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Brazilian green propolis modulates inflammation, angiogenesis and fibrogenesis in intraperitoneal implant in mice.

Lima LD, Andrade SP, Campos PP, Barcelos LS, Soriani FM, Moura SA, Ferreira MA - BMC Complement Altern Med (2014)

Bottom Line: Propolis was able to decrease intraperitoneal permeability.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.These 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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Antônio Carlos 6627- Pampulha, Belo Horizonte, Minas Gerais CEP 31,270-901, Brazil. andrades@icb.ufmg.br.

ABSTRACT

Background: Chronic 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.

Methods: Chronic 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.

Results: Propolis 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.

Conclusions: These 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).

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Representative images of the sponge implant disc. Sponge disc before implantation in the peritoneal cavity (A). In (B) sponge disc 5 days after implantation. The implant is extensively adhered to the intestine and liver by a bridge of fibrous tissue. In C and D representative histological sections (5 μm, stained with Gomori Trichrome) of intraperitoneal implant. The matrix of the synthetic sponge is occupied with inflammatory cells, spindle-shaped cells and blood vessels. The fibrovascular tissue in implants of non-treated mice (C) is denser and more vascularized than the treated implant (D). Black arrow: blood vessels; *: The sponge material is seen as triangular objects under the microscope; 60x; Bar: 50 μm.
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Figure 1: Representative images of the sponge implant disc. Sponge disc before implantation in the peritoneal cavity (A). In (B) sponge disc 5 days after implantation. The implant is extensively adhered to the intestine and liver by a bridge of fibrous tissue. In C and D representative histological sections (5 μm, stained with Gomori Trichrome) of intraperitoneal implant. The matrix of the synthetic sponge is occupied with inflammatory cells, spindle-shaped cells and blood vessels. The fibrovascular tissue in implants of non-treated mice (C) is denser and more vascularized than the treated implant (D). Black arrow: blood vessels; *: The sponge material is seen as triangular objects under the microscope; 60x; Bar: 50 μm.

Mentions: Systemic administration of propolis (500 mg/kg/200 μL) for 4 days showed no signs of toxicity such as weight loss, sedation, or changes in the animals’ motor activity. The surgical procedure and sponge matrix implantation were well tolerated by all animals, causing no infection or rejection yet inducing adhesion-like tissue.The intraperitoneal implants were enveloped by a fibrous capsule and firmly adherent to visceral organs (liver and/or intestines) by day 5. Figures 1A and B show the aspect of the sponge discs before and after implantation (5 days). Histological analysis (H&E) showed that this procedure induced a fibrovascular response causing the synthetic sponge matrix to be filled with newly-formed tissue. The intraperitoneal implants were infiltrated by fibrovascular stroma occupying the entire sponge by day 5. The tissue was composed of an inflammatory infiltrate with various cell types such as leukocytes, mesothelial-like cells, and microvessels (Figure 1C). In the propolis-treated group, vascularization of the implants was decreased and inflammatory cell infiltrate showed no visible histological change when compared with the implants from non-treated animals (Figure 1D).


Brazilian green propolis modulates inflammation, angiogenesis and fibrogenesis in intraperitoneal implant in mice.

Lima LD, Andrade SP, Campos PP, Barcelos LS, Soriani FM, Moura SA, Ferreira MA - BMC Complement Altern Med (2014)

Representative images of the sponge implant disc. Sponge disc before implantation in the peritoneal cavity (A). In (B) sponge disc 5 days after implantation. The implant is extensively adhered to the intestine and liver by a bridge of fibrous tissue. In C and D representative histological sections (5 μm, stained with Gomori Trichrome) of intraperitoneal implant. The matrix of the synthetic sponge is occupied with inflammatory cells, spindle-shaped cells and blood vessels. The fibrovascular tissue in implants of non-treated mice (C) is denser and more vascularized than the treated implant (D). Black arrow: blood vessels; *: The sponge material is seen as triangular objects under the microscope; 60x; Bar: 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4061536&req=5

Figure 1: Representative images of the sponge implant disc. Sponge disc before implantation in the peritoneal cavity (A). In (B) sponge disc 5 days after implantation. The implant is extensively adhered to the intestine and liver by a bridge of fibrous tissue. In C and D representative histological sections (5 μm, stained with Gomori Trichrome) of intraperitoneal implant. The matrix of the synthetic sponge is occupied with inflammatory cells, spindle-shaped cells and blood vessels. The fibrovascular tissue in implants of non-treated mice (C) is denser and more vascularized than the treated implant (D). Black arrow: blood vessels; *: The sponge material is seen as triangular objects under the microscope; 60x; Bar: 50 μm.
Mentions: Systemic administration of propolis (500 mg/kg/200 μL) for 4 days showed no signs of toxicity such as weight loss, sedation, or changes in the animals’ motor activity. The surgical procedure and sponge matrix implantation were well tolerated by all animals, causing no infection or rejection yet inducing adhesion-like tissue.The intraperitoneal implants were enveloped by a fibrous capsule and firmly adherent to visceral organs (liver and/or intestines) by day 5. Figures 1A and B show the aspect of the sponge discs before and after implantation (5 days). Histological analysis (H&E) showed that this procedure induced a fibrovascular response causing the synthetic sponge matrix to be filled with newly-formed tissue. The intraperitoneal implants were infiltrated by fibrovascular stroma occupying the entire sponge by day 5. The tissue was composed of an inflammatory infiltrate with various cell types such as leukocytes, mesothelial-like cells, and microvessels (Figure 1C). In the propolis-treated group, vascularization of the implants was decreased and inflammatory cell infiltrate showed no visible histological change when compared with the implants from non-treated animals (Figure 1D).

Bottom Line: Propolis was able to decrease intraperitoneal permeability.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.These 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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Antônio Carlos 6627- Pampulha, Belo Horizonte, Minas Gerais CEP 31,270-901, Brazil. andrades@icb.ufmg.br.

ABSTRACT

Background: Chronic 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.

Methods: Chronic 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.

Results: Propolis 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.

Conclusions: These 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).

Show MeSH
Related in: MedlinePlus