Pár A, Róth E, Rumi G, Kovács Z, Nemes J, Mózsik G
Pécsi Tudományegyetem, Altalános Orvostudományi Kar, I. Belgyógyászati Klinika.
Orv Hetil. 2000 Jul 23;141(30):1655-9.
In the past decade it became accepted that free radicals, lipid peroxidation and antioxidant defense play a role in various tissues damages, thus in certain liver diseases as well. Since only limited data have been reported concerning the oxidative stress in viral hepatitis, a comparative study was performed in patients (pts) with chronic hepatitis C and alcoholic liver disease. In addition, the effects of a flavonolignan drug silymarin were assessed. 10 pts with chronic hepatitis C, 5 pts with alcoholic hepatitis and 13 pts with alcoholic cirrhosis have been investigated. Biochemical liver tests (serum bilirubin, aminotransferases, ALT, AST, lactate dehydrogenase (LDH), pseudocholinesterase, prothrombin), malandialdehyde (MDA) levels in plasma and red blood cell (RBC) hemolysate, superoxide radical generating capacity of stimulated polymorphonuclear granulocytes (PMN), plasma concentrations of reduced (GSH) and oxidized (GSSG) glutathione, vitamin A, luteine and beta carotene, furthermore RBC superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase activities were determined. The level of plasma MDA--as the marker of lipid peroxidation--was highest in alcoholic cirrhosis (five times of normal) (p < 0.05), the RBC hemolysate MDA was most elevated in chronic hepatitis C (p < 0.05). The mean PMNs' superoxide radical generating capacity was 116.6% of normal control in alcoholic hepatitis, where the mean GSH level was the lowest (89.8% of normal). Plasma vitamin A content was lowest in alcoholic cirrhosis (68% of control) (p < 0.05). SOD activity was elevated in both chronic hepatitis C and alcoholic cirrhosis, where GPx activity was decreased (p < 0.05). There was a correlation between LDH and SOD activities (r = 0.77, p = 0.015). Silymarin treatment of one month duration resulted in normalization of serum bilirubin in 55% of treated pts, AST became normal in 45%, and RBC hemolyzate MDA level normalized in similar rate. A significant increase in both GSH and retinoids was found. Alterations in oxidative stress and antioxidant defense system were shown in chronic hepatitis C, not only in alcoholic liver disease. The parameters of lipid peroxidation and antioxidant defense may be useful surrogate markers for monitoring pts with liver disease during hepatoprotective treatment.
在过去十年中,自由基、脂质过氧化和抗氧化防御在各种组织损伤中发挥作用这一观点已被接受,在某些肝脏疾病中亦是如此。由于关于病毒性肝炎氧化应激的报道数据有限,因此对慢性丙型肝炎患者和酒精性肝病患者进行了一项对比研究。此外,还评估了一种黄酮木脂素药物水飞蓟宾的效果。研究了10例慢性丙型肝炎患者、5例酒精性肝炎患者和13例酒精性肝硬化患者。检测了肝脏生化指标(血清胆红素、氨基转移酶、谷丙转氨酶、谷草转氨酶、乳酸脱氢酶、假性胆碱酯酶、凝血酶原)、血浆和红细胞溶血产物中的丙二醛(MDA)水平、刺激后的多形核粒细胞(PMN)产生超氧自由基的能力、血浆中还原型(GSH)和氧化型(GSSG)谷胱甘肽、维生素A、叶黄素和β-胡萝卜素的浓度,此外还测定了红细胞超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)和过氧化氢酶的活性。作为脂质过氧化标志物的血浆MDA水平在酒精性肝硬化患者中最高(是正常水平的5倍)(p<0.05),红细胞溶血产物MDA在慢性丙型肝炎患者中升高最为明显(p<0.05)。酒精性肝炎患者中PMN产生超氧自由基的平均能力是正常对照组的116.6%,其平均GSH水平最低(是正常水平的89.8%)。酒精性肝硬化患者血浆维生素A含量最低(是对照组的68%)(p<0.05)。慢性丙型肝炎和酒精性肝硬化患者的SOD活性均升高,而GPx活性降低(p<0.05)。LDH和SOD活性之间存在相关性(r = 0.77,p = 0.015)。为期一个月的水飞蓟宾治疗使55%的治疗患者血清胆红素恢复正常,45%的患者AST恢复正常,红细胞溶血产物MDA水平以相似比例恢复正常。同时发现GSH和类维生素A均显著增加。慢性丙型肝炎不仅在酒精性肝病中出现了氧化应激和抗氧化防御系统的改变。脂质过氧化和抗氧化防御参数可能是肝病患者在保肝治疗期间进行监测的有用替代指标。