Abstract: FR-PO834
Coexposure of Melamine and Di-2-Ethylhexylphthalate Changes Mitochondrial Dynamics and Accelerates Kidney Injury in Adenine Diet-Induced CKD Mice
Session Information
- Health Maintenance, Nutrition, Metabolism - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1500 Health Maintenance, Nutrition, and Metabolism
Authors
- Tsai, I-Hsuan, Kaohsiung Medical University College of Medicine, Kaohsiung, Taiwan
- Wu, Miao-Yi, Kaohsiung Medical University College of Medicine, Kaohsiung, Taiwan
- Wu, Ming-Tsang, Kaohsiung Medical University College of Medicine, Kaohsiung, Taiwan
- Tsai, Yi-chun, Kaohsiung Medical University College of Medicine, Kaohsiung, Taiwan
- Liu, Chia-Chu, Kaohsiung Medical University College of Medicine, Kaohsiung, Taiwan
- Hsieh, Tusty-Jiuan, Kaohsiung Medical University College of Medicine, Kaohsiung, Taiwan
Background
Environmental chemical exposures have shown to be risk factors for chronic kidney disease (CKD). Even though the 2008 event of melamine-added formula milk was over, environmental melamine exposure still occurs due to the contamination in daily food products and widely uses of melamine-made tableware. Our previous study found that environmental melamine increased oxidative stress and early kidney injury in adults. Bis-2-ethylhexylphthalate (DEHP) is presented widely in plastic products and has been suggested that it could cause kidney fibrosis. Melamine and DEHP are common environmental pollutants and their interactive toxicity remains unclear. The aims of this study are to clarify the nephrotoxicity of melamine and DEHP coexposure and to investigate the role of mitochondrial oxidative stress in the pathological mechanisms using a mouse model based on the US-FDA suggested human tolerable daily intake (TDI) levels of melamine and DEHP.
Methods
An adenine-rich-diet induced CKD model was conducted in male and female ICR mice with the coexposure of TDI levels of melamine and DEHP for 4 weeks. Urine albumin-creatinine ratio (uACR) was used to monitor kidney function. Kidney injury molecule (KIM-1) immunohistochemistry, Sirius-Red staining and TUNEL assay were applied to observe kidney injury, fibrosis, and apoptosis. We used Western blotting to detect target proteins, real-time PCR to measure mitochondrial DNA (mtDNA) and MitoSOX staining to detect mitochondrial ROS.
Results
Our results showed that melamine and/or DEHP exposure increased uACR, indicating a decline of kidney function. Fibrosis, apoptotic cells and KIM-1 were increased in the kidney sections of CKD mice exposed to melamine and/or DEHP. Biomarkers of oxidative stress (MDA, 4-HNE), inflammation (NF-kB) and fibrosis (TGF-b, collagen IV) were also elevated. Melamine and DEHP increased mitochondrial ROS and changed mtDNA and mitochondrial dynamic proteins (Pink1, Parkin, Mfn2, Drp1, Fis1) in the kidney of CKD mice.
Conclusion
Our findings suggest that melamine and/or DEHP exposure accelerates a progression of kidney injury in CKD, which may be mediated by changes in mitochondrial dynamics. Avoiding exposure of environmental melamine and DEHP should be advised in patients with CKD.
Funding
- Government Support – Non-U.S.