RESUMO
Tobacco smoking remains one of the leading causes of premature death worldwide. Electronic Nicotine Delivery Systems (ENDSs) are proposed as a tool for smoking cessation. In the last few years, a growing number of different types of ENDSs were launched onto the market. Despite the manufacturing differences, ENDSs can be classified as "liquid e-cigarettes" (e-cigs) equipped with an atomizer that vaporizes a liquid composed of vegetable glycerin (VG), polypropylene glycol (PG), and nicotine, with the possible addition of flavorings; otherwise, the "heated tobacco products" (HTPs) heat tobacco sticks through contact with an electronic heating metal element. The presence of some metals in the heating systems, as well as in solder joints, involves the possibility that heavy metal ions can move from these components to the liquid, or they can be adsorbed into the tobacco stick from the heating blade in the case of HTPs. Recent evidence has indicated the presence of heavy metals in the refill liquids and in the mainstream such as arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), copper (Cu), and lead (Pb). The present review discusses the toxicological aspects associated with the exposition of heavy metals by consumption from ENDSs, focusing on metal carcinogenesis risk.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Metais Pesados , Neoplasias , Humanos , Cádmio , NíquelRESUMO
Tobacco use disorder represents a significant public health challenge due to its association with various diseases. Despite awareness efforts, smoking rates remain high, partly due to ineffective cessation methods and the spread of new electronic devices. This study investigated the impact of prolonged nicotine exposure via a heat-not-burn (HnB) device on selected genes and signaling proteins involved in inflammatory processes in the rat ventral tegmental area (VTA) and nucleus accumbens (NAc), two brain regions associated with addiction to different drugs, including nicotine. The results showed a reduction in mRNA levels for PPARα and PPARγ, two nuclear receptors and anti-inflammatory transcription factors, along with the dysregulation of gene expression of the epigenetic modulator KDM6s, in both investigated brain areas. Moreover, decreased PTEN mRNA levels and higher AKT phosphorylation were detected in the VTA of HnB-exposed rats with respect to their control counterparts. Finally, significant alterations in ERK 1/2 phosphorylation were observed in both mesolimbic areas, with VTA decrease and NAc increase, respectively. Overall, the results suggest that HnB aerosol exposure disrupts intracellular pathways potentially involved in the development and maintenance of the neuroinflammatory state. Moreover, these data highlight that, similar to conventional cigarettes, HnB devices use affects specific signaling pathways shaping neuroinflammatory process in the VTA and NAc, thus triggering mechanisms that are currently considered as potentially relevant for the development of addictive behavior.
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Núcleo Accumbens , Área Tegmentar Ventral , Animais , Ratos , Área Tegmentar Ventral/metabolismo , Área Tegmentar Ventral/efeitos dos fármacos , Masculino , Núcleo Accumbens/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/etiologia , PPAR gama/metabolismo , PPAR gama/genética , Transdução de Sinais/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , Fumaça/efeitos adversos , Nicotina/efeitos adversos , Ratos Wistar , Nicotiana/efeitos adversos , Tabagismo/metabolismo , Fosforilação/efeitos dos fármacosRESUMO
The Food and Drug Administration has recently classified the IQOS electronic cigarette as a modified-risk tobacco product. However, IQOS cigarettes still release various harmful constituents typical of conventional cigarettes (CCs), although the concentrations are markedly lower. Here, we investigated the damaging effects of IQOS smoking on the liver. Male Sprague Dawley rats were exposed, whole body, 5 days/week for 4 weeks to IQOS smoke (4 sticks/day), and hepatic xenobiotic metabolism, redox homeostasis and lipidomic profile were investigated. IQOS boosted reactive radicals and generated oxidative stress. Exposure decreased cellular reserves of total glutathione (GSH) but not GSH-dependent antioxidant enzymes. Catalase and xanthine oxidase were greater in the exposed group, as were various hepatic CYP-dependent monooxygenases (CYP2B1/2, CYP1A1, CYP2A1, CYP2E1-linked). Respiratory chain activity was unaltered, while the number of liver mitochondria was increased. IQOS exposure had an impact on the hepatic lipid profile. With regard to the expression of some MAP kinases commonly activated by CC smoking, IQOS increased the p-p38/p38 ratio, while erythroid nuclear transcription factor 2 (Nrf2) was negatively affected. Our data suggest that IQOS significantly impairs liver function, supporting the precautionary stance taken by the WHO toward the use of these devices, especially by young people and pregnant women.