Poly(ADP-ribose) polymerase (PARP-1) is a nuclear enzyme, highly involved in a variety of extremely important physiologic events, including regulation of gene expression, cellular differentiation, apoptosis, DNA replication, and DNA repair. Moreover, PARP-1 plays an important role in nicotinamide-adenine dinucleotide (NAD) degradation. As one of the end products of NAD degradation, nudifloramide significantly inhibited PARP-1 activity in vitro with an IC50 value of 8 μM (1.22 mg/L). This IC50 value fell within the range of blood nudifloramide concentrations observed in dialysis patients. The nudifloramide concentrations were many times elevated in nondialyzed chronic renal failure (CRF) patients when compared with controls. The direct correlations were found between serum nudifloramide concentrations and serum creatinine concentration, and negative correlations between serum nudifloramide concentrations and creatinine clearance. The concentration of nudifloramide decreased considerably after hemodialysis (HD) session and permanently declined after kidney transplantation suggesting that it could be a novel uremic toxin[2].
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