Chronic dehydration induces injury pathways in rats, but does not mimic histopathology of chronic interstitial nephritis in agricultural communities.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
23 10 2023
23 10 2023
Historique:
received:
26
10
2022
accepted:
26
09
2023
medline:
27
10
2023
pubmed:
24
10
2023
entrez:
23
10
2023
Statut:
epublish
Résumé
CINAC-patients present renal proximal tubular cell lysosomal lesions which are also observed in patients experiencing calcineurin inhibitor (CNI) nephrotoxicity, suggesting that CINAC is a toxin-induced nephropathy. An alternative hypothesis advocates chronic dehydration as a major etiological factor for CINAC. Here, we evaluated histological and molecular changes in dehydrated versus toxin exposed rats. Wistar rats were divided in 3 groups. Group 1 (n = 6) had free access to drinking water (control group). Group 2 (n = 8) was water deprived for 10 h per 24 h, 5 days/week and placed in an incubator (37 °C) for 30 min/h during water deprivation. Group 3 (n = 8) underwent daily oral gavage with cyclosporine (40 mg/kg body weight). After 28 days, renal function, histopathology and proteomic signatures were analysed. Cyclosporine-treated rats developed focal regions of atrophic proximal tubules with associated tubulo-interstitial fibrosis. PASM staining revealed enlarged argyrophilic granules in affected proximal tubules, identified as lysosomes by immunofluorescent staining. Electron microscopy confirmed the enlarged and dysmorphic phenotype of the lysosomes. Overall, these kidney lesions resemble those that have been previously documented in farmers with CINAC. Dehydration resulted in none of the above histopathological features. Proteomic analysis revealed that dehydration and cyclosporine both induce injury pathways, yet of a clear distinct nature with a signature of toxicity only for the cyclosporine group. In conclusion, both cyclosporine and dehydration are injurious to the kidney. However, dehydration alone does not result in kidney histopathology as observed in CINAC patients, whereas cyclosporine administration does. The histopathological analogy between CINAC and calcineurin inhibitor nephrotoxicity in rats and humans supports the involvement of an as-yet-unidentified environmental toxin in CINAC etiology.
Identifiants
pubmed: 37872220
doi: 10.1038/s41598-023-43567-z
pii: 10.1038/s41598-023-43567-z
pmc: PMC10593944
doi:
Substances chimiques
Calcineurin Inhibitors
0
Cyclosporine
83HN0GTJ6D
Immunosuppressive Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
18119Informations de copyright
© 2023. Springer Nature Limited.
Références
Ann Nutr Metab. 2015;66 Suppl 3:10-3
pubmed: 26088040
Apoptosis. 2013 Oct;18(10):1145-53
pubmed: 23670020
PLoS Biol. 2010 Jun 29;8(6):e1000412
pubmed: 20613859
Neurobiol Aging. 2019 Feb;74:77-89
pubmed: 30439596
BMC Nephrol. 2015 Aug 19;16:145
pubmed: 26282933
Semin Nephrol. 2019 May;39(3):272-277
pubmed: 31054626
Comp Biochem Physiol C Toxicol Pharmacol. 2011 Nov;154(4):288-95
pubmed: 21742055
Biotechnol Lett. 2019 Jan;41(1):59-68
pubmed: 30311029
Ann N Y Acad Sci. 2016 May;1371(1):3-14
pubmed: 27299292
