Abstract: TH-PO035
Effect of Calorie Restriction on Cisplatin-Induced Nephrotoxicity
Session Information
- AKI: Mechanisms - Primary Injury and Repair - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Kong, Min Jung, Kyungpook National University, Daegu, Korea (the Republic of)
- Kim, Jisu, Kyungpook National University, Daegu, Korea (the Republic of)
- Kim, Jee in, Keimyung University, Daegu, Korea (the Republic of)
- Park, Kwon Moo, Kyungpook National University, Daegu, Korea (the Republic of)
Background
Calorie restriction is associated with the resistance of mitochondria against stresses. Although cisplatin is a widely used and very effective anticancer drug, its nephrotoxicity limits its use. Cisplatin nephrotoxicity is associated with its mitochondrial accumulation following oxidative stress induction, so here, we investigated whether the control of food supply affects cisplatin nephrotoxicity.
Methods
C57BL6 male mice were subjected to a high-fat diet (HFD) supply, fasting, and refeeding after fasting. Afterwards, mice were administered with either cisplatin or 0.9% saline. Mitochondrial morphology and dynamics were evaluated by transmission electron microscope and mitochondrial fission and fusion regulating protein expression. ROS production and mitochondrial antioxidant enzymes were biochemically analyzed.
Results
Cisplatin increased blood urea nitrogen (BUN) concentration in mice. These increases were significantly greater in the HFD-feeding mice when compared with mice given a normal diet. In contrast, fasting and refeeding significantly reduced cisplatin-induced increase of BUN. Cisplatin increased mitochondrial reactive oxygen species (ROS) level, oxidative stress, and mitochondrial fragmentation in the kidney tubular cells. These increases were greatest in HFD feeding mice and least in fasting mice. After cisplatin injection, expression of Opa1, a mitochondria fusion protein, was most greatly decreased in HFD feeding mice and least in fasting mice. In contrast, expression of fis1, a mitochondria fission protein was highest in HFD feeding mice and lowest in fasting mice. In addition, the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcription coactivator for mitochondrial biogenesis, were most greatly decreased in the HFD feeding mouse kidneys.
Conclusion
These results indicate that fasting reduced cisplatin nephrotoxicity, whereas HFD feeding aggravated cisplatin nephrotoxicity, suggesting that the regulation of calorie restriction may be useful for the reduction of cisplatin nephrotoxicity.