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褪黑素、姜黄素、槲皮素和白藜芦醇对急性次氮基三乙酸铁(Fe-NTA)诱导的大鼠肾脏氧化损伤的影响。

Effect of melatonin, curcumin, quercetin, and resveratrol on acute ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative damage in rats.

作者信息

Eybl V, Kotyzová D, Cerná P, Koutensky J

机构信息

Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Medicine in Pilsen, Karlovarská 48, 301 66 Pilsen, Czech Republic.

出版信息

Hum Exp Toxicol. 2008 Apr;27(4):347-53. doi: 10.1177/0960327108094508.

Abstract

The influence of melatonin, curcumin, quercetin, and resveratrol pretreatment on ferric nitrilotriacetate (Fe-NTA)-induced oxidative renal damage was studied. Male Wistar rats were treated orally once daily for 3 days with melatonin (10 mg/kg), curcumin (50 mg/kg), quercetin (15 mg/kg), and resveratrol (10 mg/kg). One hour after the last dose of antioxidants, a single dose of Fe-NTA was administered (8 mg of Fe/kg body weight, i.p.) to pre-treated animals. Twenty-four hours after Fe-NTA administration, the lipid peroxidation (LP), reduced glutathione (GSH), catalase (CAT), and glutathione peroxidase (GSH-Px) were estimated in kidney homogenates. Iron, zinc, and copper concentrations were estimated in kidney tissue. Administration of Fe-NTA to rats induced renal LP (170%, P < 0.001) and inhibited catalase (78%, P < 0.05) in the kidney. The oral pretreatment with melatonin, curcumin, quercetin, and resveratrol each one was effective in decreasing the Fe-NTA-induced LP (P < 0.001); however, it did not influence the FeNTA-induced inhibition of renal CAT activity. No changes were found in renal GSH level and GSH-Px activity compared to control animals. The pretreatment with antioxidants did not affect the increase in renal iron content, blood urea nitrogen/creatinine ratio, and relative kidney weight of FeNTA-intoxicated rats. The results indicate that the pretreatment with natural antioxidants, curcumin, melatonin, quercetin, and resveratrol, significantly and equally suppressed lipid peroxidation induced by Fe-NTA but had no effect on other markers of FeNTA nephrotoxicity and iron deposition in kidneys.

摘要

研究了褪黑素、姜黄素、槲皮素和白藜芦醇预处理对次氮基三乙酸铁(Fe-NTA)诱导的氧化性肾损伤的影响。雄性Wistar大鼠每天口服一次褪黑素(10毫克/千克)、姜黄素(50毫克/千克)、槲皮素(15毫克/千克)和白藜芦醇(10毫克/千克),持续3天。在最后一剂抗氧化剂给药1小时后,给预处理的动物腹腔注射一剂Fe-NTA(8毫克铁/千克体重)。Fe-NTA给药24小时后,测定肾匀浆中的脂质过氧化(LP)、还原型谷胱甘肽(GSH)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)。测定肾组织中的铁、锌和铜浓度。给大鼠注射Fe-NTA可诱导肾LP(增加170%,P<0.001)并抑制肾中的过氧化氢酶(降低78%,P<0.05)。褪黑素、姜黄素、槲皮素和白藜芦醇的口服预处理均能有效降低Fe-NTA诱导的LP(P<0.001);然而,它并未影响Fe-NTA诱导的肾CAT活性抑制。与对照动物相比,肾GSH水平和GSH-Px活性未发现变化。抗氧化剂预处理对Fe-NTA中毒大鼠的肾铁含量增加、血尿素氮/肌酐比值和相对肾重量没有影响。结果表明,天然抗氧化剂姜黄素、褪黑素、槲皮素和白藜芦醇预处理能显著且同等程度地抑制Fe-NTA诱导的脂质过氧化,但对Fe-NTA肾毒性的其他标志物及肾中铁沉积没有影响。

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