Dihydrolipoyl histidinate zinc complex, a new antioxidant, attenuates hepatic ischemia-reperfusion injury in rats
Dihydrolipoyl histidinate zinc complex, a new antioxidant, attenuates hepatic ischemia-reperfusion injury in rats
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DOI：
10.1111/j.1440-1746.2011.06773.x
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发表时间：
2011-11-01
影响因子：
4.1
通讯作者：
Kitano, Seigo
中科院分区：
文献类型：
--
作者：
Masuda, Takashi;Iwashita, Yukio;Kitano, Seigo
背景和目标：缺血/再灌注（I/R）损伤的特征在于显著的氧化应激，其诱导抗氧化系统的特征性变化和器官损伤，导致显著的发病率和死亡率。本研究的目的是评估二氢硫辛酰组氨酸锌复合物（DHLHZn）对严重肝I/R injuries.Methods后氧化损伤的保护作用：30只雄性Wistar大鼠进行了45分钟的肝缺血，通过夹闭肝动脉和门静脉，随后6小时的再灌注期。DHLHZn（10 mg/kg）（I/R + DHLHZn组）或生理盐水（I/R组）在缺血前30 min和再灌注开始时腹腔注射两次。假手术动物（假手术组）接受等量生理盐水。在再灌注期结束时处死大鼠。测定血清谷草转氨酶和丙氨酸转氨酶水平，并进行组织学检查和肝组织氧化应激评价。此外，抗霉素A刺激的RAW264.7细胞（小鼠巨噬细胞样细胞）与DHLHZn处理，以估计其抗氧化effects.Results：血清天门冬氨酸氨基转移酶和丙氨酸氨基转移酶水平增加I/R组，但这些增加在I/R + DHLHZn组显着抑制。类似地，在I/R组中观察到的肝组织损伤在I/R + DHLHZn组中减弱。DHLHZn和抗霉素A在体外处理的细胞表现出减少活性氧活性相比，与抗霉素A单独处理的细胞。结论：新的抗氧化剂DHLHZn可能有潜在的治疗应用在肝I/R损伤，虽然这是一个有限的动物研究。
Background and Aims: 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.Methods: 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.Results: 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.Conclusion: The new antioxidant DHLHZn may have potential for therapeutic application in liver I/R injury, although this is a limited animal study.