Effects of prenatal nicotine exposure on enamel formation of offspring mice / 中华口腔医学杂志

Objective: To investigate the effects of nicotine on the morphology, structure of offspring's dental germ, enamel organ and other dental tissues and the further potential epigenetic mechanisms by establishing prenatal nicotine exposure mouse model. Methods: Ten C57BL/6 pregnant mice were randomly divided into control group (physiological saline subcutaneous injection) and prenatal nicotine exposure (PNE) group (nicotine subcutaneous injection) by using a random number table. Postnatal day 0 (P0), postnatal day 14 (P14) and postnatal day 25 (P25) offspring mice were collected for subsequent experiments. The offspring mice were divided into offspring control group and offspring PNE group according to the maternal group respectively. Weights of P0 and P25 offspring mice were recorded. Micro-CT, scanning electron microscope (SEM) and Vickers hardness test were performed to analyze the related parameters of hard tissues including alveolar bones and mandibular incisors. Total RNAs were extracted from mandible tissues and the third generation of dental epithelial stem cells (DESC) in P25 mice. The relative expression levels of osteogenic and ameloblastic differentiation related genes were measured by real-time quantitative PCR (RT-qPCR). Immunohistochemical stainings of paraffin sections were then performed to observe the distribution and expression level of proliferating cell nuclear antigen (Pcna), amelogenin (Amelx), histone H3 trimethylated at lysine 27 (H3K27me3) and enhancer of zeste homolog 2 (Ezh2). Cell counting kit-8 (CCK-8) assays were used to detect the cell viabilities of DESCs after administrations of different concentrations of nicotine (0.01, 0.1, 1 mmol/L) and GSK126 (an inhibitor of histone methyltransferase Ezh2). Results: Compared with the control group, pregnant mice in PNE group were more likely to have adverse pregnancy outcomes, such as significantly lower offspring body weight [P0: offspring control (1.20±0.04) g, offspring PNE (0.99±0.02) g, P<0.001; P25: offspring control (15.26±1.70) g, offspring PNE (9.65±1.32) g, P<0.001] and increased stillbirths rate [offspring control (0), offspring PNE (46.40±9.30) %, P<0.001]. At P14 and P25, the distance parameters between the enamel mineralized deposits of mandibular incisors and the mesial surface of the first molar in offspring PNE group [P14: (-1 349±45) μm; P25: (-1 192±147) μm] was significantly decreased compared with the control group [P14: (-506±380) μm, P25: (504±198) μm] (P<0.05, P<0.001). The enamel column and enamel column stroma of incisors in offspring PNE group were blurred, arranged loosely and disorderly than those in the control group, while the microhardness of incisor enamel in offspring PNE group [(245.7±18.4) MPa] was significantly lower compared to the control group [(371.9±28.7) MPa] (P<0.001). HE staining showed disordered pre-ameloblast (Pre-Am) arrangement and delayed mineralization deposition point in offspring PNE group compared with the control group, while the length of transit-amplifying cell (TA) and Pre-Am region were prolonged as well. Immunohistochemical staining results displayed that the overall Pcna (P<0.05), H3K27me3 (P<0.01), Ezh2 (P<0.01) expression of labial cervical loop (LaCL) in PNE group were increased, while the positive signal of Amelx in ameloblast cytoplasm was impaired. In vitro, the addition of 1 mmol/L nicotine could significantly upregulate the expression level of Pcna (P<0.01) and downregulate the expression levels of B lymphoma Mo-MLV insertion region 1 (P<0.05), leucine rich repeats and immunoglobulin like domains 1 (P<0.05), Amelx (P<0.01). In addition, 1 mmol/L nicotine could also significantly enhance the proliferation activity of DESCs (P<0.001). Addition of 10 μmol/L GSK126, could rescue the proliferation activation effect of 1 mmol/L nicotine on DESCs. Conclusions: PNE may delay the process of enamel formation and lineage differentiation, leading to the abnormal proliferation of DESCs and changes of epigenetic modification state in H3K27me3, which affect the development of enamel in offspring mice,suggesting PNE might be one of risk environmental factor for tooth development.

