Influence of Taurine on Cardiac Remodeling Induced by Tobacco Smoke Exposure

Background/Aims: To investigate the effect of taurine on cardiac remodeling induced by smoking. Methods: In the first step, rats were allocated into two groups: Group C (n=14): control; Group T (n=14): treated with taurine (3% in drinking water), for three months. In the second step, rats were allocated into two groups: Group ETS (n=9): rats exposed to tobacco smoke; Group ETS-T (n=9): rats exposed to tobacco smoke and treated with taurine for two months. Results: After three months, taurine presented no effects on morphological or functional variables of normal rats assessed by echocardiogram. on the other hand, after two months, ETS-T group presented higher LV wall thickness (ETS=1.30 (1.20-1.42); ETS-T=1.50 (1.40-1.50); p=0.029), E/A ratio (ETS=1.13 +/- 0.13; ETS-T=1.37 +/- 0.26; p=0.028), and isovolumetric relaxation time normalized for heart rate (ETS=53.9 +/- 4.33; ETS-T=72.5 +/- 12.0; p<0.001). The cardiac activity of the lactate dehydrogenase was higher in the ETS-T group (ETS=204 +/- 14 nmol/mg protein; ETS-T=232 +/- 12 nmol/mg protein; p<0.001). ETS-T group presented lower levels of phospholamban (ETS=1.00 +/- 0.13; ETS-T=0.82 +/- 0.06; p=0.026), phosphorylated phospholamban at Ser16 (ETS=1.00 +/- 0.14;ETS-T=0.63 +/- 0.10;p=0.003), and phosphorylated phosfolamban/phospholamban ratio (ETS=1.01 +/- 0.17; ETS-T=0.77 +/- 0.11; p=0.050). Conclusion: In normal rats, taurine produces no effects on cardiac morphological or functional variables. on the other hand, in rats exposed to cigarette smoke, taurine supplementation increases wall thickness and worsens diastolic function, associated with alterations in calcium handling protein and cardiac energy metabolism. Copyright (C) 2011 S. Karger AG, Basel

Aldosterone is not Involved in the Ventricular Remodeling Process Induced by Tobacco Smoke Exposure

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

β-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 β-carotene (BC), on ventricular remodeling and survival after myocardial infarction (Ml). 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 10O g were administered one of the treatments until they weighed 200 to 250 g (∼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. © 2005 American Society for Nutritional Sciences.

Influence of lisinopril on cardiac remodeling induced by tobacco smoke exposure

Background: To investigate the effect of lisinopril on cardiac remodeling induced by smoking. Material/Methods: Rats were allocated into 3 groups: group CON (n=8): control; group CSE (n=8): cigarette smoke exposure; group CSE-LIS (n=8): exposed to tobacco smoke and treated with lisinopril. Results: After 2 months, the tail systolic pressure was lower in CSE-LIS (CON=116 ±27 mm Hg, CSE=126±16, CSE-LIS=89±12; P<.001). CSE animals showed higher left ventricular systolic diameter (CON=8.25±2.16 mm/kg, CSE=11.5±1.3, CSE-LIS=9.27±2.00; P=.009) and myocyte cross-sectional area (CON=245±8 μm2, CSE=260±17, CSE-LIS=238±12; P=.01) than CON and CSE-LIS. The ejection fraction (CON =0.91±0.02, CSE=0.86±0.02, CSE-LIS=0.92±0.03; P=.002) and fractional shortening (CON=55.7±4.41%, CSE=48.7±3.43, CSE-LI=58.2±7.63; P=.006) were lower in CSE group than CON and CSE-LIS. CSE and CSE-LIS animals showed higher collagen amounts (CON=3.49±0.95%, CSE= 5.01±1.58, CSE-LIS=5.27±0.62; P=.009) than CON. CON group showed a higher connexin 43 amount in the intercalated disc (CON=3.70±0.38, CSE=2.13±0.53; CSE-LIS=2.17±0.73; P=.004) than CSE and CSE-LIS. There were no differences in IFN-g or TNF-a cardiac levels among the groups. Conclusions: Lisinopril attenuated both morphologic and functional abnormalities induced by exposure to tobacco smoke. In addition, this effect was associated with diminished blood pressure, but not alterations in connexin 43 distribution, cytokine production or collagen amount. © Med Sci Monit, 2010.

