Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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High-mobility group protein box 1 (HMGB1) is essential in the response to injury during sepsis. We hypothesized that resveratrol (RESV) administration would inhibit nuclear-cytoplasmic HMGB1 translocation in hepatocytes, which is associated with sirtuin 1 (SIRT1) upregulation. We investigated the regulatory role of SIRT1 in HMGB1 nucleocytoplasmic translocation and its effect on sepsis-induced liver injury. ⋯ Resveratrol protects against sepsis-induced liver injury through the SIRT1-mediated HMGB1 nucleocytoplasmic translocation pathway, a new potential therapeutic target in sepsis-induced liver injury.
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We explored the effects of direct peritoneal resuscitation with pyruvate-peritoneal dialysis solution (PDS) following intravenous resuscitation (VR) on intestinal ischemia-reperfusion injury in rats with hemorrhagic shock (HS). ⋯ Direct peritoneal resuscitation with Lac-PDS and Pyr-PDS after VR alleviated intestinal injury from HS in rats, and Pyr-PDS was superior to Lac-PDS in its protective effect. Mechanisms of action might include the elimination of free oxygen radicals, reduction of neutrophil infiltration, inhibition of the inflammatory response, and regulation of intestinal mucosal blood flow and barrier function.
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Overproduction of nitric oxide (NO) by inducible NO synthase contributes toward refractory hypotension, impaired microvascular perfusion, and end-organ damage in septic shock patients. Tetrahydrobiopterin (BH4) is an essential NOS cofactor. GTP cyclohydrolase 1 (GCH1) is the rate-limiting enzyme for BH4 biosynthesis. ⋯ Perturbations in blood biochemistry were similarly attenuated in GFRP OE compared with wild-type controls. These results suggest that GFRP overexpression regulates GCH1 activity during septic shock, which in turn limits BH4 bioavailability for iNOS. We conclude that the GCH1-GFRP axis is a critical regulator of BH4 and NO production and the cardiovascular derangements that occur in septic shock.
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The aim of the present study was to investigate the existence of gender-related differences in the profile of changes that occur in cardiac functionality during endotoxic shock. For this, both male and female Wistar rats received a single injection of lipopolysaccharide (LPS; 10 mg/kg, i.p.) at 6 h (LPS 6-h group) or 24 h (LPS 24-h group) before the induction of anesthesia and insertion of a pressure-volume catheter using the closed-chest method. Control animals received sterile saline. ⋯ Nevertheless, only male rats from the LPS 24-h group still presented decreased stroke work and reduced dP/dtmax, P@dP/dtmax, and preload-recruitable stroke work indices. The end-systolic volume presented slight changes during the pressor effects of phenylephrine in all groups of male rats, as well as in females from the control and LPS 6-h groups, but it was significantly increased in females from the LPS 24-h group. These findings suggest that after induction of endotoxic shock female rats may recover the inotropic cardiac function earlier than males, as well as present improved adaptation of their left ventricle to the pressure-loading effects of phenylephrine.