Abstract
BACKGROUND: Resveratrol is recognized as a promising nutraceutical with antihypertensive and prebiotic properties; however, its bioavailability in vivo is limited. To enhance its bioactivity, we developed resveratrol butyrate esters (RBEs). This study investigates whether RBEs can mitigate hypertension induced by chronic kidney disease (CKD) and exacerbated by microplastics (MPs) exposure in juvenile rats. METHODS: Three-week-old male Sprague Dawley rats were fed either regular chow or 0.5% adenine chow for three weeks. The adenine-fed CKD rats (N = 8 per group) received either 5 μM MPs (10 mg/L) or MPs combined with RBE (25 mg/L) in their drinking water from weeks 3 to 9. RESULTS: Our results indicate that MP exposure worsened CKD-induced hypertension, while RBE treatment resulted in a reduction in systolic BP by 15 mmHg (155 ± 2 mmHg vs. 140 ± 1 mmHg, p < 0.05). The combined exposure to adenine and MPs was associated with nitric oxide (NO) deficiency, which RBE treatment alleviated. Additionally, our findings revealed that RBE modulated both the classical and nonclassical renin-angiotensin system (RAS), contributing to its protective effects. We also observed changes in gut microbiota composition, increased butyric acid levels, and elevated renal GPR41 expression associated with RBE treatment. CONCLUSIONS: In conclusion, in this juvenile rat model of combined CKD and MP exposure, RBE demonstrates antihypertensive effects by modulating NO levels, the RAS, gut microbiota, and their metabolites.