ArticleFree radical biology & medicine2015
Myeloperoxidase formation of PAF receptor ligands induces PAF receptor-dependent kidney injury during ethanol consumption.
Article in Free radical biology & medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 51 citations in OpenAlex.
- The Link between Alcohol Consumption and Kidney Injury.The American journal of pathology · 2026Review
- Neutrophil extracellular traps-related genes contribute to sepsis-associated acute kidney injury.BMC nephrology · 2025Article
- Ambient ozone pollution impairs glucose homeostasis and contributes to renal function decline: Population-based evidence.Ecotoxicology and environmental safety · 2024Article
- Review
- Platelet Activating Factor Receptor Exaggerates Microglia-Mediated Microenvironment by IL10-STAT3 Signaling: A Novel Potential Biomarker and Target for Diagnosis and Treatment of Alzheimer's Disease.Frontiers in aging neuroscience · 2022Article
- Corticosterone-Mediated Physiological Stress Alters Liver, Kidney, and Breast Muscle Metabolomic Profiles in Chickens.Animals : an open access journal from MDPI · 2021Article
- Causal effect of alcohol use on the risk of end-stage kidney disease and related comorbidities: a Mendelian randomization study.Kidney research and clinical practice · 2021Article
- Platelet-Activating Factor as an Effector for Environmental Stressors.Handbook of experimental pharmacology · 2020Article
- Binge drinking affects kidney function, osmotic balance, aldosterone levels, and arterial pressure in adolescent rats: the potential hypotensive effect of selenium mediated by improvements in oxidative balance.Hypertension research : official journal of the Japanese Society of Hypertension · 2019Article
- Alcohol Consumption Can be a "Double-Edged Sword" for Chronic Kidney Disease Patients.Medical science monitor : international medical journal of experimental and clinical research · 2019Review
- Redox (phospho)lipidomics of signaling in inflammation and programmed cell death.Journal of leukocyte biology · 2019Review
- Deoxysphingolipids and ether-linked diacylglycerols accumulate in the tissues of aged mice.Cell & bioscience · 2019Article
- Schisantherin A alleviated alcohol-induced liver injury by the regulation of alcohol metabolism and NF-kB pathway.Experimental animals · 2018Article
- Enhanced Platelet-Activating Factor Synthesis Facilitates Acute and Delayed Effects of Ethanol-Intoxicated Thermal Burn Injury.The Journal of investigative dermatology · 2018Article
- Ameliorative effect of taurine-chloramine in azathioprine-induced testicular damage; a deeper insight into the mechanism of protection.BMC complementary and alternative medicine · 2018Article
- Chronic ethanol ingestion induces glomerular filtration barrier proteins genes expression alteration and increases matrix metalloproteinases activity in the kidney of rats.Interventional medicine & applied science · 2018Article
- Alcohol Misuse and Kidney Injury: Epidemiological Evidence and Potential Mechanisms.Alcohol research : current reviews · 2017Review
- Inflammatory PAF Receptor Signaling Initiates Hedgehog Signaling and Kidney Fibrogenesis During Ethanol Consumption.PloS one · 2015Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cytochrome P450 2E1 (CYP2E1) induction and oxidative metabolism of ethanol in hepatocytes inflame and damage liver. Chronic ethanol ingestion also induces kidney dysfunction, which is associated with mortality from alcoholic hepatitis. Whether the kidney is directly affected by ethanol or is secondary to liver damage is not established. We found that CYP2E1 was induced in kidney tubules of mice chronically ingesting a modified Lieber-deCarli liquid ethanol diet. Phospholipids of kidney tubules were oxidized and fragmented in ethanol-fed mice with accumulation of azelaoyl phosphatidylcholine (Az-PC), a nonbiosynthetic product formed only by oxidative truncation of polyunsaturated phosphatidylcholine. Az-PC stimulates the inflammatory PAF receptor (PTAFR) abundantly expressed by neutrophils and kidney tubules, and inflammatory cells and myeloperoxidase-containing neutrophils accumulated in the kidneys of ethanol-fed mice after significant hysteresis. Decreased kidney filtration and induction of the acute kidney injury biomarker KIM-1 in tubules temporally correlated with leukocyte infiltration. Genetic ablation of PTAFR reduced accumulation of PTAFR ligands and reduced leukocyte infiltration into kidneys. Loss of this receptor in PTAFR(-/-) mice also suppressed oxidative damage and kidney dysfunction without affecting CYP2E1 induction. Neutrophilic inflammation was responsible for ethanol-induced kidney damage, because loss of neutrophil myeloperoxidase in MPO(-/-) mice was similarly protective. We conclude that ethanol catabolism in renal tubules results in a self-perpetuating cycle of CYP2E1 induction, local PTAFR ligand formation, and neutrophil infiltration and activation that leads to myeloperoxidase-dependent oxidation and damage to kidney function. Hepatocytes do not express PTAFR, so this oxidative cycle is a local response to ethanol catabolism in the kidney.
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Registered trials
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