Journal of Toxicology and Environmental Health, Part A最新文献

{"title":"Risk assessment of <i>in vitro</i> cytotoxicity, antioxidant and antimicrobial activities of <i>Mentha piperita</i> L. essential oil.","authors":"W M F Silva,&nbsp;N P Bona,&nbsp;N S Pedra,&nbsp;K F Da Cunha,&nbsp;A M Fiorentini,&nbsp;F M Stefanello,&nbsp;E R Zavareze,&nbsp;A R G Dias","doi":"10.1080/15287394.2021.1999875","DOIUrl":"https://doi.org/10.1080/15287394.2021.1999875","url":null,"abstract":"<p><p>The objective of this study was to determine the chemical composition as well as antioxidant, antibacterial, and cytotoxic properties of the essential oil of <i>Mentha piperita</i> L. (peppermint). Fifteen chemical constituents were identified in the essential oil, for a total of 99.99% of the compounds. The essential oil exhibited antimicrobial activity against two Gram-positive bacteria <i>Staphylococcus aureus</i> and <i>Listeria monocytogenes</i>. The minimum inhibitory concentration (MIC) of essential oil of <i>Mentha piperita</i> L. for <i>Staphylococcus aureus</i> and <i>Listeria monocytogenes</i> was 1.84 μg/ml, whereas the minimum bactericidal concentration (MBC) values were 3.7 and 7.43 μg/ml, respectively. The oil displayed potent antioxidant activity inhibiting up to approximately73% of 2,2'-azinothiobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals. In the cytotoxicity assay, the highest essential oil concentration (100 μg/ml) resulted in viability of approximately 90% human epidermal keratinocyte (HaCaT) cells. With respect to antitumor activity in C6 rat glioma cells, there was significant reduction in cell viability: 56-74% in 24 hr, and 71-77% in 48 hr. Data suggest that in presence of the essential oil of <i>Mentha piperita</i> L. antioxidant, antibacterial, antitumor and non-cytotoxic properties were noted.</p>","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":" ","pages":"230-242"},"PeriodicalIF":2.6,"publicationDate":"2022-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39626934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systems toxicology approach explores target-pathway relationship and adverse health impacts of ubiquitous environmental pollutant bisphenol A.","authors":"Manigandan Nagarajan,&nbsp;Gobichettipalayam Balasubramaniam Maadurshni,&nbsp;Jeganathan Manivannan","doi":"10.1080/15287394.2021.1994492","DOIUrl":"https://doi.org/10.1080/15287394.2021.1994492","url":null,"abstract":"<p><p>The effects of environmental chemicals on health outcomes may be underestimated due to deficiency of knowledge regarding the actions of compounds on toxico-pathogenic mechanisms underlying biological systems outcomes. In this regard, the current study aimed to explore the potential target-pathway-disease relationship attributed to bisphenol A (BPA) responses in target tissues. Computational methods including reverse pharmacophore mapping approach, structural similarity based search and kinome wide interaction profiling were employed with molecular docking validation. Gene ontology (GO) enrichment analysis and protein-protein interaction (PPI) network based illustrations were utilized to prioritize target-pathway and disease relationships. Data illustrated that BPA possessed multi-target nature since this chemical potentially interacted with various protein targets where many of these were validated through docking. Potential BPA targets were significantly enriched to various cellular signaling pathways including steroid biosynthesis, peroxisome proliferator-activated receptor gamma (PPARℽ) and cancer. Further, hypertension was prioritized as disease target. In addition, BPA targeted 17 cell signaling kinases encompassed in the human kinome. In addition, inflammatory (5-LO) and apoptosis regulators (Bcl-X and Bcl-2) were also explored as novel targets. Evidence indicates that the multi-target nature and plausible mechanisms underlying BPA actions in a system wide manner aids toward understanding of adverse effects. This observation may lead us to more precise method to elucidate the toxico-pathogenic mechanisms of BPA with an environmental health perspective.