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Attenuated function and expression of P-glycoprotein at blood-brain barrier and increased brain distribution of phenobarbital in streptozotocin-induced diabetic mice.

Abstract：

: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_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Liu H,Zhang D,Xu X,Liu X,Wang G,Xie L,Pang X,Liu L

doi

10.1016/j.ejphar.2007.01.062

subject

Has Abstract

pub_date

2007-04-30 00:00:00

pages

226-32

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(07)00126-4

journal_volume

561

pub_type

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Attenuated function and expression of P-glycoprotein at blood-brain barrier and increased brain distribution of phenobarbital in streptozotocin-induced diabetic mice.