Oxidative damage in the liver induced by ischemia-reperfusion: protection by melatonin.
Oxidative damage in the liver induced by ischemia-reperfusion: protection by melatonin.
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发表时间：
1996-07
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通讯作者：
E. Sewerynek;R. Reiter;D. Melchiorri;G. Ortiz;A. Lewiński
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作者：
E. Sewerynek;R. Reiter;D. Melchiorri;G. Ortiz;A. Lewiński
目的观察美拉托宁对雄性SD大鼠肝脏缺血再灌注损伤的保护作用。生化分析材料与方法测定脂质过氧化产物[丙二醛(MDA)+4-羟基烯烃(4-HDA)]、还原型谷胱甘肽(GSH)和氧化谷胱甘肽(GSSG)水平及GSH过氧化物酶(GSH-Px)、GSH还原酶(GSSG-RD)和葡萄糖-6-磷酸酶(G6Pase)活性。组织切片计数损伤肝脏中性粒细胞(PMN)数量。结果缺血40min再灌流60min后，肝组织中MDA+4-HDA含量明显升高。褪黑素可抑制脑缺血再灌流所致的MDA+4-HDA升高。在缺血再灌流过程中，GSH含量降低，GSSG升高，褪黑素可拮抗这些变化。此外，两种抗氧化酶(GSH-Px和GSSG-RD)的活性在实验期间降低，褪黑素可阻止GSSG-RD的变化。G6Pase活性不受缺血再灌注和褪黑激素的影响。在形态上，缺血再灌注损伤的肝脏可见明显的PMN浸润，褪黑素也可部分逆转这种变化。结论在大鼠肝脏缺血再灌注损伤模型中，外源性应用褪黑素能有效地保护肝脏免受氧化损伤。褪黑素对大鼠肝脏的保护作用表现为脂质过氧化产物减少，PMN渗出减少，GSH升高，GSSG含量降低，GSSG-RD活性升高，均可诱导大鼠肝脏缺血再灌注损伤。
BACKGROUND/AIMS The protective effect of mela tonin against the damage inflicted by reactive oxygen species during liver ischemia-reperfusion was investigated in male Sprague-Dawley rats using both biochemical and morphological parameters. MATERIALS AND METHODS For biochemical analyses the levels of lipid peroxidation products [malonaldehyde (MDA) + 4-hydroxyalkenals (4-HDA)], levels of reduced glutathione (GSH) and oxidized glutathione (GSSG), and the activities of GSH peroxidase (GSH-Px), GSH reductase (GSSG-Rd) and glucose-6-phosphatase (G6Pase) were estimated. Also the number of polymorphonuclear neutrophils (PMNs) in injured livers was counted in histological sections. RESULTS After 40 min of ischemia followed by 60 min of reperfusion the hepatic levels of MDA + 4-HDA increased. Pretreatment of the animals with melatonin abolished the rise in MDA + 4-HDA induced by ischemia-reperfusion. GSH concentrations decreased and GSSG increased during ischemia-reperfusion and, again melatonin counteracted these changes. Additionally, the activities of two antioxidative enzymes (GSH-Px and GSSG-Rd) decreased during the experimental period with melatonin preventing the change in GSSG-Rd. G6Pase activity was not influenced by either ischemia-reperfusion or by melatonin administration. Morphologically, PMN infiltration was obvious in the ischemia-reperfusion damaged liver, a change also partially reversed by melatonin. CONCLUSIONS In this model of liver ischemia-reperfusion injury, exogenously administered melatonin effectively protected against oxidative damage. The hepatic parameters which illustrated this protection were reduced lipid peroxidation products, lowered PMN infiltration, increased GSH and reduced GSSG levels, and elevated GSSG-Rd activity all of which were observed in melatonin-treated rats in which damage due to ischemia-reperfusion had been induced.