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
-
Early growth response 1 (EGR-1) works as a master regulator that plays a key role in triggering inflammation-induced tissue injury after ischemia and reperfusion. This study tested the hypothesis that postconditioning (Postcon) or anti-inflammatory compound, curcumin, ameliorates inflammatory responses and further reduces infarct size by normalizing EGR-1 expression during reperfusion. In the control group, male Sprague-Dawley rats were subjected to 30-min ischemia and 180-min reperfusion. ⋯ The protection achieved with pretreatment with curcumin was comparable to the benefits gained by Postcon in all end points measured. In H9C2 rat cardiomyoblast cell line, EGR-1 siRNA downregulated hydrogen peroxide-induced EGR-1 mRNA expression and subsequently reduced tumor necrosis factor α mRNA level. These results suggest that EGR-1 seems to play a critical role in myocardial reperfusion injury because downregulation of EGR-1 either by Postcon or the use of pharmacological intervention reduces infarct size, most likely through an inhibition of inflammation-mediated processes.
-
Baicalin, as the main active ingredient of the root from Scutellaria, is usually used in the treatment of inflammatory diseases. In our study, we found that baicalin improved survival in septic mice in vivo and attenuated high-mobility group box 1 (HMGB1) and cytokine release from macrophages in vitro. The experiments in vitro showed that baicalin inhibited both viability of macrophages and the cell's secretion of HMGB1, tumor necrosis factor α, interleukin 6 (IL-6), and IL-1β induced by lipopolysaccharide. ⋯ We found that baicalin improved survival and tissue injury of septic mice in vivo. It also decreased serum HMGB1, tumor necrosis factor α, IL-6, and IL-1β in septic mice. In conclusion, baicalin inhibits the release of HMGB1 from macrophages and may be a potential therapeutic strategy for sepsis-related diseases.
-
The objective of this study was to investigate the effects of pyruvate-containing fluids on peritoneal resuscitation (PR), following intravenous fluid resuscitation from hemorrhagic shock (HS) in rats. ⋯ Peritoneal resuscitation with hyperosmolar fluids attenuated visceral vasoconstriction and splanchnic hypoperfusion and improved the intestinal barrier protein and organ function following conventional fluid resuscitation from severe HS in rats. Pyruvate was superior to lactate in PDS as PR fluids, and 2.2% pyruvate was the optimal fluid in PR.
-
Mechanical ventilation can cause structural and functional disturbances in the lung termed ventilator-induced lung injury (VILI). The aim of this study was to evaluate whether BML-111, a lipoxin receptor agonist, could attenuate VILI. Following induction of anesthesia and tracheostomy, Sprague-Dawley rats were ventilated with low tidal volume (6 mL/kg) or high tidal volume (20 mL/kg, HVT) for 4 h. ⋯ Administration with BML-111 suppressed the decrement of the nuclear factor κB (NF-κB) inhibitor IκB-α, diminished NF-κB activation, and reduced activation of mitogen-activated protein kinase in VILI. This study indicates that BML-111 attenuated VILI via a NF-κB and mitogen-activated protein kinase dependent mechanism. BML-111 may be a promising strategy for alleviation of VILI in patients subjected to mechanical ventilation.