Intestinal preconditioning prevents inflammatory response by modulating heme oxygenase-1 expression in endotoxic shock model

Abstract

Gut mucosal injury observed during ischemia-reperfusion is believed to trigger a systemic inflammatory response leading to multiple organ failure. It should be interesting to demonstrate this relationship between gut and multiple organ failure in a sepsis model. Intestinal preconditioning (PC) can be used as a tool to assess the effect of intestinal ischemia in inflammatory response after LPS challenge. The aim of this study was to investigate the protective effect of PC against LPS-induced systemic inflammatory and intestinal heme oxygenase-1 (HO-1) expression. ES was performed with LPS (10 mg/kg iv) with or without PC, which was done before LPS. Rats were first subjected to sham surgery or PC with four cycles of 1 min ischemia and 4 min of reperfusion 24 h before LPS challenge or saline administration. PC significantly reduced fluid requirements, lung edema, intestinal lactate production, and intestinal injury. Inflammatory mRNA expressions for intestine and lung ICAM and TNF were significantly reduced after PC, and these effects were significantly abolished by zinc-protoporphyrin (a specific HO-1 activity inhibitor) and mimicked by bilirubin administration. Intestinal PC selectively increased HO-1 mRNA expression in intestine, but we have observed no expression in lungs. These findings demonstrate that intestinal injury is a important event for inflammatory response and multiple organ injury after LPS challenge. Intestinal HO-1 expression attenuates LPS-induced multiple organ failure by modulating intestine injury and its consequences on inflammatory response. Identification of the exact mechanisms responsible for intestine HO-1 induction may lead to the development of new pharmacological interventions.

Effect of remote ischemic post-conditioning on systemic inflammatory response and survival rate in lipopolysaccharide-induced systemic inflammation model

“…The effects are associated with down-regulation of key steps leading to cell death and systemic inflammatory responses [10,15-17]. Indeed, intestinal ischemic preconditioning prevented inflammatory responses by modulating intestinal HO-1 expression in endotoxic shock model [18]. Furthermore, Wen et al [19] reported upregulation of HO-1 by chemical inducers prevented lipopolysaccharide (LPS)-induced acute hepatic injury.…”

Ischemic preconditioning attenuates lipid peroxidation and apoptosis in the cecal ligation and puncture model of sepsis

“…However, the effect of limb IP on sepsis-induced tissue injury has not yet been extensively studied. In only one study, the inflammatory response was shown to be modulated by intestinal IP in an endotoxemic shock model (28). …”

Intestinal Epithelium–Specific Knockout of the Cytochrome P450 Reductase Gene Exacerbates Dextran Sulfate Sodium–Induced Colitis

“…5 and 6) clearly demonstrated a major role of microsomal P450 enzymes in the protection of colon against inflammatory injury, our data do not exclude possible involvement of additional mechanisms or pathways, such as intestinal HO activity. Intestinal HO-1 expression was induced by intestinal inflammation in animal models, and increased HO-1 expression was found in colon biopsy from IBD patients (Otterbein et al, 1995;Willis et al, 1996;Paul et al, 2005;Tamion et al, 2007). Preinduction of HO-1 by cobalt protoporphyrin reduced extent of DSS-induced colitis in mice (Paul et al, 2005).…”