Metabolic profile and genotoxicity in obese rats exposed to cigarette smoke

Objective Experimental studies have shown that exposure to cigarette smoke has negative effects on lipid metabolism and oxidative stress status. Cigarette smoke exposure in nonpregnant and pregnant rats causes significant genotoxicity (DNA damage). However, no previous studies have directly evaluated the effects of obesity or the association between obesity and cigarette smoke exposure on genotoxicity. Therefore, the aim of the present investigation was to evaluate DNA damage levels, oxidative stress status and lipid profiles in obese Wistar rats exposed to cigarette smoke. Design and Methods Female rats subcutaneously (sc) received a monosodium glutamate solution or vehicle (control) during the neonatal period to induce obesity. The rats were randomly distributed into three experimental groups: control, obese exposed to filtered air, and obese exposed to tobacco cigarette smoke. After a 2-month exposure period, the rats were anesthetized and killed to obtain blood samples for genotoxicity, lipid profile, and oxidative stress status analyses. Results The obese rats exposed to tobacco cigarette smoke presented higher DNA damage, triglycerides, total cholesterol, free fatty acids, VLDL-c, HDL-c, and LDL-c levels compared to control and obese rats exposed to filtered air. Both obese groups showed reduced SOD activity. These results showed that cigarette smoke enhanced the effects of obesity. Conclusion In conclusion, the association between obesity and cigarette smoke exposure exacerbated the genotoxicity, negatively impacted the biochemical profile and antioxidant defenses and caused early glucose intolerance. Thus, the changes caused by cigarette smoke exposure can trigger the earlier onset of metabolic disorders associated with obesity, such as diabetes and metabolic syndrome. Copyright © 2012 The Obesity Society.

Morphologic and biomechanical changes of thoracic and abdominal aorta in a rat model of cigarette smoke exposure

Background: Smoking is the most relevant environmental factor that affects the development of aortic aneurysm. Smokers have elevated levels of elastase activity in the arterial wall, which leads to weakening of the aorta. The aim of this study was to verify whether cigarette smoke exposure itself is capable of altering the aortic wall. Methods: Forty-eight Wistar rats were divided into 2-, 4-, and 6-month experimental periods and into 2 groups: smokers (submitted to smoke exposure at a rate of 40 cigarettes/day) and nonsmokers. At the end of the experimental periods, the aortas were removed and cross-sectioned to obtain histologic specimens for light microscopic and morphometric analyses. The remaining longitudinal segments were stretched to rupture and mechanical parameters were determined. Results: A degenerative process (i.e., a reduction in elastic fibers, the loss of lamellar arrangement, and a reduction of smooth muscle cells) was observed, and this effect was proportional in intensity to the period of tobacco exposure. We observed a progressive reduction in the yield point of the thoracic aorta over time (P < 0.05). There was a decrease in stiffness (P < 0.05) and in failure load (P < 0.05) at 6 months in the abdominal aorta of rats in the smoking group. Conclusions: Chronic exposure to tobacco smoke can affect the mechanical properties of the aorta and can also provoke substantial structural changes of the arterial wall. © 2013 Elsevier Inc. All rights reserved.

A new experimental model of cigarette smoke-induced emphysema in Wistar rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Scanning Electron Microscopy of the Tongue, Pharynx, and Larynx of Rats Exposed to Cigarette Smoke

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cardiovascular Responses Induced by Catalase Inhibitior into the Fourth Cerebral Ventricle is Changed in Wistar Rats Exposed to Sidestream Cigarette Smoke

Objectives: This experimental study aimed to evaluate the effects of central catalase inhibition on cardiovascular responses in rats exposed to sidestream cigarette smoke (SSCS) for 3 weeks. Methodology: A total of 20 males Wistar rats (320–370g) were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4thV). Femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. Rats were exposed to SSCS for three weeks, 180 minutes per day, 5 days/week [carbon monoxide (CO): 100–300 ppm)]. Baroreflex was tested with one pressor dose of phenylephrine (PHE, 8 μg/kg, bolus) and one depressor dose of sodium nitroprusside (SNP, 50 μg/kg, bolus). Cardiovascular responses were evaluated before and 15 minutes after 3-amino-1, 2, 4-triazole (ATZ, catalase inhibitor, 0.001g/100μL) injection into the 4th V. Results: Vehicle treatment into the 4th V did not change cardiovascular responses. Central catalase inhibition increased tachycardic peak, attenuated bradycardic peak and reduced HR range at 15 minutes, increased MAP at 5, 15 and 30 min and increased HR at 5 and 15 min. In rats exposed to SSCS, central ATZ increased basal MAP after 5 min and increased HR at 5, 15 and 30 minutes, respectively, and attenuated bradycardic peak at 15 minutes. Conclusion: This study suggests that brain oxidative stress caused by SSCS influences autonomic regulation of the cardiovascular system.

