Dysfunction of very important tissues have been reported during

septic shock, as well as ARDS, ALI and acute kidney injury (AKI), which are characterized by the accumulation of a large number of neutrophils in the lungs [52]. Yildirim et al. showed that sildenafil provided a significant decrease in tissue MDA levels in a sildenafil-treated lung fibrosis group, and they also found that endogenous anti-oxidant glutathione was restored in the sildenafil-treated group [24]; these data support our study. A possible explanation for this finding might be that glutathione was conserved due to a lower level of lipid oxidation. Thus, our results showing the inhibition of tissue lipid peroxidation along with the replenishment of GSH content by sildenafil imply that the compound is beneficial SRT1720 cell line in maintaining oxidant–anti-oxidant balance. MLN2238 In a clinical study, Starkopf et al. demonstrated

an increase in lipid peroxidation levels and a decrease in serum anti-oxidant capacity induced by sepsis [53]. In septic shock, the levels and activities of SOD and GSH are due to the oppressive production of free radicals [54]. Therefore, taking these established results into account, we decided to offer insight into the possible mechanism that explains the role of oxidative stress in sepsis. The results are shown in our data, and they are in accordance with our hypothesis that sildenafil exerts ameliorating effects by decreasing LPO and MPO activities as markers of lipid peroxidation. Increased concentrations of LPO and MPO are found in rats with sepsis [55–57], and tissue MPO is a marker of lipid peroxidation levels that increase when septic shock is induced by CLP in rats [58]. GSH is an important constituent of intracellular protective mechanisms Grape seed extract against oxidative stress [59]. Ortoloni et al. showed that plasma GSH was decreased in septic

shock patients [60]. Another study showed that plasma GSH levels were decreased in children with sepsis [61]. Carbonell et al. showed that depletion of liver GSH potentiated the oxidative stress induced by endotoxins in rats, in which plasma lipid peroxide levels were raised [62]. Ritter et al. showed that MDA and plasma superoxide dismutase levels are markers of early mortality in septic rats [63]. Our study showed increased tissue LPO and MPO levels and decreased GSH and SOD after CLP, consistent with the literature [56]. Another important finding of the present study was that sildenafil attenuated the up-regulation of proinflammatory cytokine TNF-α. Increased serum early release of proinflammatory cytokines is important in the pathogenesis of septic shock [64].