Ivan Ana L M, Campanini Marcela Z, Martinez Renata M, Ferreira Vitor S, Steffen Vinicius S, Vicentini Fabiana T M C, Vilela Fernanda M P, Martins Frederico S, Zarpelon Ana C, Cunha Thiago M, Fonseca Maria J V, Baracat Marcela M, Georgetti Sandra R, Verri Waldiceu A, Casagrande Rúbia
Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina Londrina-UEL, Hospital Universitário, Avenida Robert Koch, 60, 86039-440 Londrina, Paraná, Brazil.
Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP, Av. do Café s/n, 14049-903 Ribeirão Preto, São Paulo, Brazil.
J Photochem Photobiol B. 2014 Sep 5;138:124-33. doi: 10.1016/j.jphotobiol.2014.05.010. Epub 2014 May 27.
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.
紫外线B（UVB）照射可能会导致氧化应激和炎症相关的皮肤癌以及皮肤过早老化。吡咯烷二硫代氨基甲酸盐（PDTC）是一种抗氧化剂，可抑制核因子-κB（NF-κB）的激活。在本研究中，通过无细胞氧化剂/抗氧化剂检测、对无毛小鼠进行体内UVB照射以及检测角质形成细胞中UVB诱导的NFκB激活，对PDTC的作用机制进行了研究。PDTC具有清除2,2'-联氮双（3-乙基苯并噻唑啉-6-磺酸）自由基（ABTS）、2,2-二苯基-1-苦基肼自由基（DPPH）和羟基自由基（OH）的能力；还能有效抑制铁依赖性和非铁依赖性脂质过氧化以及螯合铁。在体内，PDTC治疗显著减轻了UVB诱导的皮肤水肿、髓过氧化物酶（MPO）活性、促炎细胞因子白细胞介素-1β（IL-1β）和基质金属蛋白酶-9（MMP-9）的产生，通过铁还原抗氧化能力（FRAP）和ABTS检测发现皮肤中还原型谷胱甘肽（GSH）水平增加以及抗氧化能力增强。PDTC还减少了UVB诱导的角质形成细胞中IκB的降解。这些结果表明，PDTC在体外具有抗氧化和抗炎作用，这与PDTC抑制UVB照射诱导的小鼠皮肤炎症和氧化应激的作用相吻合。这些数据表明，PDTC治疗可能是减少UVB照射引起的皮肤损伤的一种有前景的方法，值得进一步进行临床前和临床研究。
