کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2536294 | 1559149 | 2007 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Attenuated function and expression of P-glycoprotein at blood–brain barrier and increased brain distribution of phenobarbital in streptozotocin-induced diabetic mice Attenuated function and expression of P-glycoprotein at blood–brain barrier and increased brain distribution of phenobarbital in streptozotocin-induced diabetic mice](/preview/png/2536294.png)
The aim of the study was to investigate whether diabetes mellitus modulated the function and expression of P-glycoprotein and the distribution of phenobarbital in the brain of 3-week streptozotocin-induced diabetic mice. P-glycoprotein function in blood–brain barrier was assessed by measuring the brain-to-plasma concentration ratios of rodamine123, a well-known P-glycoprotein substrate, in non-diabetic mice and diabetic mice. P-glycoprotein expression in the brain cortex was evaluated with western blot. Whether diabetes mellitus changed the distribution of phenobarbital (60 mg/kg, i.v.) in brain of mice was measured, and whether the changed distribution caused the difference of phenobarbital (80 and 100 mg/kg) -induced loss of the righting reflex in non-diabetic and diabetic mice were also investigated. The results showed that the brain-to-plasma concentration ratio value of rodamine123 in diabetic mice was significantly higher than that of non-diabetic mice, western blot suggested that the protein level of P-glycoprotein in the brain of 3-week diabetic mice was significantly lower than that of non-diabetic mice, and insulin treatment restored the impairment of P-glycoprotein. The exposure of phenobarbital in brain of diabetic mice was 1.30-fold of that of non-diabetic mice, while in plasma the fold was 1.09. The increased distribution of phenobarbital in the brain of diabetic mice significantly increased the duration of phenobarbital-induced loss of the righting reflex and reduced the latency time of loss of the righting reflex. All the results suggested that the function and expression of P-glycoprotein might be impaired and the brain distribution of phenobarbital was increased in brain of streptozotocin-induced diabetic mice.
Journal: European Journal of Pharmacology - Volume 561, Issues 1–3, 30 April 2007, Pages 226–232