Nitration of indoxyl sulfate facilitates its cytotoxicity in human renal proximal tubular cells via expression of heme oxygenase-1.

Peroxynitrite, the reaction product of superoxide [Formula: see text] and nitric oxide (NO), nitrates tyrosine residues, unsaturated fatty acids, cyclic guanosine monophosphate and other phenolics. We report herein that indoxyl sulfate (IS) is also nitrated by peroxynitrite in vitro and forms 2-nitro-IS, as determined from spectral characteristics and (1)H-NMR. IS is one of the very important uremic toxins that accelerate the progression of chronic kidney disease via various mechanisms.

Albumin domain II mutant with high bilirubin binding affinity has a great potential as serum bilirubin excretion enhancer for hyperbilirubinemia treatment.

Background: 4Z,15Z-bilirubin-IXα (BR), an endogenous toxic compound that is sparingly soluble in water, binds human serum albumin (HSA) with high affinity in a flexible manner. Our previous findings suggest that both Lys195 and Lys199 in subdomain IIA are important for the high-affinity binding of BR, and especially Lys199 in stand-alone domain II plays a prominent role in the renal elimination of BR. Our hypothesis is that HSA-domain II with high BR binding would be a useful therapeutic agent to treat hyperbilirubinemia in patients with impaired liver function.