Protective effect of omega 3 and vitamin D in preventing lung-tissue damage of newborn rats exposed to cigarette smoke during intrauterine period / Efecto protector de omega 3 y vitamina D en la prevención del daño en el tejido pulmonar de ratas recién nacidas expuestas al humo del cigarrillo durante el período intrauterino

SUMMARY: This study aimed to investigate the toxic effects of cigarette smoke exposure on lung and the protective role of Omega 3 and Vitamin D against these toxic effects biochemically and histologically. 28 pregnant Wistar Albino rats were divided into four groups. The first group was control group; the second group was exposed to smoke of 10 cigarette by puff device 2 hours/day after pregnancy; the third group was exposed to cigarette smoke together with Omega 3 (0.5 mg/kg/day) and the fourth group was exposed to cigarette smoke together with vitamin D (42 microgram/kg/day). Finally, lung tissue sections of the newborn rats were stained with Hemotoxilen eosine and Masson tricromite. Malondialdehyde (MDA) and Fluorescent Oxidation Products (FOU) levels were measured. Fetal weights and the number of fetuses were significantly lower in the group received only cigarette smoke (both p<0.001). Histopathologically, pulmonary volume, number of developed alveols and parenchyma elasticity decreased significantly, meanwhile interstitial tissue increased, elastin and collagen did not develop adequately. Histopathologic changes significantly decreased in the group given Omega 3 and Vitamin D. Statistically, MDA and FOU levels were found to be higher in the group exposed to cigarette smoke compared to the control group, and MDA and FOU levels were lower in the group given Omega 3 along with cigarette smoke (p<0.001). Cigarette smoke caused histologically significant damage to fetal lung tissue, oxidative stress and increased MDA and FOU levels. This damage was significantly reduced with Omega 3 and Vitamine D supplementation. Omega 3 is an important antioxidant; vitamin D has no significant antioxidant effect.

RESUMEN: Este estudio tuvo como objetivo investigar los efectos tóxicos de la exposición al humo de cigarrillo en el pulmón, y el papel protector de Omega 3 y la Vitamina D contra esos efectos. 28 ratas Wistar albino preñadas fueron separadas en cuatro grupos. El primer grupo grupo control; el segundo grupo estuvo expuesto al humo de 10 cigarrillos por dispositivo de inhalación 2 horas / día después de la preñez; el tercer grupo se expuso al humo del cigarrillo junto con Omega 3 (0,5 mg / kg / día) y el cuarto grupo se expuso al humo del cigarrillo junto con vitamina D (42 microgramos / kg / día). Secciones de tejido pulmonar de las ratas recién nacidas se tiñeron con Hematoxilina Eosina y tricrómico de Masson. Se midieron los niveles de malondialdehído (MDA) y productos de oxidación fluorescente (POF). Los pesos fetales y el número de fetos fueron significativamente más bajos en el grupo que recibió solamente humo de cigarrillo (ambos p <0,001). Histopatológicamente, el volumen pulmonar, el número de alveolos desarrollados y la elasticidad del parénquima disminuyeron significativamente; mientras que el tejido intersticial aumentó y la elastina y el colágeno no se desarrollaron adecuadamente. Los cambios histopatológicos disminuyeron significativamente en el grupo que recibió Omega 3 y Vitamina D. Estadísticamente, se encontró que los niveles de MDA y POF eran más altos en el grupo expuesto al humo de cigarrillo en comparación con el grupo control, además los niveles de MDA y POF fueron más bajos en el grupo que recibió Omega 3 junto con el humo del cigarrillo (p <0,001). El humo del cigarrillo causó daños histológicamente significativos en el tejido pulmonar fetal, el estrés oxidativo y el aumento de los niveles de MDA y FOU. Este daño se redujo significativamente con los suplementos de Omega 3 y Vitamina D. El omega 3 es un importante antioxidante; la vitamina D no tiene ningún efecto antioxidante significativo.

Protective effect of curcumin against nicotine-induced damage on reproductive parameters in male mice / Efecto protector de la curcumina contra el daño inducido por la nicotina sobre los parámetros reproductivos en ratones machos

Nicotine consumption can decrease fertility drive in males through inducing oxidative stress and DNA damage. The color of turmeric is because of a substance called curcumin for which some anti-oxidative and anti-inflammatory properties have been identified. In this study, various doses of curcumin (10, 30 and 60 mg/kg) and curcumin plus nicotine (10, 30 and 60 mg/kg) were administered intraperitoneally to male mice for 28 consequent days and reproductive parameters were determined. The results indicated that nicotine administration (0.5 mg/kg) significantly decreased testosterone level, count and motility of sperms, and testis weight compared to control group. However, increasing the dose of curcumin significantly increased reproductive indices in most of the groups. Thus, it seems that curcumin inhibits nicotine-induced adverse effects on reproductive parameters.

