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磺酰脲类药物格列本脲对链脲佐菌素诱导的糖尿病大鼠肝脏和肾脏抗氧化酶的影响。

Effect of the sulphonylurea glibenclamide on liver and kidney antioxidant enzymes in streptozocin-induced diabetic rats.

作者信息

Elmalí Esra, Altan Nilgün, Bukan Neslihan

机构信息

Department of Biochemistry, Gazi University, Medical Faculty, Beşevler, Ankara, Turkey.

出版信息

Drugs R D. 2004;5(4):203-8. doi: 10.2165/00126839-200405040-00003.

Abstract

BACKGROUND

Alterations in catalase (CAT) and superoxide dismutase (SOD) activity have been reported in diabetes mellitus. Glibenclamide (glyburide), a member of the second-generation sulphonylureas, provides effective treatment for patients with moderate diabetes. The action of the liver plays an important role in its glucose-lowering effect, suggesting that glibenclamide also exerts a direct effect on liver enzyme activities.

OBJECTIVE

To evaluate the effect of glibenclamide on the activities of antioxidant enzymes (CAT and SOD) in liver and kidney tissue of diabetic rats.

METHODS

Thirty-nine rats were included in this study. Moderate diabetes mellitus was induced with streptozocin (freshly dissolved in citrate buffer, ph 4.5) 55 mg/kg in 22 rats. Eight of these diabetic rats were left untreated, insulin was administered to six diabetic rats, and glibenclamide was administered to eight rats with moderate diabetes. Liver and kidney CAT and SOD activities were measured in all rats.

RESULTS

Hepatic CAT and SOD activities were significantly reduced in diabetic animals (p < 0.05 for both activities). Glibenclamide treatment of diabetic rats for 5 weeks reversed the changes observed in diabetic liver tissues (p < 0.05). However, renal CAT and SOD activities were unchanged. In addition, high blood glucose levels of diabetic rats were decreased following glibenclamide treatment.

CONCLUSION

Administration of glibenclamide to diabetic rats reversed diabetes-induced changes, suggesting that glibenclamide may directly increase liver CAT and SOD activity.

摘要

背景

糖尿病患者体内过氧化氢酶(CAT)和超氧化物歧化酶(SOD)活性会发生改变。第二代磺酰脲类药物之一的格列本脲(优降糖)能有效治疗中度糖尿病患者。肝脏在其降糖作用中发挥重要作用,这表明格列本脲对肝脏酶活性也有直接影响。

目的

评估格列本脲对糖尿病大鼠肝脏和肾脏组织中抗氧化酶(CAT和SOD)活性的影响。

方法

本研究纳入39只大鼠。22只大鼠用链脲佐菌素(新鲜溶解于pH 4.5的柠檬酸盐缓冲液中)55 mg/kg诱导中度糖尿病。其中8只糖尿病大鼠未接受治疗,6只糖尿病大鼠给予胰岛素,8只中度糖尿病大鼠给予格列本脲。测定所有大鼠肝脏和肾脏的CAT和SOD活性。

结果

糖尿病动物肝脏中的CAT和SOD活性显著降低(两种活性均p < 0.05)。格列本脲治疗糖尿病大鼠5周后,逆转了糖尿病肝脏组织中观察到的变化(p < 0.05)。然而,肾脏中的CAT和SOD活性未发生改变。此外,格列本脲治疗后糖尿病大鼠的高血糖水平降低。

结论

给糖尿病大鼠服用格列本脲可逆转糖尿病引起的变化,这表明格列本脲可能直接增加肝脏中CAT和SOD的活性。

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