Inhibition of tobacco smoke-induced lung inflammation by a catalytic antioxidant 1 11The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily reflect the views and the policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

Smith, Kevin R.; Uyeminami, Dale; Kodavanti, Urmila P.; Crapo, James D.; Chang, Lingying; Pinkerton, Kent E.

doi:10.1016/s0891-5849(02)01003-1

Cited by 107 publications

(25 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pulmonary macrophage is a key regulator of respiratory immunity and plays an important role in particle-induced inflammation. Studies assessing effects of PM exposures, including urban and diesel exhaust, as well as cigarette smoke and crystalline silica, describe significant pulmonary inflammation (Archer et al, 2004; Das, 2003; Gowdy et al, 2008; Migliaccio et al, 2008; Smith et al, 2002). Typically this inflammation includes an influx of neutrophils as well as increases in soluble markers such as TNFα, IL-1β or total protein (Gowdy et al, 2008; Migliaccio et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Adverse effects of wood smoke PM_2.5exposure on macrophage functions

Migliaccio

Kobos

King

et al. 2013

Inhalation Toxicology

View full text Add to dashboard Cite

Epidemiological studies have shown a correlation between chronic biomass smoke exposure and increased respiratory infection. Pulmonary macrophages are instrumental in both the innate and the adaptive immune responses to respiratory infection. In the present study, in vitro systems were utilized where alveolar macrophages (AM) and bone marrow-derived macrophages (BMdM) were exposed to concentrated wood smoke-derived particulate matter (WS-PM) and mice were exposed in vivo to either concentrated WS-PM or inhaled WS. In vivo studies demonstrated that WS-exposed mice inoculated with Streptococcus pneumoniae had a higher bacterial load 24 h post-exposure, and corresponding AM were found to have decreased lymphocyte activation activity. Additionally, while classic markers of inflammation (cellular infiltration, total protein, neutrophils) were not affected, there were changes in pulmonary macrophages populations, including significant decreases in macrophages expressing markers of activation in WS-exposed mice. The lymphocyte activation activity of WS-PM-exposed AM was significantly suppressed, but the phagocytic activity appeared unchanged. In an effort to determine a pathway for WS-induced suppression, RelB activation, assessed by nuclear translocation, was observed in AM exposed to either inhaled WS or instilled WS-PM. Finally, an analysis of WS-PM fractions determined the presence of 4–5 polycyclic aromatic hydrocarbons (PAHs), and preliminary work suggests a potential role for these PAHs to alter macrophage functions. These studies show a decreased ability of WS-exposed pulmonary macrophages to effectively mount a defense against infection, the effect lasts at least a week post-exposure, and appears to be mediated via RelB activation.

show abstract

Section: Discussionmentioning

confidence: 99%

Adverse effects of wood smoke PM_2.5exposure on macrophage functions

Migliaccio

Kobos

King

et al. 2013

Inhalation Toxicology

View full text Add to dashboard Cite

show abstract

“…Smoking causes a local cytokine secretion in the lung, which leads to an infiltration of leukocytes into the airways and alveolar destruction. We have previously demonstrated the ability of a catalytic antioxidant AEOL 10150 to decrease tobacco smokeinduced inflammation in the lungs of rats, suggesting a role of oxygen radicals in the induction of proinflammatory cytokines and chemokines (17), possibly through oxidant-mediated activation of the redox-sensitive transcription factor, NF-B. However, inflammation induced by tobacco smoke was not resolved to baseline levels by treatment with the antioxidant, suggesting a role of additional mediators of inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously established a model of acute inflammation in the spontaneously hypertensive (SH) rat (17). We tested in this model whether inflammation associated with short-term exposure to tobacco smoke could be altered with the use of a sEH inhibitor, 12-(3-adamantane-1-yl-ureido)-dodecanoic acid n-butyl ester (AUDA-nBE), in the absence or presence of EETs.…”

mentioning

confidence: 99%

Attenuation of tobacco smoke-induced lung inflammation by treatment with a soluble epoxide hydrolase inhibitor

