Department of Pathophysiology, Medical University, ul Jaczewskiego 8, 20-090 Lublin, Poland.
Life Sci. 2010 Jul 17;87(3-4):126-32. doi: 10.1016/j.lfs.2010.05.018.
The present study was designed to examine the effect of sulphonylureas, glimepiride (GM) and glibenclamide (GB), on paraoxonase 1 (PON1) and platelet activating factor acetylohydrolase (PAF-AH) activity in normal and streptozotocin (STZ)-induced (50 mg/kg) diabetic rats.
In treated groups, glimepiride (0.1 mg/kg) or glibenclamide (2 mg/kg) was given orally for 4 weeks. A PON1 and PAF-AH activity were estimated by spectrophotometric method.
Hyperglycemia was accompanied by a significant decrease in plasma PON1 activity toward paraoxon (P < 0.001) and phenyl acetate (P < 0.01) and increase in plasma PAF-AH activity (P < 0.01). In STZ-induced diabetic rats the administration of both GM and GB had no effect on plasma PON1 activity but reversed elevated plasma PAF-AH activity (GM: P < 0.05, GB: P < 0.01). In non-diabetic rats after either GM or GB administration the decreased PON1 activity in the plasma was observed (GM: P < 0.001, GB: P < 0.05), but plasma PAF-AH activity remained unchanged. Both GM and GB had no effect on total plasma antioxidant capacity in diabetic and control treated groups. Additionally, both drugs increased PON1 activity toward phenyl acetate in the liver, in diabetic rats (GM: P < 0.05, GB:ns) as well as in non-diabetic rats (GM: P < 0.001, GB: P < 0.001), and reduced lipid peroxidation in the liver.
These results demonstrate that in streptozotocin-induced diabetic rats as well as in normal rats glimepiride and glibenclamide have no beneficial effects on circulating PON1 and PAF-AH activities, but both drugs increase PON1 activity in the liver.
本研究旨在探讨磺酰脲类药物格列美脲（GM）和格列本脲（GB）对正常和链脲佐菌素（STZ）诱导（50mg/kg）糖尿病大鼠对对氧磷酶 1（PON1）和血小板活化因子乙酰水解酶（PAF-AH）活性的影响。
在治疗组中，给予格列美脲（0.1mg/kg）或格列本脲（2mg/kg）口服 4 周。通过分光光度法测定 PON1 和 PAF-AH 活性。
高血糖伴有血浆 PON1 对氧磷（P < 0.001）和苯乙酸（P < 0.01）的活性显著降低，而血浆 PAF-AH 活性升高（P < 0.01）。在 STZ 诱导的糖尿病大鼠中，GM 和 GB 的给药对血浆 PON1 活性没有影响，但逆转了升高的血浆 PAF-AH 活性（GM：P < 0.05，GB：P < 0.01）。在非糖尿病大鼠中，给予 GM 或 GB 后，观察到血浆中 PON1 活性降低（GM：P < 0.001，GB：P < 0.05），但血浆 PAF-AH 活性保持不变。GM 和 GB 对糖尿病和对照组治疗组的总血浆抗氧化能力均无影响。此外，两种药物均增加了糖尿病大鼠（GM：P < 0.05，GB：ns）和非糖尿病大鼠（GM：P < 0.001，GB：P < 0.001）肝脏中 PON1 对苯乙酸的活性，并降低了肝脏中的脂质过氧化。
这些结果表明，在 STZ 诱导的糖尿病大鼠以及正常大鼠中，格列美脲和格列本脲对循环 PON1 和 PAF-AH 活性没有有益影响，但两种药物均可增加肝脏中 PON1 的活性。
