New insights into the steen solution properties: breakthrough in antioxidant effects via NOX2 downregulation.
Ex vivo lung perfusion (EVLP) allows perfusion and reconditioning of retrieved lungs for organ transplantation. The Steen solution is specifically designed for this procedure but the mechanism through which it elicits its activity is still to be fully clarified. We speculated that Steen solution may encompass antioxidant properties allowing a reestablishment of pulmonary tissue homeostasis. Blood samples from 10 healthy volunteers were recruited. Platelets and white cells were incubated with Steen solution or buffer solution as control and stimulated with suitable agonists. Reactive oxidant species (ROS), soluble NOX2 (sNOX2-derived peptide), a marker of NADPH oxidase activation, p47(phox) translocation to cell membrane and isoprostanes production, as marker of oxidative stress, and nitric oxide (NO), a powerful vasodilator and antioxidant molecule, were measured upon cell stimulation. The Steen solution significantly inhibited p47(phox) translocation and NOX2 activation in platelets and white cells. Consistent with this finding was the reduction of oxidative stress as documented by a significantly lowered formation of ROS and isoprostanes by both platelets and white cells. Finally, cell incubation with Steen solution resulted in enhanced generation of NO. Herewith, we provide the first evidence that Steen solution possesses antioxidant properties via downregulation of NADPH oxidase activity and enhanced production of NO.
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, 00161 Rome (RM), Italy.
Roberto
R
Carnevale
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina (LT), Italy.
Giuseppe
G
Biondi-Zoccai
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina (LT), Italy.
Mariangela
M
Peruzzi
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina (LT), Italy.
Elena
E
De Falco
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina (LT), Italy.
Isotta
I
Chimenti
Department of Thoracic Surgery, Sapienza University of Rome, 00161 Rome (RM), Italy ; Fondazione Eleonora Lorillard Spencer Cenci, 00185 Rome (RM), Italy.
Federico
F
Venuta
Department of Thoracic Surgery, Sapienza University of Rome, 00161 Rome (RM), Italy.
Marco
M
Anile
Department of Thoracic Surgery, Sapienza University of Rome, 00161 Rome (RM), Italy.
Daniele
D
Diso
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina (LT), Italy.
Elena
E
Cavarretta
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina (LT), Italy.
Antonino G M
AG
Marullo
Department of Heart and Great Vessels, Sapienza University of Rome, 00161 Rome (RM), Italy.
Patrizio
P
Sartini
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, 00161 Rome (RM), Italy.
Pasquale
P
Pignatelli
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, 00161 Rome (RM), Italy.
Francesco
F
Violi
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina (LT), Italy ; Department of AngioCardioNeurology, IRCCS NeuroMed, 86077 Pozzilli (IS), Italy.
Giacomo
G
Frati
D000098:Acetophenones / Q000494:pharmacology; D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003911:Dextrans / Q000494:pharmacology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D028421:Isoprostanes / Q000378:metabolism; D007552:Isotonic Solutions / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012709:Serum Albumin / Q000494:pharmacology*
D000098:Acetophenones; D000975:Antioxidants; D003911:Dextrans; D028421:Isoprostanes; D007552:Isotonic Solutions; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D012709:Serum Albumin; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; C056165:acetovanillone; D015237:Dinoprost; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1