Influence of Oatp4c1-P-gp transmembrane transport system in the kidneys of obese mice on the pharmacokinetics of digoxin
- VernacularTitle:肥胖小鼠肾脏Oatp4c1-P-gp跨膜转运系统对地高辛药代动力学的影响
- Author:
Jing-wen MEN
1
;
Lu SUN
;
Hao-ran YUE
;
Zhao-yue DUAN
;
Hui-nan HOU
;
Ting GUI
;
Jun-hong XIN
;
Zhi-bo GAI
Author Information
- Publication Type:Journal Article
- Keywords: high-fat diet; obese mice; kidney; Oatp4c1-P-gp; digoxin; clearance rate
- From: Chinese Pharmacological Bulletin 2025;41(7):1318-1324
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the expression of or-ganic anion transporting polypeptide 4C1(Oatp4c1)-P-glycoprotein(P-gp)in the kidneys of obese mice in-duced by high-fat diet(HFD),and its impact on the pharmacokinetic changes of digoxin.Methods C57BL/6 mice were randomly divided into the Chow group and the HFD group.Body weight and blood glu-cose were recorded weekly.After successful model es-tablishment,digoxin was intraperitoneally injected,and blood was collected at different time points.Part of the blood samples was used for LC-MS/MS detection,and the other part was used for the detection of other bio-chemical indicators.After 16 weeks,the organs were removed and weighed.HE and immunohistochemical staining was used to observe the renal pathology and the expression of Villin,a marker of proximal tubules.Western blot and qPCR were combined to detect the expression of Villin,Oatp4c1 and P-gp.Results In the HFD group,body weight and blood glucose in-creased significantly.The blood concentration of digox-in rose,the area under the curve increased,and the half-life was prolonged.The proximal tubular epithelial cells shed,and the protein expression of Villin,Oatp4c1 and P-gp decreased significantly.Conclu-sions The down-regulation of Oatp4c1-P-gp expres-sion in the kidneys of HFD mice leads to an increase in the blood concentration of digoxin and a decrease in re-nal clearance.
