Inhibition of oxidative stress and cytokine activity by curcumin in amelioration of endotoxin-induced experimental hepatoxicity in rodents
Inhibition of oxidative stress and cytokine activity by curcumin in amelioration of endotoxin-induced experimental hepatoxicity in rodents
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DOI：
10.1111/j.1365-2249.2006.03108.x
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发表时间：
2006-08-01
影响因子：
4.6
通讯作者：
Chopra, K.
中科院分区：
文献类型：
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作者：
Kaur, G.;Tirkey, N.;Chopra, K.
本研究旨在探讨姜黄素（curcumin， CMN）对内毒素诱导的啮齿动物肝脏功能障碍和氧化应激的修复作用。以1 mg/kg的单剂量脂多糖（LPS）腹腔注射，连续7天给予CMN治疗。测定血清肝酶、血清丙氨酸转氨酶（ALT）、血清天冬氨酸转氨酶（AST）和碱性磷酸酶（ALP）、总胆红素和总蛋白。通过测定肝组织匀浆中硫代巴比妥酸活性物质（TBARS）、谷胱甘肽（GSH）含量和超氧化物歧化酶（SOD）活性来评估肝组织氧化应激。用Greiss试剂测定血清和组织亚硝酸盐，并将其作为NO生成的指标。我们进行了一组单独的实验来评估CMN对LPS刺激后小鼠血清细胞因子水平的影响。LPS诱导大鼠肝功能异常，血清ALT、AST、ALP和总胆红素水平升高（P < 0.05）。lps刺激大鼠肝脏匀浆中TBARS水平显著升高，而GSH和SOD水平降低。CMN成功地减弱了LPS的这些作用。进一步的CMN治疗还可以逆转LPS诱导的大鼠肝脏的各种结构变化，降低小鼠血浆中肿瘤坏死因子- α和白细胞介素-6的水平。综上所述，这些发现表明CMN可能通过阻止NO、氧自由基和细胞因子的细胞毒性作用来减轻lps诱导的肝毒性。
The present study is aimed at investigating the effect of curcumin (CMN) in salvaging endotoxin-induced hepatic dysfunction and oxidative stress in the liver of rodents. Hepatotoxicity was induced by administering lipopolysaccharide (LPS) in a single dose of 1 mg/kg intraperitoneally to the animals, which were being treated with CMN daily for 7 days. Liver enzymes serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST) and alkaline phosphatase (ALP), total bilirubin and total protein were estimated in serum. Oxidative stress in liver tissue homogenates was estimated by measuring thiobarbituric acid reactive substances (TBARS), glutathione (GSH) content and superoxide dismutase (SOD) activity. Serum and tissue nitrite was estimated using Greiss reagent and served as an indicator of NO production. A separate set of experiments was performed to estimate the effect of CMN on cytokine levels in mouse serum after LPS challenge. LPS induced a marked hepatic dysfunction evident by rise in serum levels of ALT, AST, ALP and total bilirubin (P < 0.05). TBARS levels were significantly increased, whereas GSH and SOD levels decreased in the liver homogenates of LPS-challenged rats. CMN administration attenuated these effects of LPS successfully. Further CMN treatment also regressed various structural changes induced by LPS in the livers of rats and decreased the levels of tumour necrosis factor-alpha and interleukin-6 in mouse plasma. In conclusion, these findings suggest that CMN attenuates LPS-induced hepatotoxicity possibly by preventing cytotoxic effects of NO, oxygen free radicals and cytokines.