Effects of Raspberry on Angiotensin II-Induced Oxidative Stress, Inflammation and Fibrosis in the Heart of Mice

Abstract

Abstract Objectives To investigate whether diet supplementation with raspberry attenuate angiotensin (Ang) II- induced increase in oxidative stress, inflammation, and fibrosis in the heart of mice. Methods Twelve-week male C57BL/6J mice were fed AIN-93M diets alone (control and Ang II groups) or supplemented with 10% w/w freeze-dried raspberry (n = 5 per group). At week 4, mice were implanted with subcutaneous osmotic minipumps that delivered 0.9% saline (Control) or Ang II (1 µg/kg body weight/day) for another four weeks. Heart was collected at sacrifice and protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase (SOD)2, and interleukin (IL)-6 were measured. Fibrosis was assessed using Masson's trichrome staining. Results were analyzed using ANOVA followed by Tukey-Kramer post-hoc test. Effect size (d) was also calculated to compare standardized changes among groups. Results Protein expression of Nrf2, a transcription factor that regulates the expression of antioxidant enzymes, was up-regulated by raspberry (1.57 ± 0.34 vs. 0.76 ± 0.15-fold, P = 0.09, d = 1.4) compared to Ang II, albeit not significantly. Ang II did not change the protein expression of the antioxidant enzyme SOD2 in the heart; however, supplementation with raspberry increased SOD2 (1.81 ± 0.33 vs. 1.09 ± 0.09-fold, P = 0.09; d = 1.1) expression compared to Ang II, though not significantly. Supplementation with raspberry significantly attenuated protein expression of the inflammatory cytokine IL-6 compared to Ang II (0.87 ± 0.19 vs. 1.4 ± 0.10-fold, P = 0.04, d = 1.8). Lastly, Ang II increased fibrosis in the heart of mice, which was attenuated by supplementation with raspberry. Conclusions Our findings indicate that raspberry may decrease Ang II-induced fibrosis by decreasing inflammation and oxidative stress in the heart. Funding Sources Arkansas Biosciences Institute & Lewis Foundation Grant Award.