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1.
Environ Pollut ; 256: 113375, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31662264

RESUMO

Some studies have indicated that formaldehyde, a ubiquitous environmental pollutant, can induce or aggravate allergic asthma. Epidemiological studies have also shown that the relative humidity indoors may be an independent and a key factor associated with the aggravation of allergic asthma. However, the synergy of humidity and formaldehyde on allergic asthma and the mechanism underlying this effect remain largely unknown. In this study, we aim to determine the effect of high relative humidity and/or formaldehyde exposure on allergic asthma and explore the underlying mechanisms. Male Balb/c mice were modeled with ovalbumin (OVA) and exposure to 0.5 mg/m3 formaldehyde and/or different relative humidity (60%/75%/90%). Histopathological changes, pulmonary function, Th1/Th2 balance, the status of mucus hypersecretion and the levels of inflammatory factors were detected to assess the exacerbation of allergic asthma. The levels of the transient receptor potential vanilloid 4 (TRPV4), calcium ion and the activation of p38 mitogen-activated protein kinases (p38 MAPK) were detected to explore the underlying mechanisms. The results showed that exposure to high relative humidity or to 0.5 mg/m3 formaldehyde alone had a slight, but not significant, affect on allergic asthma. However, the pathological response and airway hyperresponsiveness (AHR) were greatly aggravated by simultaneous exposure to 0.5 mg/m3 formaldehyde and 90% relative humidity. Blocking TRPV4or p38 MAPK using HC-067047 and SB203580 respectively, effectively alleviated the exacerbation of allergic asthma induced by this simultaneous exposure to formaldehyde and high relative humidity. The results show that when formaldehyde and high relative humidity are present this can enhance the activation of the TRPV4 ion channel in the lung leading to the aggravation of the p38 MAPK activation, resulting in the exacerbation of inflammation and hypersecretion of mucus in the airways.


Assuntos
Asma/induzido quimicamente , Formaldeído/toxicidade , Umidade/efeitos adversos , Canais de Cátion TRPV/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Asma/imunologia , Asma/metabolismo , Modelos Animais de Doenças , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Testes de Função Respiratória
2.
J Photochem Photobiol B ; 202: 111668, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734435

RESUMO

Fraxinus rhynchophylla belongs to the family of Oleaceae and also called as Chinese ash wood possesses various pharmacological properties such as neuroprotective, antimicrobial, anti-inflammatory, etc. Therefore we synthesized ZnO nanoparticles using Fraxinus rhynchophylla wood extract as reducing and capping agent. The synthesized nanoparticles were characterized with the aid of UV-Spec, DLS, FT-IR and TEM analysis. Green synthesized ZnO nanoparticles were then assessed for anti-nociceptive property by using various nociception models such as thermal stress-induced, acetic acid, glutamate, capsaicin, and formalin-induced nociception. The sedative effect of synthesized ZnO nanoparticles was evaluated with an open field test. UV-Spectroscopic analysis confirms the formation of ZnO nanoparticles and the characterization studies DLS, FT-IR, and TEM analysis prove it has ideal nanoparticle can be used as a nano-drug. Results of both thermal stress-induced methods hot plate and tail immersion nociception test verified the synthesized ZnO nanoparticles are a potent antinociceptive drug. ZnO nanoparticles effectively reduced the abdominal writhes in acetic acid-induced nociception and it also significantly decreased the nociception activity in another glutamate, capsaicin, and formalin-induced nociception models. Open field experiment proved that synthesized ZnO nanoparticles are less sedative compared to the standard antinociceptive drug morphine. Overall our findings authentically confirm ZnO nanoparticles synthesized from Fraxinus rhynchophylla wood extract is a novel drug that persuasively reduces nociception in different nociceptive induced mice models and can be the best alternative for allopathic drugs which renders severe side effects.


Assuntos
Analgésicos/uso terapêutico , Fraxinus/química , Nanopartículas Metálicas/química , Dor/tratamento farmacológico , Óxido de Zinco/química , Analgésicos/síntese química , Analgésicos/química , Animais , Modelos Animais de Doenças , Formaldeído/toxicidade , Fraxinus/metabolismo , Química Verde , Temperatura Alta , Masculino , Nanopartículas Metálicas/uso terapêutico , Camundongos , Dor/induzido quimicamente , Casca de Planta/química , Casca de Planta/metabolismo , Extratos Vegetais/química
3.
J Ethnopharmacol ; 247: 112265, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31580941