El consumo de nicotina puede disminuir la fertilidad en los hombres mediante la inducción de estrés oxidativo y daño del ADN. El color de la cúrcuma se debe a una sustancia llamada curcumina en la cual se han identificado algunas propiedades anti-oxidantes y anti-inflamatorias. En este estudio se administraron diferentes dosis de curcumina (10, 30 y 60 mg/kg) y de curcumina más nicotina (10, 30 y 60 mg/kg) por vía intraperitoneal a ratones machos durante 28 días consecutivos y se determinaron los parámetros reproductivos. La administración de nicotina (0,5 mg/kg) disminuyó significativamente el nivel de testosterona, el número y motilidad de los espermatozoides, y peso de los testículos en comparación con el grupo control. Sin embargo, el incremento de la dosis de curcumina aumentó significativamente los índices reproductivos en la mayoría de los grupos. Este estudio sugiere que la curcumina inhibe los efectos adversos inducidos por la nicotina sobre los parámetros reproductivos.

A susceptibilidade à nicotina e etanol é afetada pela exposição à nicotina, fumaça de cigarro e etanol durante o período gestacional: alterações comportamentais e eletrofisiológicas no período pós-natal de camundongos / The susceptibility to nicotine and ethanol is affected by exposure to nicotine, cigarette smoke and ethanol during pregnancy: behavioral and electrophysiological changes in the postnatal period in mice

Uma questão particularmente relevante é o fato de exposições precoces a drogas de abuso durante o desenvolvimento potencialmente aumentarem a susceptibilidade a estas drogas posteriormente durante o desenvolvimento. No presente estudo utilizando estudos comportamentais e eletrofisiológicos, investigamos efeitos tardios da exposição de camundongos à fumaça de cigarro, à nicotina e ao etanol durante o período que corresponde à gestação em humanos. Para tal, esta tese foi dividida em 2 estudos. No Estudo 1, submetemos camundongos durante o período que corresponde à gestação de humanos à fumaça de cigarro e/ou etanol visando investigar se a estas drogas de abuso, separadamente ou quando combinadas, programam maior susceptibilidade aos efeitos da nicotina durante a adolescência (PN30) ou idade adulta (PN90). Para avaliar a susceptibilidade, utilizamos 3 testes: campo aberto (CA), preferencia pela nicotina (PPN) e preferencia condicionada por lugar (CPP). No Estudo 2, os animais foram expostos a nicotina durante o período gestacional e, no período que corresponde à infância (PN9 a PN20), fatias de cérebro contendo o núcleo tegumental laterodorsal (LDT) foram expostas a etanol. Este núcleo foi escolhido uma vez que estudos recentes indicam sua participação em mecanismos de toxicodependência. Foram realizados registros eletrofisiológicos de uma única célula. No Estudo 1, identificamos maior sensibilidade para os efeitos da reexposição à nicotina na adolescência quando comparada com a idade adulta . Em animais testados no CA durante a adolescência, a nicotina foi capaz de causar aumento da atividade locomotora nos animais controle, previamente expostos à fumaça de cigarro e ao etanol. Contudo, em animais expostos à fumaça combinada com etanol, não houve aumento da locomoção. Na idade adulta, a nicotina causou um aumento da atividade locomotora no CA somente nos animais expostos à fumaça de cigarro...

Particularly relevant is the fact that early exposure to drugs of abuse during development potentially increases drug susceptibility later during development. In the present study we used mice models to investigate postnatal behavioral and electrophysiological effects of exposure to cigarette smoke, nicotine and ethanol during the period that corresponds to pregnancy in humans. To this end, this thesis was divided into two studies. In Study 1, we submitted mice to cigarette smoke and / or ethanol in order during the period that corresponds to human pregnancy to investigate whether these drugs of abuse, alone or when combined, programs increased susceptibility to the effects of nicotine during adolescence (PN30) or adulthood (PN90). To evaluate susceptibility, we use three tests: open field (OF), preference for nicotine (PFN) and conditioned place preference (CPP). In Study 2, the animals were exposed to nicotine during pregnancy and, in the period corresponding to childhood (PN9 to PN20), brain slices containing the laterodorsal tegmental nucleus (LDT) were exposed to ethanol. This nucleus was chosen based on recent studies that indicate that it participates in mechanisms of addiction. Whole cell patch clamp recordings were performed. In Study 1, a higher sensitivity to the effects of nicotine exposure was identified during adolescence when compared to adulthood. In animals tested in the OF during adolescence, nicotine was able to cause an increase in locomotor activity in controls, in mice previously exposed to cigarette smoke, and in those exposed to ethanol. However, nicotine failed to increase locomotion in mice previously exposed to smoke combined with ethanol. In adulthood, nicotine caused an increase in OF locomotor activity only in animals exposed to cigarette smoke...

