Toxicology Mechanisms and Methods最新文献

{"title":"Correction to: Abdel Baky, Fadda, Al-Rasheed, Al-Rasheed, Mohamed, and Yacoub, Neuroprotective effect of carnosine and cyclosporine-a against inflammation, apoptosis, and oxidative brain damage after closed head injury in immature rats","authors":"N. A. Baky, Laila M. Fadda, N. Al-rasheed, N. Al-Rasheed, A. Mohamed, H. Yacoub","doi":"10.1080/15376516.2017.1283773","DOIUrl":"https://doi.org/10.1080/15376516.2017.1283773","url":null,"abstract":"","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2016-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2017.1283773","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59851295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cadmium induces oxidative stress and apoptosis in lung epithelial cells","authors":"K. K. Kiran Kumar, M. Naveen Kumar, R. Patil, Rashmi Nagesh, Shubha M. Hegde, K. Kavya, R. Babu, G. Ramesh, S. C. Sharma","doi":"10.1080/15376516.2016.1223240","DOIUrl":"https://doi.org/10.1080/15376516.2016.1223240","url":null,"abstract":"Abstract Cadmium (Cd) is one of the well-known highly toxic environmental and industrial pollutants. Cd first accumulates in the nucleus and later interacts with zinc finger proteins of antiapoptotic genes and inhibit the binding of transcriptional factors and transcription. However, the role of Cd in oxidative stress and apoptosis is less understood. Hence, the present study was undertaken to unveil the mechanism of action. A549 cells were treated with or without Cd and cell viability was measured by MTT assay. Treatment of cells with Cd shows reduced viability in a dose-dependent manner with IC50 of 45 μM concentration. Cd significantly induces the reactive oxygen species (ROS), lipid peroxidation followed by membrane damage with the leakage of lactate dehydrogenase (LDH). Cells with continuous exposure of Cd deplete the antioxidant super oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes. Further, analysis of the expression of genes involved in apoptosis show that both the extrinsic and intrinsic apoptotic pathways were involved. Death receptor marker tumor necrosis factor-α (TNF-α), executor caspase-8 and pro-apoptotic gene (Bax) were induced, while antiapoptotic gene (Bcl-2) was decreased in Cd-treated cells. Fluorescence-activated cell sorting (FACS) analysis further confirms the induction of apoptosis in Cd-treated A549 cells.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2016-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1223240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59851622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An investigation of the developmental neurotoxic potential of curcumol in PC12 cells","authors":"Chunlei Yu, Xiaojie Sun, Y. Niu","doi":"10.1080/15376516.2016.1207735","DOIUrl":"https://doi.org/10.1080/15376516.2016.1207735","url":null,"abstract":"Abstract Curcuma phaeocaulis Val. is a Chinese medicinal herb that is contraindicated during pregnancy for over a thousand years in China. The aims of the present study were to evaluate the effect of curcumol (one of the major components of C. phaeocaulis Val.) on neurite outgrowth and characterize the signal transduction pathways in PC12 cells. Curcumol significantly inhibited neurite outgrowth and cell proliferation, but did not cause cell death at a concentration of 450 μM in differentiated PC12 cells. In addition, curcumol evoked oxidative stress and it was indicated by an elevation in reactive oxygen species (ROS) and lipid peroxidation (LPO). Although PC12 cells exhibited inhibition of the differentiation into the acetylcholine (ACh) phenotype following 450 μM curcumol exposure, there was no significant alteration in net shift toward the ACh phenotype or tyrosine hydroxylase (TH) phenotype was observed. Neural cell adhesion molecule (NCAM)/focal adhesion kinase (FAK) but not extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling was repressed by curcumol exposure in differentiated PC12 cells. Curcumol does not affect calpain activity and nuclear factor-κB (NF-κB) DNA-binding activity. These findings suggest that curcumol might be a developmental neurotoxicant and NCAM/FAK signaling pathway may play an important role in curcumol-evoked inhibition of neurite outgrowth.