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在Wistar大鼠肝癌发生模型中,角鲨烯不具有化学预防活性,反而会增加血浆胆固醇。

Squalene does not exhibit a chemopreventive activity and increases plasma cholesterol in a Wistar rat hepatocarcinogenesis model.

作者信息

Scolastici Clarissa, Ong Thomas Prates, Moreno Fernando Salvador

机构信息

Department of Pathology, Faculty of Medicine, São Paulo State University, Botucatu, Brazil.

出版信息

Nutr Cancer. 2004;50(1):101-9. doi: 10.1207/s15327914nc5001_13.

Abstract

The eventual chemopreventive effect of squalene (SQ), a triterpene present in olive oil, was evaluated when administered to Wistar rats during a period comprising the initiation and selection/promotion of the "resistant hepatocyte" (RH) model of hepatocarcinogenesis. During 8 consecutive wk, animals received by gavage SQ (100 or 150 mg/100 g body weight) dissolved in corn oil (CO) daily. Animals treated with only CO and submitted to the RH model were used as controls. Treatments with SQ did not result in inhibition of macroscopically visible hepatocyte nodules (P > 0.05) or of hepatic placental glutathione S-transferase- positive preneoplastic lesions (PNL; P > 0.05). Hepatic cell proliferation and apoptosis indexes were not different (P > 0.05) among the different experimental groups, both regarding PNL and surrounding normal tissue areas. There were no significant differences (P > 0.05) among comets presented by rats treated with the two SQ doses or with CO. On the other hand, SQ increased total plasma cholesterol levels when administered at both doses (P < 0.05). This indicates that the isoprenoid was absorbed. Thus, SQ did not present chemopreventive activity during hepatocarcinogenesis and had a hypercholesterolemic effect, suggesting caution when considering its use in chemoprevention of cancer.

摘要

角鲨烯(SQ)是橄榄油中的一种三萜烯,在肝癌发生的“抗性肝细胞”(RH)模型的启动和选择/促进阶段给予Wistar大鼠时,评估了其最终的化学预防效果。在连续8周内,动物每天经口灌胃给予溶解于玉米油(CO)中的SQ(100或150mg/100g体重)。仅用CO处理并接受RH模型的动物用作对照。SQ处理并未导致肉眼可见的肝细胞结节受到抑制(P>0.05),也未抑制肝胎盘谷胱甘肽S-转移酶阳性的癌前病变(PNL;P>0.05)。在不同实验组中,无论是PNL还是周围正常组织区域,肝细胞增殖和凋亡指数均无差异(P>0.05)。用两种SQ剂量或CO处理的大鼠所呈现的彗星实验结果之间无显著差异(P>0.05)。另一方面,两种剂量的SQ给药均使总血浆胆固醇水平升高(P<0.05)。这表明类异戊二烯被吸收了。因此,SQ在肝癌发生过程中未呈现化学预防活性,且具有高胆固醇血症效应,这表明在考虑将其用于癌症化学预防时应谨慎。

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