Melamine and oxalate coexposure induces early kidney tubular injury through mitochondrial aberrations and oxidative stress
Exposure to melamine, which is ubiquitous in daily life, is linked to adverse kidney outcomes. The melamine tolerable daily intake in humans is based on the no-observed-effect-level (NOEL) established in a single-toxicant murine model. However, humans are often simultaneously exposed to multiple env...
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doaj-2929ce218e3e4c75b07bc69587dfbc4b2021-10-01T04:43:45ZengElsevierEcotoxicology and Environmental Safety0147-65132021-12-01225112756Melamine and oxalate coexposure induces early kidney tubular injury through mitochondrial aberrations and oxidative stressMing-Tsang Wu0Chia-Fang Wu1Chia-Chu Liu2Yi-Chun Tsai3Chu-Chih Chen4Yin-Han Wang5Tusty-Jiuan Hsieh6Ph.D. Program of Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanResearch Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanResearch Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Pingtung Hospital, Ministry of Health and Welfare, Pingtung City, TaiwanResearch Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Divisions of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanResearch Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Population Health Sciences, National Health Research Institutes, Miaoli, TaiwanInstitute of Population Health Sciences, National Health Research Institutes, Miaoli, TaiwanResearch Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Marine Biotechnology and Resources, College of Marine Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan; Correspondence to: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Rd, Kaohsiung 807, Taiwan.Exposure to melamine, which is ubiquitous in daily life, is linked to adverse kidney outcomes. The melamine tolerable daily intake in humans is based on the no-observed-effect-level (NOEL) established in a single-toxicant murine model. However, humans are often simultaneously exposed to multiple environmental nephrotoxicants. The NOEL of melamine during coexposure with other toxicants needs to be evaluated. Oxalate is a potentially nephrotoxic terminal metabolite, and hyperoxaluria is reportedly associated with chronic kidney disease. We explored whether these two potential nephrotoxicants can interact and enhance kidney injury. We established a Sprague-Dawley rat model of coexposure to the melamine NOEL (63 mg/kg/day) and 2% hydroxy-L-proline (HLP, an oxalate precursor) in drinking water to simulate human environmental melamine exposure. Melamine/oxalate coexposure increased proximal tubular cell mitochondrial reactive oxygen species levels, lipid peroxidation and oxidative DNA damage. The degrees of mitochondrial damage, tubular cell apoptosis, tubular atrophy, and interstitial fibrosis were elevated in coexposed rat kidneys. The evidence indicated that exposure to the melamine NOEL can cause renal tubular injury via oxidative stress and that this effect may be enhanced via interaction of melamine with other environmental factors, such as oxalate. Thus, melamine risk assessment and toxicity prevention should be conducted carefully in different susceptible populations.http://www.sciencedirect.com/science/article/pii/S014765132100868XChronic kidney diseaseUrolithiasisHydroxy-L-prolineNo-observed-effect-levelReactive oxygen speciesAutophagy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ming-Tsang Wu Chia-Fang Wu Chia-Chu Liu Yi-Chun Tsai Chu-Chih Chen Yin-Han Wang Tusty-Jiuan Hsieh |
spellingShingle |
Ming-Tsang Wu Chia-Fang Wu Chia-Chu Liu Yi-Chun Tsai Chu-Chih Chen Yin-Han Wang Tusty-Jiuan Hsieh Melamine and oxalate coexposure induces early kidney tubular injury through mitochondrial aberrations and oxidative stress Ecotoxicology and Environmental Safety Chronic kidney disease Urolithiasis Hydroxy-L-proline No-observed-effect-level Reactive oxygen species Autophagy |
author_facet |
Ming-Tsang Wu Chia-Fang Wu Chia-Chu Liu Yi-Chun Tsai Chu-Chih Chen Yin-Han Wang Tusty-Jiuan Hsieh |
author_sort |
Ming-Tsang Wu |
title |
Melamine and oxalate coexposure induces early kidney tubular injury through mitochondrial aberrations and oxidative stress |
title_short |
Melamine and oxalate coexposure induces early kidney tubular injury through mitochondrial aberrations and oxidative stress |
title_full |
Melamine and oxalate coexposure induces early kidney tubular injury through mitochondrial aberrations and oxidative stress |
title_fullStr |
Melamine and oxalate coexposure induces early kidney tubular injury through mitochondrial aberrations and oxidative stress |
title_full_unstemmed |
Melamine and oxalate coexposure induces early kidney tubular injury through mitochondrial aberrations and oxidative stress |
title_sort |
melamine and oxalate coexposure induces early kidney tubular injury through mitochondrial aberrations and oxidative stress |
publisher |
Elsevier |
series |
Ecotoxicology and Environmental Safety |
issn |
0147-6513 |
publishDate |
2021-12-01 |
description |
Exposure to melamine, which is ubiquitous in daily life, is linked to adverse kidney outcomes. The melamine tolerable daily intake in humans is based on the no-observed-effect-level (NOEL) established in a single-toxicant murine model. However, humans are often simultaneously exposed to multiple environmental nephrotoxicants. The NOEL of melamine during coexposure with other toxicants needs to be evaluated. Oxalate is a potentially nephrotoxic terminal metabolite, and hyperoxaluria is reportedly associated with chronic kidney disease. We explored whether these two potential nephrotoxicants can interact and enhance kidney injury. We established a Sprague-Dawley rat model of coexposure to the melamine NOEL (63 mg/kg/day) and 2% hydroxy-L-proline (HLP, an oxalate precursor) in drinking water to simulate human environmental melamine exposure. Melamine/oxalate coexposure increased proximal tubular cell mitochondrial reactive oxygen species levels, lipid peroxidation and oxidative DNA damage. The degrees of mitochondrial damage, tubular cell apoptosis, tubular atrophy, and interstitial fibrosis were elevated in coexposed rat kidneys. The evidence indicated that exposure to the melamine NOEL can cause renal tubular injury via oxidative stress and that this effect may be enhanced via interaction of melamine with other environmental factors, such as oxalate. Thus, melamine risk assessment and toxicity prevention should be conducted carefully in different susceptible populations. |
topic |
Chronic kidney disease Urolithiasis Hydroxy-L-proline No-observed-effect-level Reactive oxygen species Autophagy |
url |
http://www.sciencedirect.com/science/article/pii/S014765132100868X |
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