Abstract 11927: Theracurmin Attenuates Cardiac NLRP3 Inflammasome Activation in a Rodent Model of Chronic Kidney Disease
Background: Theracurmin is a novel formulation of the polyphenolic compound curcumin, which has been shown to have anti-inflammatory properties in a wide range of diseases. In chronic kidney disease (CKD), NLRP3 and inflammasome-dependent cytokines IL-1β and IL-18 have been shown to contribute significantly to disease progression and ensuing cardiovascular complications. Here, we investigate the cardio-renal effects of theracurmin in a rodent model of CKD and assess its impact on NLRP3 inflammasome activation.
Methods: Sprague-Dawley rats were randomized to undergo sham or subtotal nephrectomy (SNx) surgery at 8 weeks of age. At 3 weeks post surgery, SNx animals were randomized to received 100mg/kg/day of theracurmin via once daily oral gavage. At 8 weeks post surgery, cardiac function was assessed, followed by LV and renal tissue collection for analysis.
Results: Renal dysfunction, evidenced by elevated blood pressure and proteinuria, was confirmed in SNx animals. Treatment with theracurmin had no significant effect on renal function; however, an improvement in systolic blood pressure was observed (p<0.05).
Cardiac function of SNx animals was improved with theracurmin treatment. Chamber compliance, as measured by the slope of the end diastolic pressure volume relationship was improved (p<0.05). SNx-induced LV hypertrophy and fibrosis was attenuated with theracurmin treatment (p<0.05). Cardiac NLRP3 inflammasome activation, characterized by an overexpression of NLRP3 inflammasome components in SNx animals, was also attenuated in theracurmin treated animals (p<0.001).
Conclusions: Theracurmin may be an effective compound to ameliorate cardiovascular events in the setting of CKD. The noted improvements to cardiac structure and function, albeit in the absence of significant changes to renal function, suggests a cardioprotective effect of the compound and raises the possibility of a dose-specific effect of theracurmin in the setting of CKD.
Author Disclosures: A. Bugyei-Twum: None. A. Abadeh: None. K. Thai: None. M. Mitchell: None. M.G. Kabir: None. K.A. Connelly: None.
- © 2015 by American Heart Association, Inc.