Side-Stream Cigarette Smoke Induces Dose–Response in Systemic Inflammatory Cytokine Production and Oxidative Stress

Abstract

Side-stream cigarette smoke (SSCS), a major component of secondhand smoke, induces reactive oxygen species, which promote oxidative damage in tissues and organs. Inflammatory cytokines play an important role in the pathogenesis of atherosclerosis and heart failure. The present 4-month study examined the effect of various chronic SSCS exposure levels on splenic inflammatory cytokine secretion, heart contractile function, and pathology at 60- and 120-min per day, 5 days per week, for a total of 16 weeks. Tissue vitamin E level and lipid peroxide production also were tested to estimate the oxidative stress. The study found that the pro-inflammatory cytokines, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β, significantly increased in 120-min SSCS-exposed mice. Decreased stroke volume and increased peripheral arterial resistance were observed in mice exposed to 120-min SSCS per day. Heart pathology was only found in 120-min SSCS-exposed mice. Cardiac and hepatic antioxidant vitamin E levels were decreased as a result of oxidative stress. Hepatic lipid peroxides were Increased upon 60-min SSCS exposure. The data also demonstrated that the cardiac α-tocopherol level has a strong correlation with stroke volume; splenic IL-1β has a strong negative correlation with stroke volume; splenic TNF-α has a very strong negative correlation with stroke volume. In conclusion, SSCS exposure induced systemic inflammatory responses. SSCS exposure also accentuated systemic lipid peroxidation with depletion of cardiac and hepatic antioxidant vitamin E level. Finally, SSCS exposure at 120 min per day decreased stroke volume and increased vascular resistance. Systemic IL-1 β and TNF-α production are responsible for heart contractile dysfunction. Free radicals may be responsible for the progression to heart contractile dysfunction induced, in part, by SSCS. Oxidized lipoprotein could contribute to the vascular functional changes. Exploring the mechanism of vascular dysfunction in mice is warranted. A more precise quantification of the smoking exposure dose in mice needs to be determined as well.

Effects of passive smoking on heart rate variability, heart rate and blood pressure: an observational study

“…In the experimental setting, chronic ETS exposure has been shown to increase proinflammatory cytokines and arterial resistance, to decrease concentrations of antioxidants and to increase lipid peroxidation. 30 We found no evidence of ETS-associated increases in inflammation as measured by CRP and other causal mechanisms may predominate with low-grade chronic exposure. Recent work by Bartoli and colleagues 31 suggests that particle exposures alter barometric reflexes, a pathway through which ETS exposure might also influence HRV.…”

p38 Mitogen-Activated Protein Kinase Mediates Sidestream Cigarette Smoke-Induced Endothelial Permeability

“…Thus, the chemicals in sidestream smoke extract may induce endothelial permeability through diverse signaling pathways. Exposure to second-hand smoke induces free radical generation (25,29), which could be a major cause of second-hand smoke-induced vascular injury. The oxidants can come directly from cigarette smoke and indirectly through activation of endogenous sources of free radicals, for example, NADPH oxidase (25,29).…”

Associations of Tumor Necrosis Factor G-308A with Childhood Asthma and Wheezing

“…Oxidative stress is intimately involved in multiple inflammation processes that are regulated in part by cytokines such as TNF (53,54). The TNF-308 A allele may alter gene expression and amplify the intensity of the inflammatory response to oxidants, leading to increased risk and severity of asthma and wheezing in susceptible groups.…”