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Carbon Monoxide-Releasing Molecule-2 Reduces Intestinal Epithelial Tight-Junction Damage and Mortality in Septic Rats.

Zhang S, Zheng S, Wang X, Shi Q, Wang X, Yuan S, Wang G, Ji Z - PLoS ONE (2015)

Bottom Line: CORM-2, but not iCORM-2, significantly reduced sepsis-induced damage of intestinal mucosa (including TJ disruption), TJ protein reduction (including zonula occludens-l (ZO-1), claudin-1 and occludin), MLC phosphorylation and proinflammatory cytokine release.The overall outcomes showed that CORM-2 suppressed sepsis-induced intestinal epithelial permeability changes and reduced mortality rate of those septic rats.Our data strongly suggest that CORM-2 could be a potential therapeutic reagent for sepsis by suppressing inflammation, restoring intestinal epithelial barrier and reducing mortality.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Zhongda Hospital, Southeast University Medical School, Nanjing, Jiangsu 210009, China.

ABSTRACT

Objective: Damage to intestinal epithelial tight junctions plays an important role in sepsis. Recently we found that Carbon Monoxide-Releasing Molecule-2 (CORM-2) is able to protect LPS-induced intestinal epithelial tight junction damage and in this study we will investigate if CORM-2 could protect intestinal epithelial tight junctions in the rat cecal ligation and puncture (CLP) model.

Materials and methods: The CLP model was generated using male Sprague-Dawley (SD) rats according to standard procedure and treated with CORM-2 or inactive CORM-2 (iCORM-2), 8 mg/kg, i.v. immediately after CLP induction and euthanized after 24h or 72h (for mortality rate only). Morphological changes were investigated using both transmission electron and confocal microscopy. The levels of important TJ proteins and phosphorylation of myosin light chain (MLC) were examined using Western blotting. Cytokines, IL-1╬▓ and TNF-╬▒ were measured using ELISA kits. The overall intestinal epithelial permeability was evaluated using FD-4 as a marker.

Results: CORM-2, but not iCORM-2, significantly reduced sepsis-induced damage of intestinal mucosa (including TJ disruption), TJ protein reduction (including zonula occludens-l (ZO-1), claudin-1 and occludin), MLC phosphorylation and proinflammatory cytokine release. The overall outcomes showed that CORM-2 suppressed sepsis-induced intestinal epithelial permeability changes and reduced mortality rate of those septic rats.

Conclusions: Our data strongly suggest that CORM-2 could be a potential therapeutic reagent for sepsis by suppressing inflammation, restoring intestinal epithelial barrier and reducing mortality.

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Related in: MedlinePlus

Effects of CORM-2 on CLP-induced proinflammatory cytokine release.Blood was taken from portal vein at 24h after sepsis induction by CLP. Concentrations of TNF-╬▒ and IL-1╬▓ were measured using ELISA kits. Means┬▒SD from 10 rats per group are presented. aP<0.05, compare to Sham rats; bP<0.05, compare to CLP rats; cP<0.05, compare to CLP rats treated with iCORM-2.
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pone.0145988.g006: Effects of CORM-2 on CLP-induced proinflammatory cytokine release.Blood was taken from portal vein at 24h after sepsis induction by CLP. Concentrations of TNF-╬▒ and IL-1╬▓ were measured using ELISA kits. Means┬▒SD from 10 rats per group are presented. aP<0.05, compare to Sham rats; bP<0.05, compare to CLP rats; cP<0.05, compare to CLP rats treated with iCORM-2.

Mentions: Blood samples from 40/40 rats were analyzed and means┬▒SD is shown in Fig 6. Serum TNF-╬▒ and IL-1╬▓ were elevated in CLP rats compared to the sham control. CORM-2 treatment after CLP was able to significantly alleviate the elevation, which is consistent with our in vitro data. In contrast, the same dose of iCORM could not reduce the CLP-induced elevation of both TNF-╬▒ and IL-1╬▓, indicating that CO released from CORM-2 has anti-inflammatory properties in vivo.


