Preclinical anticancer studies on the ethyl acetate leaf extracts of Datura stramonium and Datura inoxia.

BACKGROUND: Cancer is a horrific disease relentlessly affecting human population round the globe. Genus Datura encompasses numerous species with reported medicinal uses. However, its potential as a source of natural anticancer agents is yet to be determined. Datura stramonium (DS) and Datura inoxia (DI) are the two species chosen for this study. METHODS: Total phenolic and flavonoid content (TPC and TFC) as well as antioxidant activity were assessed through colorimetric method. Polyphenolic quantification was done by RP-HPLC. Following extract standardization ethyl acetate leaf extracts of both species (DSL-EA and DIL-EA) were chosen for anticancer studies. In vitro cytotoxicity using various models including cancer cell lines was monitored. Following toxicity studies, benzene (0.2 ml) was used to induce leukemia in Sprague-Dawley rats. Extracts were orally administered to preventive (100 and 200 mg/kg) and treatment (200 mg/kg only) groups. The antileukemic potential of extracts was assessed through haematological, biochemical, endogenous antioxidants and histological parameters. RESULTS: Significant TPC and TFC were estimated in DSL-EA and DIL-EA. RP-HPLC quantified (µg/mg extract) rutin (0.89 ± 0.03), gallic acid (0.35 ± 0.07), catechin (0.24 ± 0.02) and apigenin (0.29 ± 0.09) in DSL-EA while rutin (0.036 ± 0.004) and caffeic acid (0.27 ± 0.03) in DIL-EA. Both extracts exhibited significant brine shrimp cytotoxicity (LC50 < 12.5 µg/ml). DIL-EA exhibited greater cytotoxicity against PC-3, MDA-MB 231 and MCF-7 cell lines (IC50 < 3 µg/ml in each case) as well as higher protein kinase inhibitory action (MIC: 25 µg/disc) compared to DSL-EA. Leukemia induced in rats was affirmed by elevated serum levels of WBCs (7.78 ± 0.012 (× 103) /µl), bilirubin (7.56 ± 0.97 mg/dl), Thiobarbituric acid reactive substances (TBARs) (133.75 ± 2.61 nM/min/mg protein), decreased RBCs (4.33 ± 0.065 (× 106)/µl), platelets (344 ± 3.19 (× 103)/µl), total proteins (2.14 ± 0.11 g/dl), Glutathione S-transferases (GST) (81.01 ± 0.44 nM/min/ml), endogenous antioxidant enzymes levels and abnormal liver and kidney functionality in disease control rats. Both species revealed almost identical and significant (p < 0.05) alleviative effects in benzene induced leukemia. CONCLUSION: Comprehensive screening divulged the tremendous potential of selected species as potent source of natural anticancer agents in a variety of cancers particularly leukemia. Present study might provide useful finger prints in cancer research and mechanistic studies are prerequisite in logical hunt of this goal.

Chemical pneumonitis due to accidental inhalation of benzene: A case report.

Acute accidental inhaled benzene toxicity is rare; however, it associates with the complications including chemical pneumonitis frequently and rarely with the cardiac and neurological complications. The patient should be treated symptomatically since there are no specific clinical practice guidelines especially antidotes established in this regard. The follow-up and monitoring of the patient are crucial for the remission and also to rule out further complications.

Health survey and assessment of the polymorphisms BRCA1/P871L, BRCA1/Q356R, and BRCA2/N372H in female gas station workers in Rio de Janeiro.

