13-Week inhalation toxicity study of menthol cigarette smoke

Gaworski, Charles L.; Dozier, M. M.; Gerhart, James M.; Rajendran, N.; Brennecke, Lucas H.; Aranyi, Catherine; Heck, J. Daniel

doi:10.1016/s0278-6915(97)00033-1

Cited by 62 publications

(30 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cotinine levels in serum are dose dependent and increase when the number of cigarettes smoked increases. Higher cotinine levels in the sera correlates with a heavier exposure to cigarette smoke [36][37][38]. These data support the conclusion that using our methods, treatment with CSE results in a heavier exposure to cigarette smoke components over the same treatment length.…”

Section: Cse Exposure Increases Inflammatory Cell Bronchiolitissupporting

confidence: 84%

Differential in Vivo Effects of Whole Cigarette Smoke Exposure Versus Cigarette Smoke Extract on Mouse Ciliated Tracheal Epithelium

Elliott

Sisson

West

et al. 2006

Experimental Lung Research

View full text Add to dashboard Cite

In this study the authors compared the affect of vapor phase cigarette smoke (CS) versus cigarette smoke extract (CSE) on the lungs and upper airway of C57BL/6 mice. The authors found that CSE treatment significantly increased neutrophil influx (P < .001), baseline ciliary beat frequency (CBF) (P < .05), and protein kinase C activity compared to CS and controls. Isoproterenol increased CBF with CS exposure, but decreased CBF with CSE (P < .01). Isoproterenol increased protein kinase A (PKA) activity in all groups except CSE. CSE exposure induced inflammatory cell bronchiolitis. These data indicate that CSE exposure has differential effects on the lungs and tracheal epithelium compared to CS exposure.Ciliary motility provides the driving force for mucociliary clearance. Normal function of the airway mucociliary clearance system prevents the attachment and colonization of pulmonary pathogens in the upper airways. Mucociliary dysfunction caused by impaired ciliary motility results in mucus accumulation, airway obstruction, and bacterial colonization, increasing the likelihood of infection in the lower airway [1][2][3]. Mucociliary clearance is affected by exposure to a number of environmental agents [4,5], including cigarette smoke. Exposure to cigarette smoke (CS) has been linked to the development of lung cancer, emphysema, chronic bronchitis, and chronic obstructive pulmonary disease (COPD) [6]. Smokers are at a higher risk for pulmonary infection [7]. Chronic exposure to tobacco smoke is associated with increased ciliary abnormality [8] and reduced mucociliary clearance [9]. The increased risk for infection seen in smokers may be due to alterations in ciliary function in the upper airway.Several studies have revealed that ciliary activity is controlled by phosphorylation of axonemal proteins [10][11][12]. Protein kinase C (PKC) and cyclic adenosine monophosphate (CAMP)-Address correspondence to Todd A. Wyatt, PhD, University of Nebraska Medical Center, 985300 Nebraska Medical Center, Omaha, NE 68198-5300, USA. E-mail: twyatt@unmc.edu. NIH Public Access Author ManuscriptExp Lung Res. Author manuscript; available in PMC 2007 November 21. Published in final edited form as:Exp Lung Res. 2006 ; 32(3-4): 99-118. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript dependent protein kinase (PKA) are important regulators of airway ciliary beat frequency (CBF). Agents that increase PKC are associated with decreased CBF [13][14][15]. Alternatively, agents associated with increased CBF also increase PKA activity [16]. In past studies, we have shown that exposure of ciliated epithelial cells to cigarette smoke extract (CSE) in culture and whole cigarette smoke in vivo induces an increase in epithelial cell PKC activity [15,[17][18][19]. Many animal models of exposure to cigarette smoke components exist. Most recently, Miller and colleagues have developed a method of exposure consisting of intranasal administration of CSE [20]. This method was shown to induce an inflammatory response similar to ...

show abstract

Section: Cse Exposure Increases Inflammatory Cell Bronchiolitissupporting

confidence: 84%

Differential in Vivo Effects of Whole Cigarette Smoke Exposure Versus Cigarette Smoke Extract on Mouse Ciliated Tracheal Epithelium

