Study on the Function Change of Caco-2 Cell CYP3A4 and P-gp under Diabetic Conditions and Its Mecha-nism / 中国药房
China Pharmacy
;
(12): 3471-3474, 2016.
Article
in Chinese
| WPRIM
| ID: wpr-504948
ABSTRACT
OBJECTIVE:
To investigate the function change of intestinal CYP3A4 and P-glycoprotein (P-gp) under diabetic conditions and its mechanism.METHODS:
Caco-2 cells were respectively added with 25, 50 and 100 μmol/L midazolam (CYP3A4 probe substrate) for incubation for 15,30,60,120,180 min;with 0.1,0.2,0.4 μg/ml rhodamine 123 (P-gp sub-strate)for incubation for 15,30,60,90,120 min to determine the substrate concentrations and incubation time. Caco-2 cells were added with insulin,glucose and fatty acid (palmitic acid and oleic acid) at different concentrations,and then the production of 1′-OH-midazolam,the metabolite of midazolam,and the intake of rhodamine 123 were determined,in order to investigated the ef-fect on the function of CYP3A4 and P-gp.RESULTS:
The optimal substrate concentrations and incubation time were as follows as 50 μmol/L midazolam,0.1 μg/ml rhodamine 123 and incubation for 2 h. With the increase in the concentration of insulin,glucose and palmitic acid,the production of 1′-OH-midazolam and the activity of CYP3A4 reduced;the intake of rhodamine 123 in-creased,and the efflux transport function of P-gp decreased. Oleic acid had no significant effect on the production of 1′-OH-mid-azolam or the intake of rhodamine 123.CONCLUSIONS:
Under diabetes condition,the increase of insulin,glucose and palmitic acid may reduce the function of CYP3A4 and P-gp,while oleic acid has no effect on the function.
Full text:
Available
Index:
WPRIM (Western Pacific)
Language:
Chinese
Journal:
China Pharmacy
Year:
2016
Type:
Article
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