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链脲佐菌素诱导的糖尿病大鼠氧化应激参数的变化及对口服维生素E和维生素C的反应

Evolution of oxidative stress parameters and response to oral vitamins E and C in streptozotocin-induced diabetic rats.

作者信息

Rupérez Francisco J, García-Martínez Diana, Baena Beatriz, Maeso Nuria, Cifuentes Alejandro, Barbas Coral, Herrera Emilio

机构信息

Facultad de Farmacia, Universidad San Pablo-CEU, Urbanización Montepríncipe, Boadilla del Monte, 28668 Madrid, Spain.

出版信息

J Pharm Pharmacol. 2008 Jul;60(7):871-8. doi: 10.1211/jpp.60.7.0008.

Abstract

Type I diabetes in humans and streptozotocin (STZ)-induced diabetes in rats has been associated with oxidative stress, but antioxidant therapy has given contradictory results, in part related to the absence of common conditions used to evaluate in-vivo antioxidant properties. This prompted the study of an experimental model of antioxidant therapy in STZ-treated rats. Adult female rats received STZ (50 mgkg(-1)) and were studied 7 or 14 days later. Adipose tissue weight progressively decreased with the time of treatment, whereas plasma triglycerides increased at 7 days, before returning to control values at 14 days after STZ treatment. STZ diabetic rats had increased plasma thiobarbituric acid reacting substances and alpha-tocopherol levels, but the latter variable was decreased when corrected for total lipids. STZ diabetic rats showed a higher GSSG/GSH ratio at Day 14 and lower GSH + GSSG at Day 7 in liver. To evaluate the effect of short-term antioxidant therapy, rats received 5 doses of vitamins C and E over 3 days before being killed on Day 14. Treatment with antioxidants decreased plasma lactic acid and thiobarbituric acid reacting substances, as well as urine 8-isoprostane, and decreased plasma uric acid in controls. Vitamins increased the plasma alpha-tocopherol/lipids ratio only in control rats, although the plasma and liver alpha-tocopherol concentration increased in both groups. STZ diabetic rats showed moderate oxidative stress and treatment with antioxidant vitamins caused a significant change in a selected group of oxidative stress markers, which reflected an improvement in some of the complications associated with this disease. The present experimental conditions can be used as a sensitive experimental model to study the responsiveness of diabetes to other antioxidant interventions.

摘要

人类的1型糖尿病和大鼠中链脲佐菌素(STZ)诱导的糖尿病与氧化应激有关,但抗氧化治疗的结果相互矛盾,部分原因是缺乏用于评估体内抗氧化特性的常见条件。这促使人们对STZ处理的大鼠进行抗氧化治疗的实验模型进行研究。成年雌性大鼠接受STZ(50 mgkg(-1)),并在7或14天后进行研究。随着治疗时间的延长,脂肪组织重量逐渐下降,而血浆甘油三酯在7天时升高,在STZ治疗后14天恢复到对照值。STZ糖尿病大鼠血浆硫代巴比妥酸反应物质和α-生育酚水平升高,但校正总脂质后,后者变量降低。STZ糖尿病大鼠在第14天肝脏中GSSG/GSH比值较高,在第7天GSH + GSSG较低。为了评估短期抗氧化治疗的效果,大鼠在第14天处死前3天接受5剂维生素C和E。抗氧化剂治疗降低了血浆乳酸和硫代巴比妥酸反应物质以及尿8-异前列腺素,并降低了对照组的血浆尿酸。维生素仅在对照大鼠中增加了血浆α-生育酚/脂质比值,尽管两组的血浆和肝脏α-生育酚浓度均升高。STZ糖尿病大鼠表现出中度氧化应激,抗氧化维生素治疗导致一组选定的氧化应激标志物发生显著变化,这反映了与该疾病相关的一些并发症有所改善。目前的实验条件可作为一个敏感的实验模型,用于研究糖尿病对其他抗氧化干预措施的反应性。

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