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Gravidez , Ratos , Animais , Masculino , Feminino , Humanos , Fumaça , Ratos Sprague-Dawley , Produtos do Tabaco/efeitos adversos , FígadoRESUMO
Tobacco smoking remains without a doubt one of the leading causes of premature death worldwide. In combination with conventional protocols for smoking cessation, e-cigarettes have been proposed as a useful tool to quit smoking. Advertised as almost free of toxic effects, e-cigarettes have rapidly increased their popularity, becoming a sought-after device, especially among young people. Recently some health concerns about e-cigarette consumption are being raised. It is well known that they can release several toxic compounds, some of which are carcinogenic to humans, and emerging results are now outlining the risks related to the onset of respiratory and cardiovascular diseases and even cancer. The present review shows the emerging evidence about the role of technical components of the devices, the e-liquid composition as well as customization by consumers. The primary topics we discuss are the main toxicological aspects associated with e-cigarette consumption, focusing on the molecular pathways involved. Here it will be shown how exposure to e-cigarette aerosol induces stress/mitochondrial toxicity, DNA breaks/fragmentation following the same pathological pathways triggered by tobacco smoke, including the deregulation of molecular signalling axis associated with cancer progression and cell migration. Risk to fertility and pregnancy, as well as cardiovascular risk associated with e-cigarette use, have also been reported.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Abandono do Hábito de Fumar , Adolescente , Feminino , Humanos , Gravidez , Fumaça , Fumar , Abandono do Hábito de Fumar/métodos , NicotianaRESUMO
INTRODUCTION: Recently, the Food and Drug Administration authorized the marketing of IQOS Tobacco Heating System as a Modified Risk Tobacco Product based on an electronic heat-not-burn technology that purports to reduce the risk. METHODS: Sprague-Dawley rats were exposed in a whole-body mode to IQOS aerosol for 4 weeks. We performed the chemical characterization of IQOS mainstream and we studied the ultrastructural changes in trachea and lung parenchyma of rats exposed to IQOS stick mainstream and tissue pro-inflammatory markers. We investigated the reactive oxygen species amount along with the markers of tissue and DNA oxidative damage. Moreover, we tested the putative genotoxicity of IQOS mainstream through Ames and alkaline Comet mutagenicity assays. RESULTS: Here, we identified irritating and carcinogenic compounds including aldehydes and polycyclic aromatic hydrocarbons in the IQOS mainstream as sign of incomplete combustion and degradation of tobacco, that lead to severe remodelling of smaller and largest rat airways. We demonstrated that IQOS mainstream induces lung enzymes that activate carcinogens, increases tissue reactive radical concentration; promotes oxidative DNA breaks and gene level DNA damage; and stimulates mitogen activated protein kinase pathway which is involved in the conventional tobacco smoke-induced cancer progression. CONCLUSIONS: Collectively, our findings reveal that IQOS causes grave lung damage and promotes factors that increase cancer risk. IMPLICATIONS: IQOS has been proposed as a safer alternative to conventional cigarettes, due to depressed concentration of various harmful constituents typical of traditional tobacco smoke. However, its lower health risks to consumers have yet to be determined. Our findings confirm that IQOS mainstream contains pyrolysis and thermogenic degradation by-products, the same harmful constituents of traditional cigarette smoke, and, for the first time, we show that it causes grave lung damage and promotes factors that increase cancer risk in the animal model.