The Role of Lipotoxicity in Smoke Cardiomyopathy

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

ENVIRONMENTAL TOBACCO SMOKE INDUCES OXIDATIVE STRESS IN DISTINCT BRAIN REGIONS OF INFANT MICE

Environmental tobacco smoke (ETS) leads to the death of 600,000 nonsmokers annually and is associated with disturbances in antioxidant enzyme capacity in the adult rodent brain. However, little is known regarding the influence of ETS on brain development. The aim of this study was to determine levels of malonaldehyde (MDA) and 3-nitrotyrosine (3-NT), as well as enzymatic antioxidant activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), and superoxide dismutase (SOD), in distinct brain structures. BALB/c mice were exposed to ETS twice daily for 1 h from postnatal day 5 through postnatal day 18. Acute exposure was performed for 1 h on postnatal day 18. Mice were euthanized either immediately (0) or 3 h after the last exposure. Immediately after an acute exposure there were higher GR and GST activities and MDA levels in the hippocampus, higher GPx and SOD activities in the prefrontal cortex, and higher GST activity and MDA levels in the striatum and cerebellum. Three hours later there was an increase in SOD activity and MDA levels in the hippocampus and a decrease in the activity of all enzymes in the prefrontal cortex. Immediately after final repeated exposure there were elevated levels of GST and GR activity and decreased GPx activity in the hippocampus. Moreover, a rise was found in GPx and GST activities in the prefrontal cortex and increased GST and GPx activity in the striatum and cerebellum, respectively. After 3 h the prefrontal cortex showed elevated GR and GST activities, and the striatum displayed enhanced GST activity. Data showed that enzymatic antioxidant system in the central nervous system responds to ETS differently in different regions of the brain and that a form of adaptation occurs after several days of exposure.

ACETYL RADICAL IN TOBACCO SMOKE: DETECTION, QUANTIFICATION AND SIMULATION

Free radicals are present in cigarette smoke and can have a negative effect on human health by attacking lipids, nucleic acids, proteins and other biologically important species. However, because of the complexity of the tobacco smoke system and the dynamic nature of radicals, little is known about the identity of the radicals, and debate continues on the mechanisms by which those radicals are produced. In this study, acetyl radicals were trapped from the gas phase using 3-amino-2, 2, 5, 5- tetramethyl-proxyl (3AP) on solid support to form stable 3AP adducts for later analysis by high performance liquid chromatography (HPLC), mass spectrometry/tandem mass spectrometry (MS-MS/MS) and liquid chromatography- mass spectrometry (LC-MS). Simulations of acetyl radical generation were performed using Matlab and the Master Chemical Mechanism (MCM) programs. A range of 10- 150 nmol/cigarette of acetyl radical was measured from gas phase tobacco smoke of both commerial and research cigarettes under several different smoking conditions. More radicals were detected from the puff smoking method compared to continuous flow sampling. Approximately twice as many acetyl radicals were trapped when a GF/F particle filter was placed before the trapping zone. Computational simulations show that NO/NO2 reacts with isoprene, initiating chain reactions to produce a hydroxyl radical, which abstracts hydrogen from acetaldehyde to generate acetyl radical. With initial concentrations of NO, acetaldehyde, and isoprene in a real-world cigarette smoke scenario, these mechanisms can account for the full amount of acetyl radical detected experimentally. This study contributes to the overall understanding of the free radical generation in gas phase cigarette smoke.

Effects of cigarette smoking and exposure to cadmium and lead on phenotypic variability of hepatic CYP2A6 and renal function biomarkers in men

Effects of cigarette smoking and exposure to dietary cadmium (Cd) and lead (Pb) on urinary biomarkers of renal function and phenotypic variability of cytochrome P450 2A6 (CYP2A6) were investigated in a group of 96 healthy Thai men with mean age of 36.7 year (19-57 years). In non-smokers, Cd burden increased with age (r = 0.47, P < 0.001). In current smokers, Cd burden increased with both age (r = 0.45, P = 0.01) and number of cigarettes smoked per day (r = 0.32, P = 0.05). Cd-linked renal tubular dysfunction was seen in both smokers and non-smokers, but Pb-linked glomerular dysfunction was seen in smokers only, possibly due to more recent exposure to high levels of Cd and Pb, as reflected by 30-50% higher serum Cd and Pb levels in smokers than non-smokers (P < 0.05). Exposure to dietary Cd and Pb appeared to be associated with mild tubular dysfunction whereas dietary exposure plus cigarette smoking was associated with tubular plus glomerular dysfunction. Hepatic CYP2A6 activity in non-smokers showed a positive association with Cd burden (adjusted P = 0.38, P = 0.006), but it showed an inverse correlation with Pb (adjusted beta = -0.29, P = 0.003), suggesting opposing effects of Cd and Pb on hepatic CYP2A6 phenotype. In contrast, CYP2A6 activity in current smokers did not correlate with Cd or Pb, but it showed a positive correlation with serum ferritin levels (r = 0.45, P = 0.01). These finding suggest that Pb concentrations in the liver probably were too low to inhibit hepatic synthesis of heme and CYP2A6 and that the concurrent induction of hepatic CYP2A6 and ferritin was probably due to cigarette smoke constituents other than the Cd and Pb. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

