Sepsis is one of the most important causes of death in intensive care units. Despite the fact that sepsis pathogenesis remains obscure, there is increasing evidence that oxidants and antioxidants play a key role. The imbalance of the abovementioned substances in favor of oxidants is called oxidative stress, and it contributes to sepsis process. The most important consequences are vascular permeability impairment, decreased cardiac performance, and mitochondrial malfunction leading to impaired respiration. Nitric oxide is perhaps the most important and well-studied oxidant. Selenium, vitamin C, and 3N-acetylcysteine among others are potential therapies for the restoration of redox balance in sepsis. Results from recent studies are promising, but there is a need for more human studies in a clinical setting for safety and efficiency evaluation.

Hypochlorous acid (HOCl) is toxic and causes cell death. However, this effect is inhibited by reaction with taurine, which generates taurine chloramine (TauCl), thereby protecting the cells from HOCl-generated toxicity. TauCl has been shown to inhibit the production of inflammatory mediators like O2•−, H2O2 and NO. In this study, RAW 264.7 macrophages treated with TauCl were protected from death caused by H2O2. TauCl increased the expression of peroxiredoxin-1, thioredoxin-1 and heme oxygenase (HO)-1, the anti-oxidant enzymes normally induced by activation of NF-E2-related factor-2 (Nrf2). TauCl increased nuclear translocation of Nrf2 and binding to the anti-oxidant response element. These data suggest that TauCl produced abundantly in the activated neutrophils and released to surrounding cells in the inflamed tissues may induce the expression of cytoprotective anti-oxidant enzymes. Elevation of HO activity via induction of HO-1 expression within neighboring cells may provide protection from cytotoxicity caused by inflammatory oxidants like H2O2.

These findings indicate that CRIF1 plays an important role in maintaining mitochondrial and endothelial function through its effects on the SIRT1-eNOS pathway. Antioxid. Redox Signal. 27, 234-249.

Taurine chloramine is the major chloramine generated in activated neutrophils via the reaction between the overproduced hypochlorous acid and the stored taurine. Taurine chloramine has anti-inflammatory and cytoprotective effects in inflamed tissues by inhibiting the production of inflammatory mediators. Taurine chloramine increases heme oxygenase activity and also protects against hydrogen peroxide (H2O2)-derived necrosis in macrophages. In this study, we examined further whether taurine chloramine could protect RAW 264.7 macrophages from apoptosis caused by H2O2. Macrophages treated with 0.4 mM H2O2 underwent apoptosis without showing immediate signs of necrosis, and the cells pretreated with taurine chloramine were protected from the H2O2-derived apoptosis. Taurine chloramine increased heme oxygenase-1 expression and heme oxygenase activity. The taurine chloramine-derived upregulation of heme oxygenase-1 expression was blocked by inhibition of ERK phosphorylation. Taurine chloramine decreased cellular glutathione (GSH) levels initially, but the GSH level increased above the control level by 10 h. Taurine chloramine also increased catalase expression and protected macrophages from the apoptotic effect of H2O2. Combined, these results indicate that the taurine chloramine, produced and released endogenously by the activated neutrophils, can protect the macrophages in inflamed tissues from the H2O2-derived apoptosis not only by increasing the expression of cytoprotective enzymes like heme oxygenase-1 and catalase, but also by increasing the intracellular antioxidant GSH level.