Disfunções endócrinas no modelo de programação pela exposição à fumaça de cigarro na lactação / Endocrine disorders in the programming model by exposure tobacco smoke in lactation

Eventos ou estímulos no início da vida podem afetar o desenvolvimento do indivíduo; dentre esses o tabagismo materno. A exposição materna isolada à nicotina, principal componente do cigarro, causa na prole alterações metabólicas, em curto e longo prazo, como aumento da adiposidade, resistência à leptina, e disfunção tireoideana e adrenal. Entretanto é sabido que na fumaça de cigarro estão presentes outros componentes com potenciais efeitos tóxicos. Assim propomos comparar o efeito de duas formas de exposição neonatal à fumaça do cigarro sobre o perfil endócrino-metabólico da prole em curto e longo prazo. Para isso, no 3º dia após o nascimento, ratos lactentes foram submetidos a dois modelos: Modelo I (exposição pelo leite materno), ninhadas separadas em: exposição à fumaça (EF; n=8) – lactantes expostas à fumaça de cigarros 2R1F (1,7 mg de nicotina/cigarro por 1h, 4 vezes ao dia), separadas de suas proles e grupo controle (C; n=8), onde as mães foram separadas de suas proles e expostas ao ar filtrado; Modelo II (exposição direta à fumaça), ninhadas separadas em: exposição à fumaça (EF; n=8) – mães e proles expostas à fumaça de cigarros 2R1F e controle (C; n=8) – mães e proles expostas ao ar filtrado. A exposição ao tabaco ocorreu até o desmame. Mães sacrificadas aos desmame e proles aos desmame e aos 180 dias de idade. As mães lactantes expostas à fumaça (EF) apresentaram hipoleptinemia (-46%), hiperprolactinemia (+50%), hipoinsulinemia (-40%) e diminuição de triglicérides (-53%). Quanto a composição bioquímica do leite, as lactantes EF mostraram aumento de lactose (+52%) e triglicérides (+78%). No modelo I, as proles EF apresentaram ao desmame: diminuição da gordura corporal total (-24%), aumento de proteína corporal total (+17%), diminuição da glicemia (-11%), hiperinsulinemia (+28%), hipocorticosteronemia (-40%) e aumento de triglicérides (+34%). Quando adultas, as proles EF apresentaram somente alteração da função adrenal onde observou-se menor ...

Events or stimuli during early life can affect the development; among these events, there is the maternal smoking. Children born from smoking mothers showed low birth body weight and overweight in childhood and adolescence. Maternal nicotine exposure, the main cigarette component, causes in the offspring several metabolic changes in short- and long-term, such as increase in adiposity, hyperleptinemia, leptin resistance as well as thyroid and adrenal dysfunction. However, it is known that there are other toxic components in tobacco smoke. Then, we compared the effects of two models of tobacco smoke exposure on endocrine-metabolic profile in offspring at short- and long-term. For this, in the 3rd day of birth, suckling rats were submitted to two different experiments: Model I (through breast milk exposure), in which litters were separated into, smoke exposure (SE; n=8) – lactating mothers exposed to 2R1F cigarettes smoke (1.7 mg nicotine/cigarette/1h, 4 times per day) separated from their offspring; and control (C; n=8) – mothers were separated of their pups and exposed to filtered air. Model II (direct exposure), in which litters were separated into: Smoke exposure (SE; n=8) – lactating mothers and their offspring were exposed to 2R1F cigarettes smoke; and control (C; n=8) – mothers and their pups were exposed to filtered air. The smoke exposure occurred until the weaning, when mothers and half of pups were killed. The other offspring were killed at 180 days-old. SE dams presented hypoleptinemia (-46%), hyperprolactinemia (+50%), hypoinsulinemia (-40%) and lower triglycerides (-53%). Concerning milk compositon, SE dams showed higher lactose (+52%) and triglycerides (+78%). In model I (through breast milk exposure), EF offspring showed at weaning lower total body fat (-24%) and higher total body protein (+17), lower serum glucose (-11%), hyperinsulinemia (+28%), hypocorticosteronemia (-40%) and higher triglycerides (+34%). In adulthood, these parameters were ...