Trans R Soc Trop Med Hyg. 2007 Oct;101(10):1013-7
pubmed: 17643458
J Proteomics. 2012 Jun 27;75(12):3720-32
pubmed: 22575385
PLoS One. 2014 Sep 22;9(9):e108448
pubmed: 25244654
Q J Exp Physiol Cogn Med Sci. 1964 Apr;49:162-70
pubmed: 14141261
Alzheimers Dement. 2018 Jul;14(7):961-975
pubmed: 29551332
Biochimie. 2011 Dec;93(12):2126-31
pubmed: 21802484
Aging (Albany NY). 2019 Dec 3;11(23):11268-11313
pubmed: 31794429
Front Endocrinol (Lausanne). 2016 Jan 18;6:191
pubmed: 26834700
Apoptosis. 2017 Jul;22(7):955-969
pubmed: 28466106
Arch Biochem Biophys. 2019 Sep 15;672:108072
pubmed: 31422074
Neuroendocrinology. 1983 May;36(5):364-70
pubmed: 6856043
Kidney Int. 2014 Aug;86(2):294-302
pubmed: 24336030
Rev Panam Salud Publica. 2019 Mar 14;43:e35
pubmed: 31093259
Mech Ageing Dev. 2019 Dec;184:111150
pubmed: 31574270
Am J Physiol Renal Physiol. 2023 Apr 1;324(4):F387-F403
pubmed: 36794752
Cancer Lett. 2019 Jun 28;452:1-13
pubmed: 30905820
Occup Environ Med. 2016 Jan;73(1):3-12
pubmed: 26177651
J Proteome Res. 2010 Feb 5;9(2):865-75
pubmed: 19994912
Dev Cell. 2011 Sep 13;21(3):421-30
pubmed: 21889421
Kidney Int. 2018 Mar;93(3):681-690
pubmed: 29162294
PLoS One. 2013 Apr 30;8(4):e62665
pubmed: 23646135
FASEB J. 2011 Aug;25(8):2688-99
pubmed: 21536685
Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):17119-24
pubmed: 24085853
Arch Biochem Biophys. 2007 Nov 1;467(1):76-86
pubmed: 17888864
Crit Care Res Pract. 2019 Apr 16;2019:5912804
pubmed: 31179128
PLoS One. 2018 Jul 12;13(7):e0200487
pubmed: 30001384
Clin J Am Soc Nephrol. 2016 Aug 8;11(8):1472-1483
pubmed: 27151892
EMBO Rep. 2014 Apr;15(4):428-37
pubmed: 24591568
Methods. 2016 Jan 1;92:51-63
pubmed: 25986936
BMC Nephrol. 2013 Aug 27;14:180
pubmed: 23981540
Kidney Int. 2012 Mar;81(5):442-8
pubmed: 22113526
J Cell Biochem. 2014 Feb;115(2):410-9
pubmed: 24339252
Cell Death Discov. 2020 May 1;6:32
pubmed: 32377395
J Am Assoc Lab Anim Sci. 2013;52(3):233-9
pubmed: 23849404
Gene. 2016 Sep 1;589(1):72-80
pubmed: 27222482
Urol Oncol. 2019 Nov;37(11):812.e9-812.e16
pubmed: 31421995
Semin Nephrol. 2003 Sep;23(5):465-76
pubmed: 13680536
Nat Clin Pract Nephrol. 2006 Jul;2(7):398-404; quiz following 404
pubmed: 16932468
Nat Rev Nephrol. 2017 Oct;13(10):629-646
pubmed: 28804120
Am J Hum Genet. 2012 Nov 2;91(5):942-9
pubmed: 23122588
Clin Nephrol. 1986;25 Suppl 1:S18-22
pubmed: 3011337
Kidney Int. 1997 Jun;51(6):1818-30
pubmed: 9186871
MEDICC Rev. 2014 Apr;16(2):49-54
pubmed: 24878649
PLoS One. 2010 Dec 17;5(12):e14352
pubmed: 21179406
PLoS One. 2018 Mar 7;13(3):e0193056
pubmed: 29513702
Int J Diabetes Dev Ctries. 2008 Apr;28(2):60-4
pubmed: 19902050
Nephrol Dial Transplant. 2017 Feb 1;32(2):234-241
pubmed: 28186530
Semin Nephrol. 2019 May;39(3):278-283
pubmed: 31054627
Front Physiol. 2013 Jan 30;4:8
pubmed: 23386833
Kidney Int. 2020 Feb;97(2):350-369
pubmed: 31892415
Rev Panam Salud Publica. 2002 Sep;12(3):202-6
pubmed: 12396639
Toxicol Lett. 2008 Nov 10;182(1-3):84-90
pubmed: 18805471
BMC Nephrol. 2017 Jan 3;18(1):1
pubmed: 28049448
Am J Kidney Dis. 1997 Dec;30(6):884-95
pubmed: 9398138
Transplantation. 2002 Dec 15;74(11):1618-24
pubmed: 12490797
Environ Health. 2017 May 23;16(1):49
pubmed: 28535811