Experimental and Toxicologic Pathology最新文献

{"title":"Cytogenotoxicological defense of retinyl palmitate in the front damage of antineoplastics","authors":"Ricardo Melo de Carvalho ,&nbsp;Rai Pablo de Sousa Aguiar ,&nbsp;Muhammad Torequl Islam ,&nbsp;Marcus Vinicius Oliveira Barros de Alencar ,&nbsp;Ana Maria Oliveira Ferreira da Mata ,&nbsp;Antonio Lima Braga ,&nbsp;Josemar José da Silva Júnior ,&nbsp;Leonardo da Rocha Sousa ,&nbsp;Rosália Maria Tôrres de Lima ,&nbsp;Márcia Fernanda Correia Jardim Paz ,&nbsp;João Marcelo de Castro e Sousa ,&nbsp;Ana Amélia de Carvalho Melo-Cavalcante","doi":"10.1016/j.etp.2017.01.013","DOIUrl":"https://doi.org/10.1016/j.etp.2017.01.013","url":null,"abstract":"<div><p><span><span>Cancer, the multifactorial pathology and to date is the most lethal causes of death in the world. Cyclophosphamide (CPA) and </span>doxorubicin<span><span> (DOX) are the individually or combindly used two anticancer drugs. The antineoplastic drugs-mediated genetic instability can be overcome by using antioxidants. The study evaluated the cytogenotoxic modulatory potentials of </span>retinyl palmitate (RP) caused by CPA and DOX in </span></span><em>Swiss</em> mice. For this, adult <span><em>Mus musculus</em></span> of either sex were divided equally regarding to the gender. Toxicogenetic effects were induced by the intraperitoneal (i.p.) administration of the CPA (20<!--> <!-->mg/kg) and/or DOX (2<!--> <span><span>mg/kg), following to test for comet assay and </span>micronucleus<span> test in bone marrow cells after 48</span></span> <!-->h (DOX) and 7<!--> <!-->h (CPA) of the administration of RP (100 IU/kg). Both CPA and DOX significantly (p<!--> <!-->&lt;<!--> <!-->0.05) increased with the index and frequency of damages, clastogenic and/or aneugenic effects with the augmenting of micronuclei, demonstrating the cytotoxicity interference on the ratio of normochromatic to polychromatic erythrocytes and bone marrow cells of mice, that were found to reduce in RP treatment groups. In conclusion, RP has a modulatory effect on CPA and DOX-mediated cytogenotoxic events. The findings may be a good indication to manage the antioneoplastic drug-induced stress mediated detrimental effects by using RP, especially as a side effect minimizer.</p></div>","PeriodicalId":50465,"journal":{"name":"Experimental and Toxicologic Pathology","volume":"69 5","pages":"Pages 293-297"},"PeriodicalIF":0.0,"publicationDate":"2017-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.etp.2017.01.013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71830059","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":"A combined approach to early detect in vitro drug-induced hemostatic changes in preclinical safety","authors":"Myriam Defontis,&nbsp;Serge Côté,&nbsp;David Ledieu","doi":"10.1016/j.etp.2017.01.010","DOIUrl":"https://doi.org/10.1016/j.etp.2017.01.010","url":null,"abstract":"<div><p><span><span>Early detection of drug-induced alterations of hemostasis is challenging. Drugs can affect different components of the Virchow’s triad and measurement of plasmatic coagulation times lacks sensitivity. New techniques for a more global assessment of the hemostasis are now available: the impedance platelet aggregometry, the </span>thromboelastography and the thrombin generation measurement. The aim of this study was to evaluate three techniques (</span><em>i.e.</em>: Multiplate^®, TEG^® and CAT) for the <em>in vitro</em><span><span> detection of the effect of a drug<span> known to induce hemostatic alterations in a preclinical safety environment. </span></span>Cyclosporine<span><span> A was chosen and tested at 4 concentrations after solubilization in </span>DMSO<span> in Wistar rats<span> and Beagle<span> dogs. The results obtained were comparable between both species except for the thrombin generation in platelet rich plasma. Enhanced platelet aggregability was observed after ADP stimulation and alterations of the thromboelastograms consisted in decreased maximum amplitude and increased LY30. A dual effect on thrombin generation was observed and suggested that CsA may interact with platelets in rat platelet rich plasma and speed up thrombin generation. The results of this study indicate that using a combined approach on hemostasis testing in preclinical safety it is possible to detect </span></span></span></span></span><em>in vitro</em> drug-induced alterations of hemostasis.