Ascorbate protects human kidney organoids from damage induced by cell-free hemoglobin.
Acute kidney injury
Cell-free hemoglobin
Induced pluripotent stem cells
Kidney
Organoids
Sepsis
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
01 Dec 2023
01 Dec 2023
Historique:
received:
06
06
2023
accepted:
02
11
2023
medline:
4
12
2023
pubmed:
9
11
2023
entrez:
9
11
2023
Statut:
ppublish
Résumé
Sepsis-associated acute kidney injury is associated with high morbidity and mortality in critically ill patients. Cell-free hemoglobin (CFH) is released into the circulation of patients with severe sepsis and the levels of CFH are independently associated with mortality. CFH treatment increased cytotoxicity in the human tubular epithelial cell line HK-2. To better model the intact kidney, we cultured human kidney organoids derived from induced pluripotent stem cells. We treated human kidney organoids grown using both three-dimensional and transwell protocols with CFH for 48 h. We found evidence for increased tubular toxicity, oxidative stress, mitochondrial fragmentation, endothelial cell injury and injury-associated transcripts compared to those of the untreated control group. To evaluate the protective effect of clinically available small molecules, we co-treated CFH-injured organoids with ascorbate (vitamin C) or acetaminophen for 48 h. We found significantly decreased toxicity, preservation of endothelial cells and reduced mitochondrial fragmentation in the group receiving ascorbate following CFH treatment. This study provides direct evidence that ascorbate or ascorbic acid protects human kidney cells from CFH-induced damage such as that in sepsis-associated acute kidney injury.
Identifiants
pubmed: 37942584
pii: 334691
doi: 10.1242/dmm.050342
pmc: PMC10695115
pii:
doi:
Substances chimiques
Ascorbic Acid
PQ6CK8PD0R
Hemoglobins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R25 GM134979
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY008126
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007028
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020593
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA068485
Pays : United States
Organisme : NIH HHS
ID : 5T32ES007028
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024975
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK059637
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK058404
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL158906
Pays : United States
Organisme : NIH HHS
ID : CA68485
Pays : United States
Organisme : NCRR NIH HHS
ID : G20 RR030956
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002243
Pays : United States
Organisme : BLRD VA
ID : I01 BX004845
Pays : United States
Organisme : NIH HHS
ID : R25GM134979
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL164937
Pays : United States
Informations de copyright
© 2023. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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