Allopurinol Ameliorates Thioacetamide-Induced Acute Liver Failure by Regulating Cellular Redox-Sensitive Transcription Factors in Rats
Allopurinol Ameliorates Thioacetamide-Induced Acute Liver Failure by Regulating Cellular Redox-Sensitive Transcription Factors in Rats
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DOI：
10.1007/s10753-012-9470-5
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发表时间：
2012-08-01
期刊：
影响因子：
5.1
通讯作者：
Bahcecioglu, Ibrahim Halil
中科院分区：
文献类型：
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作者：
Demirel, Ulvi;Yalniz, Mehmet;Bahcecioglu, Ibrahim Halil
氧化应激在急性肝衰竭的发生发展中起重要作用。在这项研究中，我们研究了别嘌呤醇（AP）对硫代乙酰胺（TAA）诱导的肝损伤的影响，以及AP治疗导致炎症改善的潜在机制。腹腔注射TAA （300 mg/kg/天，连续2天）诱导急性肝衰竭。将35只大鼠分为5组：对照组（1组）、TAA组（2组）、TAA + 25AP组（3组）、TAA + 50ap组（4组）、TAA + 100AP组（5组）。每组7只。研究结束时进行组织病理学、生化和免疫印迹分析。TAA治疗显著提高血清转氨酶水平、肝脏丙二醛（MDA）、核因子- κ B （NF-O > B）、激活蛋白-1 （AP-1）、肿瘤坏死因子- α (tnf - α)、环氧化酶-2 （COX-2）和白细胞介素-6 （IL-6）水平以及坏死-炎症评分。然而，TAA降低了肝脏中核因子e2相关因子-2和血红素氧合酶-1 （HO-1）的表达。AP处理显著降低血清转氨酶水平（P < 0.01）和肝脏MDA、nf - κ B、AP-1、tnf - α、COX-2、IL-6的表达（P < 0.05）。此外，AP可以恢复肝脏Nrf2和HO-1的表达，并显著改善坏死-炎症评分。AP通过调节细胞氧化还原敏感转录因子和促炎和抗氧化防御机制的表达，改善氧化应激诱导的肝损伤。AP可能通过其自由基清除能力以剂量依赖的方式发挥这些有益的特征。
Oxidative stress plays important role in the development of acute liver failure. In this study, we investigated effects of allopurinol (AP) upon thioacetamide (TAA)-induced liver injury and the potential mechanisms leading to amelioration in inflammation with AP treatment. Acute liver failure was induced by intraperitoneal administration of TAA (300 mg/kg/day for 2 days). Thirty-five rats were divided into five groups as control (group 1), TAA (group 2), TAA + 25AP (group 3), TAA + 50 AP (group 4), and TAA + 100AP (group 5). The number of animals in each group was seven. At the end of the study, histopathological, biochemical, and western blot analysis were done. TAA treatment significantly increased serum levels of aminotransferases, liver malondialdehyde (MDA), nuclear factor-kappa B (NF-O > B ), activator protein-1 (AP-1), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels, and the necro-inflammation scores. Nevertheless, nuclear factor E2-related factor-2 and heme oxygenase-1 (HO-1) expressions in the liver were decreased by TAA. AP treatment significantly lowered the serum levels of aminotransferases (P < 0.01) and liver MDA, NF-kappa B, AP-1, TNF-alpha, COX-2, and IL-6 expressions (P < 0.05). Moreover, AP restored the liver Nrf2 and HO-1 expressions and improved the necro-inflammation scores significantly. AP improves oxidative stress-induced liver damage by regulating cellular redox-sensitive transcriptor factors and expression of pro-inflammatory and antioxidant defense mechanisms. AP probably exerts these beneficiary features by its free radical scavenging ability in a dose-dependent manner.