Nephrotoxic Study Of D-serine

D-Ser (D-serine) is a common D-amino acid. Being the endogenousagonist of Glycine site of NMDA receptor, D-Ser acts as the regulatorysubstance and is potential in curing seizure disorder and schizophrenia,thus making the toxicological study of great importance.The metabolism of D-Ser is believed to be related to DAAO(D-amino acid oxidase), in which hydrogen peroxide, one of theproduct of DAAO reaction, is directly responsible for D-Sernephrotoxicity. In this study, we put forward several studies in order tosearch for the core mechanism.In animal studies, SD rat was selected as the model animal withintraperitoneal injection of D-Ser (500mg/kg) of high dose, and urinevolume, plasma creatinine, urine glucose and urine protein as theevaluation criteria. Swiss mice is not sensitive in D-Ser nephrotoxicity,and D-Ala (D-alanine) and L-Ser did not induce nephrotoxicity.Subcutaneous injection of D-Ser was compared in the experiment, inwhich it was found to be less effective in nephrotoxicity. DAAOactivity, measured in post-injection rats, was declining with time. Subcutaneous injection of CBIO, a potent and specific DAAO inhibitor,was effective in releasing D-Ser nephrotoxicity, confirming thatDAAO’s involvement.In cell experiment, NRK-52E, the immortalized rat nephrocyte, wasselected as the model cell. D-Ser, along with D-Ala and hydrogenperoxide, is cytotoxic, different from the result of animal experiment.CBIO, the DAAO inhibitor, and PBN, the free radical scavenger, wascapable of alleviation of D-Ser nephrotoxicity. Immortalized humannephrocyte, HEK293, was found to be sensitive in similar circumstance,alerting us the risk of D-Ser in human.