</p>","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":" ","pages":"217-229"},"PeriodicalIF":2.6,"publicationDate":"2022-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39563760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of <i>in vitro</i> cytotoxicity and <i>in vivo</i> potential toxicity of the extract from <i>in vitro</i> cultivated <i>Anoectochilus roxburghii</i> Lindl.","authors":"Doan Chinh Chung,&nbsp;Thanh Long Le,&nbsp;Nguyen Quynh Chi Ho,&nbsp;Thi Thuy Nguyen,&nbsp;Dang Giap Do,&nbsp;Duc Thang Do,&nbsp;Thi Phuong Mai Nguyen,&nbsp;Thi Phuong Thao Nguyen,&nbsp;Nghia Son Hoang","doi":"10.1080/15287394.2021.1963363","DOIUrl":"https://doi.org/10.1080/15287394.2021.1963363","url":null,"abstract":"<p><p><i>Anoectochilus roxburghii</i> Lind. (<i>A. roxburghii</i>) has promising anti-oxidant, hyperglycemic, hepatoprotective, and immunomodulatory activities as well as anti-tumor effects. However, the pharmacological actions of <i>in vitro</i> cultured plants remain to be determined. Therefore, the objective of the study was to assess <i>in vitro</i> cytotoxicity and <i>in vivo</i> potential toxicity of an extract derived from <i>in vitro</i> cultivated <i>A. roxburghii</i>, termed as iARE. The total flavonoid content and predominant flavonoid compounds of extract were identified and quantitatively analyzed. <i>The in vitro</i> cytotoxicity of iARE was examined using several cancer and normal cell lines. The apoptotic activity and expression of apoptosis-associated genes were also examined in MCF7 cells to determine the underlying mechanisms related to anti-proliferative effects. <i>In vivo</i> potential toxicity of iARE was assessed following acute and subchronic oral administration in Sprague Dawley rats. Quercetin, kaempferol, and isorhamnetin were three flavonoid components identified in iARE. The extract exerted cytotoxic effects on various cancer cells but not normal fibroblasts. Apoptosis in MCF7 cells was induced by iARE in a concentration-dependent manner associated with increased Bax/Bcl-2 ratio and reduced mitochondrial membrane potential ΔΨm, leading to release of cytochrome c, activation of caspase-3/7 and caspase-9, and cleavage of PARP. In the acute oral toxicity study, no mortality or toxicological signs were observed in rats at 1000 or 5000 mg/kg. In a subchronic oral toxicity study, iARE at a dosage of up to 1000 mg/kg produced no mortality or treatment-related adverse effects on general behavior, food intake, body weight, relative organ weights. No apparent marked changes in the histopathology of the liver and kidney were detected. Data demonstrated that iARE induced <i>in vitro</i> cytotoxic effects in cancer cells are associated with lackof <i>invivo</i> toxicity. Thus, iARE was suggested to be considered as apotential therapeutic candidate for cancer treatment.</p>","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":" ","pages":"987-1003"},"PeriodicalIF":2.6,"publicationDate":"2021-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39315475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of tobacco compound 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on the expression of epigenetically regulated genes in lung carcinogenesis.","authors":"Sun Woo Jin,&nbsp;Jong Seung Im,&nbsp;Jae Hyeon Park,&nbsp;Hyung Gyun Kim,&nbsp;Gi Ho Lee,&nbsp;Se Jong Kim,&nbsp;Seung Jun Kwack,&nbsp;Kyu-Bong Kim,&nbsp;Kyu Hyuck Chung,&nbsp;Byung Mu Lee,&nbsp;Sam Kacew,&nbsp;Hye Gwang Jeong,&nbsp;Hyung Sik Kim","doi":"10.1080/15287394.2021.1965059","DOIUrl":"https://doi.org/10.1080/15287394.2021.1965059","url":null,"abstract":"<p><p>Cigarette smoking is a major cause of lung cancer. Although tobacco smoking-induced genotoxicity has been well established, there is apparent lack of abundance functional epigenetic effects reported On cigarette smoke-induced lung carcinogenesis. The aim of this study was to determine effects of intratracheal administration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) utilizing target gene expression DNA methylation patterns in lung tissues of mice following twice weekly for 8 weeks treatment. An unbiased approach where genomic regions was undertaken to