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Ac2-26 Mimetic Peptide of Annexin A1 Inhibits Local and Systemic Inflammatory Processes Induced by Bothrops moojeni Venom and the Lys-49 Phospholipase A2 in a Rat Model.

Stuqui B, de Paula-Silva M, Carlos CP, Ullah A, Arni RK, Gil CD, Oliani SM - PLoS ONE (2015)

Bottom Line: In the kidneys, CV and MjTX-II administrations were associated with an increased number of macrophages and morphological alterations in the juxtamedullary nephrons in proximal and distal tubules.Ac2-26 promoted significant recovery of the juxtamedullary structures, decreased the number of macrophages and diminished the AnxA1 in epithelial cells from distal tubules and renal capsules.Our results show that Ac2-26 treatment significantly attenuates local and systemic inflammatory processes and indicate this peptide as a potential target for the development of new therapeutic strategies for the snakebite envenomation treatment.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunomorphology, Department of Biology, São Paulo State University (UNESP), São José do Rio Preto, São Paulo, Brazil.

ABSTRACT
Annexin A1 (AnxA1) is an endogenous glucocorticoid regulated protein that modulates anti-inflammatory process and its therapeutic potential has recently been recognized in a range of systemic inflammatory disorders. The effect of the N-terminal peptide Ac2-26 of AnxA1 on the toxic activities of Bothrops moojeni crude venom (CV) and its myotoxin II (MjTX-II) were evaluated using a peritonitis rat model. Peritonitis was induced by the intraperitoneal injection of either CV or MjTX-II, a Lys-49 phospholipase A2. Fifteen minutes after the injection, the rats were treated with either Ac2-26 or PBS. Four hours later, the CV and MjTX-II-induced peritonitis were characterized by neutrophilia (in the peritoneal exudate, blood and mesentery) and increased number of mesenteric degranulated mast cells and macrophages. At 24 hours post-injection, the local inflammatory response was attenuated in the CV-induced peritonitis while the MjTX-II group exhibited neutrophilia (peritoneal exudates and blood). Ac2-26 treatment prevented the influx of neutrophils in MjTX-II-induced peritonitis and diminished the proportion of mesenteric degranulated mast cells and macrophages in CV-induced peritonitis. Additionally, CV and MjTX-II promoted increased levels of IL-1β and IL-6 in the peritoneal exudates which were significantly reduced after Ac2-26 treatment. At 4 and 24 hours, the endogenous expression of AnxA1 was upregulated in the mesenteric neutrophils (CV and MjTX-II groups) and mast cells (CV group). In the kidneys, CV and MjTX-II administrations were associated with an increased number of macrophages and morphological alterations in the juxtamedullary nephrons in proximal and distal tubules. Ac2-26 promoted significant recovery of the juxtamedullary structures, decreased the number of macrophages and diminished the AnxA1 in epithelial cells from distal tubules and renal capsules. Our results show that Ac2-26 treatment significantly attenuates local and systemic inflammatory processes and indicate this peptide as a potential target for the development of new therapeutic strategies for the snakebite envenomation treatment.

No MeSH data available.


Related in: MedlinePlus

Histopathological analysis of kidneys after CV- and MjTX-II-induced peritonitis.(A) Normal histological condition of proximal (PT) and distal convuluted tubules (DT) in the renal control. (B-E) CV- and MjTX-II PLA2-induced peritonitis provoked renal damage characterized by the presence of pyknotic nuclei (arrowheads), karyolisis (white arrow) and hyaline casts (asterisks) in proximal tubules. (F) Ac2-26 peptide restores the normal morphological aspect of juxtamedullary structures. Stain: Hematoxylin-Eosin. Scale bars: 20 μm.
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pone.0130803.g005: Histopathological analysis of kidneys after CV- and MjTX-II-induced peritonitis.(A) Normal histological condition of proximal (PT) and distal convuluted tubules (DT) in the renal control. (B-E) CV- and MjTX-II PLA2-induced peritonitis provoked renal damage characterized by the presence of pyknotic nuclei (arrowheads), karyolisis (white arrow) and hyaline casts (asterisks) in proximal tubules. (F) Ac2-26 peptide restores the normal morphological aspect of juxtamedullary structures. Stain: Hematoxylin-Eosin. Scale bars: 20 μm.

Mentions: After the characterization of the local effects of CV and MjTX-II administration, we evaluated the systemic damage. For this evaluation, the kidneys were examined 4 and 24 hours after CV and MjTX-II–induced peritonitis. As expected, morphological alterations were detected specially in the proximal (PT) and distal (DT) tubules of juxtamedullary nephrons in the treated group compared to the control group (Fig 5). At 4 hours, the CV group exhibited renal tubular epithelial cells with conspicuous and pyknotic nucleus (Fig 5B) and, at 24 hours, some epithelial cells from the proximal tubules lacked nuclei (Fig 5C), which indicates a process of necrosis and karyolisis. Additionally, hyaline casts, produced by detachment of epithelial cells, were detected in the renal tubular lumens in both CV and MjTX-II groups and at both time points (Fig 5B–5E). Post pharmacological treatment with Ac2-26 promoted significant recovery of juxtamedullary structures in the CV (Fig 5F) and MjTX-II groups.