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hymenaea cangaceira Pinto, Mansano & Azevedo (Fabaceae) is a Brazilian medicinal plant widely known as "Jatobá". In folk medicine, it is used to treat infections, respiratory problems, rheumatism, antitumoral, inflammation and pain, however, no activity has been scientifically validated. AIM OF THE STUDY: This study investigated chemical composition of essential oil from Hymenaea cangaceira (EOHc), antimicrobial, antinociceptive and antioxidant activities besides protection against DNA damage and hemolysis. MATERIAL AND METHODS: The essential oil was obtained by hydrodistillation, and characterized by GC-MS and GC-FID. The evaluation of antimicrobial activity was performed by microdilution method. The evaluation of the antioxidant activity was performed using the radicals DPPH, ABTS, O2- and OH-, and the protection of DNA damage using plasmid pBR322. Different experimental models were used to evaluate the antinociceptive effect (acetic acid and formalin), and evaluate the mechanisms of action involved with pharmacological antagonists (naloxone, atropine and gibenclamide) in mice. The essential oil was evaluated for hemolysis on human erythrocytes. RESULTS: The extraction of EOHc showed a yield of 0.18% on a dry basis, presenting high content of hydrocarbon sesquiterpenes (79.04%), high antioxidant activity and protect DNA from damage, besides presenting antifungal and antibacterial activity against Gram-positive and Gram-negative bacteria in vitro. It was found that the essential oil had no acute toxicity in mice up to 5000 mg/kg oral administration (o.a.), in addition to no hemolysis on human erythrocytes. The reduction of antinociceptive activity was 75%, with the opioid system as the mechanism of action. CONCLUSION: Our results validate the main activities by the traditional use attributed to H. cangaceira for antimicrobial and analgesic activity. In addition, the oil has a potent antioxidant activity, protecting the body against oxidative stress damage, adding new value to an endemic species not known to the industry.


Assuntos
Analgésicos/farmacologia , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Hymenaea/química , Óleos Voláteis/farmacologia , Óleos Vegetais/farmacologia , Ácido Acético/toxicidade , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Brasil , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Etanol/química , Etnofarmacologia , Formaldeído/toxicidade , Humanos , Medicina Tradicional/métodos , Camundongos , Testes de Sensibilidade Microbiana , Nociceptividade/efeitos dos fármacos , Óleos Voláteis/química , Óleos Voláteis/uso terapêutico , Dor/induzido quimicamente , Dor/diagnóstico , Dor/tratamento farmacológico , Medição da Dor , Óleos Vegetais/química , Óleos Vegetais/isolamento & purificação , Testes de Toxicidade Aguda
4.
Arq. ciências saúde UNIPAR ; 23(3): 157-161, set-dez. 2019.
Artigo em Português | LILACS-Express | ID: biblio-1046142

RESUMO

O processo de alisamento capilar é uma prática comum realizada nos salões de beleza. O procedimento exige a utilização de substâncias com capacidade de rompimento das cadeias dissulfídricas da fibra capilar com posterior modelamento para o efeito desejado, sendo o formol um dos compostos mais utilizados para esta finalidade, porém indevidamente. De acordo com a legislação vigente, o formol só pode ser utilizado em produtos cosméticos com a função de conservante em uma concentração máxima de 0,2%. Devido a seu uso incorreto em produtos capilares o presente trabalho teve como objetivo realizar uma análise semi-quantitativa da presença de formol em amostras de alisantes capilares, bem como verificar o pH destes produtos. Foram obtidas 22 amostras de alisantes capilares doadas por salões de beleza da região de Umuarama - PR. A determinação da presença de formol foi realizada através da reação de Shiff e comparação com escala colorimétrica de concentrações padronizadas de formaldeído variando de 0,005% a 10%. A verificação do pH foi realizada através da preparação de soluções aquosas de 10% do alisante e posterior aferição em pHmetro digital. Das amostras analisadas, verificou-se 22,72% encontraram-se em conformidade, apresentando quantidade de formaldeído adequada com a legislação (até 0,2%) ou ausência do composto, enquanto que 77,28% apresentaram valores acima do permitido. Já o pH adequado foi constatado em apenas 13,64% amostras. O uso incorreto ou exagerado do formol pode acarretar danos à saúde, como cefaléia, dispnéia, queimadura, edema pulmonar e até câncer. Uma maior fiscalização deve ser realizada nos estabelecimentos que realizam procedimentos de alisamento capilar, bem como nas indústrias produtoras e ainda em importadoras, para uma melhor garantia do cumprimento da legislação tanto para a preservação da saúde dos profissionais quando dos usuários.


The hair-straightening process is a common practice in most beauty salons. The procedure requires the use of substances capable of disrupting the disulfide chains of the hair fiber with subsequent modeling for the desired effect, with formaldehyde being one of the most commonly but improperly used compounds for this purpose. According to the current legislation, formaldehyde can only be used in cosmetic products as a preservative function in a maximum concentration of 0.2%. Due to its incorrect use in capillary products, this work has the purpose of developing a semi-quantitative analysis of the presence of formaldehyde in samples of hair straighteners, as well as verifying the pH of those products. Twenty-two samples of hair straighteners were donated by beauty salons from the region of Umuarama-PR. The determination of the presence of formaldehyde was performed using the Shiff reaction and compared using the colorimetric scale for standard formaldehyde concentrations varying from 0.005% to 10%. The pH verification was carried out by the preparation of 10% aqueous solutions of the straightener and subsequent measurement in a digital pH meter. From the analyzed samples, 22.72% were found to be in compliance, presenting the amount of formaldehyde within the legislation (up to 0.2%) or absence of the compound, while 77.28% presenting values above the legal limitations. Additionally, adequate pH was verified in only 13.64% of the samples. Incorrect or exaggerated use of formaldehyde can lead to health issues, such as headache, dyspnea, burns, pulmonary edema and even cancer. Greater surveillance should be carried out in establishments that perform hair straightening procedures as well as in the producing and importing industries in order to guarantee better compliance with the legislation both for the preservation of the health of professionals and users alike.