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

INTRODUÇÃO E OBJETIVO: Sabe-se que o tabagismo pode provocar alterações cardiovasculares e redução na sensibilidade à insulina, e que o exercício físico melhora este quadro. O objetivo do estudo foi avaliar o efeito do tabagismo e da prática de atividade física sobre a sensibilidade à insulina em músculo cardíaco de ratos, através da avaliação de expressão do transportador de glicose GLUT4. MÉTODOS: Ratos machos Wistar foram divididos em quatro grupos: (CS) controle, (CE) controle exercitado, (FS) fumante sedentário e (FE) fumante submetido ao exercício físico. Os grupos FS e FE foram submetidos à combustão de quatro cigarros/30 min/60 dias, 2x/dia. Os grupos CE e FE executaram corrida em esteira rolante durante 60 min/60 dias. Foi realizado teste de tolerância à insulina, e a expressão de GLUT4 no coração foi feita através de Western Blotting - ECL e RT-PCR. Foi utilizado método estatístico descritivo e o teste ANOVA, e as diferenças entre os grupos foram consideradas significantes quando P < 0,05. RESULTADOS: Nem o tabagismo nem a atividade física alteraram o peso corpóreo (CS: 364,7 ± 9,7; CE: 372,4 ± 7,2, FS: 368,9 ± 6,7; FE: 376,4 ± 7,8g) e o peso do coração (CS: 1,12 ± 0,05; CE: 1,16 ± 0,04; FS: 1,14 ± 0,05; FE: 1,19 ± 0,05g). A sensibilidade à insulina foi reduzida no grupo fumante, porém, a prática de exercício físico melhorou este quadro (CS: 3,7 ± 0,3; CE: 5,28 ± 0,5*; FS: 2,1 ± 0,7*; FE: 4,8 ± 0,09** %/min; *P < 0,05 vs. CS, **P < 0,05 vs. FS). Os conteúdos de RNAm e de proteína não se alteraram entre os grupos. Porém, quando se calculou o conteúdo total de proteína GLUT4 por grama de tecido, observou-se que o tabagismo causou redução e que o exercício induziu aumento neste parâmetro (CS: 119,72 ± 9,98; CE: 143,09 ± 9,09; FS: 84,36 ± 10,99*; FE: 132,18 ± 11,40# UA/g tecido, *P < 0,05 vs. CS, #P < 0,01 vs. FS). CONCLUSÃO: Conclui-se que o tabagismo reduz a sensibilidade à insulina e a capacidade do coração captar glicose. Já a prática de exercício físico moderado reverte este quadro por completo.

Low-Level Laser Therapy on the Viability of Skin Flap in Rats Subjected to Deleterious Effect of Nicotine

Objective: The purpose of this study was to evaluate the effect of 830-nm laser in blocking the action of nicotine on the viability of skin flap. Background data: The authors have analyzed the deleterious effect of cigarette smoke or nicotine on the skin flap alone with evidence of increased skin necrosis in the flap. Materials and methods: Twenty-four Wistar-albino rats were divided into three groups of eight animals each: Group 1 (control), subjected to a surgical technique to obtain a flap for cranial base, laser irradiation simulation, and a subcutaneous injection of saline; Group 2, similar to Group 1, with subcutaneous injection of nicotine (2mg/kg/day) for a period of 1 week before and 1 week after surgery; and Group 3, similar to Group 2, with skin flaps subjected to a lambda 830-nm laser irradiation. The laser parameters used were: power 30 mW, beam area 0.07cm(2), irradiance 429 mW/cm(2), irradiation time 84 sec, total energy 2.52J, and energy density 36J/cm(2). The laser was used immediately after surgery and for 4 consecutive days, in one point at 2.5 cm of the flap cranial base. The areas of necrosis were examined by two macroscopic analyses: paper template and Mini-Mop (R). The pervious blood vessels were also counted. Results: The results were statistically analyzed by ANOVA and post-test contrast orthogonal method (multiple comparisons), showing that the laser decreased the area of necrosis in flaps subjected to nicotine, and consequently, increased the number of blood vessels (p < 0.05). Conclusions: The laser proved to be an effective way to decrease the area of necrosis in rats subjected to nicotine, making them similar to the control group.