</p></div>","PeriodicalId":50465,"journal":{"name":"Experimental and Toxicologic Pathology","volume":"69 5","pages":"Pages 275-283"},"PeriodicalIF":0.0,"publicationDate":"2017-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.etp.2017.01.010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71830053","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":"Pathological and biochemical evaluation of coumarin and chlorophyllin against aflatoxicosis in rat","authors":"Mohamed S. Abdel-Latif ,&nbsp;Khaled M. Elmeleigy ,&nbsp;Tahany A.A. Aly ,&nbsp;Marwa S. Khattab ,&nbsp;Sara M. Mohamed","doi":"10.1016/j.etp.2017.01.014","DOIUrl":"https://doi.org/10.1016/j.etp.2017.01.014","url":null,"abstract":"<div><p><span><span><span>Aflatoxin contamination of animal diet has adverse effects on animal health and productivity. This study was performed to investigate the effect of using </span>coumarin and/or </span>chlorophyllin<span> in rat diet against aflatoxicosis. Fifty-four rats were assigned into 7 groups (6 rats each). G1 was a negative control. G2 received water with coumarin 0.5%. G3 received water with chlorophyllin 0.5%. G4 received water with coumarin 0.5% and chlorophyllin 0.5%. G5-8 fed aflatoxin B</span></span>₁ 1000<!--> <span><span><span>ppb in diet. Group 6–8 were administered similar treatments as G2-4. The experiment ended after 8 weeks. Random glucose, total lipid, total cholesterol, total </span>triglycerides<span>, total protein, serum ALT, </span></span>AST<span><span>, creatinine, and urea were measured. Histopathology<span> of liver, kidney<span> and pancreas and immunohistochemical staining of placental glutathione-S-transferase (GST-P) in liver were performed. The glucose serum level, cholesterol, AST, and ALT were elevated in G5 compared to G6-8. The liver and kidney lesions in G5 included vacuolation and necrosis which subsided in G6-8. The necrosis and inflammatory </span></span></span>cells infiltration in the pancreas of G5 were absent in G6-8. GST-P positive hepatocytes were abundant in G5, few in G6 and absent in G7 and G8. In conclusion, the chlorophyllin and coumarin possessed protective and anti-carcinogenic effect against aflatoxicosis in rats.</span></span></p></div>","PeriodicalId":50465,"journal":{"name":"Experimental and Toxicologic Pathology","volume":"69 5","pages":"Pages 285-291"},"PeriodicalIF":0.0,"publicationDate":"2017-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.etp.2017.01.014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71830058","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 copper on viability and functional properties of hippocampal neurons in vitro.","authors":"M. R. Kapkaeva, O. Popova, R. Kondratenko, P. Rogozin, E. E. Genrikhs, E. Stelmashook, V. Skrebitsky, L. Khaspekov, N. Isaev","doi":"10.1016/j.etp.2017.01.011","DOIUrl":"https://doi.org/10.1016/j.etp.2017.01.011","url":null,"abstract":"","PeriodicalId":50465,"journal":{"name":"Experimental and Toxicologic Pathology","volume":"24 1","pages":"259-264"},"PeriodicalIF":0.0,"publicationDate":"2017-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77111837","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 copper on viability and functional properties of hippocampal neurons in vitro","authors":"Marina R. Kapkaeva ,&nbsp;Olga V. Popova ,&nbsp;Rodion V. Kondratenko ,&nbsp;Pavel D. Rogozin ,&nbsp;Elisaveta E. Genrikhs ,&nbsp;Elena V. Stelmashook ,&nbsp;Vladimir G. Skrebitsky ,&nbsp;Leonid G. Khaspekov ,&nbsp;Nickolay K. Isaev","doi":"10.1016/j.etp.2017.01.011","DOIUrl":"https://doi.org/10.1016/j.etp.2017.01.011","url":null,"abstract":"<div><p>Copper (Cu²⁺<span><span>) is an essential metal presented in the mammalian brain and released from </span>synaptic vesicles following neuronal depolarization. However, the disturbance of Cu</span>²⁺<span><span> homeostasis<span> results in neurotoxicity. In our study we performed for the first time a combined functional investigation of </span></span>cultured hippocampal neurons under Cu</span>²⁺<span> exposure, its effect on spontaneous spike activity of hippocampal neuronal network cultured on multielectrode array<span> (MEA), and development of long-term potentiation (LTP) in acute hippocampal slices in the presence of Cu</span></span>²⁺. Application of 0.2<!--> <!-->mM CuCl₂ for 24<!--> <span>h reduced viability of cultured neurons to 40</span> <!-->±<!--> <!-->6%, whereas 0.01<!--> <!-->mM CuCl₂ did not influence significantly on the neuronal survival. However, exposure to the action of 0.01<!--> <!