Carbon Monoxide-Releasing Molecule-2 Reduces Intestinal Epithelial Tight-Junction Damage and Mortality in Septic Rats.

Zhang S, Zheng S, Wang X, Shi Q, Wang X, Yuan S, Wang G, Ji Z - PLoS ONE (2015)

Effects of CORM-2 on CLP-induced proinflammatory cytokine release.Blood was taken from portal vein at 24h after sepsis induction by CLP. Concentrations of TNF-╬▒ and IL-1╬▓ were measured using ELISA kits. Means┬▒SD from 10 rats per group are presented. aP<0.05, compare to Sham rats; bP<0.05, compare to CLP rats; cP<0.05, compare to CLP rats treated with iCORM-2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4697838&req=5

pone.0145988.g006: Effects of CORM-2 on CLP-induced proinflammatory cytokine release.Blood was taken from portal vein at 24h after sepsis induction by CLP. Concentrations of TNF-╬▒ and IL-1╬▓ were measured using ELISA kits. Means┬▒SD from 10 rats per group are presented. aP<0.05, compare to Sham rats; bP<0.05, compare to CLP rats; cP<0.05, compare to CLP rats treated with iCORM-2.
Mentions: Blood samples from 40/40 rats were analyzed and means┬▒SD is shown in Fig 6. Serum TNF-╬▒ and IL-1╬▓ were elevated in CLP rats compared to the sham control. CORM-2 treatment after CLP was able to significantly alleviate the elevation, which is consistent with our in vitro data. In contrast, the same dose of iCORM could not reduce the CLP-induced elevation of both TNF-╬▒ and IL-1╬▓, indicating that CO released from CORM-2 has anti-inflammatory properties in vivo.

Bottom Line: CORM-2, but not iCORM-2, significantly reduced sepsis-induced damage of intestinal mucosa (including TJ disruption), TJ protein reduction (including zonula occludens-l (ZO-1), claudin-1 and occludin), MLC phosphorylation and proinflammatory cytokine release.The overall outcomes showed that CORM-2 suppressed sepsis-induced intestinal epithelial permeability changes and reduced mortality rate of those septic rats.Our data strongly suggest that CORM-2 could be a potential therapeutic reagent for sepsis by suppressing inflammation, restoring intestinal epithelial barrier and reducing mortality.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Zhongda Hospital, Southeast University Medical School, Nanjing, Jiangsu 210009, China.

ABSTRACT

Objective: Damage to intestinal epithelial tight junctions plays an important role in sepsis. Recently we found that Carbon Monoxide-Releasing Molecule-2 (CORM-2) is able to protect LPS-induced intestinal epithelial tight junction damage and in this study we will investigate if CORM-2 could protect intestinal epithelial tight junctions in the rat cecal ligation and puncture (CLP) model.

Materials and methods: The CLP model was generated using male Sprague-Dawley (SD) rats according to standard procedure and treated with CORM-2 or inactive CORM-2 (iCORM-2), 8 mg/kg, i.v. immediately after CLP induction and euthanized after 24h or 72h (for mortality rate only). Morphological changes were investigated using both transmission electron and confocal microscopy. The levels of important TJ proteins and phosphorylation of myosin light chain (MLC) were examined using Western blotting. Cytokines, IL-1╬▓ and TNF-╬▒ were measured using ELISA kits. The overall intestinal epithelial permeability was evaluated using FD-4 as a marker.

Results: CORM-2, but not iCORM-2, significantly reduced sepsis-induced damage of intestinal mucosa (including TJ disruption), TJ protein reduction (including zonula occludens-l (ZO-1), claudin-1 and occludin), MLC phosphorylation and proinflammatory cytokine release. The overall outcomes showed that CORM-2 suppressed sepsis-induced intestinal epithelial permeability changes and reduced mortality rate of those septic rats.

Conclusions: Our data strongly suggest that CORM-2 could be a potential therapeutic reagent for sepsis by suppressing inflammation, restoring intestinal epithelial barrier and reducing mortality.

Show MeSH
Related in: MedlinePlus