title: Efficacy and safety of S-acyl glutathione 2% cream vs. placebo against UVB-induced erythema: a randomized, double-blinded clinical trial.
abstract: BACKGROUND
  Reactive oxygen species have a major role in the UV-induced short- and long-term damage, thus the exogenous supplementation of antioxidant molecules may allow better skin protection. Despite glutathione has pivotal properties in the complex cytoplasmic antioxidant system, its supplementation is hampered by limited transmembrane absorption. Modification of glutathione pharmacokinetic properties via acetylation with long-chain polyunsaturated fatty acid may improve its passage through phospholipidic membranes.
  
  
  METHODS
  This was a single center randomized double-blinded clinical trial, versus placebo, cross-sectional pairwise at time 0. The participants were 10 healthy volunteers with skin phototypes II or III and age ≥18 years interested in performing minimal erythema dose (MED) evaluation performed by photoallergology unit of Division of Dermatology at P. Palagi Hospital, in Florence. Each volunteer underwent UVB phototesting, treating four different areas with increasing UVB doses in four different conditions. One arm was treated as standard procedure (naïve arm), one applying linolenic-glutathione conjugate (Lin-GSH) cream 2% before irradiation (pre-Lin-GSH arm), one with placebo (placebo arm) and one applying Lin-GSH cream 2% (SoloSale Srl, Florence, Italy) after irradiation (post-Lin-GSH arm). The main endpoint was to evaluate efficacy of Lin-GSH cream 2% before UVB irradiation compared with placebo. A secondary endpoint was the evaluation of the same cream applied after irradiation compared to no treatment. Another secondary objective is the evaluation of safety in both conditions. Mean MED was evaluated at distinct conditions. Safety was evaluated reporting all grade 3-4 adverse events up to 30 days after treatment. All volunteers were treated in all four experimental conditions. The pre-Lin-GSH and placebo arms were applied in a double-blind condition for each volunteer. Neither the volunteer nor the investigator executing MED evaluation knew which arm was given Lin-GSH and which one placebo.
  
  
  RESULTS
  Ten volunteers among 12 recruited for the study were correctly randomized and completed all study evaluations. Recruitment went from April 1st, 2016 to May 1st, 2016, up to adequate population number. Mean MED in pre-Lin-GSH arm was superior to mean MED in placebo arm (135±5.53 mJ/cm2 vs. 105±7.64 mJ/cm2, P=0.0003). No difference was observed among mean MED in post-Lin-GSH and naïve arms. No grade 3-4 adverse events were reported.
  
  
  CONCLUSIONS
  Lin-GSH 2% cream seems a safe and effective in producing a significant increase in MED compared with placebo thanks to its antioxidant properties.
authors.affiliation: Unit of Dermatology, Department of Surgery and Translational Medicine, P. Palagi Hospital, University of Florence, Florence, Italy - vieri.grandi@unifi.it.
authors.forename: Vieri
authors.initials: V
authors.lastname: Grandi
authors.affiliation: Unit of Dermatology, Department of Surgery and Translational Medicine, P. Palagi Hospital, University of Florence, Florence, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Milanesi
authors.affiliation: L. Donatelli Section of Pharmacology, Department of Experimental Medicine, L. Vanvitelli University of Campania, Naples, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sessa
authors.affiliation: Unit of Dermatology, Department of Surgery and Translational Medicine, P. Palagi Hospital, University of Florence, Florence, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Gola
authors.affiliation: Unit of Dermatology, Department of Surgery and Translational Medicine, P. Palagi Hospital, University of Florence, Florence, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Cappugi
authors.affiliation: Unit of Dermatology, Department of Surgery and Translational Medicine, P. Palagi Hospital, University of Florence, Florence, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Pimpinelli
mesh_terms: D000107:Acetylation; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D004890:Erythema / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D005978:Glutathione / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism; D063465:Skin Cream; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D005978:Glutathione