Assuntos
Colorimetria/métodos , Formaldeído/toxicidade , Cabelo/química
5.
Ecotoxicol Environ Saf ; 183: 109576, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31509928

RESUMO

Formaldehyde (FA), a ubiquitous indoor environmental pollutant, has been classified as a carcinogen. There are many studies showed that low levels of FA could promote cell proliferation, however, little is known about the signal pathways. To determine the potential molecular mechanisms, human chronic myeloid leukemia cells (K562 cells) and human bronchial epithelial cells (16HBE cells) were exposed to different concentrations of FA. The data showed that FA at 0-125 µM or 0-60 µM promoted the proliferation of K562 cells or 16HBE cells respectively, indicating that FA did have the Hormesis effect. FA at 75 µM (K562 cells) and 40 µM (16HBE cells) significantly promoted cell proliferation, increased intracellular reactive oxygen species (ROS) levels, and decreased glutathione (GSH) content. At the same time, FA treatment induced a marked increase in the key molecules of cell division like CyclinD-cdk4 and E2F1. In addition, pyruvate kinase isozyme M2 (PKM2), glucose, glucose transporter 1 (GLUT1), lactic acid and lactate dehydrogenase A (LDHA) content in the Warburg effect were increased. Administering Vitamin E (VE), significantly disrupted cell division and disturbed the Warburg effect, effectively indicating the decrease of cell activity. Conclusively, these findings suggested that low concentrations of FA could promote cell proliferation by accelerating cell division process or enhancing the Warburg effect to embody the Hormesis effect.


Assuntos
Divisão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Formaldeído/toxicidade , Hormese/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Glucose/metabolismo , Humanos , Células K562 , Piruvato Quinase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
6.
Ecotoxicol Environ Saf ; 183: 109589, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31509929

RESUMO

A microbial fuel cell (MFC) was successfully developed as a toxicity biomonitoring system to enable a quick response to wastewater with unknown toxicity in toxic events. The objective was to quantitatively assess the toxicity of wastewater by a rapid method. Different concentrations of formaldehyde were introduced into the anode chamber, which led to different stages of voltage change. A relationship between the linear slope of the voltage drop stage and the formaldehyde concentration was established through dose-response fitting results. This relationship makes it possible to convert an unknown toxicity of wastewater into the equivalent concentration of formaldehyde. The minimum detection limit in this study was 13 mg/L formaldehyde equivalents. As the toxicity of the wastewater increased, the test time could be reduced to as low as 921 s or even shorter, with a detection error of 3-12 mg/L. By using this evaluation method, oxidized tail gas scrubber wastewater was identified as the main toxic wastewater component in a phenol acetone production plant.


Assuntos
Fontes de Energia Bioelétrica , Técnicas Biossensoriais/métodos , Águas Residuárias/toxicidade , Acetona/toxicidade , Eletrodos , Formaldeído/toxicidade , Modelos Teóricos , Fenol/toxicidade , Águas Residuárias/química
7.
Andrologia ; 51(9): e13362, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31321807

RESUMO

Formaldehyde is a common agent in our surrounding environment and can adversely affect the male reproductive system. In this study, the effectiveness of Matricaria chamomilla (MC) extract as an antioxidant was investigated in rats treated with formaldehyde. Thirty-two male Wistar rats were randomly divided into six groups: F (10 mg/kg formaldehyde), M200 (200 mg/kg MC extract), M500 (500 mg/kg MC extract), FM200 (10 mg/kg formaldehyde and 200 mg/kg MC extract), FM500 (10 mg/kg formaldehyde and 500 mg/kg MC extract) and control group (0.9% normal saline). Formaldehyde and MC extract were administered daily for 30 consecutive days via intraperitoneal injection. Hormonal status, sperm parameters, testis tissue histology, germinal cells apoptosis and stereological analyses of testis tissue were investigated. Testosterone and LH levels were significantly increased in FM200, FM500, F200 and F500 groups compared to F group (p ≤ 0.05). Sperm count, motility and viability were significantly enhanced in FM200, FM500, F200 and F500 groups compared to F group (p ≤ 0.05). A decrease in the number of apoptotic germ cells in FM200, FM500, M200 and M500 groups (p ≤ 0.05) was evident. In particular, the MC extract in dose 500 mg/kg is seen to reduce the adverse effects of formaldehyde on the reproductive system of male rats.


