DSM-RX78, a new phosphodiesterase inhibitor, suppresses superoxide anion production in activated human neutrophils and attenuates hemorrhagic shock-induced lung injury in rats

Osthol attenuates neutrophilic oxidative stress and hemorrhagic shock-induced lung injury via inhibition of phosphodiesterase 4

“…An elevated intracellular cAMP level and PKA activity are well known to depress human neutrophil activation, including respiratory burst and integrin expression [9,13]. The concentration of intracellular cAMP is regulated either by being degraded by PDEs or by being synthesized by ACs.…”

“…The changes in fluorescence were measured by a spectrofluorometer (Hitachi F-4500) with a thermostat set at 37°C. The excitation wavelength was 488 nm, and the emission wavelength was 520 nm [13].…”

“…The cytosolic fraction and membrane fraction, respectively, were used to determine the PDE and AC activities. PDE activity was determined using a tritium scintillation proximity assay (SPA) system (Amersham Biosciences) and AC activity was assayed using a commercial cAMP enzyme immunoassay kit (Amersham Biosciences) as described [13].…”

“…It is well known that increases in the intracellular cAMP level suppress inflammatory mediator release by innate immune cells [10]. Previous studies from our laboratory and others have reported that elevation of the cellular cAMP level is able to suppress the destruction caused by activated neutrophils and to limit lung injury in vivo [11][12][13]. Phosphodiesterase 4 (PDE4), which exists in human neutrophils, has a critical effect on the regulation of intracellular cAMP concentration by catalyzing cAMP hydrolysis.…”

Passive targeting of phosphatiosomes increases rolipram delivery to the lungs for treatment of acute lung injury: An animal study

“…MPO activity in lung homogenates was analyzed as described previously [18]. Briefly, the lung tissue (100 mg) was suspended in pH 6 buffer (1 ml) by MagNA Lyser (Roche, Indianapolis, IN, USA).…”