Sample records for toxicogenetics
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Shen, Dan-na; Yi, Xu-fu; Chen, Xiao-gang; Xu, Tong-li; Cui, Li-juan
2007-10-01
Individual response to drugs, toxicants, environmental chemicals and allergens varies with genotype. Some respond well to these substances without significant consequences, while others may respond strongly with severe consequences and even death. Toxicogenetics and toxicogenomics as well as pharmacogenetics explain the genetic basis for the variations of individual response to toxicants by sequencing the human genome and large-scale identification of genome polymorphism. The new disciplines will provide a new route for forensic specialists to determine the cause of death.
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Toxicogenetic study of Persea americana fruit pulp oil and its effect on genomic instability.
Nicolella, Heloiza Diniz; Neto, Francisco Rinaldi; Corrêa, Mariana Beltrame; Lopes, Danillo Henrique; Rondon, Edilaura Nunes; Dos Santos, Luiz Felipe Ribeiro; de Oliveira, Pollyanna Francielli; Damasceno, Jaqueline Lopes; Acésio, Nathália Oliveira; Turatti, Izabel Cristina Casanova; Tozatti, Marcos Gomide; Cunha, Wilson Roberto; Furtado, Ricardo Andrade; Tavares, Denise Crispim
2017-03-01
Persea americana Mill., commonly known as avocado, is a tree native to Central America that is widely used as a food source and for the treatment of diseases. This plant has various biological properties such as analgesic, anti-inflammatory and total cholesterol-lowering activity. In view of its pharmacological potential, we conducted a toxicogenetic study of the fruit pulp oil of P. americana (PAO) and investigated its influence on genotoxicity induced by methyl methanesulfonate (MMS) and doxorubicin. V79 cells and Swiss mice were used for the assays. The results showed no genotoxic effects of PAO in the in vitro or in vivo test systems. However, the highest PAO dose tested led to an increase in the levels of aspartate aminotransferase, indicating hepatic/tissue damage. This effect may be related to high concentrations of palmitic acid, the main component of PAO. Furthermore, PAO was effective in reducing the chromosome damage induced by MMS and doxorubicin. These results contribute to the safety assessment of PAO as a medicinal plant for human use. Copyright © 2017 Elsevier Ltd. All rights reserved.
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de Castro E Sousa, João Marcelo; Peron, Ana Paula; da Silva E Sousa, Louridânya; de Moura Holanda, Mércia; de Macedo Vieira Lima, Ataíde; de Oliveira, Vitor Alves; da Silva, Felipe Cavalcanti Carneiro; de Morais Lima, Leonardo Henrique Guedes; Matos, Leomá Albuquerque; de Moura Dantas, Sandra Maria Mendes; de Aguiar, Raí Pablo Sousa; Islam, Muhammad Torequl; de Carvalho Melo-Cavalcante, Ana Amélia; Bonecker, Cláudia Costa; Junior, Horácio Ferreira Júlio
2017-06-01
In general, tropical rivers have a great impact on human activities. Bioaccumulation of toxins is a worldwide problem nowadays and has been, historically, overlooked by the supervisory authorities. This study evaluated cytogenotoxic effects of Guaribas river (a Brazilian river) water during dry and rainy seasons of 2014 by using the Allium cepa test system. The toxicogenetic variables, including root growth, mitotic index, and chromosomal aberrations, were analyzed in meristematic cells of A. cepa exposed to water samples taken from the up-, within, and downstream of the city Picos (state: Piauí). The physical-chemical parameters were also analyzed to explain water quality and possible anthropogenic action. Additionally, the presence of heavy metals was also analyzed to explain water quality and possible damaging effects on eukaryotic cells. The results suggest that the river water exerted cytotoxic, mutagenic, and genotoxic effects, regardless of the seasons. In addition, Guaribas river presented physico-chemical values outside the Brazilian laws, which can be a characteristic of human pollution (domestic sewage, industrial, and local agriculture). The genetic damage was positively correlated with higher levels of heavy metals. The pollution of the Guaribas river water may link to the chemical contamination, including the action of heavy metals and their impacts on genetic instability in the aquatic ecosystem. In conclusion, necessary steps should be taken into account for further toxicogenetic studies of the Guaribas river water, as it has an influence in human health of the same region of Brazil.
