Abstract
BackgroundChronic inflammatory processes in the peritoneal cavity develop as a result of ischemia, foreign body reaction, and trauma. Brazilian green propolis, a beeswax product, has been shown to exhibit multiple actions on inflammation and tissue repair. Our aim was to investigate the effects of this natural product on the inflammatory, angiogenic, and fibrogenic components of the peritoneal fibroproliferative tissue induced by a synthetic matrix.MethodsChronic inflammation was induced by placing polyether-polyurethane sponge discs in the abdominal cavity of anesthetized Swiss mice. Oral administration of propolis (500/mg/kg/day) by gavage started 24 hours after injury for four days. The effect of propolis on peritoneal permeability was evaluated through fluorescein diffusion rate 4 days post implantation. The effects of propolis on the inflammatory (myeloperoxidase and n-acetyl-β-D-glucosaminidase activities and TNF-α levels), angiogenic (hemoglobin content-Hb), and fibrogenic (TGF-β1 and collagen deposition) components of the fibrovascular tissue in the implants were determined 5 days after the injury.ResultsPropolis was able to decrease intraperitoneal permeability. The time taken for fluorescence to peak in the systemic circulation was 20 ± 1 min in the treated group in contrast with 15 ± 1 min in the control group. In addition, the treatment was shown to down-regulate angiogenesis (Hb content) and fibrosis by decreasing TGF-β1 levels and collagen deposition in fibroproliferative tissue induced by the synthetic implants. Conversely, the treatment up-regulated inflammatory enzyme activities, TNF-α levels and gene expression of NOS2 and IFN-γ (23 and 7 fold, respectively), and of FIZZ1 and YM1 (8 and 2 fold) when compared with the untreated group.ConclusionsThese observations show for the first time the effects of propolis modulating intraperitoneal inflammatory angiogenesis in mice and disclose important action mechanisms of the compound (downregulation of angiogenic components and activation of murine macrophage pathways).
Highlights
Chronic inflammatory processes in the peritoneal cavity develop as a result of ischemia, foreign body reaction, and trauma
Chronic inflammatory processes in the peritoneal cavity are reported to develop as a result of ischemia, foreign body reaction, and trauma to the peritoneum
We have recently reported that implantation of a synthetic matrix in the peritoneal cavity in mice induced a fibroproliferative process whose components, inflammatory cell recruitment, angiogenesis, and extracellular matrix deposition were identified and modulated by various compounds [9,10]
Summary
Chronic inflammatory processes in the peritoneal cavity develop as a result of ischemia, foreign body reaction, and trauma. Platelet accumulation and activation at lesion sites are the first events to take place followed by coagulum formation that provides a framework for inflammatory cells attachment, Several groups have reported that local or systemic administration of propolis extract exerts immunomodulatory, antimicrobial, anti-inflammatory, antioxidant, and antiangiogenic effects on a number of pathological conditions, including accelerating repair phases in various experimental wound healing models. This natural beehive product presents minimal adverse effects and no toxicity [5,6,7,8]. Considering that cytokines/chemokines play critical roles in fibroproliferative processes [11,12,13] and peritoneal macrophages express traits associated with both classical and alternative activation gene expression [14,15], we set out to study a possible effect of propolis in modulating these parameters in sponge-induced intraperitoneal inflammatory angiogenesis
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