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AOP: 447
Title
Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
Short name
Graphical Representation
Point of Contact
Contributors
- Yann GUEGUEN
- Marie FREREJACQUES
- Brendan Ferreri-Hanberry
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
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This AOP was last modified on May 26, 2024 20:39
Revision dates for related pages
Page | Revision Date/Time |
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Inhibition, Mitochondrial Electron Transport Chain Complexes | March 22, 2023 11:04 |
Decrease, Mitochondrial membrane potential | April 30, 2020 12:41 |
Altered gene expression, NRF2 dependent antioxidant pathway | August 19, 2021 07:35 |
Inhibition, Nuclear factor kappa B (NF-kB) | March 02, 2023 01:58 |
Activation of ER stress | November 02, 2020 07:09 |
Increased, Oxidative Stress | February 03, 2022 14:20 |
Increase, Apoptosis | April 15, 2017 16:17 |
Increase in inflammation | May 03, 2019 14:27 |
Occurrence, renal proximal tubular necrosis | September 16, 2017 10:16 |
Occurrence, Kidney toxicity | March 04, 2022 10:58 |
Increased, Kidney Failure | June 21, 2024 10:52 |
Mitochondrial dysfunction | April 17, 2024 08:26 |
Inhibition, ETC complexes of the respiratory chain leads to Decrease, MMP | April 08, 2022 08:27 |
Decrease, MMP leads to Mitochondrial dysfunction | March 14, 2024 10:38 |
Mitochondrial dysfunction leads to Altered expression of NRF2 pathway-dependent genes | March 14, 2024 10:39 |
Mitochondrial dysfunction leads to Inhibition, Nuclear factor kappa B (NF-kB) | March 14, 2024 10:39 |
Mitochondrial dysfunction leads to Increase, Apoptosis | February 21, 2024 15:39 |
Altered expression of NRF2 pathway-dependent genes leads to ER stress | April 08, 2022 08:31 |
Altered expression of NRF2 pathway-dependent genes leads to Increased, Oxidative Stress | April 08, 2022 08:32 |
ER stress leads to Increase, Apoptosis | April 08, 2022 08:32 |
Inhibition, Nuclear factor kappa B (NF-kB) leads to Increase in inflammation | April 08, 2022 08:32 |
Increased, Oxidative Stress leads to Occurrence, renal proximal tubular necrosis | December 03, 2016 16:38 |
Increase, Apoptosis leads to Occurrence, renal proximal tubular necrosis | April 08, 2022 08:34 |
Increase in inflammation leads to Occurrence, renal proximal tubular necrosis | April 08, 2022 08:34 |
Occurrence, renal proximal tubular necrosis leads to Occurrence, Kidney toxicity | April 08, 2022 08:35 |
Occurrence, Kidney toxicity leads to Increased, Kidney Failure | April 08, 2022 08:35 |
Uranium | August 05, 2021 14:28 |
Uranium, soluble salts | April 08, 2022 08:55 |
Abstract
U metal-ions are filtered through the glomerular membrane of the kidneys, then concentrate in cortical and juxtaglomerular areas and bind to the brush border membrane of the proximal convoluted tubules. U uptake by epithelial cells occurs through endocytosis and the sodium-dependent phosphate co-transporter (NaPi-IIa). Molecular key events start with U induce mitochondrial ETC inhibition (KE1), decrease MMP (KE2) and mitochondrial disruption (KE3). The collapse of mitochondrial membrane potential triggers the Nrf2 (KE3), NF-κB (KE4) or endoplasmic reticulum-stress (KE5) pathways. The resulting cellular key events include oxidative stress (KE6), apoptosis (KE7), and pro-inflammatory effects (KE8). Finally, the main adverse outcome is tubular cell necrosis (KE9), leading to kidney toxicity (KE10) and then kidney failure (AO).
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
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KE | 105 | Inhibition, Mitochondrial Electron Transport Chain Complexes | Inhibition, ETC complexes of the respiratory chain |
KE | 1770 | Decrease, Mitochondrial membrane potential | Decrease, MMP |
KE | 177 | Mitochondrial dysfunction | Mitochondrial dysfunction |
KE | 1917 | Altered gene expression, NRF2 dependent antioxidant pathway | Altered expression of NRF2 pathway-dependent genes |
KE | 202 | Inhibition, Nuclear factor kappa B (NF-kB) | Inhibition, Nuclear factor kappa B (NF-kB) |
KE | 1815 | Activation of ER stress | ER stress |
KE | 1088 | Increased, Oxidative Stress | Increased, Oxidative Stress |
KE | 1365 | Increase, Apoptosis | Increase, Apoptosis |
KE | 1633 | Increase in inflammation | Increase in inflammation |
KE | 1097 | Occurrence, renal proximal tubular necrosis | Occurrence, renal proximal tubular necrosis |
KE | 814 | Occurrence, Kidney toxicity | Occurrence, Kidney toxicity |
AO | 759 | Increased, Kidney Failure | Increased, Kidney Failure |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
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