Acute Tobacco Smoke Exposure Research Articles

Acute tobacco smoke exposure exacerbates the inflammatory response to corneal wounds in mice via the sympathetic nervous system

Exposure to tobacco smoke is a major public health concern that can also affect ophthalmic health. Based on previous work demonstrating the important role of the sympathetic nervous system (SNS) in corneal wound repair, we postulated that acute tobacco smoke exposure (ATSE) may act through the SNS in the impairment of corneal wound repair. Here we find that ATSE rapidly increases the markers of inflammatory response in normal corneal limbi. After an abrasion injury, ATSE exaggerates inflammation, impairs wound repair, and enhances the expression of nuclear factor-κB (NF-κB) and inflammatory molecules such as interleukin-6 (IL-6) and IL-17. We find that chemical SNS sympathectomy, local adrenergic receptor antagonism, NF-κB1 inactivation, and IL-6/IL-17A neutralization can all independently attenuate ATSE-induced excessive inflammatory responses and alleviate their impairment of the healing process. These findings highlight that the SNS may represent a major molecular sensor and mediator of ATSE-induced inflammation.

The Effect of Nrf2 Knockout on Ocular Surface Protection from Acute Tobacco Smoke Exposure: Evidence from Nrf2 Knockout Mice

Ocular surface mucosa is the first-line ocular tissue to be exposed to environmental stress. We evaluated tear functions and keratoconjunctival epithelial alterations after sidestream cigarette smoke (SCS) exposure and tried to clarify the role of the transcription factor nuclear factor erythroid 2-related factor 2 (Nfe2l2, also known as Nrf2), on the ocular surface. In wild-type and Nrf2(-/-) mice, tear volume did not change after SCS exposure. Tear film breakup time (tear stability) in Nrf2(-/-) mice was significantly shorter than that in wild-type mice after SCS exposure. Vital staining scores, including fluorescein and Rose Bengal staining, showed significantly higher values in Nrf2(-/-) mice than in wild-type mice after SCS exposure. Excessive oxidative stress accumulation was detected in Nrf2(-/-) mice after SCS exposure using immunohistochemical analysis. Immunohistochemical analysis also revealed decreased mucin 1 (Muc1) and Muc5ac staining in Nrf2(-/-) mice after SCS exposure. mRNA expression levels of Muc1, Muc4, and Muc5ac and of SAM-pointed domain epithelial-specific transcription factor in Nrf2(-/-) mice were lower than those in wild-type mice after SCS exposure. Mean tear IL-6 concentrations increased significantly in Nrf2(-/-) mice after SCS exposure. In conclusion, SCS exposure induced decreased tear stability, ocular surface damage, and altered conjunctival phenotype in Nrf2(-/-) mice. Nrf2 could play an important role in protection of the ocular surface against SCS exposure.

Acute Tobacco Smoke Exposure Promotes Mitochondrial Permeability Transition in Rat Heart

Chronic exposure to tobacco smoke is known to impair mitochondrial function. However, the effect of acute tobacco smoke exposure (ATSE) in vivo, as might occur in social settings, on mitochondrial function and calcium handling of cardiac cells has not been examined. It was hypothesized that ATSE might adversely modify mitochondrial function as reflected in mitochondrial energetics, membrane potential, and calcium transport. Mitochondria were isolated from the hearts of adult rats either exposed to 6 h of environmental tobacco smoke (∼60 mg/mm3 tobacco smoke particles) or sham exposure. To model a calcium stress similar to ischemia/reperfusion, mitochondria were exposed to a Ca2+ bolus with measurement of membrane potential, energetics, Ca2+uptake and release, and redox state. ATSE mitochondria were characterized by significantly higher ADP-stimulated ATP production and a more reduced redox state (NADH ratio) under basal conditions without observed changes in resting Ψm. Exposure of ATSE mitochondria to Ca2+stress resulted in significantly more rapid depolarization of Ψm. The initial rate of Ca2+uptake was not altered in ATSE mitochondria, but CsA-sensitive Ca2+ release was significantly increased. ATSE does not significantly alter resting mitochondrial function. However, ATSE modifies the response of cardiac mitochondria to calcium stress, resulting in a more rapid depolarization and subsequent release of Ca2+ via the mitochondrial permeability transition (MPT). This research was supported by a Philip Morris External Research program grant. We thank Mike Goldsmith and Dale Uyeminami at the Center for Health and Environment for invaluable assistance in the smoke exposure experiments.

The use of horseradish peroxidase to demonstrate degenerate cells in rat larynx after acute tobacco smoke exposure

Horseradish peroxidase (HRP) was administered topically to laryngeal epithelia of rats exposed to tobacco smoke for a single 20-min period. The HRP demonstrated the distribution of degenerate and/or injured cells. These cells were specifically located in the ciliated epithelium in the ventrolateral region, at the base of the epiglottis.

The effect of acute tobacco smoke exposure on pulmonary benzo[ a]pyrene metabolism

The influence of whole tobacco smoke or the gas phase from smoke on the pulmonary metabolism of [ 14C]benzo[ a]pyrene was examined. [ 11C]Benzo[ a]pyrene disappears from plasma-perfusing isolated rabbit lungs according to first-order kinetics. When these lungs are ventilated with freshly generated whole cigarette smoke, the slope of [ 14C]benzo[ a]pyrene disappearance curves are altered dramatically; the amount of this alteration is dependent on the dose of smoke administered. If the particulate phase is filtered out of the smoke and the resulting gas phase is administered to the lung, relatively little effect is seen. These results suggest that the acute effect of whole smoke on benzo[ apyrene metabolism by the isolated perfused lung is inhibition and that this effect is primarily due to the materials present in the particulate phase of smoke.

Acute tobacco smoke exposure alters the profile of metabolites produced from benzo[ a]pyrene by the isolated perfused rabbit lung

The influence of whole tobacco smoke or the gas phase from smoke on the metabolism of [ 14 C]benzo[a] pyrene was e xamined using the isolated perfused rabbit lung model. Fresh whole tobacco smoke mixed with the air ventilating the perfused lung produces an immediate and dose related decrease in the metabolism of [ 14 C]benzo[a] pyrene . The metabolites of [ 14 C]benzo[a] pyrene , diols, quinones, phenols and polar compounds are generally decreased in quantity. At the lowest level of smoke administered the percentage of BP-7,8-diol produced is increased dramatically. The results indicate that one of the factors contributing to the carcinogenicity of tobacco smoke may be its ability to produce an immediate alteration in the pulmonary metabolism of polycyclic aromatic hydrocarbons.