Efeitos da exposição à nicotina e/ou ao etanol durante a adolescência: alterações glutamatérgicas e na memória visuoespacial de camundongos / Effect of nicotine and/or etanol exposure during adolescence: glutamatergic and visuospatial memory alterations in mice

Adolescentes humanos frequentemente associam o fumo do tabaco ao consumo de bebidas alcoólicas. A despeito desta associação, pouco se sabe sobre a neurobiologia básica da coexposição no cérebro adolescente. No presente estudo, avaliamos os efeitos da exposição, que ocorreu do 30º ao 45º dia de vida pós natal (PN30 a PN45), à nicotina e/ou ao etanol durante a adolescência (PN38-45) e da retirada (PN50-57) na memória visuoespacial através do Labirinto Aquático de Morris (LAM: 6 sessões + 1 prova, 3 tentativas/sessão, latência = 2 min), em 4 grupos de camundongos Suíços machos e fêmeas: (1) exposição concomitante à NIC [solução de nicotina free base (50 μg/ml) em sacarina a 2% para beber] e ETOH [solução de etanol (25%, 2 g/kg) injetada i.p. em dias alternados]; (2) exposição à NIC; (3) exposição ao ETOH; (4) veículo (VEH). Uma vez que os resultados comportamentais podem sofrer a interferência de alterações motoras, avaliamos (a) a atividade locomotora no Teste de Campo Aberto (sessão única, 5 min) e (b) a coordenação e o equilíbrio no Teste de Locomoção Forçada sobre Cilindro Giratório (5 tentativas, latência = 2 min). Para os efeitos da exposição à NIC e/ou ao ETOH na eficiência do transporte de aminoácidos excitatórios, avaliamos a captação de [3H] D-aspartato no hipocampo. A expressão do transportador glial GLAST/EAAT1 foi avaliada por Western-blot. Durante a exposição, animais ETOH e NIC+ETOH apresentaram déficits de memória nas sessões de teste e de prova no LAM enquanto, na retirada, os grupos NIC e NIC+ETOH apresentaram prejuízos na retenção. Não houve diferenças significativas entre os grupos de tratamento em nenhum dos parâmetros testados em ambos os testes motores, tanto na exposição quanto na abstinência. Os grupos NIC, ETOH e NIC+ETOH tiveram uma diminuição significativa na captação de [3H] D-aspartato ao final do período de exposição, com uma normalização da atividade dos EAATs na retirada das drogas...

Human adolescents frequently associate tobacco smoke and alcoholic drinks. Despite this association, little is known about the basic neurobiology of co-exposure in the adolescent brain. In the present study, we assessed the effects of nicotine and/or ethanol exposure (postnatal days 30 to 45: PN30-45) during adolescence (PN38-45) and withdrawal (PN50-57) on visuospacial memory through the Morris Water Maze (MWM: 6 sessions + 1 probe, 3 trials/session, latency = 2 min), in four groups of male and female Swiss mice: (1) Concomitant NIC [nicotine free base solution (50µg/ml) in 2% saccharin to drink] and ETOH [ethanol solution (25%, 2g/kg) i.p. injected every other day] exposure; (2) NIC exposure; (3) ETOH exposure; (4) Vehicle (VEH). Once behavioral results can be affected by motor disorders, we assessed (a) locomotor activity through the Open field Test (one session, 5 min) and (b) coordination and balance through the ROTAROD Test (5 trials, latency = 2 min). To investigate the effects of NIC and/or ETOH exposure on the efficiency on excitatory amino acid transport, we assessed the [3H] D-aspartate uptake in mice hippocampus. The GLAST/EAAT1, a glial transporter, was assessed by Western-blot technique. During exposure, ETOH and NIC+ETOH animals showed deficits on memory through the session and probe trial in WMW while, during withdrawal, NIC and NIC+ETOH groups showed impairments on retention. There were no significant differences between the experimental groups in any parameters assessed in both motor tests, either during exposure and withdrawal. There was a significant decrease in the [3H] D-aspartate for NIC, ETOH and NIC+ETOH groups in the end of exposure, turning to the normal levels of EAATs activity during withdrawal...