Assuntos
Fumaça , Produtos do Tabaco , Animais , DNA , Pulmão , Ratos , Ratos Sprague-Dawley , Fumar , Nicotiana , Produtos do Tabaco/toxicidadeRESUMO
Electronic cigarette (e-cigarette; e-cig) use has grown exponentially in recent years despite their unknown health effects. E-cig aerosols are now known to contain hazardous chemical compounds, including carbonyls and reactive oxygen species (ROS), and these compounds are directly inhaled by consumers during e-cig use. Both carbonyls and ROS are formed when the liquid comes into contact with a heating element that is housed within an e-cig's atomizer. In the present study, the effect of coil resistance (1.5â¯Ω and 0.25â¯Ω coils, to obtain a total wattage of 8⯱â¯2â¯W and 40⯱â¯5â¯W, respectively) on the generation of carbonyls (formaldehyde, acetaldehyde, acrolein) and ROS was investigated. The effect of the aerosols generated by different coils on the viability of H1299 human lung carcinoma cells was also evaluated. Our results show a significant (pâ¯<â¯0.05) correlation between the low resistance coils and the generation of higher concentrations of the selected carbonyls and ROS in e-cig aerosols. Moreover, exposure to e-cig vapor reduced the viability of H1299â¯cells by up to 45.8%, and this effect was inversely related to coil resistance. Although further studies are needed to better elucidate the potential toxicity of e-cig emissions, our results suggest that these devices may expose users to hazardous compounds which, in turn, may promote chronic respiratory diseases.
Assuntos
Aerossóis/toxicidade , Sistemas Eletrônicos de Liberação de Nicotina , Exposição por Inalação/efeitos adversos , Doenças Respiratórias/prevenção & controle , Vaping/efeitos adversos , Acetaldeído/química , Acetaldeído/toxicidade , Acroleína/química , Acroleína/toxicidade , Aerossóis/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doença Crônica/prevenção & controle , Eletricidade , Formaldeído/química , Formaldeído/toxicidade , Calefação/efeitos adversos , Humanos , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/toxicidade , Doenças Respiratórias/induzido quimicamente , Testes de Toxicidade Crônica/métodosRESUMO
The main purpose of this study was to compare the benefits of SSJ supplementation in obese rats with those achieved only by switching the alimentary regimen from high-fat (HFD) to the regular one (RD) in liver, ileum and prostate. Furthermore, changings in caecal chime microbiota were investigated. SSJ was administered to rats in combination with a RD (HFD-RD + SSJ). The switch from HFD to RD led to a weight loss of almost 9.8 g, and the total cholesterol was found to be significantly lower. In the HFD-RD + SSJ group, all values were improved compared with the HFD control, and the weight decrement was higher (-23.29 g) with respect to HFD-RD. HFD led to a widespread increment of oxidative stress (OS) markers in liver, ileum and prostate. SSJ has shown to improve the results achieved by the suspension of HFD and it has proven effective wherever the only switch in diet regimen failed.
Assuntos
Dieta Saudável , Disbiose/prevenção & controle , Sucos de Frutas e Vegetais , Microbioma Gastrointestinal , Obesidade/dietoterapia , Raphanus/química , Plântula/química , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Ceco , Dieta Hiperlipídica/efeitos adversos , Dieta Redutora , Disbiose/etiologia , Disbiose/imunologia , Disbiose/microbiologia , Conteúdo Gastrointestinal/microbiologia , Microbioma Gastrointestinal/imunologia , Íleo/imunologia , Íleo/metabolismo , Fígado/enzimologia , Fígado/imunologia , Fígado/metabolismo , Masculino , Obesidade/metabolismo , Obesidade/microbiologia , Obesidade/fisiopatologia , Estresse Oxidativo , Próstata/imunologia , Próstata/metabolismo , Carbonilação Proteica , Distribuição Aleatória , Ratos Sprague-Dawley , Redução de PesoRESUMO
For the first time, the aspartame case shows how a corporation decided to ban an artificial ingredient in the wake of public opinion notwithstanding the regulatory assurance claims that it is safe. PepsiCo Inc. made an unprecedented decision most likely based on life-span carcinogenicity bioassay studies from the Cesare Maltoni Cancer Research Center of the Ramazzini Institute (CMCRC/RI), which provide consistent evidence of aspartame's carcinogenicity in rodents. Although CMCRC/RI experiments have been criticized for not complying with Organisation for Economic Co-operation and Development (OECD) guidelines, the newly launched aspartame-free soft drink may not be an isolated case. In the light of vinyl chloride-, formaldehyde- or benzene-associated carcinogenicity discovered for the first time by CMCRC/RI in the same way, it seems the guidelines need to be re-evaluated to avoid the credibility of international regulatory agencies being compromised by consumer opinion.