Ac2-26 Mimetic Peptide of Annexin A1 Inhibits Local and Systemic Inflammatory Processes Induced by Bothrops moojeni Venom and the Lys-49 Phospholipase A2 in a Rat Model.

Stuqui B, de Paula-Silva M, Carlos CP, Ullah A, Arni RK, Gil CD, Oliani SM - PLoS ONE (2015)

Histopathological analysis of kidneys after CV- and MjTX-II-induced peritonitis.(A) Normal histological condition of proximal (PT) and distal convuluted tubules (DT) in the renal control. (B-E) CV- and MjTX-II PLA2-induced peritonitis provoked renal damage characterized by the presence of pyknotic nuclei (arrowheads), karyolisis (white arrow) and hyaline casts (asterisks) in proximal tubules. (F) Ac2-26 peptide restores the normal morphological aspect of juxtamedullary structures. Stain: Hematoxylin-Eosin. Scale bars: 20 μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492549&req=5

pone.0130803.g005: Histopathological analysis of kidneys after CV- and MjTX-II-induced peritonitis.(A) Normal histological condition of proximal (PT) and distal convuluted tubules (DT) in the renal control. (B-E) CV- and MjTX-II PLA2-induced peritonitis provoked renal damage characterized by the presence of pyknotic nuclei (arrowheads), karyolisis (white arrow) and hyaline casts (asterisks) in proximal tubules. (F) Ac2-26 peptide restores the normal morphological aspect of juxtamedullary structures. Stain: Hematoxylin-Eosin. Scale bars: 20 μm.
Mentions: After the characterization of the local effects of CV and MjTX-II administration, we evaluated the systemic damage. For this evaluation, the kidneys were examined 4 and 24 hours after CV and MjTX-II–induced peritonitis. As expected, morphological alterations were detected specially in the proximal (PT) and distal (DT) tubules of juxtamedullary nephrons in the treated group compared to the control group (Fig 5). At 4 hours, the CV group exhibited renal tubular epithelial cells with conspicuous and pyknotic nucleus (Fig 5B) and, at 24 hours, some epithelial cells from the proximal tubules lacked nuclei (Fig 5C), which indicates a process of necrosis and karyolisis. Additionally, hyaline casts, produced by detachment of epithelial cells, were detected in the renal tubular lumens in both CV and MjTX-II groups and at both time points (Fig 5B–5E). Post pharmacological treatment with Ac2-26 promoted significant recovery of juxtamedullary structures in the CV (Fig 5F) and MjTX-II groups.

Bottom Line: In the kidneys, CV and MjTX-II administrations were associated with an increased number of macrophages and morphological alterations in the juxtamedullary nephrons in proximal and distal tubules.Ac2-26 promoted significant recovery of the juxtamedullary structures, decreased the number of macrophages and diminished the AnxA1 in epithelial cells from distal tubules and renal capsules.Our results show that Ac2-26 treatment significantly attenuates local and systemic inflammatory processes and indicate this peptide as a potential target for the development of new therapeutic strategies for the snakebite envenomation treatment.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunomorphology, Department of Biology, São Paulo State University (UNESP), São José do Rio Preto, São Paulo, Brazil.

ABSTRACT
Annexin A1 (AnxA1) is an endogenous glucocorticoid regulated protein that modulates anti-inflammatory process and its therapeutic potential has recently been recognized in a range of systemic inflammatory disorders. The effect of the N-terminal peptide Ac2-26 of AnxA1 on the toxic activities of Bothrops moojeni crude venom (CV) and its myotoxin II (MjTX-II) were evaluated using a peritonitis rat model. Peritonitis was induced by the intraperitoneal injection of either CV or MjTX-II, a Lys-49 phospholipase A2. Fifteen minutes after the injection, the rats were treated with either Ac2-26 or PBS. Four hours later, the CV and MjTX-II-induced peritonitis were characterized by neutrophilia (in the peritoneal exudate, blood and mesentery) and increased number of mesenteric degranulated mast cells and macrophages. At 24 hours post-injection, the local inflammatory response was attenuated in the CV-induced peritonitis while the MjTX-II group exhibited neutrophilia (peritoneal exudates and blood). Ac2-26 treatment prevented the influx of neutrophils in MjTX-II-induced peritonitis and diminished the proportion of mesenteric degranulated mast cells and macrophages in CV-induced peritonitis. Additionally, CV and MjTX-II promoted increased levels of IL-1β and IL-6 in the peritoneal exudates which were significantly reduced after Ac2-26 treatment. At 4 and 24 hours, the endogenous expression of AnxA1 was upregulated in the mesenteric neutrophils (CV and MjTX-II groups) and mast cells (CV group). In the kidneys, CV and MjTX-II administrations were associated with an increased number of macrophages and morphological alterations in the juxtamedullary nephrons in proximal and distal tubules. Ac2-26 promoted significant recovery of the juxtamedullary structures, decreased the number of macrophages and diminished the AnxA1 in epithelial cells from distal tubules and renal capsules. Our results show that Ac2-26 treatment significantly attenuates local and systemic inflammatory processes and indicate this peptide as a potential target for the development of new therapeutic strategies for the snakebite envenomation treatment.

No MeSH data available.


Related in: MedlinePlus