Comparative study of natural antioxidants - curcumin, resveratrol and melatonin - in cadmium-induced oxidative damage in mice

Comparative study of natural antioxidants - curcumin, resveratrol and melatonin - in cadmium-induced oxidative damage in mice
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DOI:
10.1016/j.tox.2006.05.011
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发表时间:
2006-08-15
期刊:
影响因子:
4.5
通讯作者:
Koutensky, Jaroslav
Koutensky, Jaroslav
中科院分区:
医学3区
文献类型:
--
作者:
Eybl, Vladislav;Kotyzova, Dana;Koutensky, Jaroslav

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本研究旨在研究姜黄素、白藜芦醇和褪黑素预处理对镉诱导的小鼠氧化损伤和镉分布的抗氧化作用。将雄性CD小鼠用姜黄素(50 mg/kg b.w.,p.o.),白藜芦醇(20 mg/kg b.w.,p.o.)或褪黑素(12 mg/kg,p.o.),分散在0.5%甲基纤维素中。在最后一剂抗氧化剂氯化镉给药后1小时(7 mg/kg b.w.,s.c.)给药前动物和接受甲基纤维素的对照动物。染毒后24 h,测定肝匀浆中脂质过氧化(LP --以丙二醛的生成表示)、还原型谷胱甘肽(GSH)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx)的含量,用原子吸收法测定肝、肾、睾丸和脑中镉的含量。氯化镉可诱导小鼠肝脏脂质过氧化反应(至133%,p < 0.001),降低GSH含量(至65%,p < 0.001),抑制过氧化氢酶(至68%,p < 0.001)和GPx活性(至60%,p < 0.001)。姜黄素、白藜芦醇和褪黑激素口服预处理完全防止镉诱导的脂质过氧化和镉诱导的GPx肝活性抑制。白藜芦醇对镉诱导的过氧化氢酶活性抑制有明显的拮抗作用(p < 0.001)。姜黄素、白藜芦醇或褪黑激素预处理不能阻止肝脏GSH水平的降低。在单独用抗氧化剂处理的小鼠中,LP、GSH、GPx或CAT的水平与对照水平没有差异。抗氧化剂预处理不影响镉中毒小鼠组织中镉的分布。结果表明,姜黄素,白藜芦醇和褪黑激素预处理有效地防止镉诱导的脂质过氧化反应,并改善镉对抗氧化状态的不利影响,而没有任何减少组织镉负荷。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
The present study was designed to examine the antioxidative effect of curcumin, resveratrol and melatonin pre-treatment on cadmium-induced oxidative damage and cadmium distribution in an experimental model in mice. Male CD mice were treated once daily for 3 days with curcumin (50mg/kg b.w., p.o.), resveratrol (20mg/kg b.w., p.o.) or melatonin (12mg/kg, p.o.), dispersed in 0.5% methylcellulose. One hour after the last dose of antioxidants cadmium chloride was administered (7 mg/kg b.w., s.c.) to pre-treated animals and control animals receiving methylcellulose. At 24th h after Cd administration the lipid peroxidation (LP - expressed as malondialdehyde production), reduced glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx) were estimated in liver homogenates.Cadmium concentration was-measured in the liver, kidneys, testes and brain by AAS. Cadmium chloride administration to mice induced hepatic lipid peroxidation (to 133%, p < 0.001), decreased GSH content (to 65%, p < 0.001) and inhibited catalase (to 68%, p < 0.001) and GPx activity (to 60%, p < 0.001) in the liver. Curcumin, resveratrol and melatonin oral pre-treatment completely prevented the Cd-induced lipid peroxidation and Cd-induced inhibition of GPx hepatic activity. Resveratrol was effective against Cd-induced inhibition of catalase activity (p < 0.001). The decrease in hepatic GSH level was not prevented by curcumin, resveratrol or melatonin pre-treatment. In mice treated with dritioxidants alone the level of LP, GSH, GPx or CAT was not different from control levels. The pre-treatment with antioxidants did not affect cadmium distribution in the tissues of Cd-intoxicated mice. The results demonstrate that curcumin, resveratrol and melatonin pre-treatment effectively protect against cadmium-induced lipid peroxidation and ameliorate the adverse effect of cadmium on antioxidant status without any reduction in tissue Cd burden. (c) 2006 Elsevier Ireland Ltd. All rights reserved.