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Aspartame/toxicidade , Testes de Carcinogenicidade/métodos , Testes de Carcinogenicidade/normas , Saúde Pública/normas , Edulcorantes/toxicidade , Animais , Bioensaio/métodos , Bioensaio/normas , Humanos , CamundongosRESUMO
The oxidative stress theory of aging has brought to the implicit expectation that oxidative stress increases with aging. Unfortunately, a broad investigation in humans is missing due to limitations of conventional oxidative stress status (OSS) analyses. Here we show that the OSS measured in peripheral blood of 247 healthy volunteers, aged 2 days-104 years, using the electron paramagnetic resonance "EPR-radical probe" technique, negatively correlated with age (-1.1 %/year; p < 0.0001) both by simple and multiple linear regression analyses and that it was only marginally affected by sex. These findings stimulate further mechanistic studies.
Assuntos
Envelhecimento/metabolismo , Estresse Oxidativo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Espectroscopia de Ressonância de Spin Eletrônica , Feminino , Voluntários Saudáveis , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Masculino , Pessoa de Meia-IdadeRESUMO
Halophyte species represent valuable reservoirs of natural antioxidants, and, among these, Salicornia europaea stands out as a promising edible plant. In this study, young and old S. europaea leaves were compared for the content of bioactive compounds and antioxidant activity to assess changes in different growth phases; then, the potential protective effects against low-dose CCl4-induced toxicant-associated fatty liver disease (TAFLD) were investigated by administering an aqueous suspension of young leaves to rats daily for two weeks. Quantification of total and individual phenolic compounds and in vitro antioxidant activity assays (DPPH, FRAP, and ORAC) showed the highest values in young leaves compared to mature ones. Salicornia treatment mitigated CCl4-induced hepatic oxidative stress, reducing lipid peroxidation and protein carbonyl levels, and preserving the decrease in glutathione levels. Electronic paramagnetic resonance (EPR) spectroscopy confirmed these results in the liver and evidenced free radicals increase prevention in the brain. Salicornia treatment also attenuated enzymatic disruptions in the liver's drug metabolizing system and Nrf2-dependent antioxidant enzymes. Furthermore, histopathological examination revealed reduced hepatic lipid accumulation and inflammation. Overall, this study highlights Salicornia's potential as a source of bioactive compounds with effective hepatoprotective properties capable to prevent TAFLD.
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Although the Food and Drug Administration has authorized the marketing of "heat-not-burn" (HnB) electronic cigarettes as a modified risk tobacco product (MRTP), toxicological effects of HnB smoke exposure on the brain are still unexplored. Here, paramagnetic resonance of the prefrontal cortex (PFC) of HnB-exposed rats shows a dramatic increase in reactive radical species (RRS) yield coupled with an inflammatory response mediated by NF-κB-target genes including TNF-α, IL-1ß, and IL-6 and the downregulation of peroxisome proliferator-activated receptor (PPAR) alpha and gamma expression. The PFC shows higher levels of 8-hydroxyguanosine, a marker of DNA oxidative damage, along with the activation of antioxidant machinery and DNA repair systems, including xeroderma pigmentosum group C (XPC) protein complex and 8-oxoguanine DNA glycosylase 1. HnB also induces the expression of drug-metabolizing enzymes such as CYP1A1, CYP2A6, CYP2B6, and CYP2E, particularly involved in the biotransformation of nicotine and several carcinogenic agents such as aldehydes and polycyclic aromatic hydrocarbons here recorded in the HnB stick smoke. Taken together, these effects, from disruption of redox homeostasis, inflammation, PPAR manipulation along with enhanced bioactivation of neurotoxicants, and upregulation of cMYC protooncogene to impairment of primary cellular defense mechanisms, suggest a possible increased risk of brain cancer. Although the HnB device reduces the emission of tobacco toxicants, our findings indicate that its consumption may carry a risk of potential adverse health effects, especially in non-smokers so far. Further studies are needed to fully understand the long-term effects of these devices.