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Pharmacogenetics and forensic toxicology.
Musshoff, Frank; Stamer, Ulrike M; Madea, Burkhard
2010-12-15
Large inter-individual variability in drug response and toxicity, as well as in drug concentrations after application of the same dosage, can be of genetic, physiological, pathophysiological, or environmental origin. Absorption, distribution and metabolism of a drug and interactions with its target often are determined by genetic differences. Pharmacokinetic and pharmacodynamic variations can appear at the level of drug metabolizing enzymes (e.g., the cytochrome P450 system), drug transporters, drug targets or other biomarker genes. Pharmacogenetics or toxicogenetics can therefore be relevant in forensic toxicology. This review presents relevant aspects together with some examples from daily routines. Copyright © 2010. Published by Elsevier Ireland Ltd.
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Cardanol: toxicogenetic assessment and its effects when combined with cyclophosphamide
Schneider, Beatriz Ursinos Catelan; Meza, Alisson; Beatriz, Adilson; Pesarini, João Renato; de Carvalho, Pamela Castilho; Mauro, Mariana de Oliveira; Karaziack, Caroline Bilhar; Cunha-Laura, Andréa Luiza; Monreal, Antônio Carlos Duenhas; Matuo, Renata; de Lima, Dênis Pires; Oliveira, Rodrigo Juliano
2016-01-01
Abstract Cardanol is an effective antioxidant and is a compound with antimutagenic and antitumoral activity. Here, we evaluated the genotoxic and mutagenic potential of saturated side chain cardanol and its effects in combination with cyclophosphamide in preventing DNA damage, apoptosis, and immunomodulation. Swiss mice were treated with cardanol (2.5, 5 and 10 mg/kg) alone or in combination with cyclophosphamide (100 mg/kg). The results showed that cardanol is an effective chemopreventive compound, with damage reduction percentages that ranged from 18.9 to 31.76% in the comet assay and from 45 to 97% in the micronucleus assay. Moreover, cardanol has the ability to reduce the frequency of apoptosis induced by cyclophosphamide. The compound did not show immunomodulatory activity. A final interpretation of the data showed that, despite its chemoprotective capacity, cardanol has a tendency to induce DNA damage. Hence, caution is needed if this compound is used as a chemopreventive agent. Also, this compound is likely not suitable as an adjuvant in chemotherapy treatments that use cyclophosphamide. PMID:27303909
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Evaluation of an in vitro toxicogenetic mouse model for hepatotoxicity
DOE Office of Scientific and Technical Information (OSTI.GOV)
Martinez, Stephanie M.; Bradford, Blair U.; Soldatow, Valerie Y.
2010-12-15
Numerous studies support the fact that a genetically diverse mouse population may be useful as an animal model to understand and predict toxicity in humans. We hypothesized that cultures of hepatocytes obtained from a large panel of inbred mouse strains can produce data indicative of inter-individual differences in in vivo responses to hepato-toxicants. In order to test this hypothesis and establish whether in vitro studies using cultured hepatocytes from genetically distinct mouse strains are feasible, we aimed to determine whether viable cells may be isolated from different mouse inbred strains, evaluate the reproducibility of cell yield, viability and functionality overmore » subsequent isolations, and assess the utility of the model for toxicity screening. Hepatocytes were isolated from 15 strains of mice (A/J, B6C3F1, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, BALB/cByJ, AKR/J, MRL/MpJ, NOD/LtJ, NZW/LacJ, PWD/PhJ and WSB/EiJ males) and cultured for up to 7 days in traditional 2-dimensional culture. Cells from B6C3F1, C57BL/6J, and NOD/LtJ strains were treated with acetaminophen, WY-14,643 or rifampin and concentration-response effects on viability and function were established. Our data suggest that high yield and viability can be achieved across a panel of strains. Cell function and expression of key liver-specific genes of hepatocytes isolated from different strains and cultured under standardized conditions are comparable. Strain-specific responses to toxicant exposure have been observed in cultured hepatocytes and these experiments open new opportunities for further developments of in vitro models of hepatotoxicity in a genetically diverse population.« less
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Silva, Marcelo Jose Dias; Vilegas, Wagner; da Silva, Marcelo Aparecido; de Moura, Carolina Foot Gomes; Ribeiro, Flávia Andressa Pidone; da Silva, Victor Hugo Pereira; Ribeiro, Daniel Araki
