Abstract
3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) is accumulated markedly in uremic serum. To detemtine cell-toxicity of CMPF, its effect on mouse erythroid colony formation (CFU-E) and mitochondrial respiration was studied. Bone marrow cells obtained from mouse were cultured, and the effect of CMPF on CFU-E was studied. CMPF inhibited CFU-E significantly at a concentration of 200μg/ml. To determine the mechanism of cytotoxicity of CMPF, the effect of CMPF on respiration of mitochondria obtained from mouse liver was studied using oxygen electrode. CMPF inhibited mitochondrial state 3 respiration dose-dependently. The inhibition was also observed in the presence of serum albumin, and even at a concentration of 50μg/ml, which is comparable to the serum level of CMPF in uremic patients undergoing hemodialysis. These results indicate that CMPF is toxic to cells due to inhibition of energy (ATP) synthesis by inhibiting oxidative phosphorylation of mitochondria.