RESUMO
In recent years, health protection by natural products has received considerable attention, and a multitude of nutraceuticals have been characterized and their use promoted. Dietary consumption of Cruciferous vegetables, rich in glucosinolates (GLs), and their myrosinase-mediated hydrolysis products isothiocyanates (ITCs), were associated with reductions in cancer risk. In this study, the chemo-preventive potential of sprout extract of Tuscan black cabbage (Brassica oleracea L. var. acephala subvar. Laciniata L.) (TBCSE), through modulation of the xenobiotic-metabolizing apparatus and antioxidant defenses, was investigated in Sprague-Dawley rat liver. TBCSE was administered either orally or intraperitoneally, at a dose of 15mg/kg b.w., daily for twenty-one consecutive days, in the absence or presence of exogenous myrosinase, ß-thioglucoside glucohydrolase (MYR), to distinguish the effects of intact GLs and ITCs, in the context of the extract. A complex, mild modulation pattern of P450-related monooxygenases was observed, mainly regarding CYP content (up to 36% loss), NADPH cytochrome (P450) c-reductase (up to 26% loss), CYP1A1 (up to 23% loss), but no evident distinctions among the effects of the extracts containing GLs or ITCs, were noted. In contrast, significant inductions of phase-II enzymes (up to 107% for UDP-glucuronosyl-transferase, and up to 36% for glutathione S-transferase) were recorded only where the GLs to ITCs conversion had occurred. A boosting effect on catalase (up to 38%), NAD(P)H:quinone reductase (up to 70%), glutathione reductase and glutathione peroxidase (up to 10%) was also recorded, suggesting an indirect antioxidant capacity of the extracts. Overall, the general phase-I inhibition, together with the up-regulation of detoxifying phase-II and antioxidant enzymes, exerted by the TBCSE supplementation, seem to be in line with the classical chemopreventive theory, but whether the addition of exogenous MYR is relevant, still remains to be clarified. These results are in support of the potential health-promoting application of TBCSE, as a nutraceutical.
Assuntos
Benzoatos/farmacologia , Brassica/química , Glucosídeos/farmacologia , Fígado/enzimologia , Extratos Vegetais/farmacologia , Xenobióticos/metabolismo , Animais , Anticarcinógenos/farmacologia , Antioxidantes/farmacologia , Peso Corporal/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/metabolismo , Glicosídeo Hidrolases/metabolismo , Isotiocianatos/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Desintoxicação Metabólica Fase II , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Evidence from both epidemiological and experimental observations has fuelled the belief that the high consumption of fruits and vegetables rich in nutrients and phytochemicals may help prevent cancer and heart disease in humans. This concept has been drastically simplified from the dietary approaches to the use of single bioactive components both as a single supplement or in functional foods to manipulate xenobiotic metabolism. These procedures, which aim to induce mutagen/carcinogen detoxification or inhibit their bioactivation, fail to take into account the multiple and paradoxical biological outcomes of enzyme modulators that make their effects unpredictable. Here, we show that the idea that the physiological roles of specific catalysts may be easily manipulated by regular long-term administration of isolated nutrients and other chemicals derived from food plants is not viable. In contrast, we claim that the consumption of healthy diets is most likely to reduce mutagenesis and cancer risk, and that both research endeavours and dietary recommendations should be redirected away from single molecules to dietary patterns as a main strategy for public health policy.
Assuntos
Dietoterapia/métodos , Dieta , Enzimas/metabolismo , Medicina Baseada em Evidências , Neoplasias/dietoterapia , Neoplasias/fisiopatologia , Xenobióticos/uso terapêutico , Animais , Humanos , Modelos BiológicosRESUMO
Epidemiological studies have shown an association between consumption of disinfected drinking water and adverse health outcomes. The chemicals used to disinfect water react with occurring organic matter and anthropogenic contaminants in the source water, resulting in the formation of disinfection by-products (DBPs). The observations that some DBPs are carcinogenic in animal models have raised public concern over the possible adverse health effects for humans. Here, the modulation of liver cytochrome P450-linked monooxygenases (MFO) and the genotoxic effects in erythrocytes of Cyprinus carpio fish exposed in situ to surface drinking water in the presence of disinfectants, such as sodium hypochlorite (NaClO), chlorine dioxide (ClO(2)) and peracetic acid (PAA), were investigated in winter and summer. A complex induction/suppression pattern of CYP-associated MFOs in winter was observed for all disinfectants. For example, a 3.4- to 15-fold increase was recorded of the CYP2B1/2-linked dealkylation of penthoxyresorufin with NaClO (10 days) and PAA (20 days). In contrast, ClO(2) generated the most notable inactivation, the CYP2E1-supported hydroxylation of p-nitrophenol being decreased up to 71% after 10 days' treatment. In summer, the degree of modulation was modest, with the exception of CYP3A1/2 and CYP1A1 supported MFOs (62% loss after 20 days PAA). The micronucleus (MN) induction in fish circulating erythrocytes was also analysed as an endpoint of genotoxic potential in the same fish population. Significant increases of MN induction were detected at the latest sampling time on fish exposed to surface water treated with chlorinate-disinfectants, both in winter (NaClO) and summer (NaClO and ClO(2)), while no effect was observed in fish exposed to PAA-treated water. These results show that water disinfection may be responsible for harmful outcomes in terms of MFO perturbation and DNA damage; if extrapolated to humans, they ultimately offer a possible rationale for the increased urinary cancer risk recorded in regular drinking water consumers.
