P0534THE EFFECT OF HIGH FAT DIET INTAKE AND FOOD SUPPLY RESTRICTION ON CISPLATIN NEPHROTOXICITY IN MICE

Abstract

Abstract Background and Aims Nephrotoxicity is a major side effect of cis-diamminedichloroplatinum (II) (cisplatin), which is widely used for cancer therapy. The nephrotoxicity is associated with the excessive formation of reactive oxygen species (ROS) and oxidation of cell components. Here, we investigate whether cisplatin nephrotoxicity can be controlled by the regulation of food supply which is associated with cellular production of ROS. Method Male mice were administered with either cisplatin or saline. Before cisplatin administration, mice were high-fat diet (HFD) feeding for 7 days, no-food supply for 2 days, 2 days no-food supply and refeeding with normal diet (ND), and normal diet. Renal function was analyzed by plasma creatinine (PCr) and blood urea nitrogen (BUN) concentration. Kidney cell damage was evaluated by periodic acid shiff staining and transmission electron microscope analysis. Results Cisplatin injection induced the disruption of kidney tubular cells and also increased BUN and PCr concentration. These increases were greatest in the HFD feeding mice, whereas .these increases were lowest in the food restricted mice. Levels of DNA oxidation and lipid peroxidation increased in the kidney after cisplatin injection and these increase were also greatest in the kidney of HFD feeding mice and lowest food restricted mice. Mitochondrial damage was observed in the proximal tubule cells after cisplatin injection and this mitochondria damage was more severe in the HFD feeding mice than ND feeding mice. Cisplatin increased the expression of fission 1 in the kidney, whereas reduced the expression of opa-1 expression. These cisplatin induced changes were greater in the HFD feeding mice than the ND feeding mice. Conclusion High fat diet feeding worsens cisplatin-induced nephrotoxicity along with increased oxidative stress and mitochondrial damage, whereas food restriction reduces this cisplatin nephrotoxicity. These data indicate that cisplatin nephrotoxicity is controlled by food supply, suggesting that energy metabolism is associated with cisplatin nephrotoxicity.