Assuntos
Antioxidantes/administração & dosagem , Formaldeído/toxicidade , Infertilidade Masculina/tratamento farmacológico , Matricaria/química , Extratos Vegetais/administração & dosagem , Animais , Antioxidantes/isolamento & purificação , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Etanol/química , Humanos , Infertilidade Masculina/induzido quimicamente , Masculino , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Wistar , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/efeitos dos fármacos , Testículo/patologia , Água/química
8.
Nat Commun ; 10(1): 3087, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300648

RESUMO

The dorsal root ganglia (DRG) contain the somas of first-order sensory neurons critical for somatosensation. Due to technical difficulties, DRG neuronal activity in awake behaving animals remains unknown. Here, we develop a method for imaging DRG at cellular and subcellular resolution over weeks in awake mice. The method involves the installation of an intervertebral fusion mount to reduce spinal movement, and the implantation of a vertebral glass window without interfering animals' motor and sensory functions. In vivo two-photon calcium imaging shows that DRG neuronal activity is higher in awake than anesthetized animals. Immediately after plantar formalin injection, DRG neuronal activity increases substantially and this activity upsurge correlates with animals' phasic pain behavior. Repeated imaging of DRG over 5 weeks after formalin injection reveals persistent neuronal hyperactivity associated with ongoing pain. The method described here provides an important means for in vivo studies of DRG functions in sensory perception and disorders.


Assuntos
Gânglios Espinais/diagnóstico por imagem , Microscopia Intravital/métodos , Percepção da Dor/fisiologia , Células Receptoras Sensoriais/fisiologia , Animais , Técnicas de Observação do Comportamento/instrumentação , Técnicas de Observação do Comportamento/métodos , Comportamento Animal/fisiologia , Cálcio/química , Feminino , Formaldeído/administração & dosagem , Formaldeído/toxicidade , Gânglios Espinais/citologia , Gânglios Espinais/fisiologia , Proteínas de Fluorescência Verde/química , Proteínas de Fluorescência Verde/genética , Microscopia Intravital/instrumentação , Masculino , Camundongos , Camundongos Transgênicos , Modelos Animais , Imagem Óptica/instrumentação , Imagem Óptica/métodos , Dor/induzido quimicamente , Dor/fisiopatologia , Fótons , Vigília
9.
Pak J Pharm Sci ; 32(3 (Supplementary)): 1167-1173, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31303586

RESUMO

Medicinal plants are playing an imperative role in the therapy for treating various chronic ailments including arthritis. The present study was focused on finding in-vitro and in-vivo anti-arthritic potential of P. braunii roots. In vitro protein denaturation, membrane stabilization and anti-trypsinase assays were carried out to demonstrate anti-arthritic activity of the extracts. Furthermore, the extracts exerting promising in vitro anti-arthritic potential were tested orally at 150, 300 and 600mg/kg/day against formaldehyde induced arthritis in Wistar rats. The methanolic, aqueous and ethyl acetate extracts of the plant revealed noteworthy in vitro anti-arthritic activities while mitigating formaldehyde induced paw edema in dose dependent manner. Methanolic and aqueous extracts showed the highest inhibition (p<0.05) of paw edema, arthritic indices, reduced elevated level of platelets and leukocytes while increasing hemoglobin and body weight of arthritic rats. Anti-arthritic activity of the plant extracts may be due to inhibition of protein denaturation and lysosomal membrane stabilization. The plant exhibited good anti-arthritic potential.


Assuntos
Artrite Experimental/tratamento farmacológico , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Polystichum/química , Albuminas/química , Albuminas/efeitos dos fármacos , Animais , Artrite Experimental/induzido quimicamente , Avaliação Pré-Clínica de Medicamentos , Membrana Eritrocítica/efeitos dos fármacos , Feminino , Formaldeído/toxicidade , Humanos , Masculino , Medicina Tradicional do Leste Asiático , Paquistão , Extratos Vegetais/química , Raízes de Plantas/química , Desnaturação Proteica/efeitos dos fármacos , Ratos Wistar , Soroalbumina Bovina/efeitos dos fármacos
10.
Food Chem Toxicol ; 132: 110598, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31228601

RESUMO

Polyoxymethylene (POM) is a polymer of formaldehyde used inter alia for kitchenware and food processing machines. By migration into food, consumers may be exposed to small additional amounts of formaldehyde in food. In order to address such potential exposures, Specific Migration Limits are derived using all studies with oral exposure in mammals and birds. The assessment is not only based on local irritation observed in a 2-year rat study that has previously served to calculate acceptable exposure levels, but also on systemic effects, namely on effects on the kidney in adult rats and testes in birds before sexual maturity. At the relatively high oral exposure levels (up to 2000 ppm in drinking water) long-term effects caused by formic acid, the first step metabolite of formaldehyde, such as acidosis, cannot be excluded. The lowest Specific Migration Limit of 2.74 mg/dm2, corresponding to 16.5 mg formaldehyde/kg food, is based upon kidney effects in rats, leading to potential exposures that range between 2900 and 4400 times below the endogenous turnover of formaldehyde. Lastly, a recent migration study with POM showed that migration of formaldehyde into food simulants is over an order of magnitude below the lowest Specific Migration Limit derived herein.


