Tempol reduces inflammation and oxidative damage in cigarette smoke-exposed mice by decreasing neutrophil infiltration and activating the Nrf2 pathway

Autor(es)

da Silva, Danielba Almeida ^[1] ; Correia, Thiago Macedo Lopes ^[2] ; Pereira, Rafael ^{[3, 2]} ; da Silva, Robson Amaro Augusto ^[2] ; Augusto, Ohara ^[4] ; Queiroz, Raphael Ferreira ^{[1, 3, 5]}

Afiliação do(s) autor(es)

^[1] Univ Fed Bahia, Programa Posgrad Biociencias, Campus Anisio Teixeira, Vitoria Da Conquista - Brazil

^[2] Univ Fed Bahia, Programa Multictr Ciencias Fisiol, Campus Anisio Teixeira, Vitoria Da Conquista - Brazil

^[3] Univ Estadual Sudoeste Bahia, Programa Multictr Bioquim & Biol Mol, Vitoria Da Conquista - Brazil

^[4] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo - Brazil

^[5] Univ Estadual Sudoeste Bahia, Dept Ciencias Nat, Estr Bem Querer, Km 4, BR-45031900 Vitoria Da Conquista, BA - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Chemico-Biological Interactions; v. 329, SEP 25 2020.
• Citações Web of Science: 0

Resumo

Cigarette smoke is a complex mixture capable of triggering inflammation and oxidative damage in animals at pulmonary and systemic levels. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) reduces tissue injury associated with inflammation in vivo by mechanisms that are not completely understood. Here we evaluated the effect of tempol on inflammation and oxidative damage induced by acute exposure to cigarette smoke in vivo. Male C57BL/6 mice (n = 32) were divided into 4 groups (n = 8 each): 1) control group exposed to ambient air (GC), 2) animals exposed to cigarette smoke for 5 days (CSG), mice treated 3) prior or 4) concomitantly with tempol (50 mg/kg/day) and exposed to cigarette smoke for 5 days. The results showed that the total number of leukocytes and neutrophils increased in the respiratory tract and lung parenchyma of mice exposed to cigarette smoke. Likewise, MPO levels and activity as well as lipid peroxidation and lung protein nitration and carbon-ylation also increased. Administration of tempol before or during exposure to cigarette smoke inhibited all the above parameters. Tempol also reduced the pulmonary expression of the inflammatory cytokines Il-6, Il-1 beta and Il17 to basal levels and of Tnf-alpha by approximately 50%. In contrast, tempol restored Il-10 and Tgf-beta levels and enhanced the expression of Nrf2-associated genes, such as Ho-1 and Gpx2. Accordingly, total GPx activity increased in lung homogenates of tempol-treated animals. Taken together, our results show that tempol protects mouse lungs from inflammation and oxidative damage resulting from exposure to cigarette smoke, likely through reduction of leukocyte infiltration and increased transcription of some of the Nrf2-controlled genes. (AU)

• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs