Resistance to acute septic peritonitis in poly(ADP-ribose) polymerase-1-deficient mice

Francisco Garcia Soriano, Lucas Liaudet, Éva Szabó, László Virág, Jon G. Mabley, Pál Pacher, Csaba Szabo

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

Sepsis is associated with a widespread production of proinflammatory cytokines and various oxidant species. Activation of the enzyme poly(ADP-ribose) polymerase (PARP) has been shown to contribute to cell necrosis and organ failure in various diseases associated with inflammation and reperfusion injury. The aim of the current study was to elucidate the role of PARP activation in the multiple organ dysfunction complicating sepsis in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Mice genetically deficient in PARP (PARP-/-) and their wild-type littermates (PARP+/+) were subjected to CLP. After 12 and 24 h, the proinflammatory cytokines TNF-α and IL-6, as well as the anti-inflammatory cytokine IL-10, and nitrite/nitrate were measured in plasma samples. Organs were harvested for the measurement of myeloperoxidase (MPO) and malondialdehyde (MDA) levels, and immunohistochemical staining for nitrotyrosine and poly(ADP ribose) was performed in gut sections. PARP-/- mice, and their wild-type littermate showed a similar time-dependent increase in plasma nitrite/nitrate and in gut and lung MDA content, as well as the presence of nitrotyrosine in the gut. In contrast to wild-type mice showing a PARP activation in the gut, PARP-/- mice had no staining for poly(ADP ribose). PARP-/- mice had significantly lower plasma levels of TNF-α, IL-6, and IL-10, and they exhibited a reduced degree of organ inflammation, indicated by decreased MPO activity in the gut and lung. These effects were associated with a significant improvement in the survival of CLP in PARP-/- mice. Thus, PARP activation has an important role in systemic inflammation and organ damage in the present model of polymicrobial septic shock.

Original languageEnglish
Pages (from-to)286-292
Number of pages7
JournalShock
Volume17
Issue number4
StatePublished - Apr 2002
Externally publishedYes

Fingerprint

Poly(ADP-ribose) Polymerases
Peritonitis
Punctures
Poly Adenosine Diphosphate Ribose
Ligation
Sepsis
Cytokines
Nitrites
Inflammation
Malondialdehyde
Interleukin-10
Nitrates
Peroxidase
Interleukin-6
Mouse Parp1 protein
Staining and Labeling
Lung
Enzyme Activation
Septic Shock
Reperfusion Injury

Keywords

  • Cytokines
  • Inflammation
  • PARP
  • Peritonitis
  • Sepsis
  • Shock

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

Cite this

Soriano, F. G., Liaudet, L., Szabó, É., Virág, L., Mabley, J. G., Pacher, P., & Szabo, C. (2002). Resistance to acute septic peritonitis in poly(ADP-ribose) polymerase-1-deficient mice. Shock, 17(4), 286-292.

Resistance to acute septic peritonitis in poly(ADP-ribose) polymerase-1-deficient mice. / Soriano, Francisco Garcia; Liaudet, Lucas; Szabó, Éva; Virág, László; Mabley, Jon G.; Pacher, Pál; Szabo, Csaba.

In: Shock, Vol. 17, No. 4, 04.2002, p. 286-292.

Research output: Contribution to journalArticle

Soriano, FG, Liaudet, L, Szabó, É, Virág, L, Mabley, JG, Pacher, P & Szabo, C 2002, 'Resistance to acute septic peritonitis in poly(ADP-ribose) polymerase-1-deficient mice', Shock, vol. 17, no. 4, pp. 286-292.
Soriano FG, Liaudet L, Szabó É, Virág L, Mabley JG, Pacher P et al. Resistance to acute septic peritonitis in poly(ADP-ribose) polymerase-1-deficient mice. Shock. 2002 Apr;17(4):286-292.
Soriano, Francisco Garcia ; Liaudet, Lucas ; Szabó, Éva ; Virág, László ; Mabley, Jon G. ; Pacher, Pál ; Szabo, Csaba. / Resistance to acute septic peritonitis in poly(ADP-ribose) polymerase-1-deficient mice. In: Shock. 2002 ; Vol. 17, No. 4. pp. 286-292.
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abstract = "Sepsis is associated with a widespread production of proinflammatory cytokines and various oxidant species. Activation of the enzyme poly(ADP-ribose) polymerase (PARP) has been shown to contribute to cell necrosis and organ failure in various diseases associated with inflammation and reperfusion injury. The aim of the current study was to elucidate the role of PARP activation in the multiple organ dysfunction complicating sepsis in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Mice genetically deficient in PARP (PARP-/-) and their wild-type littermates (PARP+/+) were subjected to CLP. After 12 and 24 h, the proinflammatory cytokines TNF-α and IL-6, as well as the anti-inflammatory cytokine IL-10, and nitrite/nitrate were measured in plasma samples. Organs were harvested for the measurement of myeloperoxidase (MPO) and malondialdehyde (MDA) levels, and immunohistochemical staining for nitrotyrosine and poly(ADP ribose) was performed in gut sections. PARP-/- mice, and their wild-type littermate showed a similar time-dependent increase in plasma nitrite/nitrate and in gut and lung MDA content, as well as the presence of nitrotyrosine in the gut. In contrast to wild-type mice showing a PARP activation in the gut, PARP-/- mice had no staining for poly(ADP ribose). PARP-/- mice had significantly lower plasma levels of TNF-α, IL-6, and IL-10, and they exhibited a reduced degree of organ inflammation, indicated by decreased MPO activity in the gut and lung. These effects were associated with a significant improvement in the survival of CLP in PARP-/- mice. Thus, PARP activation has an important role in systemic inflammation and organ damage in the present model of polymicrobial septic shock.",
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