Changes in renal excretion pathways in rats with adenine-induced chronic renal failure

doi:10.5246/jcps.2021.04.026

Abstract

Abstract:

Chronic renal failure (CRF) is a type of progressive chronic kidney disease with the alteration of substrates excretion. However, changes in renal excretion pathways remain unclear in CRF. This study aimed to evaluate the changes in renal excretion pathways of exogenous and endogenous substrates in CRF rats. Results showed that the levels of cystatin C, creatinine, and urea nitrogen were dramatically increased in the adenine (50 or 100 mg/kg)-induced CRF rats. The levels of rOCT2 were dose-dependently up-regulated by adenine, and rMRP2 and rMATE1 levels were dose-dependently down-regulated, while rMRP4 was induced by adenine (50). Plasma concentrations of metformin, p-aminohippurate, and furosemide in the adenine (100) group were significantly increased compared with the control group. However, plasma concentrations of metformin and p-aminohippurate were slightly changed in the adenine (50) group. Consistently, urinary excretions of metformin and p-aminohippurate were unaffected. In addition, renal N1-methylnicotinamide uptakes were increased in rats treated with adenine, and renal phenyl-β-D-glucuronide and hippuric acid uptakes were induced by adenine (50). These results showed that adenine (100)-induced CRF caused the reduced function of GFR-rOCTs-rMATE1 and GFR-rOAT1/rOAT3-rMRP pathway, and oppositely the renal tubular transport pathways of rOCTs-rMATE1 and rOAT1-MRPs were induced in rats with the treatment of adenine (50).

Key words: Chronic renal failure, Renal excretion pathways, Transporter, Adenine

Supporting:

Yanrong Ma, Mingyan Xin, Juanli Wu, Dangju Wang, Huan Wang, Xin'an Wu. Changes in renal excretion pathways in rats with adenine-induced chronic renal failure[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(4): 319-333.

Figures/Tables 10

Table 1. MRM of the transitions of compounds.

Table 2. The effects of adenine-induced CRF on drugs pharmacokinetic parameters (mean ± SD, n = 6).

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