title: Pyrrolidine dithiocarbamate inhibits UVB-induced skin inflammation and oxidative stress in hairless mice and exhibits antioxidant activity in vitro.
abstract: Ultraviolet B (UVB) irradiation may cause oxidative stress- and inflammation-dependent skin cancer and premature aging. Pyrrolidine dithiocarbamate (PDTC) is an antioxidant and inhibits nuclear factor-κB (NF-κB) activation. In the present study, the mechanisms of PDTC were investigated in cell free oxidant/antioxidant assays, in vivo UVB irradiation in hairless mice and UVB-induced NFκB activation in keratinocytes. PDTC presented the ability to scavenge 2,2'-azinobis-(3-ethyl benzothiazoline-6-sulfonic acid) radical (ABTS), 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH) and hydroxyl radical (OH); and also efficiently inhibited iron-dependent and -independent lipid peroxidation as well as chelated iron. In vivo, PDTC treatment significantly decreased UVB-induced skin edema, myeloperoxidase (MPO) activity, production of the proinflammatory cytokine interleukin-1β (IL-1β), matrix metalloproteinase-9 (MMP-9), increase of reduced glutathione (GSH) levels and antioxidant capacity of the skin tested by the ferric reducing antioxidant power (FRAP) and ABTS assays. PDTC also reduced UVB-induced IκB degradation in keratinocytes. These results demonstrate that PDTC presents antioxidant and anti-inflammatory effects in vitro, which line up well with the PDTC inhibition of UVB irradiation-induced skin inflammation and oxidative stress in mice. These data suggest that treatment with PDTC may be a promising approach to reduce UVB irradiation-induced skin damages and merits further pre-clinical and clinical studies.
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina Londrina-UEL, Hospital Universitário, Avenida Robert Koch, 60, 86039-440 Londrina, Paraná, Brazil. Electronic address: analauraivan@hotmail.com.
authors.forename: Ana L M
authors.initials: AL
authors.lastname: Ivan
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina Londrina-UEL, Hospital Universitário, Avenida Robert Koch, 60, 86039-440 Londrina, Paraná, Brazil. Electronic address: marcelazbm@hotmail.com.
authors.forename: Marcela Z
authors.initials: MZ
authors.lastname: Campanini
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina Londrina-UEL, Hospital Universitário, Avenida Robert Koch, 60, 86039-440 Londrina, Paraná, Brazil. Electronic address: renatafarma_55@yahoo.com.br.
authors.forename: Renata M
authors.initials: RM
authors.lastname: Martinez
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina Londrina-UEL, Hospital Universitário, Avenida Robert Koch, 60, 86039-440 Londrina, Paraná, Brazil. Electronic address: vsottero@hotmail.com.
authors.forename: Vitor S
authors.initials: VS
authors.lastname: Ferreira
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina Londrina-UEL, Hospital Universitário, Avenida Robert Koch, 60, 86039-440 Londrina, Paraná, Brazil. Electronic address: vsteffen@gmail.com.
authors.forename: Vinicius S
authors.initials: VS
authors.lastname: Steffen
authors.affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP, Av. do Café s/n, 14049-903 Ribeirão Preto, São Paulo, Brazil. Electronic address: fabianatmcv@hotmail.com.
authors.forename: Fabiana T M C
authors.initials: FT
authors.lastname: Vicentini
authors.affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP, Av. do Café s/n, 14049-903 Ribeirão Preto, São Paulo, Brazil. Electronic address: nandajm@fcfrp.usp.br.
authors.forename: Fernanda M P
authors.initials: FM
authors.lastname: Vilela
authors.affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP, Av. do Café s/n, 14049-903 Ribeirão Preto, São Paulo, Brazil. Electronic address: fsmfarmacia@hotmail.com.
authors.forename: Frederico S
authors.initials: FS
authors.lastname: Martins
authors.affiliation: Departamento de Patologia, Universidade Estadual de Londrina-UEL, Rod. Celso Garcia Cid, Km 380, PR 445, Cx. Posta 10.001, 86057-970 Londrina, Paraná, Brazil. Electronic address: ana.zarpelon@hotmail.com.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Zarpelon
authors.affiliation: Departamento de Farmacologia, Faculdade de Medicina de Ribeirao Preto-USP, Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, São Paulo, Brazil. Electronic address: thicunha@usp.br.
authors.forename: Thiago M
authors.initials: TM
authors.lastname: Cunha
authors.affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP, Av. do Café s/n, 14049-903 Ribeirão Preto, São Paulo, Brazil. Electronic address: magika@fcfrp.usp.br.
authors.forename: Maria J V
authors.initials: MJ
authors.lastname: Fonseca
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina Londrina-UEL, Hospital Universitário, Avenida Robert Koch, 60, 86039-440 Londrina, Paraná, Brazil. Electronic address: baracat1903@yahoo.com.br.
authors.forename: Marcela M
authors.initials: MM
authors.lastname: Baracat
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina Londrina-UEL, Hospital Universitário, Avenida Robert Koch, 60, 86039-440 Londrina, Paraná, Brazil. Electronic address: sangeorgetti@gmail.com.
authors.forename: Sandra R
authors.initials: SR
authors.lastname: Georgetti
authors.affiliation: Departamento de Patologia, Universidade Estadual de Londrina-UEL, Rod. Celso Garcia Cid, Km 380, PR 445, Cx. Posta 10.001, 86057-970 Londrina, Paraná, Brazil. Electronic address: waldiceujr@yahoo.com.br.
authors.forename: Waldiceu A
authors.initials: WA
authors.lastname: Verri
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina Londrina-UEL, Hospital Universitário, Avenida Robert Koch, 60, 86039-440 Londrina, Paraná, Brazil. Electronic address: rubiacasa@yahoo.com.br.
authors.forename: Rúbia
authors.initials: R
authors.lastname: Casagrande
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004487:Edema / Q000209:etiology*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D009195:Peroxidase / Q000378:metabolism; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*; D012867:Skin / Q000528:radiation effects*; D013859:Thiocarbamates / Q000737:chemistry / Q000494:pharmacology*; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D009195:Peroxidase; D020780:Matrix Metalloproteinase 9; D005978:Glutathione
keywords: Antioxidant activity; Free radical; Inflammation; Oxidative stress; PDTC; UVB irradiation