Smith

Pinkerton

Watanabe

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

161

137

View full text Add to dashboard Cite

Changes in the lungs due to smoking include inflammation, epithelial damage, and remodeling of the airways. Airway inflammation is likely to play a critical role in the genesis and progression of tobacco smoke-induced airway disease. Soluble epoxide hydrolase (sEH) is involved in the metabolism of endogenous chemical mediators that play an important role in inflammation. Epoxyeicosatrienoic acids (EETs) have demonstrated antiinflammatory properties, and hydrolysis of these epoxides by sEH is known to diminish this activity. To examine whether acute tobacco smokeinduced inflammation could be reduced by a sEH inhibitor, 12-(3-adamantane-1-yl-ureido)-dodecanoic acid n-butyl ester was given by daily s.c. injection to spontaneously hypertensive rats exposed to filtered air or tobacco smoke for a period of 3 days (6 h͞day). Acute exposure to tobacco smoke significantly increased by 3.2-fold (P < 0.05) the number of cells recovered by bronchoalveolar lavage. The sEH inhibitor significantly decreased total bronchoalveolar lavage cell number by 37% in tobacco smoke-exposed rats with significant reductions noted in neutrophils, alveolar macrophages, and lymphocytes. A combination of sEH inhibitor and EETs was more significant in its ability to further reduce tobacco smokeinduced inflammation compared with the sEH inhibitor alone. The sEH inhibitor led to a shift in some plasma epoxides and diols that are consistent with the hypothetical action of these compounds. We conclude that an sEH inhibitor, in the presence or absence of EETs, can attenuate, in part, inflammation associated with acute exposure to tobacco smoke. epoxyeicosatrienoic acids ͉ pulmonary ͉ antiinflammatory

show abstract

“…The first class includes several macrocyclic Mn(II)-pentaazamacrocyclic ligands, such as M40401, M40403, and M40419 [24–25]. Mn(III)-metaloporphyrins, such as AEOL-10113 and AEOL-10150 form the second class of SOD mimetics [26–27], and Mn(III)-salen complexes forms the third class. Since the ‘Salens’ are also reported to have catalase-like activity, they can therefore neutralize H 2 O 2 in the cells.…”

Section: Antioxidant Enzyme Mimetics and Spin Trapsmentioning

confidence: 99%

Pharmacological antioxidant strategies as therapeutic interventions for COPD

Rahman

2012

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

102

View full text Add to dashboard Cite

Cigarette/tobacco smoke/biomass fuel-induced oxidative and aldehyde/carbonyl stress are intimately associated with the progression and exacerbation of chronic obstructive pulmonary disease (COPD). Therefore, targeting systemic and local oxidative stress with antioxidants/redox modulating agents, or boosting the endogenous levels of antioxidants are likely to have beneficial effects in the treatment/management of COPD. Various antioxidant agents, such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine and N-acystelyn, erdosteine, fudosteine, ergothioneine, and carbocysteine), all have been reported to modulate various cellular and biochemical aspects of COPD. These antioxidants have been found to scavenge and detoxify free radicals and oxidants, regulate of glutathione biosynthesis, control nuclear factor-kappaB (NF-kappaB) activation, and hence inhibiting inflammatory gene expression. Synthetic molecules, such as specific spin traps like α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419, iNOS inhibitors, lipid peroxidation inhibitors/blockers edaravone, and lazaroids/tirilazad have also been shown to have beneficial effects by inhibiting the cigarette smoke-induced inflammatory responses and other carbonyl/oxidative stress-induced cellular alterations. A variety of oxidants, free radicals, and carbonyls/aldehydes are implicated in the pathogenesis of COPD, it is therefore, possible that therapeutic administration or supplementation of multiple antioxidants and/or boosting the endogenous levels of antioxidants will be beneficial in the treatment of COPD. This review discusses various novel pharmacological approaches adopted to enhance lung antioxidant levels, and various emerging beneficial and/or prophylactic effects of antioxidant therapeutics in halting or intervening the progression of COPD.

show abstract

Cited by 107 publications

References 44 publications

Adverse effects of wood smoke PM_2.5exposure on macrophage functions

Adverse effects of wood smoke PM_2.5exposure on macrophage functions

Attenuation of tobacco smoke-induced lung inflammation by treatment with a soluble epoxide hydrolase inhibitor

Pharmacological antioxidant strategies as therapeutic interventions for COPD

Contact Info

Product

Resources

About

Cited by 107 publications

References 44 publications

Adverse effects of wood smoke PM2.5exposure on macrophage functions

Adverse effects of wood smoke PM2.5exposure on macrophage functions

Attenuation of tobacco smoke-induced lung inflammation by treatment with a soluble epoxide hydrolase inhibitor

Pharmacological antioxidant strategies as therapeutic interventions for COPD

Contact Info

Product

Resources

About

Adverse effects of wood smoke PM_2.5exposure on macrophage functions

Adverse effects of wood smoke PM_2.5exposure on macrophage functions