Department of Physiology, University of Barcelona, 645 Diagonal Avenue, 08028 Barcelona, Spain.
Exp Physiol. 2013 Jun;98(6):1115-24. doi: 10.1113/expphysiol.2012.071365. Epub 2013 Jan 25.
There is growing interest in using hypothermia to prevent hypoxic damage in clinical and experimental models, although the mechanisms regulated by hypothermia are still unclear. As reactive oxygen and nitrogen species are the main factors causing cellular damage, our objective was to study the scope of hypothermia in preventing hypoxia-induced oxidative damage. We analysed systemic and hepatic indicators of oxidative stress after an acute hypoxic insult (10% oxygen in breathing air) in normothermic (37°C body temperature) and hypothermic conditions (22°C) in rats. Exposure to hypoxia resulted in tissue damage (aspartate aminotransferase increased from 54.6 ± 6.9 U l(-1) in control animals to 116 ± 1.9 U l(-1) in hypoxia, and alanine aminotransferase increased from 19 ± 0.8 to 34 ± 2.9 U l(-1)), oxidative stress (nitric oxide metabolites increased from 10.8 ± 0.4 μM in control rats to 23 ± 2.7 μM in hypoxia, and thiobarbituric reactive substances increased from 3.3 ± 0.2 to 5.9 ± 0.4 nm) and antioxidant consumption (reduced/oxidized glutathione ratio changed from 9.8 ± 0.3 to 6.8 ± 0.3). In contrast, when hypothermia was applied prior to hypoxia, the situation was reversed, with a reduction in aspartate aminotransferase (from 116 ± 1.9 in hypoxic animals to 63 ± 7.8 U l(-1) in animals exposed to hypothermia followed by hypoxia), alanine aminotransferase (from 34 ± 2.9 to 19 ± 0.9 U l(-1)), oxidative stress (nitric oxide metabolites decreased from 23 ± 2.7 to 17.8 ± 1.9 μM and thiobarbituric acid-reactive substances decreased from 5.9 ± 0.4 to 4.3 ± 0.2 nm) and antioxidant preservation (reduced/oxidized glutathione ratio changed from 6.8 ± 0.3 to 11.1 ± 0.1). Hypoxia induced a decrease in liver enzymatic antioxidant activities even during hypothermia. Both treatments, hypoxia and hypothermia, produced a similar increase in hepatic caspase-3 activity. In conclusion, hypothermia prevented the tissue damage and oxidative stress elicited by hypoxia. Our results provide new evidence concerning the protective mechanism of hypothermia in vivo.
人们对使用低温来预防临床和实验模型中的缺氧损伤越来越感兴趣，尽管低温调节的机制仍不清楚。由于活性氧和氮物种是导致细胞损伤的主要因素，我们的目标是研究低温在预防缺氧诱导的氧化损伤中的范围。我们分析了在正常体温（37°C 体温）和低温（22°C）条件下，急性缺氧（呼吸空气中的 10%氧气）对大鼠全身和肝组织氧化应激的系统和肝内指标。缺氧导致组织损伤（天冬氨酸氨基转移酶从对照动物的 54.6±6.9 U l(-1)增加到 116±1.9 U l(-1)，丙氨酸氨基转移酶从 19±0.8 增加到 34±2.9 U l(-1)）、氧化应激（一氧化氮代谢物从对照大鼠的 10.8±0.4 μM 增加到 23±2.7 μM，硫代巴比妥酸反应物质从 3.3±0.2 增加到 5.9±0.4nm）和抗氧化剂消耗（还原/氧化谷胱甘肽比从 9.8±0.3 改变为 6.8±0.3）。相比之下，当低温在缺氧之前应用时，情况发生了逆转，天冬氨酸氨基转移酶（从缺氧动物的 116±1.9 降低到暴露于低温后再缺氧的动物的 63±7.8 U l(-1)）、丙氨酸氨基转移酶（从 34±2.9 降低到 19±0.9 U l(-1)）、氧化应激（一氧化氮代谢物从 23±2.7 降低到 17.8±1.9 μM，硫代巴比妥酸反应物质从 5.9±0.4 降低到 4.3±0.2nm）和抗氧化剂的保存（还原/氧化谷胱甘肽比从 6.8±0.3 改变为 11.1±0.1）。即使在低温下，缺氧也会导致肝酶抗氧化活性下降。缺氧和低温两种处理方式都导致肝组织中半胱天冬酶-3 活性相似增加。总之，低温预防了缺氧引起的组织损伤和氧化应激。我们的结果提供了关于低温在体内保护机制的新证据。
