Rats with congenital hydronephrosis show increased susceptibility to renal ischemia-reperfusion injury.
hydronephrosis
pharmacokinetics
renal ischemia-reperfusion
ultrasonography
Journal
Physiological reports
ISSN: 2051-817X
Titre abrégé: Physiol Rep
Pays: United States
ID NLM: 101607800
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
18
05
2020
revised:
08
10
2020
accepted:
12
10
2020
entrez:
18
11
2020
pubmed:
19
11
2020
medline:
28
9
2021
Statut:
ppublish
Résumé
Many drug candidates have shown significant renoprotective effects in preclinical models; however, there is no clinically used effective pharmacotherapy for acute kidney injury. The failure to translate from bench to bedside could be due to misleading results from experimental animals with undetected congenital kidney defects. This study was performed to assess the effects of congenital hydronephrosis on the functional capacity of tubular renal transporters as well as kidney sensitivity to ischemia-reperfusion (I-R)-induced injury in male Wistar rats. Ultrasonography was used to distinguish healthy control rats from rats with hydronephrosis. L-carnitine or furosemide was administered, and serial blood samples were collected and analyzed to assess the effects of hydronephrosis on the pharmacokinetic parameters. Renal injury was induced by clamping the renal pedicles of both kidneys for 30 min with subsequent 24 hr reperfusion. The prevalence of hydronephrosis reached ~30%. The plasma concentrations after administration of L-carnitine or furosemide were similar in both groups. I-R induced more pronounced renal injury in the hydronephrotic rats than the control rats, which was evident by a significantly higher kidney injury molecule-1 concentration and lower creatinine concentration in the urine of the hydronephrotic rats than the control rats. After I-R, the gene expression levels of renal injury markers were significantly higher in the hydronephrotic kidneys than in the kidneys of control group animals. In conclusion, our results demonstrate that hydronephrotic kidneys are more susceptible to I-R-induced damage than healthy kidneys. Unilateral hydronephrosis does not affect the pharmacokinetics of substances secreted or absorbed in the renal tubules.
Identifiants
pubmed: 33207081
doi: 10.14814/phy2.14638
pmc: PMC7673629
doi:
Substances chimiques
Cell Adhesion Molecules
0
Diuretics
0
Havcr1protein, rat
0
Furosemide
7LXU5N7ZO5
Carnitine
S7UI8SM58A
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14638Informations de copyright
© 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.
Références
Biochem J. 1995 Jul 15;309 ( Pt 2):643-7
pubmed: 7626031
Nurs Clin North Am. 2018 Dec;53(4):499-510
pubmed: 30388976
Lab Anim. 1977 Jul;11(3):193-4
pubmed: 886833
Pflugers Arch. 1975 Jul 28;358(3):265-74
pubmed: 1239006
Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H292-8
pubmed: 17351065
J Biol Chem. 1998 Aug 7;273(32):20378-82
pubmed: 9685390
J Hypertens. 2006 Jul;24(7):1437-43
pubmed: 16794495
BMC Bioinformatics. 2012 Jun 18;13:134
pubmed: 22708584
J Cardiovasc Pharmacol. 1987;9 Suppl 1:S39-43
pubmed: 2441183
Kidney Int. 1979 May;15(5):567-71
pubmed: 480788
Lab Anim Sci. 1988 Aug;38(4):402-6
pubmed: 3184846
Lancet. 2019 Nov 23;394(10212):1949-1964
pubmed: 31777389
Crit Care. 2019 Jan 24;23(1):24
pubmed: 30678696
Am J Physiol Heart Circ Physiol. 2011 Jun;300(6):H2206-13
pubmed: 21460193
Lab Invest. 1987 Mar;56(3):273-81
pubmed: 3821068
Am J Physiol Renal Physiol. 2012 Dec 1;303(11):F1487-94
pubmed: 22993069
J Am Soc Nephrol. 2007 Jan;18(1):37-45
pubmed: 17135398
Circ Res. 2015 Jan 2;116(1):116-26
pubmed: 25552691
Nat Biotechnol. 2010 May;28(5):478-85
pubmed: 20458318
J Am Soc Nephrol. 1994 Jul;5(1):93-101
pubmed: 7948788
Am J Physiol Renal Physiol. 2016 Jul 1;311(1):F145-61
pubmed: 27194714
Int J Urol. 2003 Oct;10(10):536-43
pubmed: 14516401
J Nephrol. 2019 Aug;32(4):539-547
pubmed: 30635875
Physiol Behav. 2008 Oct 20;95(3):341-7
pubmed: 18640137
Annu Rev Med. 2016;67:293-307
pubmed: 26768243
J Am Soc Nephrol. 2016 Aug;27(8):2393-406
pubmed: 26701981
Acta Neuropsychiatr. 2019 Dec;31(6):348-349
pubmed: 31647038
Front Physiol. 2019 Feb 26;10:153
pubmed: 30873045
PLoS One. 2019 Sep 12;14(9):e0222354
pubmed: 31513644
Nature. 2016 May 25;533(7604):452-4
pubmed: 27225100
Ultrasound Med Biol. 2007 Mar;33(3):483-6
pubmed: 17188800
PLoS Biol. 2010 Jun 29;8(6):e1000412
pubmed: 20613859
Kidney Int. 2002 Jul;62(1):237-44
pubmed: 12081583
Nephrology (Carlton). 2010 Apr;15(3):350-3
pubmed: 20470306