PS-B06-4: ADENINE NEPHROPATHY IS ALLEVIATED BY ANTI-INFLAMMATORY PROPERTY OF SODIUM BENZOATE

Abstract

Background: D-amino acid oxidase (DAO), a molecule distributed in brain, liver, and kidney in human, oxidases d-amino acids to alpha-keto acids to produce hydrogen peroxides. Sodium benzoate (SB), a known DAO enzyme inhibitor, has anti-inflammatory property, although its effect has not been investigated in chronic kidney disease (CKD). Methods: Adenine induced CKD (AdCKD) or 2,8-dihydroxyadenine (2,8-DHA) nephropathy is applied for rodent CKD studies. AdCKD was induced by oral administration of adenine in C57BL/6JJcl mice with or without SB oral administration. AdCKD was also induced in DAO enzyme deficient mice (DAO-/-) and treated with or without SB. Human THP-1 cells and macrophages induced from THP-1 cells by phorbol 12-myristate 13-acetate were stimulated by LPS or TNF-alpha with or without SB to confirm the anti-inflammatory effect of SB. Results: AdCKD showed increased serum creatinine and urea nitrogen levels as well as kidney interstitial fibrosis and tubular atrophy score, which were significantly attenuated by the treatment of SB. Survival of AdCKD mice were significantly prolonged by 2.6-fold by SB administration. SB significantly decreased elevated kidney positive F4/80 immunohistochemistry area and renal mRNA level of macrophage markers and inflammatory markers of AdCKD. Human THP-1 cells and macrophages stimulated either by LPS or human TNF-alpha showed increased inflammatory gene mRNA expressions, which were significantly reduced by SB treatment. Conclusions: SB significantly ameliorated renal damage in AdCKD by suppressing inflammatory gene expressions and macrophage infiltration.