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

• Published in: Chemico-biological interactions 2020-09, Vol.329, p.109210-109210, Article 109210
• Main Authors: Silva, Danielba Almeida da, Correia, Thiago Macêdo Lopes, Pereira, Rafael, da Silva, Robson Amaro Augusto, Augusto, Ohara, Queiroz, Raphael Ferreira
• Format: Article
• Language: English
• Subjects: Acute inflammation; Chemotaxis; Cigarette smoke; Nrf2; Oxidative damage; Tempol
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2020.109210

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 carbonylation 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-1β and Il-17 to basal levels and of Tnf-α by approximately 50%. In contrast, tempol restored Il-10 and Tgf-β 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. [Display omitted] •Cigarette smoke exposure promotes inflammation and injury in lung parenchyma.•Leukocytes release inflammatory mediators under acutely cigarette smoke exposure.•Tempol attenuates inflammation and oxidative damage caused by cigarette smoke.•Tempol activates Nrf2 pathway and reduces chemotaxis into inflammatory site.