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2016-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1207735","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59851096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does age matter? Comparison of neurobehavioral effects of paraquat exposure on postnatal and adult C57BL/6 mice","authors":"D. Lou, Qiaochu Wang, Min Huang, Zhijun Zhou","doi":"10.1080/15376516.2016.1223241","DOIUrl":"https://doi.org/10.1080/15376516.2016.1223241","url":null,"abstract":"Abstract Epidemiological studies have revealed that environmentally relevant low levels of paraquat (PQ) exposure is listed on the etiology of neurological disorders such as Parkinson’s disease (PD). The behavioral effects of PQ are of current interest, especially when exposure occurs in the period of early stage of life. To characterize whether and how age affects neurobehavioral performances of mice after PQ exposure, 21 days postnatal (PN21) and adult male C57BL/6 mice were daily administrated by oral gavage with 0 mg/kg (saline, control), 5 mg/kg or 10 mg/kg of PQ for 28 consecutive days. Survival rate and body weight were analyzed. Subsequently, mice were subjected to Morris water maze tests (MWM). The results showed that mice exposed to PQ had significantly longer latencies than those in the control group, with a dose-dependent manner. Furthermore, PN21 mice tended to have longer latencies than adult mice in the same dose group. Our data suggested that PQ exposure induced significant learning and memory impairment and more severely in PN21 mice when compared with adult mice.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2016-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1223241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59851216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An investigation of the mutagenic activity of salamide – a major impurity of hydrochlorothiazide","authors":"E. Emerce, I. Cok, Sibel Sarı, Omur Bostanci","doi":"10.1080/15376516.2016.1222642","DOIUrl":"https://doi.org/10.1080/15376516.2016.1222642","url":null,"abstract":"Abstract Hydrochlorothiazide is a widely used antihypertensive agent and one of its major impurities, salamide (4-amino-6-chlorobenzene-1,3-disulphonamide), has a chemical structure containing a primary amino group, a functional group that has previously been reported to be associated with carcinogenic activity. It is known that hydrochlorothiazide purity is a challenging problem for the pharmaceutical industry. As there were no prior mutagenicity data for the impurity salamide, the aim was to investigate its mutagenicity in this study. Salamide was tested for mutagenic potential in Salmonella typhimurium TA98, TA100, TA 1535, TA 1537, and E. coli WP2 uvrA + E. coli WP2 [pKM101] strains at six different concentrations, the highest concentration being the 5000 μg/plate. In both the presence and absence of the metabolic activation system, no mutagenic activity was observed. Results indicated that salamide should be classified as an ordinary impurity and controlled according to Q3A(R2) and Q3B(R2) guidelines.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2016-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1222642","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59851611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic and skeletal muscle mitochondrial toxicity of chitosan oligosaccharides of normal and diabetic rats","authors":"J. Teodoro, A. P. Gomes, A. T. Varela, F. V. Duarte, A. Rolo, C. Palmeira","doi":"10.1080/15376516.2016.1222643","DOIUrl":"https://doi.org/10.1080/15376516.2016.1222643","url":null,"abstract":"Abstract Diabetes and associated conditions are now considered a worldwide epidemic, with increasing costs and burdens with no cure yet developed. The chitin-derived glucosamine biopolymer chitosan has shown promising results when supplied to diabetic patients. However, no study has investigated the possible toxic side effects of chitosan treatments, in particular when regarding the most important bioenergetic organelle, mitochondria. As such, we aimed to understand if supplementation of chitosan to the diet of normal and diabetic rats could compromise mitochondrial function on two of the major organs involved in diabetes, obesity, and metabolic regulation, the liver and skeletal muscle. We supplemented the drinking water of normal Wistar and diabetic Goto–Kakizaki rats with 0.5% chitosan for 6 weeks. We show here that, in terms of hepatic bioenergetics, chitosan was relatively inert and had no major side effects. However, regarding skeletal muscle bioenergetics, chitosan significantly affected various bioenergetic parameters. As such, we conclude that chitosan, at the tested doses, is relatively safe for treatment of diabetic situations. Nonetheless, the potential for adverse toxicological side effects appears to be present, which might be relevant if higher doses are utilized.