2014-12-01
The Mimosa (Mimosa caesalpiniifolia) is a plant native from South America; it is used in the traditional medicine systems for treating bacterial, fungal, parasitic and inflammatory conditions. The aim of this study was to evaluate the antigenotoxic and antioxidant activities induced by mimosa (M. caesalpiniifolia) in multiple rodent organs subjected to intoxication with cadmium chloride. A total of 40 Wistar rats (8 weeks old, 250 g) were distributed into eight groups (n = 5), as follows: Control group (non-treated group, CTRL); Cadmium exposed group (Cd); cadmium exposure and treated with extract at 62.5 mg/kg/day; cadmium exposure and treated with extract at 125 mg/kg/day; cadmium exposure and treated with extract at 250 mg/kg/day; cadmium exposure and treated with ethyl acetate fraction at 62.5 mg/kg/day. For evaluating the toxicogenetic potential of mimosa, two groups were included in the study being treated with extract at 250 mg/kg/day and acetate fraction of mimosa at 62 mg/kg/day, only. Extract of mimosa at concentrations of 62.5 and 125 mg decreased DNA damage in animals intoxicated with cadmium when compared to cadmium group. In a similar manner, treatment with ethyl acetate fraction of mimosa at 62.5 mg concentration in animals previously exposed to cadmium reduced genetic damage in peripheral blood cells. In a similar manner, the treatment with ethyl acetate fraction reduced DNA damage in liver cells. Oxidative DNA damage was reduced to animals exposed to cadmium and treated with 125 mg of extract as well as those intoxicated to cadmium and treated with 62.5 of acetate fraction of mimosa. Taken together, our results indicate that mimosa prevents genotoxicity induced by cadmium exposure in liver and peripheral blood cells of rats as a result of antioxidant activity.
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Dubey, Manish K.; Aamir, Mohd; Kaushik, Manish S.; Khare, Saumya; Meena, Mukesh; Singh, Surendra; Upadhyay, Ram S.
2018-01-01
Out of the various mycotoxigenic food and feed contaminant, the fungal species belonging to Penicillium genera, particularly Penicillium roqueforti is of great economic importance, and well known for its crucial role in the manufacturing of Roquefort and Gorgonzola cheese. The mycotoxicosis effect of this mold is due to secretion of several metabolites, of which PR toxin is of considerable importance, with regard to food quality and safety challenges issues. The food products and silages enriched with PR toxin could lead into damage to vital internal organs, gastrointestinal perturbations, carcinogenicity, immunotoxicity, necrosis, and enzyme inhibition. Moreover, it also has the significant mutagenic potential to disrupt/alter the crucial processes like DNA replication, transcription, and translation at the molecular level. The high genetic diversities in between the various strains of P. roqueforti persuaded their nominations with Protected Geographical Indication (PGI), accordingly to the cheese type, they have been employed. Recently, the biosynthetic mechanism and toxicogenetic studies unraveled the role of ari1 and prx gene clusters that cross-talk with the synthesis of other metabolites or involve other cross-regulatory pathways to negatively regulate/inhibit the other biosynthetic route targeted for production of a strain-specific metabolites. Interestingly, the chemical conversion that imparts toxic properties to PR toxin is the substitution/oxidation of functional hydroxyl group (-OH) to aldehyde group (-CHO). The rapid conversion of PR toxin to the other derivatives such as PR imine, PR amide, and PR acid, based on conditions available reflects their unstability and degradative aspects. Since the PR toxin-induced toxicity could not be eliminated safely, the assessment of dose-response and other pharmacological aspects for its safe consumption is indispensable. The present review describes the natural occurrences, diversity, biosynthesis, genetics, toxicological aspects, control and prevention strategies, and other management aspects of PR toxin with paying special attention on economic impacts with intended legislations for avoiding PR toxin contamination with respect to food security and other biosafety purposes. PMID:29651243
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Dubey, Manish K; Aamir, Mohd; Kaushik, Manish S; Khare, Saumya; Meena, Mukesh; Singh, Surendra; Upadhyay, Ram S
2018-01-01
