Hepatoprotective effect of curcumin and alpha-tocopherol against cisplatin-induced oxidative stress.

Hepatoprotective effect of curcumin and alpha-tocopherol against cisplatin-induced oxidative stress.
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DOI:
10.1186/1472-6882-14-111
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发表时间:
2014-03-28
影响因子:
--
通讯作者:
Suwannalert P
Suwannalert P
中科院分区:
医学3区
文献类型:
--
作者:
Palipoch S;Punsawad C;Koomhin P;Suwannalert P

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顺式二氯二氨铂(II)(cisplatin)是一种重要的抗癌药物,可用于治疗各种癌症。不幸的是,它会在各种组织中产生不必要的副作用,包括肝脏。本研究探讨了姜黄素和α-生育酚对顺铂治疗后大鼠氧化应激诱导的肝毒性的可能保护作用。雄性Wistar大鼠分为5组(n = 5)。生理盐水组和Cis组,大鼠腹腔内(i. p.)注射生理盐水和顺铂[20 mg/kg体重(b.w.)],分别Cis + α-生育酚组、Cis + Cur组和Cis + α-生育酚+ Cur组,大鼠单次给予α-生育酚(250 mg/kg b.w.),姜黄素(200 mg/kg b.w.)在顺铂给药前24 h分别联合α-生育酚和姜黄素。首次注射72 h后,采集标本。检测肝酶、脂质过氧化指标、肝组织病理学和肝脏NADPH氧化酶基因表达。顺铂显示了显着增加肝丙二醛(MDA)水平和显着降低肝超氧化物歧化酶(SOD)和过氧化氢酶活性相比,生理盐水组。它引起血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平显著升高,并显示肝脏病理学,包括肝充血、肝索紊乱和肝细胞毛玻璃样外观。与生理盐水组相比,NADPH氧化酶基因表达也显著增加。姜黄素和α-生育酚联合预处理可改善顺铂治疗大鼠的肝酶、脂质过氧化生物标志物、肝组织病理学和肝脏NADPH氧化酶基因表达。结果表明,姜黄素和α-生育酚联合预处理对顺铂诱导的肝毒性具有保护作用,包括生化、组织学和分子生物学方面。NADPH氧化酶基因表达的下调可能通过减少活性氧(ROS)的产生而参与消除氧化应激。
cis-Diammineplatinum (II) dichloride (cisplatin) is the important anti-cancer agent useful in treatment of various cancers. Unfortunately, it can produce unwanted side effects in various tissues, including the liver. The present study investigated the possible protective role of curcumin and α-tocopherol against oxidative stress-induced hepatotoxicity in rats upon cisplatin treatment. Male Wistar rats were divided into five groups (n = 5). Saline and Cis groups, rats were intraperitoneal (i.p.) injected with normal saline and cisplatin [20 mg/kg body weight (b.w.)], respectively. Cis + α-tocopherol group, Cis + Cur group and Cis + α-tocopherol + Cur group, rats were pre-treated with a single dose of α-tocopherol (250 mg/kg b.w.), curcumin (200 mg/kg b.w.) and combined α-tocopherol with curcumin, respectively, for 24 h prior the administration of cisplatin. After 72 h of first injection, specimens were collected. Liver enzyme, lipid peroxidation biomarker, liver histopathology and gene expression of liver nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were investigated. Cisplatin revealed a significant increase of hepatic malondialdehyde (MDA) levels and a significant reduction of hepatic superoxide dismutase (SOD) and catalase activities compared to the saline group. It elicited a marked increase of the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and demonstrated the liver pathologies including liver congestion, disorganization of hepatic cords and ground glass appearance of hepatocytes. It also demonstrated a significant increase of NADPH oxidase gene expression compared to saline group. Pre-treatment with combined curcumin and α-tocopherol improved the liver enzymes, lipid peroxidation biomarker, liver histopathology and gene expression of liver NADPH oxidase in cisplatin-treated rats. The findings indicate that pre-treatment with combined curcumin and α-tocopherol can protect cisplatin-induced hepatotoxicity including the biochemical, histological and molecular aspects. The down-regulations of NADPH oxidase gene expression may be involved in abrogating oxidative stress via reduction of reactive oxygen species (ROS) production.
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