Assuntos
Exposição Dietética/normas , Contaminação de Alimentos , Formaldeído/normas , Administração Oral , Animais , Galinhas , Cães , Formaldeído/metabolismo , Formaldeído/toxicidade , Rim/efeitos dos fármacos , Contagem de Leucócitos , Masculino , Nível de Efeito Adverso não Observado , Codorniz , Ratos Sprague-Dawley , Ratos Wistar , Resinas Sintéticas/química , Medição de Risco , Especificidade da Espécie , Estômago/efeitos dos fármacos , Testículo/efeitos dos fármacos
11.
Ecotoxicol Environ Saf ; 181: 89-95, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31176251

RESUMO

BACKGROUDS: Formaldehyde (FA) is an important chemicals that can induce sick house syndrome and may be an incentive of childhood leukemia, however the exact mechanism is unclear. Oxidative stress may be an underlying reason of cancer occurring, while diverse antioxidants can protect the bone marrow cells (BMCs) from damaged. PeroxiredoxinⅡ (PrxⅡ) is an important member of the peroxiredoxin family, can remove reactive oxygen species (ROS), and is closely related with the occurrence of tumor. The present study aimed to detect a possible relationship between PrxⅡ gene and FA-induced bone marrow toxicity. METHODS: The BMCs were taken out from BALB/c mice, then exposed to control and different doses of FA (50, 100, 200 µmol/L). The cell viability, ROS level and expressions of PrxⅡ gene were examined. Afterwards, we used a small interfering RNA (siRNA) to inhibit the expression of PrxⅡ gene, and chose 100 µmol/L FA for exposure dose, to examine the cell viability, ROS level, cell cycle, apoptotic rate, expressions of PrxⅡ gene in BMCs. RESULTS: After a 24 h exposure to different doses of FA, the cell viability, expressions of PrxⅡ gene were decreased with the increasing of FA concentration, while the ROS level was increased. Inhibiting PrxⅡ gene's expression could enhance above FA-induced events. Additionally, siRNA targeting of PrxⅡcould aggravate cell cycle arrest to inhibit cell's growth and development, as well as increase apoptotic rates induced by FA. CONCLUSION: These results demonstrated that PrxⅡ gene was involved in FA-induced bone marrow toxicity, and siRNA targeting of PrxⅡcould enhance this toxic process.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Formaldeído/toxicidade , Peroxirredoxinas/genética , Animais , Células da Medula Óssea/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Estresse Oxidativo , Peroxirredoxinas/antagonistas & inibidores , Peroxirredoxinas/metabolismo , RNA Interferente Pequeno , Espécies Reativas de Oxigênio/metabolismo
12.
Mol Med Rep ; 20(1): 341-349, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115571

RESUMO

The International Agency for Research on Cancer has classified formaldehyde (FA) as a leukemogen to humans in 2012; however, the underlying mechanism remains unclear. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor­suppressor gene and can negatively regulate the phosphoinositide 3­kinase (PI3K)/protein kinase B (Akt) signal transduction pathway, which is associated with cell proliferation, apoptosis and carcinogenesis. To determine the association between FA and the PTEN/PI3K/Akt signal transduction pathway, flow cytometry, reverse transcription­quantitative polymerase chain reaction, western blotting and immunohistochemical analysis were conducted. Bone marrow cells were obtained from BALB/c mice, divided into the control (untreated cells) and FA groups, which were treated with various doses of FA (50, 100 and 200 µmol/l). Following treatment with FA for 24 h, cell viability, the cell cycle, apoptosis, and the expression of PTEN, PI3K and Akt, as well as the protein expression of B­cell lymphoma 2 (Bcl­2), Bcl­2­associated X (Bax), and Caspases­3 and ­9 were examined. Furthermore, 10 µmol/PI3K inhibitor (LY294002) was applied to inhibit the PTEN/PI3K/Akt signal transduction pathway and 100 µmol/l FA was selected for treatment; alteration in the cell cycle were analyzed. The results demonstrated that FA could suppress cell viability, and downregulate PTEN and Bcl­2; the expression of PI3K, Akt, Bax, and Caspases­3 and ­9 were upregulated. Additionally, FA was reported to induce cell cycle arrest at the G0/G1 phase and apoptosis. Following the application of LY294002 to inhibit the PTEN/PI3K/Akt signal transduction pathway, the numbers of cells arrested in the G0/G1 phase were significantly increased in the PI3K inhibitor group compared with the control (P<0.01); however, no significant change in the number of G0/G1 cells compared with FA group was observed (P>0.05). The results of the present study suggested that the PTEN/PI3K/Akt signal transduction pathway served an important role in the process of FA­induced apoptosis, which may be associated with regulating the cell cycle; thus, cell proliferation may be affected.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Formaldeído/toxicidade , Proteínas de Neoplasias/genética , Neoplasias/genética , Animais , Apoptose/efeitos dos fármacos , Células da Medula Óssea/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromonas/farmacologia , Formaldeído/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Morfolinas/farmacologia , Neoplasias/induzido quimicamente , Neoplasias/patologia , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos
13.
Toxicol Lett ; 312: 167-172, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31100492

