Characterization of cytotoxic effects of aristolochic acids on the vascular endothelium.
AMP-Activated Protein Kinases
/ genetics
Animals
Aorta, Thoracic
/ drug effects
Aristolochic Acids
/ pharmacology
Calcium
/ metabolism
Cell Line
Endothelial Cells
/ drug effects
Endothelium, Vascular
/ drug effects
Humans
Male
Rats, Wistar
Reactive Oxygen Species
/ metabolism
Superoxide Dismutase
/ metabolism
Aortic ring
Aristolochic acid
Endothelial cells
Intracellular calcium
Oxidative stress
Journal
Toxicology in vitro : an international journal published in association with BIBRA
ISSN: 1879-3177
Titre abrégé: Toxicol In Vitro
Pays: England
ID NLM: 8712158
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
26
11
2019
revised:
09
02
2020
accepted:
23
02
2020
pubmed:
3
3
2020
medline:
23
12
2020
entrez:
3
3
2020
Statut:
ppublish
Résumé
Aristolochic acid nephropathy (AAN) is characterized by interstitial fibrosis, proximal tubular atrophy, and hypoxia. A correlation between a reduced peritubular capillary density and the severity of fibrosis has been demonstrated. As calcium, redox and energetic homeostasis are crucial in maintaining endothelial cell function and survival, we aimed to investigate AA-induced disturbances involved in endothelial cell injury. Our results showed a cytotoxic effect of AA on EAhy926 endothelial cells. Exposure of aortic rings to AA impaired vascular relaxation to Acetylcholine (ACh). Increased levels of intracellular reactive oxygen species (ROS) were observed in cells exposed to AA. Pre-treatment with antioxidant N-acetyl cysteine inhibited AA-induced cell death. Superoxide dismutase resulted in restoring ACh-induced relaxation. An increase in intracellular calcium level ([Ca
Identifiants
pubmed: 32119997
pii: S0887-2333(19)30825-2
doi: 10.1016/j.tiv.2020.104811
pii:
doi:
Substances chimiques
Aristolochic Acids
0
Reactive Oxygen Species
0
Superoxide Dismutase
EC 1.15.1.1
AMP-Activated Protein Kinases
EC 2.7.11.31
PRKAA1 protein, human
EC 2.7.11.31
Calcium
SY7Q814VUP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104811Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no knownfinancial or nonfinancial conflicts of interest.