Gas station workers are exposed to chemicals known to be carcinogenic, especially benzene. The objective was to analyze the health problems of female gas station workers by means of sociodemographic and clinical questionnaires, and laboratorial exams. We performed the genotyping of the polymorphisms BRCA1/P871L and BRCA1/Q356R by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism, and of variant allele BRCA2/N372H through direct sequencing. The female workers showed a higher concentration of monocytes (P = 0.039); a greater number of spontaneous abortions (P = 0.025, OR = 4.977, 95% CI = 1.135-30.669); higher tobacco consumption (P = 0.013); and higher alcohol consumption (P = 0.05). The statistical analysis of the polymorphisms associated with the variables monocyte concentration and miscarriage number did not reveal a significant relationship, and smoking and spontaneous abortion were not statistically associated either. Environ. Mol. Mutagen. 58:730-734, 2017. © 2017 Wiley Periodicals, Inc.

Protective role of glycerol against benzene stress: insights from the Pseudomonas putida proteome.

Chemical activities of hydrophobic substances can determine the windows of environmental conditions over which microbial systems function and the metabolic inhibition of microorganisms by benzene and other hydrophobes can, paradoxically, be reduced by compounds that protect against cellular water stress (Bhaganna et al. in Microb Biotechnol 3:701-716, 2010; Cray et al. in Curr Opin Biotechnol 33:228-259, 2015a). We hypothesized that this protective effect operates at the macromolecule structure-function level and is facilitated, in part at least, by genome-mediated adaptations. Based on proteome profiling of the soil bacterium Pseudomonas putida, we present evidence that (1) benzene induces a chaotrope-stress response, whereas (2) cells cultured in media supplemented with benzene plus glycerol were protected against chaotrope stress. Chaotrope-stress response proteins, such as those involved in lipid and compatible-solute metabolism and removal of reactive oxygen species, were increased by up to 15-fold in benzene-stressed cells relative to those of control cultures (no benzene added). By contrast, cells grown in the presence of benzene + glycerol, even though the latter grew more slowly, exhibited only a weak chaotrope-stress response. These findings provide evidence to support the hypothesis that hydrophobic substances induce a chaotropicity-mediated water stress, that cells respond via genome-mediated adaptations, and that glycerol protects the cell's macromolecular systems. We discuss the possibility of using compatible solutes to mitigate hydrocarbon-induced stresses in lignocellulosic biofuel fermentations and for industrial and environmental applications.

Human risk assessment of benzene after a gasoline station fuel leak / Avaliacao de risco humano a benzeno apos vazamento de combustivel em posto de gasolina / Evaluacion de riesgo humano al benceno posterior al derrame de combustible en gasolinera

OBJECTIVE: To assess the health risk of exposure to benzene for a community affected by a fuel leak. METHODS: Data regarding the fuel leak accident with, which occurred in the Brasilia, Federal District, were obtained from the Fuel Distributor reports provided to the environmental authority. Information about the affected population (22 individuals) was obtained from focal groups of eight individuals. Length of exposure and water benzene concentration were estimated through a groundwater flow model associated with a benzene propagation model. The risk assessment was conducted according to the Agency for Toxic Substances and Disease Registry methodology. RESULTS: A high risk perception related to the health consequences of the accident was evident in the affected community (22 individuals), probably due to the lack of assistance and a poor risk communication from government authorities and the polluting agent. The community had been exposed to unsafe levels of benzene (> 5 µg/L) since December 2001, five months before they reported the leak. The mean benzene level in drinking water (72.2 µg/L) was higher than that obtained by the Fuel Distributer using the Risk Based Corrective Action methodology (17.2 µg/L).The estimated benzene intake from the consumption of water and food reached a maximum of 0.0091 µg/kg bw/day (5 x 10-7 cancer risk per 106 individuals). The level of benzene in water vapor while showering reached 7.5 µg/m3 for children (1 per 104 cancer risk). Total cancer risk ranged from 110 to 200 per 106 individuals. CONCLUSIONS: The population affected by the fuel leak was exposed to benzene levels that might have represented a health risk. Local government authorities need to develop better strategies to respond rapidly to these ...