RESUMO

The inherent complexity of generating and monitoring a test article in an inhalation chamber can make inhalation toxicity testing challenging. Poor study design, human error, and electrical and mechanical problems can adversely affect an inhalation exposure and undermine a study's results. We have developed a process for evaluating seven key elements of exposure quality in inhalation chamber studies: 1) test article characterization, 2) generation method, 3) chamber sampling and analytical method, 4) chamber concentrations, 5) particle size characteristics, 6) chamber type, and 7) controls. For each study evaluated, exposure deficiencies are documented, and a study is given an overall rating (Robust, Adequate, or Poor) for the quality of its exposure characterization and documentation. In combination with the systematic consideration of experimental features other than exposure, these ratings can inform the utility of a study for use in hazard identification and/or exposure-response analysis. Exposure quality evaluations of 204 formaldehyde inhalation studies are presented as a case study. Of these, 34% were rated Robust because they had comprehensive exposure documentation and no serious deficiencies in the key elements of exposure quality. Another 19% of studies with minor uncertainties or limitations were rated Adequate. Conversely, 47% of the studies were rated Poor due to multiple serious exposure deficiencies. This formaldehyde case study illustrates the need to carefully consider the exposure quality of inhalation toxicity studies when their results are used to support hazard and risk assessments.


Assuntos
Poluentes Atmosféricos/toxicidade , Formaldeído/administração & dosagem , Formaldeído/toxicidade , Exposição por Inalação/normas , Monitoramento Ambiental , Formaldeído/química , Humanos , Pesquisa/normas
14.
Chem Res Toxicol ; 32(5): 820-830, 2019 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-30964647

RESUMO

Alzheimer's disease (AD) is the most common form of dementia. The accumulation of ß-amyloid plaques and intracellular neurofibrillary tangles of hyperphosphorylated tau protein are two hallmarks of AD. The ß-amyloid and tau proteins have been at the center of AD research and drug development for decades. However, most of the clinical trials targeting ß-amyloid have failed. Whereas the safety and efficacy of most tau-targeting drugs have not yet been completely assessed, the first tau aggregation inhibitor, LMTX, failed in a late-stage trial, leading to further recognition of the complexities of AD and reconsideration of the amyloid hypothesis and perhaps the tau hypothesis as well. Multilevel complex interactions between genetic, epigenetic, and environmental factors contribute to the occurrence and progression of AD. Formaldehyde (FA) is a widespread environmental organic pollutant. It is also an endogenous metabolite in the human body. Recent studies suggest that elevation of FA in the body by endogenous and/or exogenous exposure may play important roles in AD development. We have demonstrated that FA reduces lysine acetylation of cytosolic histones, thereby compromising chromatin assembly and resulting in the loss of histone content in chromatin, a conserved feature of aging from yeast to humans. Aging is an important factor for AD progression. Therefore, FA-induced inhibition of chromatin assembly and the loss of histones may contribute to AD initiation and/or development. This review will briefly summarize current knowledge on mechanistic insights into AD, focusing on epigenetic alterations and the involvement of FA in AD development. The exploration of chemical exposures as contributing factors to AD may provide new insights into AD mechanisms and could identify potential novel therapeutic targets.


Assuntos
Doença de Alzheimer/etiologia , Epigênese Genética/efeitos dos fármacos , Epigenômica/métodos , Formaldeído/toxicidade , Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Animais , Cromatina/genética , Cromatina/metabolismo , DNA/genética , DNA/metabolismo , Histonas/genética , Histonas/metabolismo , Humanos , Inflamação/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Proteínas tau/metabolismo
15.
Environ Pollut ; 250: 650-661, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31035147

