Long-term effects of inhaled nicotine

Waldum, Helge L.; Nilsen, Odd G.; Nilsen, Turid; H, Rørvik; Syversen, Unni; Sandvik, Arne K.; Haugen, Øystein; Torp, Sverre Helge; Brenna, Eiliv

doi:10.1016/0024-3205(96)00100-2

Cited by 108 publications

(90 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Both intact and OVX rats administered nicotine weighed less than vehicle-treated controls. This is consistent with short-term (<4 weeks) [10,11] as well as long-term (2 years) [26,28] studies of rats administered nicotine at relatively high doses. Reduced food intake [21,22] and increased energy expenditure [lo] have been shown to contribute to weight loss or decreases in weight gain with nicotine administration.…”

Section: Discussionsupporting

confidence: 89%

Effects of nicotine on bone mass and strength in aged female rats

Akhter

Iwaniec

Haynatzki

et al. 2003

Journal Orthopaedic Research

View full text Add to dashboard Cite

This study investigated the effects of nicotine on bone mass and biomechanical properties in aged, estrogen-replete (shamoperated) and estrogen-deplete (ovariectomized) female rats. Eight month old, retired breeder, sham-operated and ovariectomized Sprague-Dawley rats were left untreated for 12 weeks to establish cancellous osteopenia in the ovariectomized group. The animals were then administered saline, low dose nicotine (6.0 mg/kg/day) or high dose nicotine (9.0 mg/kg/day) via osmotic minipumps for 12 weeks. Vertebrae and femora were collected at necropsy for determination of bone mass and strength. As expected, ovariectomy had a negative effect on most endpoints evaluated. Vertebral body bone mineral content (BMC) and density (BMD) and the structural (ultimate load and yield load) and material (ultimate stress, yield stress, and flexural modulus of elasticity) strength properties were lower in the OVX rats than in the sham-operated rats. Femoral diaphysis BMC, BMD, ultimate load, and flexural modulus were also lower in the OVX rats than in the sham-operated rats. The nicotine doses administered resulted in serum nicotine levels that averaged 1.54.5-fold greater than those observed in heavy smokers. Despite the high doses used, nicotine had no effect on vertebral BMC, BMD, or any of the structural and material strength properties in either the OVX or the Sham rats. In addition, nicotine had no effect on femoral diaphysis BMC, BMD, ultimate load, stiffness, ultimate stress, or flexural modulus. Femoral yield load and stress were lower in low dose nicotine-treated rats than in vehicle-treated rats. However, differences were not detected between the high dose nicotine-and vehicle-treated rats for either femoral yield load or stress. The results suggest that tobacco agents other than nicotine are responsible for the decreased bone density and increased fracture risk as observed in smokers.

show abstract

Section: Discussionsupporting

confidence: 89%

Effects of nicotine on bone mass and strength in aged female rats

Akhter

Iwaniec

Haynatzki

et al. 2003

Journal Orthopaedic Research

View full text Add to dashboard Cite

show abstract

“…This phenomenon was previously found in our guinea-pig model of chronic cigarette smoke exposure [1], and has recently also been found in rats exposed chronically to nicotine vapour [19]. In humans, there is a known relationship between lung function and somatic growth [20], and we have previously shown that both lung volumes and flow rates are related to weight in the guinea-pig model [3].…”

Section: Discussionmentioning

confidence: 69%

A longitudinal analysis of pulmonary function in rats during a 12 month cigarette smoke exposure