Assuntos
Carpas/metabolismo , Compostos Clorados/toxicidade , Sistema Enzimático do Citocromo P-450/metabolismo , Dano ao DNA/efeitos dos fármacos , Desinfetantes/toxicidade , Óxidos/toxicidade , Hipoclorito de Sódio/toxicidade , Animais , Carpas/genética , Ensaio Cometa , Sistema Enzimático do Citocromo P-450/genética , Água Potável/química , Monitoramento Ambiental/métodos , Modelos Animais , Nitrofenóis/metabolismo , Ácido Peracético/metabolismo , Estações do Ano , Poluentes Químicos da Água/toxicidadeRESUMO
Herein we characterized the bioactive metabolites of the aqueous extract of Kavolì®, a commercial product composed of a mixture of Brassica oleracea leaves, and assessed its potential ameliorating effects in a rat model of non-alcoholic fatty liver disease (NAFLD). Kavolì® extract showed high levels of bioactive compounds and strong in vitro antioxidant activities. Chlorogenic and neochlorogenic acids were identified as the most representative polyphenols. The administration of brassica extract to steatotic rats significantly ameliorated the levels of blood lipids and transaminases, and lipid content and inflammatory markers in liver. Oxidative stress parameters were significantly improved in both liver and brain of steatotic rats. Moreover, plasma and feces levels of short chain fatty acids (SCFAs) were bring back close to control values by Kavolì® treatment, in spite of high fat diet/streptozotocin (HFD/STZ)-induced alterations. The efficacy of Kavolì® in treating hypercholesterolemia, reducing the level of inflammation and cardiovascular disease biomarkers, steatosis and oxidative stress parameters, as well as the ability in modulating SCFAs levels is probably related to the bioactive compounds of the water extract administered to the rat model of NAFLD. In particular, the ameliorating effects are largely attributable to the high content in polyphenols observed in our study.
Assuntos
Brassica , Hepatopatia Gordurosa não Alcoólica , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/metabolismo , Brassica/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fígado , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo , Polifenóis/metabolismo , Ratos , ÁguaRESUMO
Despite the lack of knowledge of the effects of electronic cigarettes (e-cigarettes, e-cigs) on public health, they have been proposed as a part of smoking cessation efforts. Recently, several basic scientific studies have pointed out how e-cigs can generate carcinogens, such as e-cig liquid thermal degradation by-products, and how the exposure can lead to genomic damage through inhibiting DNA repair or disrupting the redox homeostasis. However, scientific studies have pointed out how e-cigs can generate carcinogens and their release could be avoided setting the device to a low-voltage regimen. To test this feasibility, we show the effects of e-cig vapour generated from a low-voltage device filled with a nicotine-free liquid on rat testicular functions. The chemical analysis revealed the presence of carbonyls, such as formaldehyde, acetaldehyde and acrolein. Rats exposed reported a lower relative testis weight and higher levels of lactate dehydrogenase (LDH) as tissue damage marker, along with an impairment of 3ß-hydroxysteroid dehydrogenase (3ß-HSD), 17ß-hydroxysteroid dehydrogenase (17ß-HSD) and glucose-6-phosphate dehydrogenase (G6PDH) as key enzymes in the steroidogenesis pathway. The pro-oxidative environment was confirmed by the higher amount of reactive oxygen species (ROS), the development of lipid peroxidation and protein carbonylation, as well as from the disruption of antioxidant capability. Finally, we observed a higher rate of DNA unwinding in white blood cell line and boosted lipoxygenase (LOX)-linked activity, a tumour promotion marker. Even with the device setting at weak conditions, our results if extrapolated to humans suggest that exposure to e-cig vapours might alter gonads function in male vapers.
