Pyridoxamine Protects Proteins From Damage by Hypohalous Acids In Vitro and In Vivo
Open accessAbstract
Diabetes is characterized, in part, by activation of toxic oxidative and glycoxidative pathways that are triggered by persistent hyperglycemia and contribute to diabetic complications. Inhibition of these pathways may benefit diabetic patients by delaying the onset of complications. One such inhibitor, pyridoxamine (PM), had shown promise in clinical trials. However, the mechanism of PM action in vivo is not well understood. We have previously reported that hypohalous acids can cause disruption of the structure and function of renal collagen IV in experimental diabetes (K.L. Brown et al., Diabetes 64:2242-2253, 2015). In the present study, we demonstrate that PM can protect protein functionality from hypochlorous and hypobromous acid-derived damage via a rapid direct reaction with and detoxification of these hypohalous acids. We further demonstrate that PM treatment can ameliorate specific hypohalous acid-derived structural and functional damage to the renal collagen IV network in a diabetic animal model. These findings suggest a new mechanism of PM action in diabetes, namely sequestration of hypohalous acids, which may contribute to known therapeutic effects of PM in human diabetic nephropathy.
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B6-vitamers exert protection against chlorination stress in in vivo disease models, an effect attributed to formation of stabilized chloramine derivatives.
“Among these biomolecules, B6-vitamers deserve special recognition since they have been shown to exert protection against chlorination stress as assessed using in vivo disease models, an effect attributed to formation of stabilized chloramine derivatives (110).”
From Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer (2022) · cites this paper as [110]
Nephrotoxicity and urogenital tract dysfunction are established pathological outcomes of chlorination stress.
“Nephrotoxity and urogenital tract dysfunction are established pathological outcomes of chlorination stress.”
From Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer (2022) · cites this paper as [110]
Acute kidney injury, glomerulonephritis, diabetic nephropathy, and bladder cancer have been associated with exposure to pathological chlorination stress.
“Among other pathologies, acute kidney injury, glomerulonephritis, diabetic nephropathy, and bladder cancer have been associated with exposure to pathological chlorination stress (110, 162–166).”
From Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer (2022) · cites this paper as [110]
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- Authors
- Madu, H., Avance, J., Chetyrkin, S., Darris, C., Rose, K. L., Sanchez, O. A., Hudson, B., & Voziyan, P.
- Affiliations
- Vanderbilt University Medical Center (US)
- Corresponding author
- Voziyan, Paul
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 89
- Pages
- 83-90
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC4684779
- OpenAlex
- W1813245795
- Cited by
- 11
- References
- 30
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2020: 3 · 2019: 1 · 2018: 1 · 2016: 1
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DK65123)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- pyridoxamine, hypohalous acids, hypochlorous acid, hypobromous acid, protein damage, glycoxidation, oxidative stress, diabetic nephropathy, hyperglycemia, diabetes complications
- MeSH terms
- Amino Acid Sequence, Animals, Bromates, Chromatography, Liquid, Diabetes Mellitus, Experimental, Humans, Hypochlorous Acid, Kidney, Male, Molecular Sequence Data, Oxidation-Reduction, Pyridoxamine, Vitamin B Complex, Oxidants, Rats, Sprague-Dawley, Collagen Type IV, Rats, Tandem Mass Spectrometry, Proteolysis, In Vitro Techniques
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