Department of Surgery I, Oita University Faculty of Medicine, Oita, Japan.
J Gastroenterol Hepatol. 2011 Nov;26(11):1652-8. doi: 10.1111/j.1440-1746.2011.06773.x.
Ischemia/reperfusion (I/R) injury is characterized by significant oxidative stress, which induces characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. The aim of this study was to evaluate the protective effect of dihydrolipoyl histidinate zinc complex (DHLHZn) on oxidative damage after severe hepatic I/R injury.
Thirty male Wistar rats were subjected to 45 min of hepatic ischemia by clamping of the hepatic artery and portal vein, followed by a 6-h reperfusion period. DHLHZn (10 mg/kg) (I/R + DHLHZn group) or saline (I/R group) was administered intraperitoneally twice, 30 min before ischemia and at the beginning of the reperfusion. Sham-operated animals (sham group) received equal amounts of saline. The rats were killed at the end of the reperfusion period. Serum levels of aspartate aminotransferase and alanine aminotransferase were determined, and histological examination and oxidative stress were evaluated in liver tissues. In addition, antimycin A-stimulated RAW264.7 cells (murine macrophage-like cells) were treated with DHLHZn to estimate its antioxidant effect.
Serum aspartate aminotransferase and alanine aminotransferase levels were increased in the I/R group, but these increases were significantly inhibited in the I/R + DHLHZn group. Similarly, liver tissue damage observed in the I/R group was attenuated in the I/R + DHLHZn group. Cells treated in vitro with both DHLHZn and antimycin A showed reduced reactive oxygen species activity compared to cells treated with antimycin A alone.
The new antioxidant DHLHZn may have potential for therapeutic application in liver I/R injury, although this is a limited animal study.
缺血/再灌注（I/R）损伤的特征是显著的氧化应激，这会诱导抗氧化系统和器官损伤的特征性变化，导致显著的发病率和死亡率。本研究的目的是评估二氢-L-组氨酸锌复合物（DHLHZn）对严重肝 I/R 损伤后氧化损伤的保护作用。
30 只雄性 Wistar 大鼠通过夹闭肝动脉和门静脉进行 45 分钟的肝缺血，然后进行 6 小时的再灌注期。DHLHZn（10mg/kg）（I/R+DHLHZn 组）或生理盐水（I/R 组）在缺血前 30 分钟和再灌注开始时腹腔内给药两次。假手术动物（假手术组）接受等量的生理盐水。在再灌注期末处死大鼠。测定血清天门冬氨酸氨基转移酶和丙氨酸氨基转移酶水平，并在肝组织中评估组织学检查和氧化应激。此外，用 DHLHZn 处理抗霉素 A 刺激的 RAW264.7 细胞（鼠巨噬样细胞），以评估其抗氧化作用。
I/R 组血清天门冬氨酸氨基转移酶和丙氨酸氨基转移酶水平升高，但在 I/R+DHLHZn 组中这些升高明显受到抑制。同样，I/R+DHLHZn 组减轻了 I/R 组肝组织损伤。与单独用抗霉素 A 处理的细胞相比，用 DHLHZn 和抗霉素 A 处理的细胞的活性氧物种活性降低。
新型抗氧化剂 DHLHZn 可能具有治疗肝 I/R 损伤的应用潜力，尽管这是一项有限的动物研究。