1997

View full text Add to dashboard Cite

A longitudinal analysis of pulmonary function in rats during a 12 month cigarette smoke exposure. J.L. Wright, J-P. Sun, S. Vedal. ERS Journals Ltd 1997. ABSTRACT: We wanted to examine the longitudinal effects of chronic cigarette smoke exposure, and to determine whether the chronic alterations in pulmonary function induced by long-term cigarette smoke exposure in an animal model could be predicted by initial or early alterations in function.A group of Sprague Dawley rats was exposed to the smoke of 7 cigarettes·day -1 for 5 days·week -1 during a total period of 12 months. Lung volume, flow-volume curves and pressure-volume curves were recorded at baseline, and after 2, 4, 8 and 12 months of smoke exposure. A control group of rats was subjected to the same regimen of testing, but was not exposed to smoke.Thirteen rats completed the study in the smoke-exposed group and seven rats in the control group. We found that chronic exposure to cigarette smoke produced early abnormalities in pulmonary function, with the forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio showing an acceleration of ageing effect, particularly between 4 and 8 months of exposure. In this model, although the two groups had significantly different airflow after 12 months, the initial values in each group were remarkably similar, and we could not identify any pulmonary function test which had predictive value.We conclude that longitudinal studies of cigarette smoke exposure in this rat model allow better characterization of the nature and time course of the effects of smoking on the lung. Eur Respir J 1997; 10: 1115-1119. In our laboratory, we have previously developed a guinea-pig model of cigarette smoke-induced alterations in pulmonary function [1,2]. Although this model has proved successful in that we have been able to show clear evidence of airflow obstruction and emphysematous lung destruction in smoke-exposed animals, it has also illustrated the problems inherent in such kinds of cross-sectional studies. In the guinea-pig, there was significant interanimal variation in pulmonary function, even when accounting for animal age and weight [3]. Furthermore, we found that our cross-sectional studies were biased by a "healthy smoker" effect, whereby the animals that were most affected by cigarette smoke tended to die before the end of the experiment; the final results were, thus, derived from the animals with the least disease [2,4]. Finally, the use of a single pulmonary function end-point does not allow for analysis of the temporal profile of the development of abnormalities, or for analysis of results that might predict response to cigarette smoke.It was for these reasons that, in the present study, a longitudinal study design was chosen, whereby each animal was used as its own control and function tests were performed at multiple time-points, thus making it possible to track each animal's function by calculating a percentage change from control values. This type of longitudinal analysis also had the advantage that...

show abstract

“…Other nicotine exposure studies in experimental animals also do not indicate that nicotine alone is tumorigenic (39)(40)(41). As a tumor promoter, however, nicotine has been reported to increase the frequency of tumors induced by agents other than NNK such as 7,12-dimethylbenz(a) anthracene (42), N-methyl-N 0 -nitro-N-nitrosoguanidine (43), and N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (44).…”

mentioning

confidence: 99%

Long-term Nicotine Replacement Therapy: Cancer Risk in Context

Shields

2011

Cancer Prevention Research

View full text Add to dashboard Cite

Nicotine replacement therapy (NRT) for up to 12 weeks is well established, safe and efficacious for fostering smoking cessation. Some smokers at a high risk of relapse may benefit from long-term use, and so long-term NRT safety and efficacy have become a paramount question for the FDA and others. Laboratory studies have indicated a carcinogenic potential of nicotine. Animal model studies reported in this issue of the journal by Maier and colleagues (beginning on page 1743) and Murphy and colleagues (beginning on page 1752), however, provide additional reassurance that NRT does not promote lung cancer. Very long-term studies of NRT effects do not yet exist and would be needed to definitively answer the question about NRT efficacy and cancer risk and some decision making will need to be made based on limited human data and experimental studies. The overall NRT safety question is complex and requires consideration of three contexts and comparator groups (long-term NRT/abstinence vs. smoking, long-term intermittent NRT/ reduced smoking vs. smoking, and long-term NRT/abstinence vs. abstinence without long-term NRT). Although the data on these issues are insufficient, the first comparison seems intuitive and may be compelling enough to allow the FDA to approve a long-term indication for NRT. An important public health goal is to help smokers and their health care providers understand the implications of potential long-term NRT risks in the context of its potential benefits and the far greater risks of continued smoking. Cancer Prev Res; 4(11); 1719-23. Ó2011 AACR.The efficacy and safety of short-term nicotine replacement therapy (NRT) for fostering long-term smoking cessation is well established, and up to 12 weeks of therapy is approved by the U.S. Food and Drug Administration (FDA; refs. 1-4). A meta-analysis indicates that there are measurable benefits in studies of 12 to 18 months of continued NRT use for relapse prevention (5), and other studies also indicate that this use is cost effective (6). An important question of considerable interest that remains today, however, is whether NRT can be recommended for long-term use, even years, to continue to promote smoking abstinence. The answer to this question requires both an efficacy and safety assessment. In this context, NRT conceptually has substantial benefits compared with long-term smoking but also, as explained later and addressed in this issue of the journal, laboratory studies suggest a potential for nicotine to foster the development of cancer.The premise of long-term NRT use is that it would prevent smoking relapse, and the risks would be limited to maintaining nicotine addiction, but without the adverse consequences of continued smoking, such as increased lung cancer risk. Like the consideration of other long-term medications, on face value it is a simple risk-benefits equation. In actuality, however, this question is not simple to answer because the risk can be considered in 3 different contexts and comparator groups namely: (i) what is the risk o...

show abstract

Long-term effects of inhaled nicotine

Cited by 108 publications

References 24 publications

Effects of nicotine on bone mass and strength in aged female rats

Effects of nicotine on bone mass and strength in aged female rats

A longitudinal analysis of pulmonary function in rats during a 12 month cigarette smoke exposure

Long-term Nicotine Replacement Therapy: Cancer Risk in Context

Contact Info

Product

Resources

About