assess early methylation changes within mouse pulmonary tissues. A methylated-CpG island recovery assay (MIRA) was performed to map the DNA methylome in lung tissues, with the position of methylated DNA determined using a Genome Analyzer (MIRA-SEQ). Alterations in epigenetic-regulated target genes were confirmed with quantitative reverse transcription-PCR, which revealed 35 differentially hypermethylated genes including <i>Cdkn1C, Hsf4, Hnf1a, Cdx1</i>, and <i>Hoxa5</i> and 30 differentially hypomethylated genes including <i>Ddx4, Piwi1, Mdm2</i>, and <i>Pce1</i> in NNK-exposed lung tissue compared with controls. The main pathway of these genes for mediating biological information was analyzed using the Kyoto Encyclopedia of Genes and Genomes database. Among them, <i>Rssf1</i> and <i>Mdm2</i> were closely associated with NNK-induced lung carcinogenesis. Taken together, our data provide valuable resources for detecting cigarette smoke-induced lung carcinogenesis.</p>","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":" ","pages":"1004-1019"},"PeriodicalIF":2.6,"publicationDate":"2021-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39368962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of models for predicting pediatric fraction unbound in plasma for human health risk assessment.","authors":"Yejin Esther Yun,&nbsp;Andrea N Edginton","doi":"10.1080/15287394.2020.1835761","DOIUrl":"https://doi.org/10.1080/15287394.2020.1835761","url":null,"abstract":"<p><p>Pediatric physiologically based pharmacokinetic (PBPK) models facilitate the prediction of PK parameters in children under specific exposure conditions. Pharmacokinetic outcomes are highly sensitive to fraction unbound in plasma (fup) as incorporated into PBPK models. Rarely is fup in children (fup_child) experimentally derived and prediction is based upon fup in adults (fup_adult) as well as a ratio of plasma protein concentrations between children and adults. The objectives were to (i) evaluate protein concentration vs. age profile derived from ontogeny models, (ii) assess predictive performances of fup ontogeny models, and (iii) determine overall uncertainty in fup_child prediction resulting from a combination of quantitative structure-property relationship (QSPR) model and ontogeny models. The plasma albumin and alpha-acid glycoprotein (AAG) concentration data for pediatrics and fup_child and fup_adult data were obtained from literature. The protein concentration vs. age profile derived from ontogeny models were compared to observed levels. Fup_child values were calculated according to ontogeny models using both observed and QSPR-predicted fup_adult as inputs and predictive performances of ontogeny models assessed by comparing predicted fup_child to observed values. Protein concentrations vs. age profiles derived from non-linear equations were more congruent with observed albumin levels than linear or step-wise models. When observed fup_adult values were used as input, the fup_child data were under-predicted with average fold error (AFE) amounts ranging 0.79-0.81 and 0.77-0.97 for albumin and AAG ontogeny models, respectively. When QSPR-predicted fup_adult values were used as input, AFE of fup_child ranged 1.2-1.35 and 0.98-1.2 for albumin and AAG models, respectively. The choice of ontogeny model with respect to prediction accuracy is more important for AAG, highly bound compounds and infants. For these compounds and scenarios, experimental determination of fup_child for inclusion into a pediatric PBPK model is necessary to have confidence in PBPK model outputs.