Efeitos da nicotina e/ou etanol no hipocampo de camundongos adolescentes: morte celular e densidade neuronal e glial ao final da exposição e após a retirada das drogas / Effects of nicotine and/or ethanol in the hippocampus of adolescent mice: cell death and neuronal and glial densities at the end of exposure and during drugs withdrawal

Fumar e consumir bebidas alcoólicas estão frequentemente associados durante a adolescência. Contudo, poucos estudos em modelos animais têm como foco as bases neurobiológicas da exposição combinada à nicotina e ao etanol no cérebro de adolescentes. Nesse estudo investigamos morte celular e alterações na densidade neuronal e glial nas regiões granulosa do giro denteado (GrDG), camada molecular (Mol), CA1, CA2 e CA3 do hipocampo, durante a exposição e dois e cinco dias após o seu término. Para tanto, do 30º ao 45º dia pós-natal (PN30-PN45), 233 camundongos C57BL/6 machos e fêmeas foram expostos à nicotina (NIC) e /ou etanol (ETOH). Assim, quatro grupos experimentais foram utilizados: 1) NIC+ETOH: exposição concomitante a NIC (50ug/ml em 2% de sacarina na água de beber) e ETOH (25%, 2g/kg i.p. em dias alternados), 2) exposição à NIC, 3) exposição ao ETOH, 4) exposição ao veículo. Avaliamos morte celular por apoptose pela técnica do TUNEL, densidades neuronal e glial pelo método do Disector óptico e espessuras das regiões durante a exposição (PN45) e dois (PN47) e cinco dias (PN50) após o seu término. ANOVAS foram utilizadas para detectar efeitos do tratamento e/ou interações do tratamento com outros fatores. O grau de significância assumido foi de p<0.05. Em PN45, a exposição ao etanol aumentou o número de células TUNEL+ em todas as regiões hipocampais quando comparado ao grupo veículo e a nicotina provocou uma resposta menos severa e dependente da região. Os animais que receberam nicotina+etanol não diferiram dos animais veículo em todas as regiões hipocampais. Em PN47, ainda foi identificado aumento no número de células TUNEL+ nos grupos ETOH e NIC, mas em menor magnitude que os efeitos identificados durante a exposição. Esses resultados foram acompanhados por redução das densidades neuronal e glial em todos os grupos tratados. Em PN50, a abstinência de nicotina e/ou etanol foi associada com reduções compensatórias de células TUNEL+...

Smoking and consumption of alcoholic beverages are frequently associated during adolescence. However, there have been few animal studies on the neurobiological bases of the combined exposure in the adolescent brain. In the present study, we investigated the effects of adolescent nicotine and/or ethanol exposure and withdrawal on the following regions of the hippocampus: Granular layer of the Dentate Gyrus (GrDG), Molecular layer (Mol), CA1, CA2 and CA3. From the 30th to the 45th postnatal day (PN30-PN45), 233 C57BL/6 male and female mice were exposed to nicotine free base (NIC) and/or ethanol (ETOH). Four groups were analyzed: 1) concomitant NIC (50 ug/ml in 2% saccharin to drink) and ETOH (25%, 2 g/kg i.p. injected every other day) exposure; 2) NIC exposure; 3) ETOH exposure; 4) vehicle. We evaluated cell degeneration (TUNEL assay), neuronal and glial densities (optical Disector) and region thicknesses during the exposure (PN45) and two (PN47) and five (PN50) days post-exposure. ANOVAs were used to identify treatment effects and/or interactions with other factors. Significance was assumed at the level of p<0.05. On PN45, ETOH elicited an increase in the number of TUNEL+ cells relative to the vehicle group in all hippocampal regions. NIC elicited less severe region-dependent effects. Concomitant NIC and ETOH failed to elicit significant changes in the number of TUNEL+ cells. On PN47, the effects were similar to those described for PNB45, even though smaller in magnitude. These results were paralleled by reductions in neuronal and glial cells densities for all treatment groups. In contrast, on PN50, ethanol and/or nicotine withdrawal were associated with compensatory reductions in TUNEL+ cells in all hippocampal regions. These results were paralleled by a reversal of effects on neuronal and glial densities. There were no effects on region thicknesses both during exposure and withdrawal. These results suggest that deleterious effects of nicotine...

Effect of nicotine on lipid profile, peroxidation & antioxidant enzymes in female rats with restricted dietary protein.