OBJETIVO: Avaliar os riscos à saúde da exposição ao benzeno de comunidade afetada por acidente de vazamento de combustível. MÉTODOS: Dados de acidente de vazamento de combustível ocorrido em Brasília, DF, em 2002, foram obtidos dos relatórios produzidos pelo distribuidor de combustível e submetidos a autoridade ambiental. Informação sobre a população afetada foi obtida em grupos focais com oito participantes. Foram estimados o tempo de exposição e concentração de benzeno na água usando modelo de fluxo subterrâneo acoplado a outro de transporte. A avaliação de risco foi conduzida de acordo com a metodologia da Agência de Registro de Substâncias Tóxicas e Doenças ( Agency for Toxic Substances and Disease Registry ). RESULTADOS: Alta percepção de risco à saúde relacionada ao acidente foi observada na população afetada (22 indivíduos), provavelmente devido à falta de assistência e à comunicação de risco deficiente do governo e agente poluidor. A comunidade esteve exposta a níveis inseguros de benzeno na água (> 5 µg/L) a partir de dezembro de 2001, cinco meses antes de ser reportado o vazamento. A concentração média de benzeno na água consumida (72,2 µg/L) foi maior que aquela estimada pelo distribuidor usando a metodologia Ação Corretiva Baseada em Risco ( Risk Based Corrective Action ) (17,2 µg/L). A ingestão estimada de benzeno pelo consumo de água e frutas alcançou 0,0091 µg/kg pc/dia (risco de 5 x 10-7 câncer per 106 indivíduos). O nível de benzeno no vapor d´água durante o banho atingiu 7,5 µg/m3 para ...

OBJETIVO: Evaluar los riesgos para la salud de la exposición al benceno en comunidad afectada por accidente de derrame de combustible. MÉTODOS: Datos del accidente ocurrido en el Distrito Federal (Brasil), fueron obtenidos de los informes realizados por el distribuidor de combustible y sometidos a la autoridad ambienta. Información sobre la población afectada fue obtenida en grupos focales con 8 participantes. Se hicieron estimaciones del tiempo de exposición y concentración de benceno en el agua usando modelo de flujo subterráneo acoplado a otro de transporte. La evaluación de riesgo fue conducida de acuerdo con la metodología de la "Agency for Toxic Substances and Disease Registry". RESULTADOS: Alta percepción de riesgo para la salud relacionada con el accidente fue observada en la población afectada (22 individuos), probablemente debido a la falta de asistencia y a la comunicación de riesgo deficiente del gobierno y agente contaminante. La comunidad estuvo expuesta a niveles inseguros de benceno en el agua (>5 µg/L) a partir de diciembre de 2001, cinco meses antes de ser reportado el derrame. La concentración promedio de benceno en el agua consumida (72,2 µg/L) fue mayor que la estimada por el distribuidor usando la metodología "Risk Based Corrective Action" (17,2 µg/L). La ingestión estimada de benceno por el consumo de agua y frutas alcanzó 0,0091 µg/kg pc/día (riesgo de 5 x 10-7 de cáncer per 106 individuos). El nivel de benceno en el vapor de agua durante el baño alcanzó 7,5 µg/m3 en niños (riesgo de cáncer de hasta 1 per 104). El Riesgo carcinogénico total fue de 110 a 200 per 106 individuos. CONCLUSIONES: La población afectada por el derrame de combustible estuvo expuesta ...

Toxicity of benzene combined with formaldehyde on reproductive cells in mice / 吉林大学学报(医学版)

Objective To study the toxicity of benzene combining with formaldehyde on reproductive cells in mice.Methods Male mice were randomly divided into different groups:three experimental groups with different doses of benzene combining with formaldehyde(mg?kg~(-1))(10+10,50+50 and 100+100),control group and vegetable oil group(n=10).After 8 weeks by oral poison,the mice were killed,testis was weighed,sperm count was peformed,the rate of sperm deformation was counted and the SOD activity was measured.Results The quantities of sperm in various poison groups were obvious decreased and the rate of sperm deformation were obvious increased with dose increasing.Compared with control group,they both had obvious difference(P