</p>","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":" ","pages":"67-83"},"PeriodicalIF":2.6,"publicationDate":"2021-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15287394.2020.1835761","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40567436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the effects of repeated doses of potassium iodide intake during pregnancy on male and female rat offspring using metabolomics and lipidomics.","authors":"Clément Rosique,&nbsp;Dalila Lebsir,&nbsp;Philippe Lestaevel,&nbsp;Sheherazade Benatia,&nbsp;Pierre Guigon,&nbsp;François Caire-Maurisier,&nbsp;Marc Benderitter,&nbsp;Djawed Bennouna,&nbsp;Maâmar Souidi,&nbsp;Jean-Charles Martin","doi":"10.1080/15287394.2019.1625474","DOIUrl":"https://doi.org/10.1080/15287394.2019.1625474","url":null,"abstract":"<p><p>Preparedness for nuclear accident responsiveness includes interventions to protect pregnancies against prolonged exposure to radioactive iodine. The aim of this study was to investigate a new design consisting of repeated administration of potassium iodide (KI, 1 mg/kg) for 8 days in late pregnancy gestational day 9-16 (GD9-GD16) in rats. The later-life effects of this early-life iodine thyroid blocking (ITB) strategy were assessed in offspring two months afterbirth. Functional behavioral tests including forced swimming test (FST) and rotarod test (RRT) in rats of both genders showed lower FST performance in KI-treated females and lower RRT performance in KI-treated male pups. This performance decline was associated with metabolic disruptions in cortex involving amino acid metabolism, tyrosine metabolism, as well as docosahexaenoic acid (DHA) lipids and signaling lipids in males and females. Beyond these behavior-associated metabolic changes, a portion of the captured metabolome (17-25%) and lipidome (3.7-7.35%) remained sensitive to <i>in utero</i> KI prophylactic treatment in both cortex and plasma of post-weaning rats, with some gender-related variance. Only part of these disruptions was attributed to lower levels of TSH and T4 (males only). The KI-induced metabolic shifts involved a broad spectrum of functions encompassing metabolic and cell homeostasis and cell signaling functions. Irrespective Regardless of gender and tissues, the predominant effects of KI affected neurotransmitters, amino acid metabolism, and omega-3 DHA metabolism. Taken together, data demonstrated that repeated daily KI administration at 1 mg/kg/day for 8 days during late pregnancy failed to protect the mother-fetus against nuclear accident radiation. <b>Abbreviations:</b> CV-ANOVA: Cross-validation analysis of variance; DHA: Docosahexaenoic acid; FST: Forced swimming test; FT3: plasma free triiodothyronine; FT4: plasma free thyroxine; GD: Gestational day; ITB: Iodine thyroid blocking; KI: potassium iodide; LC/MS: Liquid chromatography coupled with mass spectrometry; MTBE: Methyl tert-butyl ether; m/z: mass-to-charge ratio; PLS-DA: Partial least squares-discriminant analysis; PRIODAC: Repeated stable iodide prophylaxis in accidental radioactive releases; RRT: Rotarod test; TSH: Thyroid-stimulating hormone; VIP: Variable importance in projection.</p>","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":" ","pages":"603-615"},"PeriodicalIF":2.6,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15287394.2019.1625474","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40563498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function.","authors":"Aleksandra Nikolić-Kokić,&nbsp;Nikola Tatalović,&nbsp;Jelena Nestorov,&nbsp;Milica Mijović,&nbsp;Ana Mijusković,&nbsp;Marko Miler,&nbsp;Zorana Oreščanin-Dušić,&nbsp;Milan Nikolić,&nbsp;Verica Milošević,&nbsp;Duško Blagojević,&nbsp;Mihajlo Spasić,&nbsp;Čedo Miljević","doi":"10.1080/15287394.2018.1495587","DOIUrl":"https://doi.org/10.1080/15287394.2018.1495587","url":null,"abstract":"<p><p>Atypical antipsychotics produce severe side effects including myocarditis that may be attributed to oxidative stress. The aim of this study was to investigate the influence of clozapine, ziprasidone, and sertindole on rat heart morphology and determine whether redox imbalane plays a role in development of histopathological changes. Adult 3-month-old male Wistar rats were treated with recommended daily dose for selected drugs. After 4 week treatment histopathological analysis of the heart was performed and expression and activity of antioxidant enzymes determined. All examined drugs induced histopathological changes that were characterized as toxic myocarditis. Degenerative changes in cardiomyocytes were accompanied by lymphocytic infiltration as well as pericardial histopathological alterations in all treated groups. The least prominent