Gut-Derived Protein-Bound Uremic Toxins
Abstract
:1. Introduction
2. PBUT Derivation and Pathological Mechanisms
2.1. Advanced Glycation End Products (AGEs)
2.2. Hippurates
2.3. Indoles
2.4. Phenols
2.5. Polyamines
2.6. Other
3. PBUTs and the Gut Microbiome
3.1. Gut Microbial Dysbiosis
3.2. Reducing Gut-Derived PBUTs
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Gut-Derived PBUT Class | Toxin | Derivation | Pathological Mechanisms | Associated Comorbidities |
---|---|---|---|---|
AGEs | 3-Deoxyglucosone Fructoselysine Glyoxal Methylglyoxal N(6)-Carboxymethyllysine Pentosidine | Diet | ECM crosslink formation Impaired endothelial progenitor cell function NF- kB/MAPK/JNK signaling RAGE signaling | Arterial stiffness Diabetic nephropathy Endothelial dysfunction Immune system dysregulation |
Hippurates | Hippuric acid Hydroxyhippuric acid | Diet | Activation of mitochondrial fission Albumin binding Free radical production NF- kB signaling | Altered drug pharmacokinetics Endothelial dysfunction Renal tubule damage |
Indoles | Indole-3-acetic acid Indoxyl glucuronide Indoxyl sulfate Kynurenine Kynurenic acid Melatonin Quinolinic acid | Microbial metabolism | AhR activation Excessive glutamate release Impaired mitochondrial OXPHOS NF- kB/MAPK signaling NMDA receptor activation Reduced PTH expression | Bone disease Cardiovascular disease Endothelial dysfunction Inflammation Muscle weakness/atrophy Neurotoxicity Oxidative stress |
Phenols | Hydroquinone p-cresyl glucuronide p-cresyl sulfate Phenol Phenylacetic acid | Microbial metabolism | Apoptosis Chromosomal aberrations Inhibition of iNOS expression NADPH oxidase activation ROS production Stimulates Rho-associated protein kinase | All-cause mortality Cardiovascular disease Inflammation Oxidative stress Renal fibrosis Vascular remodeling |
Polyamines | Putrescine Spermidine Spermine | Microbial metabolism/Diet | Inhibition of erythropoietin | Anemia |
Other | CMPF Homocysteine | Diet | Albumin binding Altered hepatic metabolism CMPF radical adducts Competitive reabsorption by OAT Degradation of gut epithelial TJ VSMC proliferation | Altered drug pharmacokinetics Atherosclerosis Increased intestinal permeability Neurological abnormalities Renal tubule damage |
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Graboski, A.L.; Redinbo, M.R. Gut-Derived Protein-Bound Uremic Toxins. Toxins 2020, 12, 590. https://doi.org/10.3390/toxins12090590
Graboski AL, Redinbo MR. Gut-Derived Protein-Bound Uremic Toxins. Toxins. 2020; 12(9):590. https://doi.org/10.3390/toxins12090590
Chicago/Turabian StyleGraboski, Amanda L., and Matthew R. Redinbo. 2020. "Gut-Derived Protein-Bound Uremic Toxins" Toxins 12, no. 9: 590. https://doi.org/10.3390/toxins12090590
APA StyleGraboski, A. L., & Redinbo, M. R. (2020). Gut-Derived Protein-Bound Uremic Toxins. Toxins, 12(9), 590. https://doi.org/10.3390/toxins12090590