Brazilian red propolis attenuates hypertension and renal damage in 5/6 renal ablation model

Abstract

The pathogenic role of inflammation and oxidative stress in chronic kidney disease (CKD) is well known. Anti-inflammatories and antioxidant drugs has demonstrated significant renoprotection in experimental nephropathies. Moreover, the inclusion of natural antioxidants derived from food and herbal extracts (such as polyphenols, curcumin and lycopene) as an adjuvant therapy for slowing CKD progression has been largely tested. Brazilian propolis is a honeybee product, whose anti-inflammatory, antimicrobial and antioxidant effects have been widely shown in models of sepsis, cancer, skin irritation and liver fibrosis. Furthermore, previous studies demonstrated that this compound promotes vasodilation and reduces hypertension. However, potential renoprotective effects of propolis in CKD have never been investigated. The aim of this study was to evaluate the effects of a subtype of Brazilian propolis, the Red Propolis (RP), in the 5/6 renal ablation model (Nx). Adult male Wistar rats underwent Nx and were divided into untreated (Nx) and RP-treated (Nx+RP) groups, after 30 days of surgery; when rats already exhibited marked hypertension and proteinuria. Animals were observed for 90 days from the surgery day, when Nx+RP group showed significant reduction of hypertension, proteinuria, serum creatinine retention, glomerulosclerosis, renal macrophage infiltration and oxidative stress, compared to age-matched untreated Nx rats, which worsened progressively over time. In conclusion, RP treatment attenuated hypertension and structural renal damage in Nx model. Reduction of renal inflammation and oxidative stress could be a plausible mechanism to explain this renoprotection.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Time course of body weight (A), tail-cuff pressure (B) and proteinuria (C).

S (open circles), S+RP (filled circles), Nx (open squares) and Nx+RP (filled squares). Comparisons were performed only between groups in the same analysis times. ap < 0.05 vs. group S, bp < 0.05 vs. group S+RP, cp < 0.05 vs. group Nx.

Figure 2. Renal function and reactive oxygen metabolites after 60 days of RP treatment (90 days after renal ablation).

Bar graphs of serum creatinine concentration (A) and urinary levels of reactive oxygen metabolites Tbars (B). S (open circles), S+RP (filled circles), Nx (open squares) and Nx+RP (filled squares). ap < 0.05 vs. group S, bp < 0.05 vs. group S+RP, cp < 0.05 vs. group Nx.

Figure 3. Representative panel of histological and immunohistochemical analysis.

Microphotographies of: PAS staining, to assessment of glomerular lesions (A), Trichromic Masson staining, to evaluate interstitial expansion (B), ED-1 immunohistochemistry, to analyze macrophage infiltration in the interstitial area (C) and in the glomeruli (D), and AII immunohistochemistry, to evaluate the presence of renal cortical interstitial cells positive to AII (E).

Figure 4. Histological parameters after 60 days of RP treatment (90 days after renal ablation).

Bar graphs of glomerulosclerosis index (A), percentage of sclerotic glomeruli (B) and interstitial expansion (C). ap < 0.05 vs. group S, bp < 0.05 vs. group S+RP, cp < 0.05 vs. group Nx.

Figure 5. Immunohistochemical analysis after 60 days of RP treatment (90 days after renal ablation).

Bar graphs of interstitial (A) and glomerular (B) macrophage infiltration, and AII positive interstitial cells (C) ap < 0.05 vs. group S, bp < 0.05 vs. group S+RP, cp < 0.05 vs. group Nx.