Elliott

Sisson

West

et al. 2006

Experimental Lung Research

View full text Add to dashboard Cite

show abstract

“…In humans, the dissociation of carboxyhemoglobin when breathing air results in a half-life of ϳ4 -6 h; animal data are not available, although COHb levels rapidly decline after smoke cessation (43). A serum cotinine level of 200 -250 ng/ml is equivalent to a mild to moderate human cigarette smoker (31,43,103,127).…”

Section: Cigarette Smoke Exposure Model Of Copdmentioning

confidence: 99%

Animal models of chronic obstructive pulmonary disease

Wright¹,

Cosio²,

Churg³

2008

American Journal of Physiology-Lung Cellular and Molecular Phys

379

326

View full text Add to dashboard Cite

-The mechanisms involved in the genesis of chronic obstructive pulmonary disease (COPD) are poorly defined. This area is complicated and difficult to model because COPD consists of four separate anatomic lesions (emphysema, small airway remodeling, pulmonary hypertension, and chronic bronchitis) and a functional lesion, acute exacerbation; moreover, the disease in humans develops over decades. This review discusses the various animal models that have been used to attempt to recreate human COPD and the advantages and disadvantages of each. None of the models reproduces the exact changes seen in humans, but cigarette smoke-induced disease appears to come the closest, and genetically modified animals also, in some instances, shed light on processes that appear to play a role. chronic obstructive pulmonary disease CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) is an increasingly important cause of morbidity and mortality. COPD is now the fifth leading cause of death worldwide (109), and recent estimates suggest that the prevalence is as high as 9 -10% of adults over age 40 (38, 131). In the developed world, cigarette smoking is by far the most important risk factor for COPD. Exposure to air pollution particles, occupational exposures to dusts and fumes (39), and, in the developing world, exposure to biomass fuels used for cooking is also believed to be etiological agents of COPD (38).There are few animal models of COPD related to air pollution particles, dusts and fumes, and biomass fuels; most COPD models have either used cigarette smoke or other approaches, including genetic modifications to mice, believed to reproduce some of the mechanisms behind cigarette smoke. We have recently reviewed mechanistic studies of smoke-exposed animal models (16). In this paper, we will focus on the pros and cons of different COPD animal models.The first question to ask in this context is what would constitute a perfect model of human COPD. This is not a simple question because human COPD consists of at least four anatomic lesions (further defined below): emphysema, small airway remodeling (including goblet cell metaplasia), chronic bronchitis, and pulmonary hypertension; a given patient may have any or all of these lesions. In addition, COPD patients may develop acute exacerbations that are believed to have an infectious basis. To further complicate matters, no matter which lesions are present, COPD develops and is slowly progressive over many years.Because COPD is closely related to the underlying anatomy of the lung, a good animal model should have pulmonary anatomy similar to that of humans. The fundamental mechanisms behind COPD should be similar in animal models and humans. The ideal model would allow the investigator to produce the various different anatomic lesions just listed, all in a short period of time. Unfortunately, all of the known animal models meet only some of the above criteria, and even another human would probably not meet all of them, because, as noted above, there is considerable human to human variation in th...

show abstract

“…Nr-COH; neutral red uptake cytoxicity assay with COH cells; SCE-COH: sister chromatid exchange assay in Chinese hamster ovary cells. Table 2 shows that the impact of tobacco additives on cigarette mainstream smoke toxicity was investigated through in vitro mutagenicity (Ames test) and mammalian cytotoxicity (Neutral red uptake) assays 29,30,31 , and in vivo sub-chronic (90 day) inhalation toxicity studies with rats 31,32,33,34 . In addition to these investigations (Table 2), a sub-chronic toxicity (26-week) study tested smoke condensates from cigarettes with and without tobacco additives for tumor promoting activity in the two-stage carcinogenicity test on mouse back skin 35 .…”

Section: S46mentioning

confidence: 99%