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双-1,7-(2-羟苯基)-庚-1,6-二烯-3,5-二酮(姜黄素类似物)可改善二甲基肼诱导的结肠癌发生过程中的肝脏氧化应激。

Bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione (a curcumin analog) ameliorates DMH-induced hepatic oxidative stress during colon carcinogenesis.

作者信息

Devasena T, Rajasekaran K N, Menon Venugopal P

机构信息

Department of Biochemistry, Faculty of Science, Annamalai University, Annamalai Nagar 608 002, Tamil Nadu, India.

出版信息

Pharmacol Res. 2002 Jul;46(1):39-45. doi: 10.1016/s1043-6618(02)00043-9.

Abstract

The protective effect of a curcumin analog [bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione] was investigated on hepatic lipid peroxidation (LPO) and antioxidant status during 1,2-dimethylhydrazine-induced colon carcinogenesis in male Wistar rats. The effects were compared with that of curcumin, a known antioxidant and anticarcinogen. Colon cancer was induced by sub-cutaneous injection of DMH at a dosage of 20mg/kg body weight (15 doses, at 1-week intervals). DMH administered rats developed gross tumours in the colon. Enhanced lipid peroxidation in the liver of colon tumour bearing rats was accompanied by a significant decrease in the activities of glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT). Intragastric administration of curcumin (80mg/kg body weight) and curcumin analog (80mg/kg body weight) to DMH-injected rats significantly reduced the number and size of tumour in the colon, lowered lipid peroxidation and enhanced the activities of GPx, GST, SOD and CAT in the liver. We speculate that the curcumin analog used in the present study exerts chemoprevention against cancer development at extrahepatic sites by modulating hepatic biotransformation enzymes and antioxidant status. The effect is comparable with that of curcumin. This shows that the hydroxyl group in the aromatic ring is responsible for the protective effect rather than the methoxy group.

摘要

研究了一种姜黄素类似物[双-1,7-(2-羟基苯基)-庚-1,6-二烯-3,5-二酮]对雄性Wistar大鼠在1,2-二甲基肼诱导的结肠癌发生过程中肝脏脂质过氧化(LPO)和抗氧化状态的保护作用。将其效果与已知的抗氧化剂和抗癌剂姜黄素的效果进行了比较。通过皮下注射剂量为20mg/kg体重的DMH(共15剂,间隔1周)诱导结肠癌。给予DMH的大鼠在结肠出现肉眼可见的肿瘤。荷结肠肿瘤大鼠肝脏中脂质过氧化增强,同时谷胱甘肽过氧化物酶(GPx)、谷胱甘肽S-转移酶(GST)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性显著降低。对注射DMH的大鼠灌胃给予姜黄素(80mg/kg体重)和姜黄素类似物(80mg/kg体重),可显著减少结肠肿瘤的数量和大小,降低脂质过氧化,并增强肝脏中GPx、GST、SOD和CAT的活性。我们推测,本研究中使用的姜黄素类似物通过调节肝脏生物转化酶和抗氧化状态,对肝外部位的癌症发展发挥化学预防作用。其效果与姜黄素相当。这表明芳香环中的羟基而非甲氧基负责这种保护作用。

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