Effect of Tempol, a Membrane-Permeable Radical Scavenger, on Mesenteric Blood Flow and Organ Injury in a Murine Cecal Ligation and Puncture Model of Septic Shock

Abstract

Background: Interventions that reduce the generation or the effects of reactive oxygen species exert beneficial effects in a variety of models of septic shock. We investigatedthe effect of tempol, a low-molecular-weight membrane-permeable radical scavenger, on mesenteric blood flow and organ injury in a murine cecal ligation and puncture (CLP) model of septic shock. Materials and Methods: Forty-four Swiss albino mice were anesthetized with chloral hydrate (400 mg/kg, i.p.) and subjected to CLP (except for the sham-operated animals). The animals were divided randomly into 4 groups: the 1st group was sham operated (sham-operated group, n = 10); the 2nd group underwent CLP and was injected with saline (CLP + saline group, n = 12); the 3rd group was sham operated and treated with tempol (10 mg/kg, i.p., sham-treated + tempol group, n = 10); the 4th group underwent CLP and was treated with tempol (10 mg/kg, i.p., CLP + tempol group, n = 12). Mesenteric arterial blood flow (MABF) was measured by Doppler ultrasound. Poly(adenosine 5′-diphosphate-ribose) polymerase (PARP) activity was examined in the liver, lung, and kidneys. Results: In the CLP + saline group, the MABF was significantly lower than in the sham-operated group (p < 0.001). After tempol administration, MABF values significantly increased (p < 0.05). We observed significantly stronger PARP-positive staining in the lungs and kidney glomeruli in the CLP + saline group than in those of the sham-operated group (p_lung = 0.0148, p_glomeruli = 0.0025). A marked reduction in PARP activity was found in the lung and kidney glomeruli of the CLP + tempol group (p_lung = 0.0026, p_glomeruli = 0.0085). There was no significant effect of CLP on PARP activity in the liver and kidney tubuli (p_liver > 0.05, p_tubuli > 0.05). Conclusion: Tempol improved MABF in a CLP-induced septic shock model. Although tempol could not prevent the activation of PARP in the liver and kidney tubuli, it did attenuate PARP activation in the lung and kidney glomeruli.

Infliximab alleviates the mortality, mesenteric hypoperfusion, aortic dysfunction, and multiple organ damage in septic rats

“…Decrease of mesenteric blood flow leads to impaired intestinal barrier integrity and therefore translocation of microorganisms into the bloodstream. Spread of the microorganisms triggers massive and uncontrolled release of inflammatory cytokines and subsequent free radicals which ultimately causes negative effects on the vessels and multiple organs (Balzan et al 2007;Erdem et al 2007;Koh et al 2002;Yuksel et al 2009). …”

“…The rats were left to stabilize for 15 minutes before recording MBF values. The obtained signals from the flowmeter were also recorded on a computer by using a MP35 Biopac data recording system (Goleta, Calif., USA) (Yuksel et al 2009). …”

“…In early septic process, invasion of microorganisms into the bloodstream following mesenteric ischaemia leads to massive and uncontrolled release of the proinflammatory cytokines, especially tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), and free oxygen radicals (De Backer et al 2014;Iskander et al 2013;Yuksel et al 2009). …”

Inhibition of Poly-(ADP-Ribose) Polymerase Protects the Kidney in a Canine Model of Endotoxic Shock

“…During endotoxic shock (ES), inflammation causes release of large amounts of reactive oxygen species, giving rise to overproduction of superoxide anions, hydrogen peroxide and nitric oxide, which directly causes single-strand DNA breakage, leading to overactivation of nuclear enzyme PARP, and subsequently cell death, inflammation exacerbation and organ dysfunction [10,14]. Inhibition of PARP overactivation prevents oxidative cell injury and ischemia-reperfusion damage [10,15].…”

Redox nanoparticles as a novel treatment approach for inflammation and fibrosis associated with nonalcoholic steatohepatitis

“…The nitroxide compounds, such as 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), a membrane-permeable radical scavenger, can catalytically react with ROS and are anticipated as new antioxidant therapies for several diseases [7]. However, these compounds have not been able to advance to the clinical setting, due in part to problems with their short half-life and several observed side effects [8].…”