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

Abstract：

: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.

journal_name

Chem Biol Interact

journal_title

Chemico-biological interactions

authors

Silva DAD,Correia TML,Pereira R,da Silva RAA,Augusto O,Queiroz RF

doi

10.1016/j.cbi.2020.109210

subject

Has Abstract

pub_date

2020-09-25 00:00:00

pages

109210

eissn

0009-2797

issn

1872-7786

pii

S0009-2797(20)30747-X

journal_volume

329

pub_type

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