Surapaneni K M, Priya V V, Mallika J
Department of Biochemistry, Saveetha Medical College and Hospital, Faculty of Medicine, Saveetha University, Saveetha Nagar, Thandalam, Chennai, Tamilnadu, India.
Eur Rev Med Pharmacol Sci. 2014;18(18):2736-41.
Non-Alcoholic Steatohepatitis (NASH) is a severe form of Non Alcoholic Fatty Liver Disease (NAFLD) spectrum, which progresses to the end stage liver disease. A common denominator in the pathogenesis of insulin resistance and nonalcoholic steatohepatitis is increased oxidative stress. Hepatic induction of the pro-oxidant enzyme Cytochrome P450 2E1 (CYP2E1) occurs in both NAFLD and type-2 diabetes. In this study, the comparative effect of pioglitazone, quercetin and hydroxy citric acid on liver CYP2E1 enzyme levels in experimentally induced NASH has been studied.
The experimental protocol consists of 5 groups viz. Control (n = 6); NASH Induced (n=6); NASH + Pioglitazone (n=6); NASH + Quercetin (n=6); NASH + Hydroxy Citric Acid (n=6). CYP2E1 enzyme levels were detected in liver by immunoblot analysis in all the groups.
CYP2E1 catalytic activity was increased in experimentally induced NASH group compared to control group as evidenced by the Immunoblot analysis. It revealed low CYP2E1 in the experimentally induced NASH, treated with pioglitazone, quercetin and hydroxy citric acid. Mild decrease in the levels of CYP2E1 level was observed in experimental NASH treated with pioglitazone compared to NASH group. Treatment with hydroxy citric acid also showed mild decrease in the levels of CYP2E1. On contrary to the action of pioglitazone and hydroxy citric acid, quercetin showed an approximate 2-fold decrease in the level of CYP2E1 in experimental NASH treated with quercetin compared to NASH group.
Being a powerful antioxidant, quercetin offers absolute protection to liver against NASH by reducing the levels of CYP2E1 and, thereby, reducing CYP2E1 mediated oxidative stress, which is believed to be the one of the key factor in the pathogenesis of NASH. On the other hand, pioglitazone and hydroxy citric acid exerted limited effect on the levels of CYP2E1. This study showed the therapeutic value of quercetin, pioglitazone and hydroxy citric acid in treating NASH.
非酒精性脂肪性肝炎（NASH）是非酒精性脂肪性肝病（NAFLD）谱系中的一种严重形式，可进展为终末期肝病。胰岛素抵抗和非酒精性脂肪性肝炎发病机制的一个共同特征是氧化应激增加。促氧化酶细胞色素P450 2E1（CYP2E1）在肝脏中的诱导在NAFLD和2型糖尿病中均会发生。在本研究中，已对吡格列酮、槲皮素和羟基柠檬酸对实验性诱导的NASH中肝脏CYP2E1酶水平的比较作用进行了研究。
实验方案包括5组，即对照组（n = 6）；NASH诱导组（n = 6）；NASH + 吡格列酮组（n = 6）；NASH + 槲皮素组（n = 6）；NASH + 羟基柠檬酸组（n = 6）。通过免疫印迹分析检测所有组肝脏中的CYP2E1酶水平。
免疫印迹分析表明，与对照组相比，实验性诱导的NASH组中CYP2E1催化活性增加。结果显示，在经吡格列酮、槲皮素和羟基柠檬酸治疗的实验性诱导的NASH中，CYP2E1水平较低。与NASH组相比，在经吡格列酮治疗的实验性NASH中观察到CYP2E1水平轻度下降。用羟基柠檬酸治疗也显示CYP2E1水平轻度下降。与吡格列酮和羟基柠檬酸的作用相反，与NASH组相比，在经槲皮素治疗的实验性NASH中，槲皮素使CYP2E1水平下降了约2倍。
作为一种强大的抗氧化剂，槲皮素通过降低CYP2E1水平，从而减少CYP2E1介导的氧化应激，为肝脏提供针对NASH的绝对保护，而氧化应激被认为是NASH发病机制的关键因素之一。另一方面，吡格列酮和羟基柠檬酸对CYP2E1水平的影响有限。本研究显示了槲皮素、吡格列酮和羟基柠檬酸在治疗NASH方面的治疗价值。
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