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首页> 外文期刊>British Biotechnology Journal >Protective Effects of CYP2E1 Inhibitors on MetabolicSyndrome-induced Liver Injury in Guinea Pigs
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Protective Effects of CYP2E1 Inhibitors on MetabolicSyndrome-induced Liver Injury in Guinea Pigs

机译：CYP2E1抑制剂对代谢综合征所致豚鼠肝损伤的保护作用

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The present work reports the effects of CYP2E1-inhibitors (quercetin, 4- methylpyrazole and disulfiram) on the indices characterizing state of the liver in guinea pigs with metabolic syndrome (MS) induced by protamine sulfate repeated administrations.The investigation of quercetin, 4-methylpyrazole and disulfiram effects on hepatic cytochrome P450 2E1 (CYP2E1) protein and activity changes was conducted. Simultaneously, the content of reactive oxygen species (ROS) and markers of liver damage were determined in experimental animals’ blood. The link between increased hepatic expression of CYP2E1, prominent ROS generation and liver damage in animals with MS has been discovered. It has been demonstrated that CYP2E1 protein content and activity in guinea pigs with MS rose almost 3 times compared to intact animals. These events were accompanied by increase in ROS generation and metabolism and liver disturbances symptoms: increase in serum glucose and cholesterol contents (2 and 2.6 times respectively), alanine aminotransferase (2.8 times), aspartate aminotransferase (6.4 times), and alkaline phosphatase (1.8 times) elevations. Our investigation suggests that administration of quercetin, 4-methylpyrazole, and disulfiram in guinea pigs with MS caused decrease in this isoenzyme protein expression (2.5, 1.7 and 2.4 respectively) as well as its enzymatic activity in liver (6.6, 1.1, and 1.7 respectively). The content of blood ROS was partially restored or normalized by all three CYP2E1 inhibitors. In turn, suppression of CYP2E1 activity and ROS generation led to decrease in hepatic MS manifestation. It is apparent from the present observation that quercetin has the highest efficiency among the investigated substances. Further studies on various quercetin doses and administration regimens could provide relevant information for the development of MS-related nonalcoholic fatty liver disease treatment.
机译：本工作报道了CYP2E1抑制剂（槲皮素，4-甲基吡唑和双硫仑）对硫酸鱼精蛋白反复给药所致豚鼠代谢综合征（MS）肝脏状态的指标的影响。槲皮素，4-进行了甲基吡唑和双硫仑对肝细胞色素P450 2E1（CYP2E1）蛋白的影响和活性变化。同时，测定实验动物血液中的活性氧（ROS）含量和肝损伤标志物。 CYP2E1的肝表达增加，明显的ROS生成与MS动物引起的肝损害之间的联系已被发现。已经证明，与完整动物相比，患有MS的豚鼠的CYP2E1蛋白含量和活性提高了近3倍。这些事件伴随着ROS的产生和代谢增加以及肝功能紊乱的症状：血清葡萄糖和胆固醇含量（分别为2倍和2.6倍），丙氨酸转氨酶（2.8倍），天冬氨酸转氨酶（6.4倍）和碱性磷酸酶（1.8倍）增加次）海拔。我们的研究表明，在患有MS的豚鼠中服用槲皮素，4-甲基吡唑和双硫仑会导致该同工酶蛋白表达降低（分别为2.5、1.7和2.4），并降低其在肝脏中的酶活性（分别为6.6、1.1和1.7）。 ）。血液ROS的含量被全部三种CYP2E1抑制剂部分恢复或标准化。反过来，CYP2E1活性和ROS生成的抑制导致肝MS表现的降低。从目前的观察结果明显看出，槲皮素在所研究的物质中具有最高的效率。对各种槲皮素剂量和给药方案的进一步研究可为与MS相关的非酒精性脂肪肝疾病治疗的发展提供相关信息。

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