Abstract
Selegiline, an anti-Parkinson drug, has antioxidant and anti-apoptotic effects. To explore the effect of selegiline on sepsis, we used a clinically relevant animal model of polymicrobial sepsis. Cecal ligation and puncture (CLP) or sham operation was performed in male rats under anesthesia. Three hours after surgery, animals were randomized to receive intravenously selegiline (3 mg/kg) or an equivalent volume of saline. The administration of CLP rats with selegiline (i) increased arterial blood pressure and vascular responsiveness to norepinephrine, (ii) reduced plasma liver and kidney dysfunction, (iii) attenuated metabolic acidosis, (iv) decreased neutrophil infiltration in liver and lung, and (v) improved survival rate (from 44% to 65%), compared to those in the CLP alone rats. The CLP-induced increases of plasma interleukin-6, organ superoxide levels, and liver inducible nitric oxide synthase and caspase-3 expressions were ameliorated by selegiline treatment. In addition, the histological changes in liver and lung were significantly attenuated in the selegiline -treated CLP group compared to those in the CLP group. The improvement of organ dysfunction and survival through reducing inflammation, oxidative stress and apoptosis in peritonitis-induced sepsis by selegiline has potential as an adjuvant agent for critical ill.
Highlights
Despite advances in critical care medicine, sepsis continues to be a serious clinical entity with mortality rate still 30–50% for severe sepsis [1]
This study provides novel evidence that the application of SEL seems to improve survival in the Cecal ligation and puncture (CLP)-induced sepsis rats as a consequence of reduced dysfunction/injury of multiple organs
This could be due to attenuation of IL-6 production and superoxide formation and suppression of iNOS and caspase-3 expression by SEL in animals with CLP-induced sepsis
Summary
Despite advances in critical care medicine, sepsis continues to be a serious clinical entity with mortality rate still 30–50% for severe sepsis [1]. Numerous clinical trials of cytokine-specific therapies failed to improve survival in patients with sepsis, recently, using pharmacological modulators to suppress apoptosis has been shown a striking efficacy in animal models of sepsis [2,3,4,5]. SEL has been shown to reduce vascular permeability and lung injury in a rodent hemorrhagic shock model, mostly due its anti-apoptotic action [18]. No studies have shown the impact of SEL at attenuating organ dysfunction and increasing survival in sepsis. We have tested, using a rat model of cecal ligation and puncture (CLP)-induced sepsis, the hypothesis that SEL improved survival in an intra-abdominal sepsis via its antioxidant and anti-apoptotic effects
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