Inhibition of glyoxylate conversion to oxalate in cultured human cells by the carbonyl-scavenging drug, aminoguanidine

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South African Journal of Science

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University of Cape Town

Calcium oxalate is the most frequent cause of kidney stones, and is responsible for the damage to kidneys and other organs observed in inherited disorders of oxalate metabolism. Most oxalate produced in the body is derived from its metabolic precursor, glyoxylate. Thus, any means of scavenging glyoxylate to a non-toxic product, thereby diverting it away from oxalate synthesis, has considerable therapeutic implications. Here we show that aminoguanidine, a compound with a proven safety record and used for many years to prevent long-term complications of diabetes, binds glyoxylate covalently and reduces its conversion to oxalate by human liver- and lymphocyte-derived cell lines by >90%. We propose that scavenging glyoxylate with aminoguanidine or its congeners may provide a means of reducing oxalate production in vivo, and advocate the tissue culture system described here as a convenient means for testing such agents in vitro. A serendipitous finding to emerge from our study was the abiotic and strongly pH-dependent formation of oxalate from ascorbate, which has implications for the contribution of ascorbate to urine oxalate excretion.