-->mM Cu²⁺<span> resulted in pronounced reduction of network spike activity and abolished LTP induced by high-frequency stimulation of Schaffer's collaterals in CA1 pyramidal neurons of hippocampal slices. Antioxidant Trolox<span>, the hydrosoluble vitamin E analogue, prevented neurotoxic effect and alterations of network activity under Cu</span></span>²⁺ exposure, but didn't change the impairment of LTP in Cu²⁺-exposured hippocampal slices. We hypothesized that spontaneous network neuronal activity probably is one of the potential targets of Cu²⁺<span>-induced neurotoxicity, in which free radicals can be involved. At the same time, it may be suggested that Cu</span>²⁺-induced alterations of long-lasting trace processes (like LTP) are not mediated by oxidative damage.</p></div>","PeriodicalId":50465,"journal":{"name":"Experimental and Toxicologic Pathology","volume":"69 5","pages":"Pages 259-264"},"PeriodicalIF":0.0,"publicationDate":"2017-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.etp.2017.01.011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71830054","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":"editorial board (IFC)","authors":"","doi":"10.1016/S0940-2993(17)30306-8","DOIUrl":"https://doi.org/10.1016/S0940-2993(17)30306-8","url":null,"abstract":"","PeriodicalId":50465,"journal":{"name":"Experimental and Toxicologic Pathology","volume":"69 5","pages":"Page IFC"},"PeriodicalIF":0.0,"publicationDate":"2017-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0940-2993(17)30306-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71830056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential protective role of taurine against 5-fluorouracil-induced nephrotoxicity in adult male rats","authors":"Hany N. Yousef,&nbsp;Hanaa R. Aboelwafa","doi":"10.1016/j.etp.2017.01.012","DOIUrl":"https://doi.org/10.1016/j.etp.2017.01.012","url":null,"abstract":"<div><p><span>Nephrotoxicity<span> is common with the use of the chemotherapeutic agent 5-Fluorouracil (5-FU). The current study aimed to investigate the probable protective effect of taurine (TAU) against 5-FU-induced nephrotoxicity in rats using biochemical, histological and ultrastructural approaches. Twenty-four rats were equally divided into control, TAU, 5-FU and 5-FU</span></span> <!-->+<!--> <!-->TAU groups.</p><p><span><span>5-FU significantly elevated levels of blood urea nitrogen<span> (BUN), creatinine, and uric acid<span><span>; while it reduced activities of superoxide dismutase (SOD), </span>catalase (CAT), and </span></span></span>glutathione peroxidase (GSH-Px). Also, 5-FU induced significant elevation in </span>malondialdehyde<span><span><span><span> (MDA) levels accompanied with marked decline in γ-glutamyltranspeptidase (GGT) and alkaline phosphatase (AP) levels in </span>kidney tissues. These biochemical alterations were accompanied by histopathological changes marked by destruction of the normal renal structure, in addition to ultrastructural alterations represented by thickened and irregular glomerular </span>basement membranes<span>, congested glomerular capillaries, damaged lining fenestrated endothelium, </span></span>mesangial cells<span> hyperplasia with expanded mesangial matrix, and distorted podocyte’s processes. Also, the proximal (PCT) and distal (DCT) convoluted tubules showed thickened basement membranes, destructed apical microvilli and loss of basal infoldings of their epithelial cells.</span></span></p><p>Administration of TAU to 5-FU-treated rats reversed most of the biochemical, histological, and ultrastructural alterations. These results indicate that TAU has a protective effect against 5-FU-induced nephrotoxicity.</p></div>","PeriodicalId":50465,"journal":{"name":"Experimental and Toxicologic Pathology","volume":"69 5","pages":"Pages 265-274"},"PeriodicalIF":0.0,"publicationDate":"2017-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.etp.2017.01.012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71830052","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":"A spontaneous high-grade undifferentiated mammary carcinoma in a seven-week-old female rat.","authors":"A. Faustino-Rocha, A. Gama, P. Oliveira, A. Alvarado, R. Ferreira, M. Ginja","doi":"10.1016/j.etp.2017.01.006","DOIUrl":"https://doi.org/10.1016/j.etp.2017.01.006","url":null,"abstract":"","PeriodicalId":50465,"journal":{"name":"Experimental and Toxicologic Pathology","volume":"212 1","pages":"241-244"},"PeriodicalIF":0.0,"publicationDate":"2017-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75586515","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 PCB-126 on aryl