Air pollution and antibodies against modified lipoproteins are associated with atherosclerosis and vascular remodeling in hyperlipemic mice

We analyzed the impact of chronic exposure to urban air pollution on the development of atherosclerosis. Hyperlipemic mice (LDLR(-/-)) were submitted to a high fat diet and air pollution for four months. We measured the susceptibility of LDL to oxidative modifications (TBARS), the presence of anti-oxLDL and an apoB-derived peptide (apoB-D) in blood and the degree of atherosclerosis in the aortic arch. Air pollution increased the susceptibility of LDL to oxidation as well as anti-oxLDL and anti-apo-B levels. These levels were even higher than in mice submitted to a high fat diet and non-polluted air. The lipid content of the atherosclerotic plaques in the aorta was increased in groups with a high cholesterol diet independently of the air quality. However, the thickness of the arterial wall was greater in mice fed a high lipid diet with polluted air. Thus, we conclude that urban air pollution exacerbates the susceptibility of LDL to oxidation, atherogenesis and vascular remodeling in hyperlipemic mice and that an immune response accompanies this process. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

CENTRAL N-ACETYLCYSTEINE EFFECTS ON BAROREFLEX IN JUVENILE SPONTANEOUSLY HYPERTENSIVE RATS

In this study, we evaluated the acute effects of central NAC administration on baroreflex in juvenile SHR and Wistar Kyoto (WKY) rats. Male SHR and WKY rats (8 10 weeks old) were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). The femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. After basal MAP and HR recordings, the baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 mu g/kg, bolus) and a depressor dose of sodium nitroprusside (SNP, 50 mu g/kg, bolus). Baroreflex was evaluated before, 5, 15, 30 and 60 minutes after NAC injection into the 4th V. Vehicle treatment did not change baroreflex responses in WKY and SHR. Central NAC slightly but significantly increased basal HR at 15 minutes and significantly reduced PHE-induced increase in MAP 30 and 60 minutes after NAC injection (p < 0.05) in WKY rats. In relation to SHR, NAC decreased HR range 15 and 30 minutes after its administration. In conclusion, acute NAC into the 4th V does not improve baroreflex in juvenile SHR.

Effects of Pentoxyfilline and Heparin on Reperfusion Injury Island Skin Flaps in Rats Exposed to Tobacco

Background. Ischemia-reperfusion injury is believed to be a major cause of transferred skin flap failure. Cigarette smoking is known to be associated with endogenous antioxidant depletion, hypercoagulability, and cutaneous vasoconstriction. This investigation was carried out to study possible effects of pentoxyfilline or heparin on rat skin reperfusion injury under tobacco exposure. Materials and Methods. Thirty-six rats were randomized into two major groups: 18 were exposed to cigarette smoke during a 4 wk period prior to surgery; the remaining 18 underwent a sham smoking procedure. Each group was further divided into three equal subgroups: heparin, pentoxyfilline, and saline solution. One identical skin flap was raised in each animal. The vasculature of the flap was clamped for 3 h and reperfused for 5 min. A venous blood sample was obtained from the flap after reperfusion for serum malondialdehyde (MDA) and myeloperoxidase (MPO) analysis. Flap survival was assessed 7 d after the procedure. Results. The lipid peroxidation levels and flap necrosis were significantly higher in the cigarette-smoking group skin flaps. There was also a decrease of MPO activity in this group compared with the nonsmoking group. Heparin-treated rats had significantly lower MDA levels and showed the most viable percent area among smoking rats. Conclusions. These data suggest that heparin had a significant beneficial effect both on flap survival and on the lipid peroxidation reduction after smoke exposure in the rat axial-pattern skin flap subjected to ischemia and reperfusion injury. Pharmacologic therapy may represent an alternative way to counteract tobacco effects in flap surgery in emergency situations. (C) 2010 Elsevier Inc. All rights reserved.

Influence of nicotine on healing process of autogenous bone block grafts in the mandible: A histomorphometric study in rats

Purpose: The aim of this study was to perform qualitative and quantitative analyses of the effect of nicotine on autogenous bone block grafts and to describe events in the initial healing phase and the differences in the repair processes between animals exposed to nicotine and controls. Materials and Methods: Forty-eight female Wistar rats were randomly divided into 2 groups, the nicotine group and the saline group. All animals received either nicotine (3 mg/kg) or saline 4 weeks before the surgical procedure and continued to receive nicotine from surgery to sacrifice at 7, 14, or 28 days. The autogenous bone block graft was harvested from the calvaria and stabilized on the external cortical area near the angle of the mandible. Results: The histologic analyses of the nicotine group depicted a delay in osteogenic activity at the bed-graft interface, as well as impairment of the organization of the granulation tissue that developed instead of blood clot. Nicotine-group specimens exhibited less bone neoformation, and the newly formed bone was poorly cellularized and vascularized. The histometric analysis revealed significantly less bone formation in the nicotine group at both 14 days (23.75% +/- 6.18% versus 51.31% +/- 8.31%) and 28 days (42.44% +/- 8.70% versus 73.00% +/- 4.99%). Conclusion: Nicotine did jeopardize the early healing process of autogenous bone block grafts in rats but did not prevent it.