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2016-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1222643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59851619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apremilast reversed carfilzomib-induced cardiotoxicity through inhibition of oxidative stress, NF-κB and MAPK signaling in rats","authors":"F. Imam, N. Al-Harbi, M. M. Al-Harbi, M. Ansari, Mashal M. Almutairi, M. Alshammari, T. S. Almukhlafi, M. Ansari, K. Aljerian, S. Ahmad","doi":"10.1080/15376516.2016.1236425","DOIUrl":"https://doi.org/10.1080/15376516.2016.1236425","url":null,"abstract":"Abstract Carfilzomib (CFZ), is a potent, selective second generation proteasome inhibitor, used for the treatment of multiple myeloma. The aim of the present study was to investigate the possible protective effect of apremilast (AP) on the CFZ -induced cardiotoxicity. Rats were randomly divided into four groups: Group 1, served as the control group, received normal saline. Group 2, served as the toxic group, received CFZ (4 mg/kg, intraperitoneally [i.p.]). Groups 3 and 4, served as treatment groups, and received CFZ with concomitant oral administration of AP in doses of 10 and 20 mg/kg/day, respectively. In the present study, administration of CFZ resulted in a significant increase in serum aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase-MB (CK-MB), which were reversed by treatment with AP. CFZ resulted in a significant increase in heart malondialdehyde (MDA) contents and decrease in cardiac glutathione (GSH) level and catalase (CAT) enzyme activity which were significantly reversed by treatment with AP. Induction of cardiotoxicity by CFZ significantly increased caspase-3 enzyme activity which were reversed by treatment with AP. RT-PCR analysis revealed an increased mRNA expression of NF-κB, ERK and JNK which were reversed by treatment with AP in cardiac tissues. Western blot analysis revealed an increased expression of caspase-3 and NF-κB p65 and a decrease expression of inhibitory kappa B-alpha (Iκbα) with CFZ, which were reversed by treatment with AP. In conclusion, apremilast showed protective effect against CFZ-induced cardiotoxicity.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2016-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1236425","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59851281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alleviation of bone markers in rats induced nano-zinc oxide by qurecetin and α-lipolic acid","authors":"Hala M Abdelkarem, Laila M. Fadda, Omyma R Kaml","doi":"10.1080/15376516.2016.1236424","DOIUrl":"https://doi.org/10.1080/15376516.2016.1236424","url":null,"abstract":"Abstract The purpose of this study was to evaluate the potential protective effect of qurecetin (Qur) and α-lipolic acid (ALA) to modulate the perturbation of bone turnover which is induced by nano-zinc oxide (n-ZnO). Rats were fasted overnight and randomly divided into two groups: G1, normal healthy animals and the other rats were administered zinc oxide nanoparticles orally by guava in a dose of 600 mg/kg body weight/d for 5 sequential days in Wistar albino male rats. N-ZnO-exposed animals were randomly sub-divided into three groups: G2, n-ZnO-exposed animals; G3, n-ZnO-exposed animals co-treated with Qur (200 mg/kg daily); and G4, n-ZnO-exposed animals co-treated with ALA (200 mg/kg). Qur and ALA were administered orally by guava daily for three sequential weeks from the beginning of the experiment. The results revealed a significant reduction of nitiric oxide (NO) and serum level and comet assay in n-ZnO exposure rats after treatment of Qur and ALA. It was found the alteration of pro-inflammatory markers (tumor necrosis factor alpha; TNF-α, interleukin-6; IL-6 and C-reactive protein; CRP), bone alkaline phosphatase (B-ALP, bone formation marker), and C-terminal peptide type I collagen (CTx, bone resorption marker) levels compared with the normal group. Co-administration of Qur and ALA in n-ZnO-exposed rats significantly alleviated the mentioned alterations of biochemical parameters. These results suggest that Qur and ALA as antioxidant agents may be a candidate for preventive and treatment applications of impaired bone markers induced bone loss caused by nano-particles of metal oxide.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2016-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1236424","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59851220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of protriptyline on [Ca2+]i and viability in MG63 human osteosarcoma cells","authors":"Ching-Kai Su, C. Chou, Ko-Long Lin, Wei-Zhe Liang, Jin‐shiung Cheng, Hong‐Tai Chang, I. Chen, T. Lu, C. Kuo, Chia-Cheng Yu, Pochuen Shieh, D. Kuo, Fu-An Chen, C. Jan","doi":"10.1080/15376516.2016.1216208","DOIUrl":"https://doi.org/10.1080/15376516.2016.1216208","url":null,"abstract":"Abstract Tricyclic antidepressants (TCA) have been clinically prescribed in the auxiliary treatment of cancer patients. Although protriptyline, a