hydrocarbon receptor, ubiquitin and p53 expression levels in Sparus aurata.","authors":"M Calò, P Licata, A Bitto, P Lo Cascio, F Giarratana, D Altavilla","doi":"10.1016/j.etp.2017.04.005","DOIUrl":"10.1016/j.etp.2017.04.005","url":null,"abstract":"<p><p>The aim of the present study is to determine if Ahr ligands as PCB-126, a dioxin-like, might contribute to inhibition of the tumor suppressor p53 by promoting its degradation through proteasome-ubiquitin system (UPS). The findings show, in the presence of PCB-126, a significant increase of p53 immunoreactivity in fish compared to the control. Subsequently, there is a decrease of p53 immunoreactivity at 24h which is maintained even at 72h. At the same time there is a slight decrease of ubiquitin immunoreactivity to 12h compared to the control and a marked decrease to 24 and 72h. The induction of ubiquitin expression is resulted very marked in the control and preserved at 12h. It's very important to underline as in our study we demonstrate a marked decrease of ubiquitin and p53 immunoreactivity at 24h and 72h. AHR activation, by ligands as PCB-126, increases p53 ubiquitation inhibiting its expression, in addition it decreases the free ubiquitin promoting disruption of Ub homeostasis; this is the first report that establishes a relationship between AhR, increases p53 ubiquitation, and reduction of free ubiquitin. Our result emphasize the need to deeply the role of this receptor in UPS regulation as potential therapeutic target for cancer treatment.</p>","PeriodicalId":50465,"journal":{"name":"Experimental and Toxicologic Pathology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35036201","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":"Anti-inflammatory effects of the selective phosphodiesterase 3 inhibitor, cilostazol, and antioxidants, enzymatically-modified isoquercitrin and α-lipoic acid, reduce dextran sulphate sodium-induced colorectal mucosal injury in mice","authors":"Yumi Kangawa ,&nbsp;Toshinori Yoshida ,&nbsp;Hajime Abe ,&nbsp;Yoshiki Seto ,&nbsp;Taishi Miyashita ,&nbsp;Michi Nakamura ,&nbsp;Tohru Kihara ,&nbsp;Shim-mo Hayashi ,&nbsp;Makoto Shibutani","doi":"10.1016/j.etp.2016.12.004","DOIUrl":"https://doi.org/10.1016/j.etp.2016.12.004","url":null,"abstract":"<div><p><span><span>Developing effective treatments<span> and preventing inflammatory bowel disease (IBD) are urgent challenges in improving patients’ health. It has been suggested that </span></span>platelet activation<span><span> and reactive oxidative species generation are involved in the pathogenesis of IBD. We examined the inhibitory effects of a selective phosphodiesterase-3 inhibitor, cilostazol<span><span> (CZ), and two antioxidants, enzymatically modified isoquercitrin (EMIQ) and α-lipoic acid (ALA), against </span>dextran sulphate sodium (DSS)-induced colitis. BALB/c mice were treated with 0.3% CZ, 1.5% EMIQ, and 0.2% ALA in their feed. </span></span>Colitis was induced by administering 5% DSS in drinking water for 8</span></span> <span><span><span>days. The inhibitory effects of these substances were evaluated by measuring relevant clinical symptoms (faecal blood, diarrhoea, and body weight loss), colon length, plasma cytokine and chemokine<span> levels, whole genome gene expression, and histopathology<span>. Diarrhoea was suppressed by each treatment, while CZ prevented shortening of the colon length. All treatment groups exhibited decreased plasma levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α compared with the DSS group. Microarray analysis<span> showed that cell adhesion, </span></span></span></span>cytoskeleton<span><span> regulation, cell proliferation, and </span>apoptosis, which might be related to </span></span>inflammatory cell<span> infiltration and mucosal healing, were affected in all the groups. DSS-induced mucosal injuries such as mucosal loss, submucosal oedema, and inflammatory cell infiltration in the distal colon were prevented by CZ or antioxidant treatment. These results suggest that anti-inflammatory effects of these agents reduced DSS-induced mucosal injuries in mice and, therefore, may provide therapeutic benefits in IBD.</span></span></p></div>","PeriodicalId":50465,"journal":{"name":"Experimental and Toxicologic Pathology","volume":"69 4","pages":"Pages 179-186"},"PeriodicalIF":0.0,"publicationDate":"2017-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.etp.2016.12.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71811986","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}