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口服原钒酸盐和胡芦巴种子粉可恢复四氧嘧啶诱导的糖尿病大鼠组织中线粒体酶的活性。

Oral administration of orthovanadate and Trigonella foenum graecum seed power restore the activities of mitochondrial enzymes in tissues of alloxan-induced diabetic rats.

作者信息

Thakran Shalini, Baquer Najma Z

机构信息

Hormone and Drug Research Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.

出版信息

Mol Cell Biochem. 2003 May;247(1-2):45-53. doi: 10.1023/a:1024188600523.

Abstract

The effect of oral administration of sodium orthovanadate (SOV) and Trigonella foenum graecum seed powder (TSP), a medicinal plant used extensively in Asia, on the mitochondrial metabolism in the alloxan diabetic rats has been investigated. Rats were injected with alloxan monohydrate (20 mg/100 g body wt) or vehicle (Na-acetate buffer), the former were treated with either 2 IU insulin i.p., 0.6 mg/ml SOV ad libitum, 5% TSP ad libitum, and a combination of 0.2% SOV and 5% TSP ad libitum for 21 days. Selected rate-limiting enzymes of the tricarboxylic acid cycle, hydrogen shuttle system, ketone body metabolism, amino acid metabolism and urea cycle were measured in the mitochondrial and cytosolic fractions of liver, kidney and brain tissues of the experimental rats. Majority of the mitochondrial enzymes in the tissues of the diabetic rats had significantly higher activities compared to the control rats. Similarly, the activities of mitochondrial and cytosolic aminotransferases and arginase were significantly higher in liver and kidney tissues of the diabetic rats. The separate administrations of SOV and TSP to diabetic rats were able to restore the activities of these enzymes to control values. The lower dose of SOV (0.2%) administered in combination with TSP to diabetic rats lowered the enzyme activities more significantly than when given in a higher dose (0.6%) separately. This is the first report of the effective combined action of oral SOV and TSP in ameliorating the altered mitochondrial enzyme activities during experimental type-1 diabetes. Our novel combined oral administration of SOV and TSP to diabetic rats thus conclusively proves as a possible method to minimize potential vanadate toxicity without compromising its positive effects in the therapy of experimental type-1 diabetes.

摘要

已对口服原钒酸钠(SOV)和胡芦巴籽粉(TSP,一种在亚洲广泛使用的药用植物)对四氧嘧啶糖尿病大鼠线粒体代谢的影响进行了研究。给大鼠注射一水合四氧嘧啶(20 mg/100 g体重)或赋形剂(醋酸钠缓冲液),前者分别腹腔注射2 IU胰岛素、随意给予0.6 mg/ml SOV、随意给予5% TSP以及随意给予0.2% SOV和5% TSP的组合,持续21天。在实验大鼠肝脏、肾脏和脑组织的线粒体和胞质部分中,测定了三羧酸循环、氢穿梭系统、酮体代谢、氨基酸代谢和尿素循环的选定限速酶。与对照大鼠相比,糖尿病大鼠组织中的大多数线粒体酶活性显著更高。同样,糖尿病大鼠肝脏和肾脏组织中线粒体和胞质转氨酶及精氨酸酶的活性也显著更高。单独给糖尿病大鼠施用SOV和TSP能够使这些酶的活性恢复到对照值。与单独给予较高剂量(0.6%)相比,联合给予糖尿病大鼠较低剂量(0.2%)的SOV和TSP能更显著地降低酶活性。这是关于口服SOV和TSP联合有效作用改善实验性1型糖尿病期间线粒体酶活性改变的首次报道。因此,我们对糖尿病大鼠联合口服SOV和TSP的新方法最终证明是一种在不损害其对实验性1型糖尿病治疗的积极作用的情况下,尽量减少潜在钒酸盐毒性的可能方法。

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