type of TCA, was used primarily in the clinical treatment of mood disorders in cancer patients, the effect of protriptyline on physiology in human osteosarcoma is unknown. This study examined the effect of protriptyline on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability in MG63 human osteosarcoma cells. Protriptyline between 50 and 250 μM evoked [Ca2+]i rises concentration-dependently. Protriptyline induced influx of Mn2+, indirectly implicating Ca2+ influx. Protriptyline-evoked Ca2+ entry was inhibited by nifedipine by 20% but was not altered by econazole, SKF96365, GF109203X, and phorbol-12-myristate-13-acetate (PMA). In Ca2+-free medium, treatment with protriptyline inhibited the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin-evoked [Ca2+]i rises. Conversely, treatment with thapsigargin inhibited 45% of protriptyline-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 failed to alter protriptyline-evoked [Ca2+]i rises. Protriptyline at 50–250 μM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, our data suggest that in MG63 cells, protriptyline induced [Ca2+]i rises by evoking Ca2+ release from the endoplasmic reticulum and other stores in a PLC-independent manner, and Ca2+ entry via a nifedipine-sensitive Ca2+ pathway. Protriptyline also caused Ca2+-independent cell death.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2016-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1216208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59850813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Special issue on electronic cigarettes","authors":"R. Dixit","doi":"10.1080/15376516.2016.1221267","DOIUrl":"https://doi.org/10.1080/15376516.2016.1221267","url":null,"abstract":"The recent rise in public interest in electronic nicotine delivery systems (ENDS) such as electronic cigarettes (e-cigarettes) has attracted significant attention from health practitioners, policy makers and regulatory authorities, investigative researchers, and the private industry. Tobacco use is clearly preventable, and according to health authorities at regulatory agencies is the single largest preventable cause of disease and death in the United States (FDA, 2016). E-cigarettes have been developed in recent years and predicated as an alternative to combustible cigarettes in a harm-reduction strategy. However, there are many outstanding questions regarding the role and impact of electronic cigarettes in public health, and many of these have been brought forth in both scientific and medical publications as well as government reports Long-term adverse health effects of e-cigarettes or ENDS remain poorly understood. Unlike combustible cigarettes or other smoked tobacco products , it is believed that e-cigarettes have less toxic and carcinogenic byproducts. However, recent data indicate that many e-cigarettes seemed to have significant amounts of for-maldehyde, acetaldehyde and heavy metals, including nickel and chromium. Additionally, continuous exposure to ENDS has resulted in increased airway resistance with increased bacterial colonization and adverse vascular hemodynamics. A current view is that there are limited data and a need for new knowledge regarding enhancing our current understanding of the potential human health effects and risks of electronic cigarettes (Callahan-Lyon, 2014). Moreover, there is a need for description of toxicological methods and monitoring for biomarkers, a better understanding of potential beneficial effects, further hazard characterization of e-liquid, and development of frameworks for assessing the risks of these new and emerging tobacco products as well as many other areas in clinical science, non-clinical science, and social science. In an effort to stimulate and increase new scientific knowledge on the toxicological aspects and methods for assessing health effects of electronic cigarettes, Toxicology Mechanisms and Methods, presents its Special Issue on Electronic Cigarettes. A brief summary of the content in this Special Issue follows. One of the components of ENDS that are often of focus by consumers is new e-liquids. E-liquids are known to contain flavors and have been shown to play an important role in the overall experience of electronic cigarettes (Costigan and Meredith, 2015). Consequently, having a framework for assessing the toxicology of e-liquids is important. In this issue, a research article appears which describes a framework using an in vitro systems toxicology assessment of e-liquids (Iskandar et …","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2016-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15376516.2016.1221267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59850891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}