Chronic low-dose melamine exposure can cause early kidney injury via increased oxidative stress

Chronic low-dose melamine exposure can cause early kidney injury via increased oxidative stress

Melamine, a chemical widely used in the production of many daily used products, emerged as a public health concern after 2008 toxic milk scandal. However, melamine contamination still remains pervasive in our environment even after several measures for prevention. It could still be detected in most urine samples obtained from the general populations of countries including US and Taiwan recently. One probable source of environmental melamine exposure is the commonly used melamine-made household products including break resistant melamine tableware from which can migrate substantial amounts of melamine, especially in high acidic soups or soups served at high temperatures. In addition to use as a food adulterant, melamine might also be a contaminant during food production.

Because ninety percent of melamine intake is excreted in urine within 24 hours, our kidneys may be more susceptible to melamine. In addition to acute nephrotoxicity happened in children by high-dose melamine added to powdered milk formulas during the 2008 toxic milk scandal, our study team has found a long-term low-dose melamine exposure could increase the risk of adverse kidney outcomes, including the urolithiasis formation and the deterioration of kidney function in adults.

We have suggested that one probable mechanism through which chronic low-dose melamine exposure leads to stone formation and early kidney injury may be via increased oxidative stress. In order to investigate the hypothesis, we conducted two human studies in 80 workers from melamine tableware manufacturing factories (melamine workers) and 309 adult patients with calcium urolithiasis (stone patients) to evaluate the relationships between urinary melamine levels and two urinary biomarkers of oxidative stress, 8-oxo-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA). Both human studies showed urinary melamine levels to be significantly and positively correlated with urinary 8-OHdG and MDA, which indicated melamine exposure could increase oxidative stress. Additionally, we found that MDA mediated 36%-53% of the total effect of melamine on a biomarker of renal tubular injury, N-Acetyl-β-D Glucosaminidase (NAG).

In conclusion, our findings suggested the exposure to low-dose environmental melamine could increase oxidative stress and further risk of early kidney injury in human. The risk assessment of melamine and suggestions of prevention should also be carefully considered especially when considering its effect on susceptible populations.

Graphical Abstract:

Application and Highlights:

1.This is the first report in literature to confirm the exposure to low-dose environmental melamine could increase oxidative stress and further risk of early kidney injury in human.

2.The risk assessment of melamine and suggestions of prevention should be more carefully considered especially on susceptible populations in the future.

Research Team Members: Chia-Chu Liu, Tusty-Jiuan Hsieh, Chia-Fang Wu, Chien-Hung Lee, Yi-Chun Tsai, Tsung-Yi Huang, Sheng-Chen Wen, Cheng-Hsueh Lee, Tsu-Ming Chien, Yung-Chin Lee, Shu-Pin Huang, Ching-Chia Li, Yii-Her Chou, Wen-Jeng Wu, Ming-Tsang Wu

Representative Department: Research Center for Environmental Medicine and Cohort Research Center

Introduction of Research Team: Our team is a cross-disciplinary research team that are assembled by different experts from the fields of clinical medicine (urology and nephrology), basic science, and public health. Our research is focused on the impact of melamine exposure on human’s health. 

Contact Email: ccliu0204@gmail.com

Publication: Journal of Hazardous Materials. 2020 Sep; 396: 122726

Full-Text Article: https://www.sciencedirect.com/science/article/abs/pii/S0304389420307159?via%3Dihub