R M Martinez1, V Fattori2, P Saito1, C B P Melo1, S M Borghi2, I C Pinto1, A J C Bussmann2, M M Baracat1, S R Georgetti1, W A Verri3, R Casagrande4. 1. Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina-UEL, Hospital Universitário, Avenida Robert Koch, 60, 86038-350 Londrina, Paraná, Brasil. 2. Departamento de Patologia, Universidade Estadual de Londrina-UEL, Rodovia Celso Garcia Cid, Km 380, PR445, Cx. Postal 10.011, 86057-970 Londrina, Paraná, Brasil. 3. Departamento de Patologia, Universidade Estadual de Londrina-UEL, Rodovia Celso Garcia Cid, Km 380, PR445, Cx. Postal 10.011, 86057-970 Londrina, Paraná, Brasil. Electronic address: waldiceujr@yahoo.com.br. 4. Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina-UEL, Hospital Universitário, Avenida Robert Koch, 60, 86038-350 Londrina, Paraná, Brasil. Electronic address: rubiacasa@yahoo.com.br.
Abstract
BACKGROUND: Lipoxin A4 (LXA4) is a metabolic product of arachidonic acid. Despite potent anti-inflammatory and pro-resolution activities, it remains to be determined if LXA4 has effect on ultraviolet (UV) radiation-induced skin inflammation. OBJECTIVE: To investigate the effects of systemic administration with LXA4 on UV radiation-induced inflammation and oxidative damage in the skin of mice. METHODS: Varied parameters of inflammation and oxidative stress in the skin of mice were evaluated after UV radiation (4.14 J/cm2). RESULTS: Pretreatment with LXA4 significantly inhibited UV radiation-induced skin edema and myeloperoxidase activity. LXA4 efficacy was enhanced by increasing the time of pre-treatment to up to 72 h. LXA4 reduced UV radiation-induced skin edema, neutrophil recruitment (myeloperoxidase activity and LysM-eGFP+ cells), MMP-9 activity, deposition of collagen fibers, epidermal thickness, sunburn cell counts, and production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-33). Depending on the time point, LXA4 increased the levels of anti-inflammatory cytokines (TGF-β and IL-10). LXA4 significantly attenuated UV radiation-induced oxidative damage returning the oxidative status to baseline levels in parameters such as ferric reducing ability, scavenging of free radicals, GSH levels, catalase activity and superoxide anion production. LXA4 also reduced UV radiation-induced gp91phox [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) subunit] mRNA expression and enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target enzyme nicotinamide adenine dinucleotide (phosphate) quinone oxidoreductase (Nqo1) mRNA expression. CONCLUSION: LXA4 inhibited UV radiation-induced skin inflammation by diminishing pro-inflammatory cytokine production and oxidative stress as well as inducing anti-inflammatory cytokines and Nrf2.
BACKGROUND:Lipoxin A4 (LXA4) is a metabolic product of arachidonic acid. Despite potent anti-inflammatory and pro-resolution activities, it remains to be determined if LXA4 has effect on ultraviolet (UV) radiation-induced skin inflammation. OBJECTIVE: To investigate the effects of systemic administration with LXA4 on UV radiation-induced inflammation and oxidative damage in the skin of mice. METHODS: Varied parameters of inflammation and oxidative stress in the skin of mice were evaluated after UV radiation (4.14 J/cm2). RESULTS: Pretreatment with LXA4 significantly inhibited UV radiation-induced skin edema and myeloperoxidase activity. LXA4 efficacy was enhanced by increasing the time of pre-treatment to up to 72 h. LXA4 reduced UV radiation-induced skin edema, neutrophil recruitment (myeloperoxidase activity and LysM-eGFP+ cells), MMP-9 activity, deposition of collagen fibers, epidermal thickness, sunburn cell counts, and production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-33). Depending on the time point, LXA4 increased the levels of anti-inflammatory cytokines (TGF-β and IL-10). LXA4 significantly attenuated UV radiation-induced oxidative damage returning the oxidative status to baseline levels in parameters such as ferric reducing ability, scavenging of free radicals, GSH levels, catalase activity and superoxide anion production. LXA4 also reduced UV radiation-induced gp91phox [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) subunit] mRNA expression and enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target enzyme nicotinamide adenine dinucleotide (phosphate) quinone oxidoreductase (Nqo1) mRNA expression. CONCLUSION:LXA4 inhibited UV radiation-induced skin inflammation by diminishing pro-inflammatory cytokine production and oxidative stress as well as inducing anti-inflammatory cytokines and Nrf2.
Authors: Renata M Martinez; Victor Fattori; Priscila Saito; Ingrid C Pinto; Camilla C A Rodrigues; Cristina P B Melo; Allan J C Bussmann; Larissa Staurengo-Ferrari; Julia Rojo Bezerra; Josiane A Vignoli; Marcela M Baracat; Sandra R Georgetti; Waldiceu A Verri; Rubia Casagrande Journal: Molecules Date: 2020-06-26 Impact factor: 4.411
Authors: Priscila Saito; Cristina P B Melo; Renata M Martinez; Victor Fattori; Talita L C Cezar; Ingrid C Pinto; Allan J C Bussmann; Josiane A Vignoli; Sandra R Georgetti; Marcela M Baracat; Waldiceu A Verri; Rubia Casagrande Journal: Front Pharmacol Date: 2018-10-31 Impact factor: 5.810
Authors: Larissa Staurengo-Ferrari; Stephanie Badaro-Garcia; Miriam S N Hohmann; Marília F Manchope; Tiago H Zaninelli; Rubia Casagrande; Waldiceu A Verri Journal: Front Pharmacol Date: 2019-01-11 Impact factor: 5.810