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Quebras de DNA , Sistemas Eletrônicos de Liberação de Nicotina/métodos , Estresse Oxidativo , Testículo/enzimologia , Testículo/fisiopatologia , Acetaldeído/análise , Acetaldeído/metabolismo , Acroleína/análise , Acroleína/metabolismo , Animais , Quebras de DNA/efeitos dos fármacos , Eletricidade , Formaldeído/análise , Formaldeído/metabolismo , Masculino , Tamanho do Órgão , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Abandono do Hábito de Fumar , Testículo/efeitos dos fármacos , Testículo/metabolismo , VolatilizaçãoRESUMO
Despite the knowledge gap regarding the risk-benefit ratio of the electronic cigarette (e-cig), its use has grown exponentially, even in teenagers. E-cig vapor contains carcinogenic compounds (eg, formaldehyde, acetaldehyde, and acrolein) and free radicals, especially reactive oxygen species (ROS) that cause toxicological effects, including DNA damage. The role of e-cig voltage customization on molecule generation has been reported, but the effects of the resistance on e-cig emissions and toxicity are unknown. Here, we show that the manipulation of e-cig resistance influences the carbonyls production from nonnicotine vapor and the oxidative and inflammatory status in a rat model. Fixing the voltage at the conventional 3.5 V, we observed that the amount of the selected aldehydes increased as the resistance decreased from 1.5 to 0.25 Ω. Under these conditions, we exposed Sprague Dawley rats to e-cig aerosol for 28 days, and we studied the pulmonary inflammation, oxidative stress, tissue damage, and blood homeostasis. We found a perturbation of the antioxidant and phase II enzymes, probably related to the increased ROS levels due to the enhanced xanthine oxidase and P450-linked monooxygenases. Furthermore, frames from scanning electron microscope showed a disorganization of alveolar and bronchial epithelium in 0.25 Ω group. Overall, various toxicological outcomes, widely recognized as smoke-related injuries, can potentially occur in e-cig consumers who use low-voltage and resistance device. Our study suggests that certain "tips for vaping safety" cannot be established, and encourages further independent investigations to help public health agencies in regulating the e-cig use.
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OBJECTIVES: Since early detection improves overall survival in lung cancer, identification of screening biomarkers for patients at risk represents an area of intense investigation. Tumor liberated protein (TLP) has been previously described as a tumor-associated antigen (complex) present in the sera from lung cancer patients. Here, we set out to identify the nature of TLP to develop this as a potential biomarker for lung cancer screening. MATERIALS AND METHODS: Beginning from the peptide epitope RTNKEASI previously identified from the TLP complex, we produced a rabbit anti-RTNKEASI serum and evaluated it in the lung cancer cell line A549 by means of immunoblot and peptide completion assay (PCA). The TLP sequence identification was conducted by mass spectrometry. The detected protein was, then, analyzed in patients with non-small cell lung cancer (NSCLC) and benign lung pathologies and healthy donors, by ELISA. RESULTS: The anti-RTNKEASI antiserum detected and immunoprecipitated a 55 kDa protein band in the lysate of A549 cells identified as aldehyde dehydrogenase isoform 1A1, revealing the molecular nature of at least one component of the previously described TLP complex. Next, we screened blood samples from a non-tumor cohort of 26 patients and 45 NSCLC patients with different disease stages for the presence of ALDH1A1 and global ALDH. This analysis indicated that serum positivity was highly restricted to patients with NSCLC (ALDH p < 0.001; ALDH1A1 p=0.028). Interestingly, the global ALDH test resulted positive in more NSCLC samples compared to the ALDH1A1 test, suggesting that other ALDH isoforms might add to the sensitivity of the assay. CONCLUSION: Our data indicate that ALDH levels are elevated in the sera of NSCLC patients, even with early stage disease, and may thus be evaluated as part of a marker panel for non-invasive detection of NSCLC.