BACKGROUND & OBJECTIVE: Nicotine intake through tobacco is very common in female population of lower socioeconomic level who are deprived of healthy diet. Women suffer consequences of smoking such as cardiovascular disorder, lung related diseases and oxidative stress, etc. No data are available of the influences of nicotine on lipid profile, lipid peroxidation and antioxidant enzymes levels under restricted dietary protein intake. The present study was carried out to investigate the effect of nicotine on such parameters of female rats fed with protein restricted diet (5% casein) as compared to those with normal protein diet (18% casein) with or without vitamin C or E supplementation. METHODS: Subcutaneous injections of nicotine tartrate (3.5 mg/kg body weights per day for 15 days) were given to the rats and subsequent measurements of plasma lipid profile, plasma and ovary lipid peroxidation and antioxidant enzymes were done. RESULTS: The results showed significant (P<0.01) increase of total cholesterol (TC) and more significant (P<0.001) increase of triglyceride and low-density lipoprotein cholesterol (LDL-C) of plasma under both dietary conditions. The increase of plasma very low-density lipoprotein cholesterol (VLDL-C) was highly significant under protein-restricted diet. The high-density lipoprotein cholesterol (HDLC) decreased significantly in both dietary conditions. Lipid peroxidation in plasma increased significantly in protein-restricted condition. Superoxide dismutase and catalase activities in the ovary tissue decreased significantly (P<0.001) by nicotine treatment in both dietary groups. INTERPRETATION & CONCLUSION: Our findings indicated that nicotine-induced toxicity is more in lipid profile (plasma) and lipid peroxidation (plasma and ovary tissue) under protein-restricted diet as compared to that of the normal protein diet. The antioxidant vitamins antagonized the nicotineinduced effects less effectively on the observed parameters under restricted dietary protein.

Nitric oxide-mediated pathogenesis during nicotine and alcohol consumption.

Nitric oxide (NO) is formed by different cell types in response to a variety of physiological and patho-physiological stimuli. The intake of nicotine and/or alcohol has patho-physiological effects on organ function, and the progression of alcohol-/tobacco-related diseases seem to be directly influenced by NO-mediated mechanisms. Nicotine has an adverse influence on blood vessel functionality, repair and maintenance. Chronic nicotine exposure augments atherosclerosis by enhancing the production of proinflammatory cytokines by macrophages which then activate atherogenic NF-kB target genes in aortic lesions. Alcohol produces NO which speeds up the apoptosis of neutrophils. Alcohol sensitizes the liver to endotoxemic shock. Nitrosative stress and increased basal levels of NO contribute to tumour growth. The progression of disease seems to be directed via a definite NO-mediated mechanism. This review gives an insight into how intake of tobacco and alcohol may affect quality of life.

Protective effect of hesperidin on nicotine induced toxicity in rats.

Nicotine administration (2.5 mg/kg of body weight, sc, 5 days a week for 22 weeks) enhanced lipid peroxidative indices (thiobarbituric acid reactive substances and hydroperoxides) accompanied by a significant increase in the marker enzymes alanine transaminase, aspartate transaminase, alkaline phosphatase and lactate dehydrogenase and elevated levels of cholesterol, triglycerides, phospholipids and free fatty acids in Wistar rats. There was a significant protection by hesperidin administration at different doses (25, 50, 75, 100 and 150 mg/kg body weight) in nicotine-treated rats. However, the effect of hesperidin was more significant at 25mg/kg dose. The results suggest that hesperidin exerts the protective effects by modulating the extent of lipid peroxidation. The results are supported by histopathological observations of lung, liver and kidney.

Tabagismo e suas peculiaridades durante a gestação: uma revisão crítica / Smoking and its peculiarities during pregnancy: a critical review

A gestação é uma ocasião especial para a promoção da cessação do tabagismo. A preocupação com a saúde do feto gera uma motivação extraordinária na gestante. Os resultados e a relação custo-efetividade das intervenções são melhores neste grupo do que na população em geral. Os ganhos extrapolam os benefícios à saúde da mulher, pois permitem também o desenvolvimento de um feto mais saudável. O conhecimento das peculiaridades do tabagismo durante a gestação é fundamental para uma abordagem direcionada e com maior probabilidade de sucesso. Este trabalho de revisão tem o objetivo de ressaltar a extensão dos malefícios do fumo, tanto para a mulher gestante quanto para seu feto, e estimular o uso de técnicas apropriadas para a suspensão do tabagismo nesta população.

Effect of nicotine (plant extract) on sex-ratio of Drosophila melanogaster (Meigen).

