Sudhahar V, Ashok Kumar S, Varalakshmi P, Sujatha V
Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India.
Mol Cell Biochem. 2008 Oct;317(1-2):11-20. doi: 10.1007/s11010-008-9786-5. Epub 2008 Jun 19.
The association between hypercholesterolemia and kidney damage has been well known for last few decades. The oxidative stress and inflammatory responses are involved in renal injury, which is upregulated in hypercholesterolemic condition. The present study is aimed to evaluate the possible effect of lupeol and its ester derivative, lupeol linoleate in renal damage associated with hypercholesterolemic rats. Hypercholesterolemia was induced in male Wistar rats by feeding them with a high cholesterol diet (HCD) comprising normal rat chow supplemented with 4% cholesterol and 1% cholic acid for 30 days. Lupeol and lupeol linoleate were supplemented (50 mg/kg body wt/day) to HCD fed rats during the last 15 days. Increased levels of renal total cholesterol, triglycerides and phospholipids, along with altered serum biochemical parameters of tissue injury indices and elevated activities of renal marker enzymes (lactate dehydrogenase and alkaline phosphatase) were noted in HCD fed rats. Elevated lipid peroxidation levels coupled with decreased antioxidant status (enzymatic and non enzymatic antioxidants) were observed in hypercholesterolemic rats, which indicate the onset of oxidative changes in the renal tissue. Renal lysosomal acid hydrolase activities (ACP, beta-Glu, beta-Gal, NAG and Cat-D) and acute phase proteins like C-Reactive protein and fibrinogen were significantly increased in HCD fed rats, which further indicates the heightening of inflammation. In addition, histopathological findings also confirmed the renal damage in hypercholesterolemic condition. Lupeol and lupeol linoleate effectively reverted the above abnormalities and was comparable with that of the control. These observations highlight the protective effect of lupeol and its ester derivative in ameliorating the renal injury associated with hypercholesterolemia.
在过去几十年中,高胆固醇血症与肾损伤之间的关联已广为人知。氧化应激和炎症反应参与了肾损伤过程,在高胆固醇血症状态下这些反应会上调。本研究旨在评估羽扇豆醇及其酯衍生物亚油酸羽扇豆醇酯对高胆固醇血症大鼠肾损伤的可能影响。通过给雄性Wistar大鼠喂食高胆固醇饮食(HCD)来诱导高胆固醇血症,该饮食由补充了4%胆固醇和1%胆酸的普通大鼠饲料组成,持续30天。在最后15天,给喂食HCD的大鼠补充羽扇豆醇和亚油酸羽扇豆醇酯(50毫克/千克体重/天)。在喂食HCD的大鼠中,观察到肾总胆固醇、甘油三酯和磷脂水平升高,同时组织损伤指标的血清生化参数改变,以及肾标记酶(乳酸脱氢酶和碱性磷酸酶)活性升高。在高胆固醇血症大鼠中观察到脂质过氧化水平升高,同时抗氧化状态(酶促和非酶促抗氧化剂)降低,这表明肾组织发生了氧化变化。喂食HCD的大鼠肾溶酶体酸性水解酶活性(酸性磷酸酶、β-葡萄糖苷酶、β-半乳糖苷酶、N-乙酰-β-氨基葡萄糖苷酶和组织蛋白酶D)以及急性期蛋白如C反应蛋白和纤维蛋白原显著增加,这进一步表明炎症加剧。此外,组织病理学结果也证实了高胆固醇血症状态下的肾损伤。羽扇豆醇和亚油酸羽扇豆醇酯有效地逆转了上述异常,且与对照组相当。这些观察结果突出了羽扇豆醇及其酯衍生物在改善高胆固醇血症相关肾损伤方面的保护作用。