/000098953. Epub 2007 Jan 24.
To evaluate the protective effect of alpha-lipoic acid in reducing oxidative damage after severe hepatic ischemia/reperfusion (IR) injury.
Wistar albino rats were subjected to 45 min of hepatic ischemia, followed by 60 min reperfusion period. Lipoic acid (100 mg/kg i.p.) was administered 15 min prior to ischemia and immediately before reperfusion period. At the end of the reperfusion period aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) activity, and cytokine, TNF-alpha and IL-1beta levels were determined in serum samples. Malondialdehyde (MDA), and glutathione (GSH) levels and myeloperoxidase (MPO) activity were determined in the liver tissue samples while formation of reactive oxygen species was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Tissues were also analyzed histologically.
Serum ALT, AST, and LDH activities and TNF-alpha and IL-1beta levels were elevated in the I/R group, while this increase was significantly lower in the group of animals treated concomitantly with lipoic acid. Hepatic GSH levels, significantly depressed by I/R, were elevated back to control levels in lipoic acid-treated I/R group. Furthermore, increases in tissue luminol and lucigenin CL, MDA levels and MPO activity due to I/R injury were reduced back to control levels with lipoic acid treatment.
Since lipoic acid administration alleviated the I/R-induced liver injury and improved the hepatic structure and function, it seems likely that lipoic acid with its antioxidant and oxidant-scavenging properties may be of potential therapeutic value in protecting the liver against oxidative injury due to ischemia-reperfusion.
评估α-硫辛酸对减轻严重肝缺血/再灌注(IR)损伤后氧化损伤的保护作用。
对Wistar白化大鼠进行45分钟的肝脏缺血,随后进行60分钟的再灌注期。硫辛酸(100mg/kg腹腔注射)在缺血前15分钟及再灌注期开始前即刻给药。在再灌注期末,测定血清样本中的天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、乳酸脱氢酶(LDH)活性以及细胞因子肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平。测定肝组织样本中的丙二醛(MDA)、谷胱甘肽(GSH)水平以及髓过氧化物酶(MPO)活性,同时使用鲁米诺和光泽精探针通过化学发光(CL)技术监测活性氧的形成。还对组织进行了组织学分析。
I/R组血清ALT、AST和LDH活性以及TNF-α和IL-1β水平升高,而在同时给予硫辛酸治疗的动物组中这种升高明显较低。I/R显著降低的肝脏GSH水平在硫辛酸治疗的I/R组中回升至对照水平。此外,I/R损伤导致的组织鲁米诺和光泽精CL、MDA水平及MPO活性增加经硫辛酸治疗后降至对照水平。
由于给予硫辛酸减轻了I/R诱导的肝损伤并改善了肝脏结构和功能,具有抗氧化和清除氧化剂特性的硫辛酸似乎在保护肝脏免受缺血再灌注引起的氧化损伤方面具有潜在治疗价值。