4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone, a nicotine derivative, induces apoptosis of endothelial cells

Tithof, Patricia K.; Elgayyar, Mona; Schüller, Hildegard M.; Barnhill, M.A.; Andrews, R.D. Frances E.

doi:10.1152/ajpheart.2001.281.5.h1946

Cited by 40 publications

(25 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The HDL was decreased in ON when compared to control group. (Wang et al, 2006), induction of oxidative stress (Grattagliano et al, 2003;Senthilkumar et al;Perlemuter et al), apoptosis and chromosome aberrations (Tithof et al, 2001;Nakamoto et al;West et al;Wang et al, 2006). Our results suggest a clear action of nicotine on the liver and blood.…”

Section: Discussionsupporting

confidence: 54%

Effects of Oral Nicotine on Rat Liver Stereology

2008

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 54%

Effects of Oral Nicotine on Rat Liver Stereology

2008

View full text Add to dashboard Cite

show abstract

“…Oxidative stress generates reactive oxygen species that are known to induce cellular senescence and apoptosis (37,38). The tobacco carcinogen NNK has been reported to induce apoptosis, either through induction of reactive oxygen species (39) or through a mechanism that involves h-adrenergic-mediated release of arachidonic acid (40). Although the cancer cases had a higher frequency of apoptotic cells than did the controls, the induction of apoptosis by NNK was lower in cases than in controls, indicating the possibility of defective apoptotic machinery in the cases, thus allowing for the survival of damaged cells.…”

Section: Discussionmentioning

confidence: 99%

Cytokinesis-Blocked Micronucleus Cytome Assay Biomarkers Identify Lung Cancer Cases Amongst Smokers

El‐Zein

Fenech

Lopez

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

The multi-endpoint cytokinesis-blocked micronucleus assay is used for assessing chromosome aberrations. We have recently reported that this assay is extremely sensitive to genetic damage caused by the tobaccospecific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and that the binucleated cells with micronuclei, nucleoplasmic bridges, and nuclear buds in lymphocytes (chromosome damage endpoints measured by the assay) are strong predictors of lung cancer risk. In the current study, we refined our analysis to include toxicity endpoints (micronuclei in mononucleated cells, apoptosis, necrosis, and nuclear division index) to investigate the benefit of including these variables on improving the predictive value of the assay. Baseline and NNK-induced micronuclei in mononucleated cells were significantly higher in patients (n = 139) than controls (n = 130; P < 0.001). Baseline apoptosis was higher among cases; however, the controls showed a significant higher fold increase in NNK-induced apoptosis compared with baseline (P < 0.001). Principal components analysis was used to derive a summary measure for all endpoints and calculate the positive predictive value (PPV) and negative predictive value (NPV) for disease status. First principal component for NNK-induced chromosome damage endpoints (binucleated cells with micronuclei, nucleoplasmic bridges, and nuclear buds) had an area under the curve = 97.9 (95% confidence interval, 95.9-99.0), PPV = 94.8, and NPV = 92.6. The discriminatory power improved when micronuclei in mononucleated cells were included: area under the curve = 99.1 (95% confidence interval, 97.9-100.0), PPV = 98.7 and NPV = 95.6. The simplicity, rapidity, and sensitivity of the assay together with potential for automation make it a valuable tool for screening and prioritizing potential cases for intensive screening. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1111 -9)

show abstract

“…52,53 Practically all risk factors for atherosclerosis may cause in situ EC apoptosis, perhaps through activation of redox-sensitive pathways. [54][55][56] Apoptotic ECs in vitro have been found to have marked thrombotic potential, owing to redistribution of phosphatidylserine residues, activation of the TF cascade, 57 and potentiation of atherothrombosis. 52,53,58,59 Furthermore, the loss of ECs in the vessel wall reduces the generation of NO, with its proatherogenic consequences.…”

Section: Discussionmentioning

confidence: 99%

Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity

Rajagopalan

Somers

Brook

et al. 2004

Blood

228

168

View full text Add to dashboard Cite

Women with systemic lupus erythematosus (SLE) are at risk for premature atherothrombosis independent of Framingham risk factors. We investigated whether endothelial cell (EC) apoptosis predicts abnormal vasomotor tone and contributes to circulating tissue factor (TF) levels in this disease. Brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation were determined in women with SLE, healthy control subjects, and subjects with coronary artery disease (CAD) (n ‫؍‬ 43/ group). Quantification of circulating apoptotic ECs was performed by flow cytometry (CD146 ؉ cells that stained for Annexin V [CD146 AnnV؉ ]) and immunofluorescent microscopy. Plasma TF was measured by enzyme-linked immunosorbent assay (ELISA). Compared with healthy control and CAD subjects, patients with SLE had higher numbers of circulating CD146 AnnV؉ cells (10 ؎ 3, 18 ؎ 5, and 89 ؎ 32 cells/mL, respectively, mean ؎ SEM; P < .01). Increased CD146 AnnV؉ cells correlated strongly with abnormal vascular function (P ‫؍‬ .037). After adjusting for known predictors of endothelial function, CD146 AnnV؉ was the only variable that predicted FMD (␤ ‫؍‬ ؊4.5, P < .001). Increased CD146 AnnV؉ was strongly associated with elevated levels of circulating TF (r ‫؍‬ .46, P ‫؍‬ .002). Circulating apoptotic ECs are elevated in young women with SLE and strongly correlate with markedly abnormal vascular function and elevated TF levels. Heightened endothelial apoptosis may represent an important mechanism for development of atherothrombosis in SLE. (Blood.

show abstract

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone, a nicotine derivative, induces apoptosis of endothelial cells

Cited by 40 publications

References 36 publications

Effects of Oral Nicotine on Rat Liver Stereology

Effects of Oral Nicotine on Rat Liver Stereology

Cytokinesis-Blocked Micronucleus Cytome Assay Biomarkers Identify Lung Cancer Cases Amongst Smokers

Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity

Contact Info

Product

Resources

About