Investigation of antioxidant, anti-inflammatory and DNA-protective properties of eugenol in thioacetamide-induced liver injury in rats
Investigation of antioxidant, anti-inflammatory and DNA-protective properties of eugenol in thioacetamide-induced liver injury in rats
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DOI：
10.1016/j.tox.2009.12.018
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发表时间：
2010-02-09
期刊：
影响因子：
4.5
通讯作者：
Venkatraman, Anuradha Carani
中科院分区：
文献类型：
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作者：
Baskaran, Yogalakshmi;Periyasamy, Viswanathan;Venkatraman, Anuradha Carani
本研究探讨了天然食品调味剂丁香酚对硫代乙酰胺（TA）诱导的大鼠肝损伤的预防作用。体重150-180 g的成年雄性Wistar大鼠用于本研究。丁香酚（10.7 mg/kg b.w./天）通过经口插管给予大鼠15天。给予TA（300 mg/kg b.w.，注射用）最后2天，间隔24 h，第16天处死大鼠。评估肝损伤标志物（天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶、γ-谷氨酰转移酶和胆红素）、炎症（髓过氧化物酶、肿瘤坏死因子-α和白细胞介素-6）、氧化应激（脂质过氧化指数、蛋白质羰基和抗氧化状态）和细胞色素P4502 E1活性。采用免疫印迹法和彗星试验分别分析环氧合酶-2（考克斯-2）的表达和DNA损伤程度。通过苏木素、伊红和马松三色染色进行组织学研究，评估肝损伤和胶原蛋白积聚。单独暴露于TA的大鼠显示血浆中肝细胞酶、脂质过氧化指数、炎症标志物和促炎细胞因子的活性增加，循环和肝脏中的抗氧化状态降低。肝损伤和坏死也通过组织学证实。丁香酚预处理通过降低CYP 2 E1活性、脂质过氧化指数、蛋白质氧化和炎症标志物以及改善抗氧化状态来预防肝损伤。单细胞凝胶电泳显示丁香酚预处理可防止TA诱导的DNA链断裂。丁香酚可抑制TA诱导的考克斯-2基因表达增加。这些结果表明，丁香酚削减TA在肝脏中的毒性作用。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
The present study investigated the preventive effect of eugenol, a naturally occurring food flavouring agent on thioacetamide (TA)-induced hepatic injury in rats. Adult male Wistar rats of body weight 150-180 g were used for the study. Eugenol (10.7 mg/kg b.w./day)was administered to rats by oral intubation for 15 days. TA was administered (300 mg/kg b.w., i.p.) for the last 2 days at 24 h interval and the rats were sacrificed on the 16th day. Markers of liver injury (aspartate transaminase, alanine transaminase, alkaline phosphatase, gamma-glutamyl transferase and bilirubin), inflammation (myeloperoxidase, tumor necrosis factor-alpha and interleukin-6), oxidative stress (lipid peroxidation indices, protein carbonyl and antioxidant status) and cytochrome P4502E1 activity were assessed. Expression of cyclooxygenase-2 (COX-2) and the extent of DNA damage were analyzed using immunoblotting and comet assay, respectively. Liver injury and collagen accumulation were assessed using histological studies by hematoxylin and eosin and Masson trichrome staining. Rats exposed to TA alone showed increased activities of hepatocellular enzymes in plasma, lipid peroxidation indices, inflammatory markers and pro-inflammatory cytokines and decreased antioxidant status in circulation and liver. Hepatic injury and necrosis were also evidenced by histology. Eugenol pretreatment prevented liver injury by decreasing CYP2E1 activity, lipid peroxidation indices, protein oxidation and inflammatory markers and by improving the antioxidant status. Single-cell gel electrophoresis revealed that eugenol pretreatment prevented DNA strand break induced by TA. Increased expression of COX-2 gene induced by TA was also abolished by eugenol. These findings suggest that eugenol curtails the toxic effects of TA in liver. (C) 2009 Elsevier Ireland Ltd. All rights reserved.