Evaluating the regulation of transporter proteins and P-glycoprotein in rats with cholestasis and its implication for digoxin clearance

doi:10.4291/wjgp.v13.i3.73

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May 22, 2022 (publication date) through Jul 27, 2024

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World Journal of Gastrointestinal Pathophysiology

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2150-5330

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

World J Gastrointest Pathophysiol. May 22, 2022; 13(3): 73-84
Published online May 22, 2022. doi: 10.4291/wjgp.v13.i3.73

Table 1 Real time polymerase chain reaction primer sequences, product size and positive controls

Target gene	Primer sequences (5’-3’)	Size (bp)	Positive control
MDR1	ATCAACTCGCAAAAGCATCC (F)	116	Kidney
MDR1	AATTCAACTTCAGGATCCGC (R)	116	Kidney
OATP1A4	TGTGATGACCTGTGATAATTTTCCA (F)	81	Liver
OATP1A4	TTCTCCACATATAGTTGGTGCTGAA (R)	81	Liver
OATP4C1	TCAAGCTGGCAAAACTTCCC (F)	239	Kidney
OATP4C1	CCGCAAAGCTCGATGTCAAT (R)	239	Kidney
GAPDH	AAGATGGTGAAGGTCGGTGT (F)	98	Liver
GAPDH	GTTGATGGCAACAATGTCCACT (R)	98	Liver

OATP: Organic anion transporting polypeptides; MDR1: Multidrug resistance 1; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase.

Table 2 Liver panel, bilirubin, blood urea nitrogen and creatinine

	Sham		BDL
	Pre-surgery	Post-surgery	Pre-surgery	Post-surgery
Tot protein	6.63 ± 0.27	6.53 ± 0.35	6.53 ± 0.42	6.75 ± 0.23
Albumin	4.08 ± 0.17	3.85 ± 0.34	4.05 ± 0.14	3.40 ± 0.13^a
ALP	137.8 ± 19.78	122.3 ± 14.45	141.5 ± 12.74	467.2 ± 59.79^a
Bilirubin, D	0.04 ± 0.01	0.03 ± 0.01	0.03 ± 0.01	6.62 ± 1.72^a
Bilirubin, T	0.04 ± 0.02	0.06 ± 0.01	0.05 ± 0.02	11.67 ± 1.82^a
ALT	36.00 ± 12.02	57.00 ± 10.47	24.83 ± 8.28	191.8 ± 42.29^a
AST	71.83 ± 11.53	82.17 ± 4.92	64.17 ± 7.57	525.8 ± 107.11^a
BUN	17.54 ± 2.71	16.17 ± 3.13	18.23 ± 4.21	19.00 ± 5.57
Creatinine	0.27 ± 0.03	0.25 ± 0.02	0.29 ± 0.03	0.28 ± 0.04

^aP < 0.05 vs pre-surgery.

Values are expressed as means ± SD of 6 rats per group. BDL: Bile duct ligation; ALT: Alanine transaminase; AST: Aspartate transaminase; ALP: Alkaline phosphatase; BUN: Blood urea nitrogen.

Table 3 Summary of the regulations of cell membrane transporters and potential effects on digoxin clearance

	Efflux	Influx	Effects
Kidney	MDR1: Up-regulated	OATP4C1: Up-regulated	Increase tubule exclusion
Intestine	MDR1: Down-regulated	OATP1A4: Down-regulated	Decrease intestinal absorption
Liver	MDR1: Up-regulated	OATP4C1: Up-regulated	Increase exclusion into bile duct

OATP: Organic anion transporting polypeptides; MDR1: Multidrug resistance 1.

Citation: Giroux P, Kyle PB, Tan C, Edwards JD, Nowicki MJ, Liu H. Evaluating the regulation of transporter proteins and P-glycoprotein in rats with cholestasis and its implication for digoxin clearance. World J Gastrointest Pathophysiol 2022; 13(3): 73-84
URL: https://www.wjgnet.com/2150-5330/full/v13/i3/73.htm
DOI: https://dx.doi.org/10.4291/wjgp.v13.i3.73