PS-B04-2: DIMETHYL FUMARATE IMPROVES RAT VIABILITY WITH SUPPRESSION OF BLOOD PRESSURE, TGF-B1 EXPRESSION AND RENAL DAMAGE IN DAHL/SALT SENSITIVE RATS

Abstract

Objective: Cardiovascular disease and chronic kidney disease are known to adversely affect each other. Inflammation is commonly involved in both diseases. Dimethyl fumarate (DMF) is an FDA-approved antioxidant and anti-inflammatory agent. DMF triggers an anti-inflammatory response by activating Nfr2, which is associated with NFkB signaling. The purpose of this study was to investigate the effect of DMF on Dahl/Salt sensitive(DS) rats. Methods: Six-week old DS rats were divided into the following three groups, namely the control group, the high-salt (HS) group, and the HS +DMF(HS+DMF) group. The HS and HS+DMF groups were given a high-salt diet (8%NaCl) from 6 weeks of age. The HS+DMF group was orally administered DMF (90 mg/kg/day) from 6 to 15 weeks of age. The systolic blood pressure (SBP) was measured using a noninvasive tail-cuff method every 2 weeks. Renal damage was evaluated with histopathologic analysis using PAS and Massons trichrome staining. Renal expression of Transforming Growth Factor-beta1 (TGF-b1) mRNA was evaluated with reverse transcription-polymerase chain reaction (RT-PCR). Results: DMF significantly improved overall survival rate of DS rats that had been shortened with HS. SBP increased in the HS group compared to the control groups, and DMF suppressed this change. DMF also improved the renal tubule damage and fibrosis confirmed in the HS group by histopathological analysis. Furthermore, renal TGFb1 mRNA expression was increased in the HS group, and it was suppressed by DMF. Conclusion: This study suggests that DMF improved overall survival rate of DS rats through the organ-protective effect.