Abstract
Cardiac fibrosis is a common finding in patients with chronic kidney disease. Here, we investigate the cardio-renal effects of theracurmin, a novel formulation of the polyphenolic compound curcumin, in a rat model of chronic kidney disease. Briefly, Sprague-Dawley rats were randomized to undergo sham or subtotal nephrectomy (SNx) surgery. At 3 weeks post surgery, SNx animals were further randomized to received theracurmin via once daily oral gavage or vehicle for 5 consecutive weeks. At 8 weeks post surgery, cardiac function was assessed via echocardiography and pressure volume loop analysis, followed by LV and renal tissue collection for analysis. SNx animals developed key hallmarks of renal injury including hypertension, proteinuria, elevated blood urea nitrogen, and glomerulosclerosis. Renal injury in SNx animals was also associated with significant diastolic dysfunction, macrophage infiltration, and cardiac NLRP3 inflammasome activation. Treatment of SNx animals with theracurmin improved structural and functional manifestations of cardiac injury associated with renal failure and also attenuated cardiac NLRP3 inflammasome activation and mature IL-1β release. Taken together, our findings suggest a significant role for the NLRP3 inflammasome in renal injury-induced cardiac dysfunction and presents inflammasome attenuation as a unique strategy to prevent adverse cardiac remodeling in the setting of chronic kidney disease.
Highlights
Left ventricular hypertrophy and interstitial cardiac fibrosis are common structural changes in the heart that occur during renal failure[3,4]
Affecting body weight (Table 1), treatment of SNx animals with theracurmin was associated with a reduction in kidney weight and an attenuation of systolic hypertension when compared to untreated SNx animals
We demonstrate that theracurmin—a novel formulation of curcumin—possesses anti-inflammatory and anti-fibrotic activity in the hearts of rats after the induction of renal injury via 5/6 subtotal nephrectomy
Summary
Left ventricular hypertrophy and interstitial cardiac fibrosis are common structural changes in the heart that occur during renal failure[3,4]. The role of the NLRP3 inflammasome in kidney disease is further emphasized by a recent study which showed that loss of NLRP3 significantly reduced inflammation and tubulointerstitial fibrosis in mice after unilateral ureteral obstruction, a relevant model of chronic kidney disease[9]. Curcumin has been reported to be both renal and cardiac protective and has been shown to suppress acute and chronic inflammation. We report that theracurmin reduces cardiac fibrosis and improves diastolic function in a rat model of chronic kidney disease. We show that theracurmin attenuates NLRP3 inflammasome activation in the heart and reduces circulating IL-1βlevels, illustrating a cardio-protective effect of the compound and the potential therapeutic benefits of a theracurmin-based treatment strategy in the setting of chronic kidney disease
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