Effects of nicotine and tobacco‐specific nitrosamines on hamster cheek pouch and gastric mucosa

Yp, Chen; Johnson, G. K.; Ca, Squier

doi:10.1111/j.1600-0714.1994.tb00054.x

Cited by 22 publications

(22 citation statements)

References 18 publications

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“…Predominant nicotine effects consist of: increase in heart rate and cardiac contractility (Franco-Cereceda et al, 1991;Benowitz et al, 2002;Pausova et al, 2003), increase in the blood pressure (Pausova et al; Ochiai et al), reduction of temperature skin (Plowchalk et al;Russell et al, 2004) and mobilization of the sugar in the blood (Gilbert et al, 2000). Reports about In vitro results shown: increase in the hormones synthesis and release (Seaman et al, 1977;Damaj, 2001;Wessler et al, 2003), activation of ERK (Chen et al, 1994;Szajerka & Kwiatkowska, 1997) and transcription nuclear factors (inflammatory factors as NFkB and AP-1) (Pennypacker et al; Pandey et al; Ueno et al), production of shock proteins Fig. 5.…”

Section: Discussionmentioning

confidence: 99%

Effects of Oral Nicotine on Rat Liver Stereology

2008

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SUMMARY:Nicotine is the more abundant component in cigarette smoke. Because nicotine is first metabolized in the liver, our aim was to investigate the effects of nicotine on this organ by biochemical and stereological methods. Male Wistar rats were treated with oral nicotine (ON) diluted in drinking water during 32 days. The control group was treated with drinking water in the same period. Rats were sacrificed 24 hours after last day, the blood was collected and the liver was removed. Lipidogram was performed by enzymatic method and collagen fibers, fat globules and hepatocytes were count in the liver by stereological methods. We observed in control group preserved hepatocytes, with no presence of inflammatory cells. However in the ON group was possible to observe varied size of hepatocytes with cloudy cellular limits and histoarchitecture loss. Capillaries were fully of red blood cells. We observed also an increase of fat globules with small size. We observed in leucogram a reduction of leukocytes number (lymphocytes, neutrophils and monocytes) in the ON group in comparison to control group. The lipidogram showed an increase of triglycerides and total cholesterol for ON group when compared to control group. Moreover, a reduction of HDL-cholesterol was observed in ON group when compared to control group. Numerical density of hepatocytes was lesser in ON group when compared to control group. We suggest harmful effects of oral nicotine in liver induced by toxic mechanism with reduction of hepatocytes number and disturbance in lipid metabolism.

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Section: Discussionmentioning

confidence: 99%

Effects of Oral Nicotine on Rat Liver Stereology

2008

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“…12, p. 1653, 2001 Copyright © 2001 1653 growth, motility, and differentiation (Heeschen et al, 2001). Although it has been reported that Nic directly affects OKC (Chen et al, 1994;Hall et al, 1984;Ringdahl et al, 1997), the kind of cellular alterations and the biochemical pathways mediating the effect of Nic remain unclear. Simultaneous exposure to Nic and hyperoxia causes tumors in hamsters, and antagonists of nAChRs inhibit this process (Schuller et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…Nic, acting through the nAChRs expressed by nonneuronal cells, has recently emerged as a candidate for the major pathogenic factor in tobacco-related morbidity because it exhibits a regulatory role in the biological processes which are intimately connected with each other, including cell growth, motility, and differentiation (Heeschen et al, 2001). Although it has been reported that Nic directly affects OKC (Chen et al, 1994;Hall et al, 1984;Ringdahl et al, 1997), the kind of cellular alterations and the biochemical pathways mediating the effect of Nic remain unclear. Simultaneous exposure to Nic and hyperoxia causes tumors in hamsters, and antagonists of nAChRs inhibit this process (Schuller et al, 1995).…”

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confidence: 99%

A Receptor-Mediated Mechanism of Nicotine Toxicity in Oral Keratinocytes

Arredondo

Nguyen

Chernyavsky

et al. 2001

Laboratory Investigation

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SUMMARY:Smoking and smokeless tobacco cause morbidity that originates from the epithelium lining of the skin and upper digestive tract. Oral keratinocytes (OKC) express nicotinic acetylcholine receptors (nAChRs) that bind nicotine (Nic). We studied the mechanism of the receptor-mediated toxicity of tobacco products on OKC. Preincubation of normal human OKC with Nic altered the ligand-binding kinetics of their nAChRs, suggesting that the nAChRs underwent structural changes. This hypothesis was confirmed by the finding that exposure of OKC to Nic causes transcriptional and translational changes. Through RT-PCR and immunoblotting, we found a 1.5-to 2.9-fold increase in the mRNA and protein levels of ␣3, ␣5, ␣7, ␤2, and ␤4 nAChR subunits. Exposure of OKC to Nic also changed the mRNA and protein levels of the cell cycle and cell differentiation markers Ki-67, PCNA, p21, cyclin D1, p53, filaggrin, loricrin, and cytokeratins 1 and 10. The nicotinic antagonist mecamylamine prevented these changes, which indicates that the Nic-induced changes in the expression of both the nAChR and the cell cycle and cell differentiation genes resulted from pharmacologic stimulation of nAChRs with Nic. To establish the relevance of these findings to the pathobiologic effects of tobacco products in vivo, we studied the above parameters in the oral tissue of rats and mice after their exposure for 3 weeks to environmental cigarette smoke or drinking water containing equivalent concentrations of Nic that are pathophysiologically relevant. The changes of the nAChRs and the cell cycle and cell differentiation genes were similar to those found in vitro. The results of indirect immunofluorescence assay of tissue specimens validated these findings. Thus, some pathobiologic effects of tobacco products in oral tissues may stem from Nic-induced alterations of the structure and function of keratinocyte nAChRs responsible for the physiologic regulation of the cell cycle by the cytotransmitter acetylcholine. (Lab Invest 2001, 81:1653-1668.T he epithelial cells lining human attached gingiva and the upper two-thirds portion of the esophagus have recently been shown to express cholinergic enzymes and receptors that mediate acetylcholine (ACh) signaling (Nguyen et al, 2000a(Nguyen et al, , 2000b. The cholinergic system of oral epithelium includes the synthesizing enzyme choline acetyltransferase, two molecular forms of the degrading enzyme acetylcholinesterase, the asymmetric and the globular forms, and two classes of ACh receptors, the nicotinic and the muscarinic receptors. The heteromeric nicotinic ACh receptor (nAChRs) channels on the cell membrane of oral keratinocytes (OKC) can be composed of ␣3, ␣5, ␤2, and ␤4 subunits, eg, ␣3␤2(␤4) Ϯ ␣5, and the homomeric channels can be made of several ␣7 or ␣9 subunits (Conti-Tronconi et al, 1994). The diversity of nAChRs expressed by OKC in the course of their development could allow a single cytotransmitter ACh to exert different effects on these cells at various stages of their development, which helps explai...

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“…3 It has also been reported that frequent nicotine exposure caused hyperkeratosis in the hamster cheek pouch. 4 NiQuitin CQ® Lozenges are NRT loz enges that come in 2 mg and 4 mg for mulations. They are kept in the mouth for up to 30 minutes and patients are instructed to take one lozenge every one to two hours, up to a maximum of 15 lozenges per day for six weeks.…”

Section: Discussionmentioning

confidence: 99%