Treatment of periodontal disease with an Er,Cr:YSGG laser in rats exposed to cigarette smoke inhalation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Respiratory immunohistochemical study in rats exposed to cigarette smoke and alcohol

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Nanoparticles increase the efficacy of cancer chemopreventive agents in cells exposed to cigarette smoke condensate

Lung cancer is a leading cause of death in developed countries. Although smoking cessation is a primary strategy for preventing lung cancer, former smokers remain at high risk of cancer. Accordingly, there is a need to increase the efficacy of lung cancer prevention. Poor bioavailability is the main factor limiting the efficacy of chemopreventive agents. The aim of this study was to increase the efficacy of cancer chemopreventive agents by using lipid nanoparticles (NPs) as a carrier. This study evaluated the ability of lipid NPs to modify the pharmacodynamics of chemopreventive agents including N-acetyl-L-cysteine, phenethyl isothiocyanate and resveratrol (RES). The chemopreventive efficacy of these drugs was determined by evaluating their abilities to counteract cytotoxic damage (DNA fragmentation) induced by cigarette smoke condensate (CSC) and to activate protective apoptosis (annexin-V cytofluorimetric staining) in bronchial epithelial cells both in vitro and in ex vivo experiment in mice. NPs decreased the toxicity of RES and increased its ability to counteract CSC cytotoxicity. NPs significantly increased the ability of phenethyl isothiocyanate to attenuate CSC-induced DNA fragmentation at the highest tested dose. In contrast, this potentiating effect was observed at all tested doses of RES, NPs dramatically increasing RES-induced apoptosis in CSC-treated cells. These results provide evidence that NPs are highly effective at increasing the efficacy of lipophilic drugs (RES) but are not effective towards hydrophilic agents (N-acetyl-L-cysteine), which already possess remarkable bioavailability. Intermediate effects were observed for phenethyl isothiocyanate. These findings are relevant to the identification of cancer chemopreventive agents that would benefit from lipid NP delivery.

Influência do tabagismo passivo associado ao exercício físico realizado por ratas durante prenhez e lactação, sobre o desenvolvimento dos filhotes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito imediato e a curto prazo do cigarro sobre o transporte mucociliar nasal de fumadores

Background and objectives: The efficiency of mucociliary transport may vary in different conditions, such as in exposure to harmful particles of the cigarette smoke. The present study evaluated the acute and short term effects of smoking on nasal mucociliary clearance in current smokers by the quantification of the Saccharin Transit Time (STT), and to investigate its correlation with the history of tobacco consumption.Methods: Nineteen current smokers (11 men, 51 +/- 16 years; BMI 23 +/- 9 kg/m(2), 27 +/- 11 cigarettes per day, 44 +/- 25 pack-years), entering a smoking cessation intervention program, responded to a questionnaire concerning smoking history and were submitted to lung function assessment (spirometry) and the STT test. STT was assessed immediately after smoking and 8 hours after smoking. The STT test was also performed in nineteen matched healthy non-smokers' who served as control group.Results: When compared to STT in non-smokers' (10 +/- 4 min; mean +/- standard deviation), smokers presented similar STT immediately after smoking (11 +/- 6 min; p = 0.87) and slower SIT 8 hours after smoking (16 +/- 6 min; p = 0.005 versus non-smokers' and p = 0.003 versus immediately after smoking). STT 8 hours after smoking correlated positively with age (r = 0.59; p = 0.007), cigarettes per day (r = 0.53; p = 0.02) and pack-years index (r = 0.74; p = 0.0003).Conclusions: In smokers, although the mucociliary clearance immediately after smoking is similar to non-smokers', eight hours after smoking it is reduced, and this reduction is closely related to the smoking habits. (C) 2010 Sociedade Portuguesa de Pneumologia. Published by Elsevier Espana, S.L. All rights reserved.

Mucociliary clearance and its relation with the level of physical activity in daily life in healthy smokers and nonsmokers

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

O exercício físico melhora a sensibilidade à insulina de ratos expostos à fumaça de cigarro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos do exercício aeróbio no músculo esquelético de ratos expostos à fumaça de cigarro

