Rosa Darlan Pase da, Bona Silvia, Simonetto Douglas, Zettler Claudio, Marroni Cláudio Augusto, Marroni Norma Possa
Lutheran University of Brazil, Canoas, RS, Brazil.
Arq Gastroenterol. 2010 Jan-Mar;47(1):72-8. doi: 10.1590/s0004-28032010000100013.
Cirrhosis is a progressive chronic hepatopathy which constitutes an irreversible stage of liver dysfunction.
To evaluate the oxidative stress in the blood of cirrhotic rats treated with the antioxidant melatonin.
Cirrhosis was induced through inhalation of carbon tetrachloride. Liver integrity was evaluated by measuring serum enzymes, oxidative damage measured by lipoperoxidation, and antioxidant enzyme activity in erythrocytes. Lipoperoxidation, total nitrates, collagen, and histology by picrosirius staining were evaluated in the livers of these animals (n = 15), which were divided in three groups: control, carbon tetrachloride, and carbon tetrachloride + melatonin. Melatonin (20 mg/kg) was administered intraperitoneal from week 10 of carbon tetrachloride inhalation. In order to shorten the cirrhosis induction time, phenobarbital (0.3 g/L) was added to the animals' drinking water.
A significant impairment in the liver integrity of melatonin-treated animals as compared to cirrhotic animals was observed. In rat erythrocytes and liver, lipoperoxidation was significantly increased in the cirrhotic rats as compared to controls, as measured through thiobarbituric acid reactive substances, and significantly decreased in melatonin-treated animals as compared to cirrhotic ones. In blood, a decrease in superoxide dismutase and glutathione peroxidase enzymes was detected in the cirrhotic group as compared to the control group, with increased superoxide dismutase activity when melatonin was administered. A reduction in the levels of total nitrates was detected in the hepatic tissue of the animals in the carbon tetrachloride group as compared to the control group and an increase of these levels in the carbon tetrachloride + melatonin group. As for hepatic collagen, we found a significant increase in the carbon tetrachloride group as compared to the controls and a regression of these values in the treated group. In histology, the rats in the carbon tetrachloride group showed fibrosis and formation of fibrotic nodules, characterizing liver cirrhosis; there was reduction of nodules and fibrosis in the melatonin treated group.
The data allow us to suggest that the observed oxidative stress is related to the damages caused by carbon tetrachloride and that the use of melatonin can minimize these damages.
肝硬化是一种进行性慢性肝病，是肝功能障碍的不可逆阶段。
评估用抗氧化剂褪黑素治疗的肝硬化大鼠血液中的氧化应激。
通过吸入四氯化碳诱导肝硬化。通过测量血清酶评估肝脏完整性，通过脂质过氧化测量氧化损伤，并评估红细胞中的抗氧化酶活性。对这些动物（n = 15）的肝脏进行脂质过氧化、总硝酸盐、胶原蛋白评估以及天狼星苦味酸染色组织学检查，将其分为三组：对照组、四氯化碳组和四氯化碳 + 褪黑素组。从吸入四氯化碳第10周开始腹腔注射褪黑素（20 mg/kg）。为了缩短肝硬化诱导时间，在动物饮用水中添加苯巴比妥（0.3 g/L）。
与肝硬化动物相比，观察到褪黑素治疗的动物肝脏完整性有显著损害。通过硫代巴比妥酸反应性物质测量，与对照组相比，肝硬化大鼠的大鼠红细胞和肝脏中的脂质过氧化显著增加，与肝硬化大鼠相比，褪黑素治疗的动物中的脂质过氧化显著降低。在血液中，与对照组相比，肝硬化组中超氧化物歧化酶和谷胱甘肽过氧化物酶活性降低，给予褪黑素后超氧化物歧化酶活性增加。与对照组相比，四氯化碳组动物肝组织中总硝酸盐水平降低，四氯化碳 + 褪黑素组中这些水平升高。至于肝胶原蛋白，与对照组相比，四氯化碳组显著增加，治疗组这些值有所回归。在组织学上，四氯化碳组大鼠表现出纤维化和纤维化结节形成，为肝硬化特征；褪黑素治疗组结节和纤维化减少。
数据表明，观察到的氧化应激与四氯化碳造成的损害有关，并且使用褪黑素可以使这些损害最小化。
