Neuroscience Research Unit, St-Luc Hospital (CHUM), University of Montreal, 1058 St-Denis Street, Montreal, Quebec, Canada, H2X 3J4.
Metab Brain Dis. 2010 Mar;25(1):23-9. doi: 10.1007/s11011-010-9186-x. Epub 2010 Mar 3.
Previous studies have demonstrated protective effects of mild hypothermia following acetaminophen (APAP)-induced acute liver failure (ALF). However, effects of this treatment in ALF due to other toxins have not yet been fully investigated. In the present study, the effects of mild hypothermia in relation to liver pathology, hepatic and cerebral glutathione, plasma ammonia concentrations, progression of encephalopathy, cerebral edema, and plasma proinflammatory cytokines were assessed in mice with ALF resulting from azoxymethane (AOM) hepatotoxicity, a well characterized model of toxic liver injury. Male C57BL/6 mice were treated with AOM (100 microg/g; i.p.) or saline and sacrificed at coma stages of encephalopathy in parallel with AOM mice maintained mildly hypothermic (35 degrees C). AOM treatment led to hepatic damage, significant increase in plasma transaminase activity, decreased hepatic glutathione levels, and brain GSH/GSSG ratios as well as selective increases in expression of plasma proinflammatory cytokines. Mild hypothermia resulted in reduced hepatic damage, improvement in neurological function, normalization of glutathione levels, and selective attenuation in expression of circulating proinflammatory cytokines. These findings demonstrate that the beneficial effects of mild hypothermia in experimental AOM-induced ALF involve both antioxidant and anti-inflammatory mechanisms.
先前的研究已经证明，在对乙酰氨基酚（APAP）诱导的急性肝衰竭（ALF）后，轻度低温有保护作用。然而，这种治疗方法在其他毒素引起的 ALF 中的效果尚未得到充分研究。在本研究中，评估了轻度低温对氧化偶氮甲烷（AOM）肝毒性引起的 ALF 小鼠肝脏病理、肝和脑谷胱甘肽、血浆氨浓度、肝性脑病进展、脑水肿和血浆促炎细胞因子的影响，AOM 肝毒性是一种典型的毒性肝损伤模型。雄性 C57BL/6 小鼠用 AOM（100 微克/克；腹腔注射）或生理盐水处理，并在肝性脑病昏迷阶段与保持轻度低温（35 摄氏度）的 AOM 小鼠同时处死。AOM 处理导致肝损伤、血浆转氨酶活性显著增加、肝谷胱甘肽水平降低和脑 GSH/GSSG 比值降低以及循环促炎细胞因子的选择性增加。轻度低温导致肝损伤减轻、神经功能改善、谷胱甘肽水平正常化以及循环促炎细胞因子的选择性减弱。这些发现表明，轻度低温对实验性 AOM 诱导的 ALF 的有益作用涉及抗氧化和抗炎机制。