RESUMO

Aldehydes are well-known air pollutants and often studied alone, while co-exposure to aldehyde mixtures is more common than single aldehydes. Unfortunately, it has been very little known about the (mechanism of) combined toxicity of aldehyde mixtures. Here, formaldehyde and acrolein were selected as the typical representatives of common aldehydes, and were used to explore to get in-depth insight into the mechanism of combined toxicity of aldehyde mixtures. The NOECs (non-observed effect concentrations) are 60 µmoL/L for formaldehyde, and 0.5 µmoL/L for acrolein, so acrolein is more toxic than formaldehyde. Formaldehyde and acrolein mixtures showed significant cytotoxicity and synergistic effects in a concentration/time-dependent way on BEAS-2B cells based on acute and chronic cytotoxicity assay. Acrolein was dominant in aldehyde mixtures in inducing cytotoxicity at environmentally relevant doses because of higher toxicity. Moreover, aldehyde mixtures significantly synergistically increased the intracellular reactive oxygen species (ROS), malondialdehyde (MDA) and lactate dehydrogenase (LDH) leakage, while caused an antagonistic effects on glutathione (GSH). Besides, formaldehyde could significantly potentiated the activation of environmental stress sensitive Nrf2 pathway induced by acrolein, even at doses at which formaldehyde treatment alone had no any response. Furthermore, as the downstream components of Nrf2 pathway, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) and heme oxygenase-1 (HO-1) were significantly synergistically induced by formaldehyde and acrolein mixtures. Antioxidants N-acetylcysteine and reduced glutathione could significantly suppress the acute and chronic combined cytotoxicity of acrolein and formaldehyde mixtures, and changed their interactions (synergism) on cytotoxicity. Taken together, aldehyde mixtures have higher toxicity than that expected for additivity based on single aldehydes even at environmentally relevant concentrations, and the combined cytotoxicity may be enhanced through oxidative stress and the related Nrf2 pathway. Prolonged exposure to pollutants containing aldehyde mixtures through inhalation may have more serious threat to respiratory system in animal and human.


Assuntos
Acroleína/toxicidade , Poluentes Atmosféricos/toxicidade , Brônquios/efeitos dos fármacos , Citotoxinas/toxicidade , Formaldeído/toxicidade , Antioxidantes/química , Brônquios/citologia , Catalase/metabolismo , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Glutationa/metabolismo , Heme Oxigenase-1/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
16.
Food Chem Toxicol ; 126: 152-161, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30790713

RESUMO

Diisodecyl phthalate (DIDP) is a new type of phthalate used in the coating of pharmaceutical pills and in plastic food wrappers. This research was conducted to investigate whether DIDP could cause learning and memory impairment in mice, using formaldehyde (FA) to construct a positive control. Behavioral analysis showed that oral administration of 15 mg kg-1·d-1 DIDP combined with inhalation of 1 mg m-3 FA led to learning and memory impairment in mice. Histopathological observations of the brain showed that the pathological alterations in the hippocampi. Detection of testosterone (T) and estradiol (E2) levels in the brain and serum showed that E2 levels were associated with learning and memory disorders. Reactive oxygen species (ROS), reduced glutathione (GSH), malondialdehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OH-dG) revealed the increased oxidative stress levels. Detection of caspase-3, NF-κB, the phosphorylated cAMP response-element binding protein (p-CREB) and the brain derived neurotrophic factor (BDNF) showed that the protective effect mediated by BDNF, is reduced. However, some of these effects were blocked by the administration of Vitmin E (VitE, 100 mg kg-1·d-1) or 17ß-estradiol (17ß-E2, 100 µg kg-1). These data suggest that DIDP may aggravate the FA-exposure-induced learning and memory impairment in mice, and that 17ß-E2 could be utilized to avoid these adverse effects.


Assuntos
Formaldeído/toxicidade , Transtornos da Memória/etiologia , Ácidos Ftálicos/toxicidade , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Aprendizagem/efeitos dos fármacos , /metabolismo , Masculino , Malondialdeído/metabolismo , Transtornos da Memória/genética , Transtornos da Memória/metabolismo , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo
18.
Mol Pain ; 15: 1744806918825046, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30632432

RESUMO

Sensitivity to different pain modalities has a genetic basis that remains largely unknown. Employing closely related inbred mouse substrains can facilitate gene mapping of nociceptive behaviors in preclinical pain models. We previously reported enhanced sensitivity to acute thermal nociception in C57BL/6J (B6J) versus C57BL/6N (B6N) substrains. Here, we expanded on nociceptive phenotypes and observed an increase in formalin-induced inflammatory nociceptive behaviors and paw diameter in B6J versus B6N mice (Charles River Laboratories). No strain differences were observed in mechanical or thermal hypersensitivity or in edema following the Complete Freund's Adjuvant model of inflammatory pain, indicating specificity in the inflammatory nociceptive stimulus. In the chronic constrictive nerve injury, a model of neuropathic pain, no strain differences were observed in baseline mechanical threshold or in mechanical hypersensitivity up to one month post-chronic constrictive nerve injury. We replicated the enhanced thermal nociception in the 52.5°C hot plate test in B6J versus B6N mice from The Jackson Laboratory. Using a B6J × B6N-F2 cross (N = 164), we mapped a major quantitative trait locus underlying hot plate sensitivity to chromosome 7 that peaked at 26 Mb (log of the odds [LOD] = 3.81, p < 0.01; 8.74 Mb-36.50 Mb) that was more pronounced in males. Genes containing expression quantitative trait loci associated with the peak nociceptive marker that are implicated in pain and inflammation include Ryr1, Cyp2a5, Pou2f2, Clip3, Sirt2, Actn4, and Ltbp4 (false discovery rate < 0.05). Future studies involving positional cloning and gene editing will determine the quantitative trait gene(s) and potential pleiotropy of this locus across pain modalities.


