Reddy G Dilip, Reddy A Gopala, Rao G Srinivasa, Haritha C, Jyothi K
Department of Pharmacology and Toxicology, College of Veterinary Science, Hyderabad, India.
Toxicol Int. 2010 Jul;17(2):90-3. doi: 10.4103/0971-6580.72678.
A total of 56 male Sprague dawley rats of uniform weight and age were randomly divided into seven groups consisting of eight rats in each group. Groups 1, 2, and 3 served as plain control, dyslipidaemic control (DL), and atorvastatin control, respectively. Groups 4, 5, 6, and 7 received 1, 0.5, 0.25, and 0.75% fresh garlic w/w in feed, respectively in addition to the high-fat and high-cholesterol diet and administered with atorvastatin orally for 12 weeks at the rate of 10, 5, 7.5, and 2.5 mg/kg b.wt., respectively. Plasma creatinine was estimated at 4-week intervals, whereas histopathology, electron microscopy, and estimation of TBARS concentration in kidney were conducted at the end of experiment. The TBARS concentration in DL was significantly (P<0.05) increased when compared with groups 1, 3, 6, and 7. On histopathological examination, kidney sections of group 3 had mild degenerative changes in the tubules with fatty change in few tubules, while groups 4 and 5 exhibited mild-to-moderate degenerative and fatty changes in tubules with inter tubular hemorrhages. The electron microscopy of group 2 showed hypertrophy of Bowman's capsule, while that of group 4 showed secretary deposits in the cytoplasm. The interaction studies on kidney indicated that high dose of atorvastatin + garlic has negative safety profile when compared with groups having low dose of statin and high dose of garlic.
总共56只体重和年龄均一的雄性Sprague dawley大鼠被随机分为七组,每组八只。第1、2和3组分别作为空白对照组、血脂异常对照组(DL)和阿托伐他汀对照组。第4、5、6和7组除高脂高胆固醇饮食外,分别在饲料中添加1%、0.5%、0.25%和0.75%(重量/重量)的新鲜大蒜,并分别以10、5、7.5和2.5 mg/kg体重的剂量口服阿托伐他汀12周。每隔4周测定血浆肌酐,而在实验结束时进行组织病理学、电子显微镜检查以及肾脏中硫代巴比妥酸反应物(TBARS)浓度的测定。与第1、3、6和7组相比,DL组的TBARS浓度显著升高(P<0.05)。组织病理学检查显示,第3组的肾脏切片肾小管有轻度退行性改变,少数肾小管有脂肪变性,而第4组和第5组表现为肾小管轻度至中度退行性和脂肪变性,并伴有肾小管间出血。第2组的电子显微镜检查显示鲍曼囊肥大,而第4组显示细胞质中有分泌性沉积物。对肾脏的相互作用研究表明,与低剂量他汀类药物和高剂量大蒜的组相比,高剂量阿托伐他汀+大蒜具有负面的安全性。