INTRODUÇÃO: Os fumantes sofrem redução da massa muscular e da resistência à fadiga e possivelmente a prática de atividade física contribua positivamente neste quadro. OBJETIVO: Este estudo teve por objetivo analisar as adaptações da musculatura esquelética frente à interação da prática de atividade física e exposição à fumaça de cigarro. MÉTODOS: 32 ratos machos foram divididos em grupos expostos à fumaça de cigarro, exercitados (G1) e sedentários (G3), e não expostos à fumaça, exercitados (G2) e sedentários (G4). A exposição à fumaça foi realizada mediante combustão de 10 cigarros em uma câmara de inalação durante 30 minutos, duas vezes ao dia, cinco dias por semana, durante 15 dias; o exercício aeróbio foi composto por sessões diárias de 60 minutos de caminhada em esteira, cinco dias por semana. Após o sacrifício, o músculo sóleo foi coletado e seus cortes foram corados pela técnica de HE e submetidos ao método histoquímico NADH-TR. RESULTADOS: O grupo G1 apresentou maior quantidade de alterações musculares, bem como ausência de atividade enzimática, o mesmo ocorrendo no G3, porém com menor intensidade; no G2 foi observado padrão normal para fibras exercitadas, estando as fibras do G4 preservadas. Quanto à morfometria, houve diferença significante para o fator exercício (p = 0,007), enquanto não foram observadas diferenças significantes para o fator exposição à fumaça (p = 0,668) e para a interação exposição à fumaça e exercício (p = 0,077). CONCLUSÃO: A interação entre inalação de fumaça de cigarro e exercício, realizada durante 15 dias em ratos machos Wistar adultos, acentuou as alterações histológicas do músculo sóleo, levando a uma alteração da atividade enzimática e acarretando em aumento do diâmetro das fibras musculares

beta-carotene attenuates the paradoxical effect of tobacco smoke on the mortality of rats after experimental myocardial infarction

The objective of this study was to investigate the effects of exposure to tobacco smoke (ETS) in rats that were or were not supplemented with dietary beta-carotene (BC), on ventricular remodeling and survival after myocardial infarction (MI). Rats (n = 189) were allocated to 4 groups: the control group, n = 45; group BC administered 500 mg/kg diet, n = 49, BC supplemented rats; group ETS, n = 55, rats exposed to tobacco smoke; and group BC+ETS, n = 40. Wistar rats weighing 100 g were administered one of the treatments until they weighed 200 to 250 g (similar to 5 wk). The ETS rats were exposed to cigarette smoke for 30 min 4 times/d, in a chamber connected to a smoking device. After reaching a weight of 200-250 g, rats were subjected to experimental MI (coronary artery occlusion) and mortality rates were determined over the next 105 d. In addition, echocardiographic, isolated heart, morphometrical, and biochemical studies were performed. Mortality data were tested using Kaplan-Meyer curves and other data by 2-way ANOVA. Survival rates were greater in the ETS group (58.2%) than in the control (33.3%) (P = 0.001) and BC+ETS rats (30.0%) (P = 0.007). The groups did not differ in the other comparisons. Left ventricular end-diastolic diameter normalized to body weight was greater and maximal systolic pressures were lower in the ETS groups than in non-ETS groups. Previous exposure to tobacco smoke induced a process of cardiac remodeling after MI. There is a paradoxical protector effect with tobacco smoke exposure, characterized by lower mortality, which is offset by BC supplementation.

Padrão de remodelação e função ventricular em ratos expostos à fumaça do cigarro

FUNDAMENTO: A relevância do padrão de remodelação no modelo de ratos expostos à fumaça do cigarro não é conhecida. OBJETIVO: Analisar a presença de diferentes padrões de remodelação nesse modelo e sua relação com a função ventricular. MÉTODOS: Ratos fumantes (n=47) foram divididos de acordo com o padrão de geometria, analisado pelo ecocardiograma: normal (índice de massa normal e espessura relativa normal), remodelação concêntrica (índice de massa normal e espessura relativa aumentada), hipertrofia concêntrica (índice de massa aumentado e espessura relativa aumentada) e hipertrofia excêntrica (índice de massa aumentado e espessura relativa normal). RESULTADOS: Os ratos fumantes apresentaram um dos quatro padrões de geometria: padrão normal, 51%; hipertrofia excêntrica:,32%; hipertrofia concêntrica, 13% e remodelação concêntrica, 4%. Os grupos normal e hipertrofia excêntrica apresentaram menores valores de fração de ejeção e porcentagem de encurtamento que o grupo hipertrofia concêntrica. Treze animais (28%) apresentaram disfunção sistólica, detectada pela fração de ejeção e pela porcentagem de encurtamento. Na análise de regressão univariada, os padrões de geometria e o índice de massa não foram fator de predição de disfunção ventricular (p>0,05). Por outro lado, o aumento da espessura relativa da parede foi fator de predição de disfunção ventricular na análise univariada (p<0,001) e na análise multivariada, após ajuste para o índice de massa (p=0,003). CONCLUSÃO: Ratos expostos à fumaça do cigarro apresentam um dos quatro diferentes padrões de remodelação. Entre as variáveis geométricas analisadas, somente o aumento da espessura relativa da parede do ventrículo esquerdo foi fator de predição de disfunção ventricular nesse modelo.