changes were observed in sertindole-treated animals, and most severe with clozapine. Clozapine increased superoxide dismutase 1 (SOD1) activity while ziprasidone reduced glutathione reductase (GR) activity. Sertindole exerted no marked effect on antioxidant enzyme function in the heart even though myocardial degeneration was noted. In conclusion, treatment with clozapine or ziprasidone induced pathophysiological alterations in rat heart, which appeared to be associated disturbances in antioxidant capacity. Abbreviation: AAP, Atypical antipsychotics; ROS, reactive oxygen species; SOD1, Copper-zinc superoxide dismutase; SOD2, Manganese superoxide dismutase; CAT, Catalase; GPx, Glutathione peroxidase; GR, Glutathione reductase; H&E, hematoxylin and eosin stain; TNF- α, tumor necrosis factor alpha.</p>","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":" ","pages":"844-853"},"PeriodicalIF":2.6,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15287394.2018.1495587","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40442853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pouteria ramiflora (Mart.) Radlk. extract: Flavonoids quantification and chemopreventive effect on HepG2 cells.","authors":"Katiuska Tuttis,&nbsp;Daryne Lu Maldonado Gomes da Costa,&nbsp;Higor Lopes Nunes,&nbsp;Ana Flávia Leal Specian,&nbsp;Juliana Mara Serpeloni,&nbsp;Lourdes Campaner Dos Santos,&nbsp;Eliana Aparecida Varanda,&nbsp;Wagner Vilegas,&nbsp;Wilner Martínez-Lopez,&nbsp;Ilce Mara de Syllos Cólus","doi":"10.1080/15287394.2018.1491911","DOIUrl":"https://doi.org/10.1080/15287394.2018.1491911","url":null,"abstract":"<p><p>Pouteria ramiflora (Mart.) Radlk., popularly known as curriola, is commonly used in Brazil as medicinal plant to treat worm infections, dysentery, pain, inflammation, hyperlipidemia, and obesity. At present the safety of this extract when used therapeutically in human remains to be determined. Thus, the aim of this study was to examine cytotoxicity, antiproliferative, and antimutagenic actions of this extract. The hydroalcoholic extract from P. ramiflora leaves consisted of flavonoids identified and quantified as myricetin-3-O-β-D-galactopyranoside (13.55 mg/g) and myricetin-3-O-α-L-rhamnopyranoside (9.61 mg/g). The extract exhibited cytotoxicity at concentrations higher than 1.5 µg/ml in human hepatocarcinoma (HepG2)and 2.5 µg/ml in non-tumoral primary gastric (GAS) cells using the MTT assay, and at concentrations higher than 3 µg/ml in HepG2 and 3.5 µg/ml in GAS cells by the neutral red assay. The extract did not show antiproliferative effect as evidenced by the nuclear division index (NDI). However, in the presence of benzo[a]pyrene (BaP) (positive control), an enhanced cytostatic effect in the NDI and flow cytometry was noted. It is of interest that when the extract was co-incubated with BaP a significant decrease in DNA damage was observed indicating an antimutagenic action. This protective effect might be attributed to myricetin and gallic acid found in P. ramiflora extract. The low cytotoxicity action and protective effect observed in the present study encourage further studies regarding other biological effects of P. ramiflora, as well as its potential use as a chemopreventive agent.</p>","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":" ","pages":"792-804"},"PeriodicalIF":2.6,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15287394.2018.1491911","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40530761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical and transcriptional analyses of cadmium-induced mitochondrial dysfunction and oxidative stress in human osteoblasts.","authors":"Cristina Monteiro,&nbsp;José Miguel P Ferreira de Oliveira,&nbsp;Francisco Pinho,&nbsp;Verónica Bastos,&nbsp;Helena Oliveira,&nbsp;Francisco Peixoto,&nbsp;Conceição Santos","doi":"10.1080/15287394.2018.1485122","DOIUrl":"https://doi.org/10.1080/15287394.2018.1485122","url":null,"abstract":"<p><p>Cadmium (Cd) accumulation is known to occur predominantly in kidney and liver; however, low-level long-term exposure to Cd may also result in bone damage. Few studies have addressed Cd-induced