Pre- and posttreatment with hydrogen sulfide prevents ventilator-induced lung injury by limiting inflammation and oxidation

Abstract

Although essential in critical care medicine, mechanical ventilation often results in ventilator-induced lung injury. Low concentrations of hydrogen sulfide have been proven to have anti-inflammatory and anti-oxidative effects in the lung. The aim of this study was to analyze the kinetic effects of pre- and posttreatment with hydrogen sulfide in order to prevent lung injury as well as inflammatory and oxidative stress upon mechanical ventilation. Mice were either non-ventilated or mechanically ventilated with a tidal volume of 12 ml/kg for 6 h. Pretreated mice inhaled hydrogen sulfide in low dose for 1, 3, or 5 h prior to mechanical ventilation. Posttreated mice were ventilated with air followed by ventilation with hydrogen sulfide in various combinations. In addition, mice were ventilated with air for 10 h, or with air for 5 h and subsequently with hydrogen sulfide for 5 h. Histology, interleukin-1β, neutrophil counts, and reactive oxygen species formation were examined in the lungs. Both pre-and posttreatment with hydrogen sulfide time-dependently reduced or even prevented edema formation, gross histological damage, neutrophil influx and reactive oxygen species production in the lung. These results were also observed in posttreatment, when the experimental time was extended and hydrogen sulfide administration started as late as after 5 h air ventilation. In conclusion, hydrogen sulfide exerts lung protection even when its application is limited to a short or delayed period. The observed lung protection is mediated by inhibition of inflammatory and oxidative signaling.

Hydrogen sulfide limits neutrophil transmigration, inflammation, and oxidative burst in lipopolysaccharide-induced acute lung injury

“…After setting the insult, an earlier H 2 S inhalation resulted in a more protective effect. However, postponed application still reduced lung inflammation 27 . Mechanistically, it has been demonstrated in LPS and other models that H 2 S-mediated lung protection is associated with the reduction of inflammatory processes.…”

“…First, GYY4137 showed anti-inflammatory effects in several experimental models using a post-injury time points of application 12 , 26 . Second, we recently demonstrated the time dependency of application 27 . After setting the insult, an earlier H 2 S inhalation resulted in a more protective effect.…”

Hydrogen sulfide, oxygen, and calcium regulation in developing human airway smooth muscle

“…In mice, absence of CSE expression promotes AHR. 29 Exogenous administration of H 2 S has been demonstrated as protective in ventilator-induced lung injury, 68,69 acute lung injury, [70][71][72][73][74] hypoxia/hyperoxia environments, [74][75][76] and during acute viral illnesses. [77][78][79] Compared to these data, there is currently no information on H 2 S in the developing bronchial airways per se.…”

Estresse oxidativo na interrupção da ventilação mecânica em pacientes vítimas de traumatismo cranioencefálico: um estudo randomizado e cego

“…Além de aumentar a produção de ácido araquidônico a partir de fosfolípidos de membrana, a bradicinina pode induzir a produção de radicais livres causando uma sobrecarga de Ca2 +. Outra fonte de ERO no TCE pode ser macrófagos/microglia e neutrófilos ativados como parte de um processo inflamatório desencadeado pela lesão inicial 29,30 .…”