Abstract
Background and Aims. Sepsis can evoke disseminated intravascular coagulation, resulting in multiple organ failure and death. Heme oxygenase-1 (HO-1) and hemopexin (HPx) can mediate cytoprotective mechanisms against these deleterious effects. This study aims to determine a role for HO-1 and HPx in coagulopathy induced by septic inflammation and define whether they can enhance the production of anti-inflammatory cytokine IL-10. Materials and Methods. 48 healthy male albino rats were divided equally into 4 groups: control group: animals subjected to laparotomy and bowel manipulation; CLP group: severe sepsis induced by cecal ligation puncture (CLP); CLP + hemin group: animals received single intraperitoneal injection of hemin (50 µmol/kg) 12 h before sepsis induction; CLP + HPx group: animals received single HPx dose (150 µg/rat, i.v.) 30 min before sepsis induction. Survival rates were calculated. Prothrombin time (PT), activated partial thromboplastin time (APTT), and activated protein C (APC), liver HO-1, serum, and liver IL-10 levels were measured, 48 hrs after sepsis induction. Liver and lung were excised for histopathological examination. Results. Hemin and HPx administration upregulated liver HO-1 and IL-10. They prolonged PT, PTT and increased APC. They reduced the inflammatory infiltrate and thrombosis in liver and lung parenchyma. However, hemin was superior in controlling coagulopathy and HO-1 production, while HPx was more potent stimulant of IL-10 expression. Conclusions. Hemin and HPx have a potential beneficial effect in severe sepsis regarding coagulopathy and inflammation.
Highlights
Sepsis is a devastating condition characterized by the activation of inflammatory and coagulation pathways in response to microbial systemic infection [1]
The Prothrombin time (PT) and activated partial thromboplastin time (APTT) values were significantly lower in cecal ligation puncture (CLP) group in comparison to the control one (P < 0.001)
Regarding the activated protein C (APC), the results showed a significant reduction in its level in CLP compared to the control group
Summary
Sepsis is a devastating condition characterized by the activation of inflammatory and coagulation pathways in response to microbial systemic infection [1]. Systemic inflammatory response to infection with the release of the proinflammatory mediators and the presence of toxins activate the coagulation cascade and evoke disseminated intravascular coagulation (DIC). This results in multiple organ failure, which is the leading cause of mortality in sepsis [3]. Free heme can cause tissue damage and programmed cell death through inducing the release of proinflammatory mediators and activation of coagulant system, and contributing to multiorgan dysfunction and death [4]. Hemin and HPx administration upregulated liver HO-1 and IL-10 They prolonged PT, PTT and increased APC. Hemin and HPx have a potential beneficial effect in severe sepsis regarding coagulopathy and inflammation
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