Experiments were conducted by using nicotine (plant extract) for its toxic effects on Drosophila melanogaster, LC50 estimated is 2.9552 microl/100 ml. Studies revealed that nicotine affects adult emergence of males and females (sex-ratio) of mutant form (Yellow) of Drosophila melanogaster.

Carcinogenic effect of nicotine on normal mammary ductal epithelial cells and the protective role of beta-carotene.

A number of carcinogens like polycyclic hydrocarbons and aromatic amines have been incriminated to induce mammary carcinomas in vitro and in vivo. Studies have supported an inter-relationship between tobacco consumption and breast cancer. Because nicotine is the major alkaloid present in tobacco this study was conducted to find the direct in vitro effect of nicotine on normal mammary ductal epithelial cells. It was seen in the present work that nicotine causes a statistically significant increase in the proliferative rate and ER (estrogen receptor) expression as compared to the control group. This change was more pronounced with a lower concentration of nicotine (650 microg/ml). Colony efficiency also showed a similar trend. Beta carotene was added in the present work to study its anti oxidant effect on nicotine induced changes. Beta carotene significantly decreased the proliferation rate induced by 650 microg/ml nicotine. It also prevented the cytotoxic effect of higher dose of nicotine, however, it failed to alter significantly the ER expression induced by lower concentration of nicotine though it showed decreasing trend.

El tabaco daña la salud. Alerta para los tejidos periodontales! / Tobacco damages the health. An alert for periodontal tissues!

En este trabajo de revisión bibliográfica se encontró que diversos autores coinciden acerca del daño que las sustancias tóxicas del tabaco, provocan a los tejidos periodontales. Conocer la influencia de la nicotina sobre dichos tejidos, servirá de motivación para trabajar en prevención, mejorar el diagnóstico, conocer la limitación del tratamiento y orientar el pronóstico de la enfermedad periodontal del fumador

Nicotine and endothelial permeability

The effect of nicotine was studied on the permeability of the coronary endothelium of Sprague Dawley rats. Nicotine was administered in drinking water from 4 to 6 week in a dose of 5mg/kg body weight/day. Endothelial permeability was studied by intramuscular injection of Evans blue dye and was found to be increased in nicotine treated animals. The mode of penetration was seen to be through the endothelial cells to begin with and later the intercellular gaps were also involved

Changes induced in the kidney of rat empryo due to the combined treatment of nicotine and gamma-rays

This work was done to investigate the synergestic influence of gamma- rays and nicotine on the fetal kidney of albino rat. Pregnant female albino rats were used in this experiment. The animals were divided into 6 groups, the 1st group was used as control. While, the 2nd was injected with nicotine [0.5 mg/100 g body weight] subcutaneously. The injection started one week prior to mating and continued to the 20th day of pregnancy. Animals of the 3rd group were exposed to gamma-rays [3 Gy] on day 6 of gestation, whereas, the 4th group was irradiated on day 12 of gestation. Animals of the 5th group were treated with nicotine, then irradiated [3 Gy] on the 6th day of pregnancy. The last group was treated with nicotine as then irradiated with [3 Gy] on day 12 of gestation. The histopathological changes recorded in this study included the degeneration of the Bowman's capsules, vacuolation of the cytoplasm, also some pyknotic nuclei in irradiated and nicotine groups. These changes became much more marked in groups exposed to gamma-rays during nicotine treatment where fibrosis and widened distal convoluted tubules were clearly detected. In histochemical studies, it has been found that the alkaline phosphatase activity was reduced with exposure to gamma-rays or nicotine treatment. While, a marked reduction in this level was obtained in the synergestic effect of nicotine and irradiation

Bile reflux in cigarette smokers

Forty patients were included in this study, divided into two groups, smokers and non smokers, twenty patients in each. All of them were suffering from dyspepsia for more than six months. Male to female ratio was 2:1 and their average age was 40 years. Determination of PH bile salts in fasting gastric aspirate, Endoscopy with gastric biopsy and determination of evacuation time of stomach were done for every patient. Gastric PH was 4.6 in the smokers group, while it was 3.8 in non smokers with P> 0.5, but in cases with bile salt reflux PH in smokers group was 6.9, and in non smokers 5.3, the P> 0.05. Bile reflux was observed in 45: of smokers group and in 25: of non smokers group, which was mild in the latter group. The incidence of gastritis was 80: and 65: in smokers and non smokers respectively. Rapid gastric evacuation time was noticed in 75: and 35: in smokers and non smokers respectively