Assuntos
Mapeamento Cromossômico , Hiperalgesia/etiologia , Inflamação/complicações , Inflamação/genética , Neuralgia/complicações , Neuralgia/genética , Animais , Modelos Animais de Doenças , Feminino , Formaldeído/toxicidade , Adjuvante de Freund/toxicidade , Inflamação/induzido quimicamente , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL/classificação , Neuralgia/induzido quimicamente , Neuralgia/patologia , Medição da Dor , Limiar da Dor/fisiologia , RNA Mensageiro/metabolismo , Especificidade da Espécie
19.
Pain ; 160(4): 784-792, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30681982

RESUMO

The counterirritation phenomenon known as conditioned pain modulation, or diffuse noxious inhibitory control in animals, is of increasing interest due to its utility in predicting chronic pain and treatment response. It features considerable interindividual variability, with large subsets of pain patients and even normal volunteers exhibiting hyperalgesia rather than hypoalgesia during or immediately after receiving a conditioning stimulus. We observed that mice undergoing tonic inflammatory pain in the abdominal cavity (the conditioning stimulus) display hyperalgesia, not hypoalgesia, to noxious thermal stimulation (the test stimulus) applied to the hindpaw. In a series of parametric studies, we show that this hyperalgesia can be reliably observed using multiple conditioning stimuli (acetic acid and orofacial formalin), test stimuli (hindpaw and forepaw-withdrawal, tail-withdrawal, hot-plate, and von Frey tests) and genotypes (CD-1, DBA/2, and C57BL/6 mice and Sprague-Dawley rats). Although the magnitude of the hyperalgesia is dependent on the intensity of the conditioning stimulus, we find that the direction of effect is dependent on the effective test stimulus intensity, with lower-intensity stimuli leading to hyperalgesia and higher-intensity stimuli leading to hypoalgesia.


Assuntos
Dor Facial/complicações , Hiperalgesia/etiologia , Hipestesia/etiologia , Dor/complicações , Dor/etiologia , Ácido Acético/toxicidade , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Formaldeído/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Medição da Dor , Traumatismos dos Nervos Periféricos/complicações , Estimulação Física/efeitos adversos , Psicofísica , Ratos , Ratos Sprague-Dawley , Especificidade da Espécie
20.
Yakugaku Zasshi ; 139(1): 135-140, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30606921

RESUMO

Nail tips are nail art materials that can be attached to the nail with adhesives. Recently, nail/finger injuries related to nail tips have been reported and one of the causes is considered to be the adhesives used for attaching nail tips. The components of nail adhesives are mostly cyanoacrylate, which is also used as an industrial instant adhesive. During curing, cyanoacrylate adhesives release formaldehyde through hydrolysis. When it is marketed as a nail adhesive, there is no regulation regarding its formaldehyde amount nor obligation to indicate its ingredients in Japan. Additionally, a biological safety test is not required for nail adhesives. Thus, because the safety of nail adhesives is inadequately confirmed, it is necessary to investigate their biological safety. Therefore, we purchased 5 commercially available nail adhesives and 1 medical adhesive and examined their formaldehyde content and cytotoxicity. We examined the cytotoxicity of the adhesives in V79 cells by a colony forming assay. In this test, 5 nail adhesives showed higher toxicity than 1 medical adhesive. Formaldehyde concentrations in the extract of adhesives were as follows: 17.5 to 24.2 µg/mL for nail adhesives and 7.4 µg/mL for medical adhesives. Cyanoacetate did not elicit cytotoxicity at the final concentration up to 1000 µM. However, formaldehyde showed cytotoxicity, with an IC50 of 79 µM (2.4 µg/mL). Taken together, the cytotoxicity of nail adhesives could be due to the formaldehyde generated by the hydrolysis of cyanoacrylate. It seems important that nail adhesives will be regulated by obligation and enhanced safety in the future.


Assuntos
Adesivos/toxicidade , Qualidade de Produtos para o Consumidor , Cosméticos/toxicidade , Cianoacrilatos/toxicidade , Fibroblastos/efeitos dos fármacos , Formaldeído/toxicidade , Unhas , Adesivos/química , Animais , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias/métodos , Cosméticos/química , Cricetinae , Cricetulus , Cianoacrilatos/química , Relação Dose-Resposta a Droga , Formaldeído/análise , Humanos , Hidrólise , Japão , Pulmão/citologia , Segurança , Testes de Toxicidade/métodos
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