Out of the various mycotoxigenic food and feed contaminant, the fungal species belonging to Penicillium genera, particularly Penicillium roqueforti is of great economic importance, and well known for its crucial role in the manufacturing of Roquefort and Gorgonzola cheese. The mycotoxicosis effect of this mold is due to secretion of several metabolites, of which PR toxin is of considerable importance, with regard to food quality and safety challenges issues. The food products and silages enriched with PR toxin could lead into damage to vital internal organs, gastrointestinal perturbations, carcinogenicity, immunotoxicity, necrosis, and enzyme inhibition. Moreover, it also has the significant mutagenic potential to disrupt/alter the crucial processes like DNA replication, transcription, and translation at the molecular level. The high genetic diversities in between the various strains of P. roqueforti persuaded their nominations with Protected Geographical Indication (PGI), accordingly to the cheese type, they have been employed. Recently, the biosynthetic mechanism and toxicogenetic studies unraveled the role of ari1 and prx gene clusters that cross-talk with the synthesis of other metabolites or involve other cross-regulatory pathways to negatively regulate/inhibit the other biosynthetic route targeted for production of a strain-specific metabolites. Interestingly, the chemical conversion that imparts toxic properties to PR toxin is the substitution/oxidation of functional hydroxyl group (-OH) to aldehyde group (-CHO). The rapid conversion of PR toxin to the other derivatives such as PR imine, PR amide, and PR acid, based on conditions available reflects their unstability and degradative aspects. Since the PR toxin-induced toxicity could not be eliminated safely, the assessment of dose-response and other pharmacological aspects for its safe consumption is indispensable. The present review describes the natural occurrences, diversity, biosynthesis, genetics, toxicological aspects, control and prevention strategies, and other management aspects of PR toxin with paying special attention on economic impacts with intended legislations for avoiding PR toxin contamination with respect to food security and other biosafety purposes.
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Liu, Yi; Junaid, Muhammad; Wang, Yan; Tang, Yu-Mei; Bian, Wan-Ping; Xiong, Wen-Xu; Huang, Hai-Yang; Chen, Chun-Di; Pei, De-Sheng
2018-06-09
Tetracycline hydrochloride (TH), indomethacin (IM), and bezafibrate (BF) belong to the three different important classes of pharmaceuticals, which are well known for their toxicity and environmental concerns. However, studies are still elusive to highlight the mechanistic toxicity of these pharmaceuticals and rank them using both, the toxicity prediction and confirmation approaches. Therefore, we employed the next generation toxicity testing in 21st century (TOX21) tools and estimated the in vitro/vivo toxic endpoints of mentioned pharmaceuticals, and then confirmed them using in vitro/vivo assays. We found significant resemblance in the results obtained via both approaches, especially in terms of in vivo LC50 s and developmental toxicity that ranked IM as most toxic among the studied pharmaceuticals. However, TH appeared most toxic with the lowest estimated AC50s, the highest experimental IC50s, and DNA damages in vitro. Contrarily, IM was found as congener with priority concern to activate the Pi3k-Akt-mTOR pathway in vitro at concentrations substantially lower than that of TH and BF. Further, IM exposure at lower doses (2.79-13.97 μM) depressed the pharmaceuticals detoxification phase I (CYP450 s), phase II (UGTs, SULTs), and phase III (TPs) pathways in zebrafish, whereas, at relatively higher doses, TH (2.08-33.27 μM) and BF (55.28-884.41 μM) partially activated these pathways, which ultimately caused the developmental toxicity in the following order: IM > TH > BF. In addition, we also ranked these pharmaceuticals in terms of their particular toxicity to myogenesis, hematopoiesis, and hepatogenesis in zebrafish embryos. Our results revealed that IM significantly affected myogenesis, hematopoiesis, and hepatogenesis, while TH and BF induced prominent effects on hematopoiesis via significant downregulation of associated genetic markers, such as drl, mpx, and gata2a. Overall, our findings confirmed that IM has higher toxicity than that of TH and BF, therefore, the consumption of these pharmaceuticals should be regulated in the same manner to ensure human and environmental safety. Copyright © 2018 Elsevier B.V. All rights reserved.