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甘蔗蜡中高分子量伯酸混合物D-003对大鼠半乳糖胺诱导的肝损伤缺乏保护作用。

Lack of protective effect of D-003, a mixture of high-molecular-weight primary acids from sugar cane wax, on liver damage induced by galactosamine in rats.

作者信息

Noa Miriam, Mendoza Sarahí, Mas Rosa, Mendoza Nilda

机构信息

Center of Natural Products from the National Center for Scientific Research, Havana City, Cuba.

出版信息

J Med Food. 2005 Fall;8(3):343-7. doi: 10.1089/jmf.2005.8.343.

Abstract

D-003 is a mixture of very-high-molecular-weight aliphatic primary acids purified from sugar cane wax, wherein octacosanoic acid is the most abundant. Experimental and clinical studies have shown that D-003 lowers cholesterol and prevents plasma lipoprotein peroxidation (LP). D-003 has protected against the histological changes characteristic of CCl4- and paracetamol-induced hepatic injury in rats, in which LP plays a pivotal role for explaining the resulting hepatotoxicity. Galactosamine induces hepatotoxicity associated with depressed RNA and protein synthesis, not with LP. The aim of this study was to evaluate whether D-003 could prevent hepatoxicity induced by mechanisms others than increased LP. We investigated the effects on galactosamine hepatotoxicity in rats distributed into five groups: a negative control group, a positive control group, and three groups treated with galactosamine and D-003 (5, 25, and 100 mg/kg). To induce liver damage, galactosamine (800 mg/kg) was injected intraperitoneally 30 minutes after dosing with vehicle or D-003. Twenty-four hours later, rats were sacrificed, and livers were immediately removed for histopathological studies. Livers from positive controls showed the characteristic pattern of galactosamine-induced damage. Galactosamine significantly reduced the percentage of normal hepatocytes, increasing both necrotic or lipid-rich hepatocytes compared with negative controls. D-003, however, did not increase the percentage of normal hepatocytes compared with positive controls, indicating that treatment was not effective for preventing the hepatic injury induced with galactosamine. Likewise, D-003 failed to change the content of necrotic and lipid-rich hepatocytes relative to positive controls. It is concluded that D-003 did not protect against the histological changes of galactosamine-induced hepatotoxicity.

摘要

D - 003是一种从甘蔗蜡中提纯的高分子量脂肪族一元酸混合物,其中二十八烷酸含量最为丰富。实验和临床研究表明,D - 003可降低胆固醇并防止血浆脂蛋白过氧化(LP)。D - 003已对大鼠四氯化碳和扑热息痛诱导的肝损伤的组织学变化起到保护作用,在这种损伤中LP在解释由此产生的肝毒性方面起关键作用。氨基半乳糖诱导的肝毒性与RNA和蛋白质合成受抑制有关,而非与LP有关。本研究的目的是评估D - 003是否能预防由LP增加以外的机制诱导的肝毒性。我们研究了D - 003对分为五组的大鼠氨基半乳糖肝毒性的影响:一个阴性对照组、一个阳性对照组以及三组用氨基半乳糖和D - 003(5、25和100毫克/千克)处理的组。为诱导肝损伤,在给予赋形剂或D - 003 30分钟后腹腔注射氨基半乳糖(800毫克/千克)。24小时后,处死大鼠,并立即取出肝脏进行组织病理学研究。阳性对照组的肝脏呈现出氨基半乳糖诱导损伤的特征模式。与阴性对照组相比,氨基半乳糖显著降低了正常肝细胞的百分比,同时增加了坏死或富含脂质的肝细胞的比例。然而,与阳性对照组相比,D - 003并未增加正常肝细胞的百分比,这表明该处理对于预防氨基半乳糖诱导的肝损伤无效。同样,相对于阳性对照组,D - 003未能改变坏死和富含脂质的肝细胞的含量。得出的结论是,D - 003不能预防氨基半乳糖诱导的肝毒性的组织学变化。

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