Vidhya A, Renjugopal V, Indira M
Indian J Physiol Pharmacol. 2013 Oct-Dec;57(4):406-17.
One of the molecular mechanisms of alcohol induced toxicities is mediated by oxidative stress. Hence our studies were focused on the effect of thiamine (antioxidant) in the reversal of alcohol induced toxicity and comparison of the reversal with abstinence. Administration of ethanol at a dose of 4 g/kg body wt/day for 90 days to Sprague Dawley rats manifested chronic alcohol induced toxicity evidenced by decreased body weight, an increase in liver-body weight ratio, increase in activities of serum and liver aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT); decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in the liver and brain. The levels of inflammatory markers, fibrosis markers and DNA fragmentation were also elevated in the serum, liver and brain. After ethanol administration for 90 days, the reversal of the alcohol induced toxicity was studied by supplementing thiamine at a dose of 25 mg/100 g body wt/day. Duration of the reversal study was 30 days. The activities of AST, ALT, GGT, scavenging enzymes as well as markers of inflammation and fibrosis in serum, liver and brain were reversed to a certain extent by thiamine. Changes in neurotransmitter levels in brain were also reversed by thiamine supplementation. DNA damage was decreased and DNA content increased in thiamine supplemented group compared to abstinence group showing a faster regeneration. In short, histopathological and biochemical evaluations indicate that thiamine supplemented abstinent rats made a faster recovery of hepatic and neuronal damage than in the abstinence group.
酒精诱导毒性的分子机制之一是由氧化应激介导的。因此,我们的研究集中在硫胺素(抗氧化剂)对逆转酒精诱导毒性的作用以及与戒酒逆转效果的比较上。以4 g/kg体重/天的剂量给Sprague Dawley大鼠连续灌胃乙醇90天,结果显示出现了慢性酒精诱导的毒性,表现为体重减轻、肝重与体重比值增加、血清和肝脏中天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、γ-谷氨酰转肽酶(GGT)活性升高;肝脏和大脑中超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶的活性降低。血清、肝脏和大脑中的炎症标志物、纤维化标志物以及DNA片段化水平也升高。在乙醇灌胃90天后,通过以25 mg/100 g体重/天的剂量补充硫胺素来研究酒精诱导毒性的逆转情况。逆转研究持续时间为30天。硫胺素在一定程度上逆转了血清、肝脏和大脑中AST、ALT、GGT、清除酶以及炎症和纤维化标志物的活性。硫胺素补充也逆转了大脑中神经递质水平的变化。与戒酒组相比,补充硫胺素组的DNA损伤减少,DNA含量增加,显示出更快的再生。简而言之,组织病理学和生化评估表明,补充硫胺素的戒酒大鼠肝脏和神经元损伤的恢复速度比戒酒组更快。