toxicity in osteoblasts, particularly upon cell mitochondrial energy processing and putative associations with oxidative stress in bone. To assess the influence of Cd treatment on mitochondrial function and oxidative status in osteoblast cells, human MG-63 cells were treated with Cd (up to 65 μM) for 24 or 48 h. Intracellular reactive oxygen species (ROS), lipid and protein oxidation and antioxidant defense mechanisms such as total antioxidant activity (TAA) and gene expression of antioxidant enzymes were analyzed. In addition, Cd-induced effects on mitochondrial function were assessed by analyzing the activity of enzymes involved in mitochondrial respiration, membrane potential (ΔΨm), mitochondrial morphology and adenylate energy charge. Treatment with Cd increased oxidative stress, concomitantly with lipid and protein oxidation. Real-time polymerase chain reaction (qRT-PCR) analyses of antioxidant genes catalase (CAT), glutathione peroxidase 1 (GPX1), glutathione S-reductase (GSR), and superoxide dismutase (SOD1 and SOD2) exhibited a trend toward decrease in transcripts in Cd-stressed cells, particularly a downregulation of GSR. Longer treatment with Cd (48 h) resulted in energy charge states significantly below those commonly observed in living cells. Mitochondrial function was affected by ΔΨm reduction. Inhibition of mitochondrial respiratory chain enzymes and citrate synthase also occurred following Cd treatment. In conclusion, Cd induced mitochondrial dysfunction which appeared to be associated with oxidative stress in human osteoblasts.</p>","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":" ","pages":"705-717"},"PeriodicalIF":2.6,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15287394.2018.1485122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40440513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reverse dosimetry modeling of toluene exposure concentrations based on biomonitoring levels from the Canadian health measures survey.","authors":"Honesty Tohon,&nbsp;Andy Nong,&nbsp;Marjory Moreau,&nbsp;Mathieu Valcke,&nbsp;Sami Haddad","doi":"10.1080/15287394.2018.1534174","DOIUrl":"https://doi.org/10.1080/15287394.2018.1534174","url":null,"abstract":"<p><p>Biomonitoring might provide useful estimates of population exposure to environmental chemicals. However, data uncertainties stemming from interindividual variability are common in large population biomonitoring surveys. Physiologically based pharmacokinetic (PBPK) models might be used to account for age- and gender-related variability in internal dose. The objective of this study was to reconstruct air concentrations consistent with blood toluene measures reported in the third Canadian Health Measures Survey using reverse dosimetry PBPK modeling techniques. Population distributions of model's physiological parameters were described based upon age, weight, and size for four subpopulations (12-19, 20-39, 40-59, and 60-79 years old). Monte Carlo simulations applied to PBPK modeling allowed converting the distributions of venous blood measures of toluene obtained from CHMS into related air levels. Based upon blood levels observed at the 50^th, 90^th and 95^th percentiles, corresponding air toluene concentrations were estimated for teenagers aged 12-19 years as being, respectively, 0.009, 0.04 and 0.06 ppm. Similarly, values were computed for adults aged 20-39 years (0.007, 0.036, and 0.06 ppm), 40-59 years (0.007, 0.036 and 0.06 ppm) and 60-79 years (0.006, 0.022 and 0.04 ppm). These estimations are well below Health Canada's maximum recommended chronic air guidelines for toluene. In conclusion, PBPK modeling and reverse dosimetry may be combined to help interpret biomonitoring data for chemical exposure in large population surveys and estimate the associated toxicological health risk.</p>","PeriodicalId":17418,"journal":{"name":"Journal of Toxicology and Environmental Health, Part A","volume":" ","pages":"1066-1082"},"PeriodicalIF":2.6,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15287394.2018.1534174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40446377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}