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1
Content available remote Scutellarein ameliorates tongue cancer cells via mitochondria
100%
Open Medicine
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2014
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tom 9
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nr 2
193-199
EN
To investigate the mechanism in Scutellarein-induced apoptosis of SAS human tongue cancer cells, inhibitory effects of Scutellarein on SAS cells were detected by MTT assay. Cell apoptosis was analyzed by flow cytometry. Ultrastructural changes of SAS cells were observed by transmission electron microscopy (TEM). Mitochondrial transmembrane potential (ΔΨm) were analyzed by JC-1 [5,5,6,6-Tetrachloro-1,1,3,3-tetraethylbenzimidazolylcarbocyanine iodide]. Western blotting was used to examine the expression level of Bcl-2, Bax and caspase-3 in SAS cells treated with Scutellarein. Scutellarein inhibited the proliferation of SAS cells in a time and dose-dependent manner and increased the percent of apoptotic cells. The mitochondrial cristae were swollen and had vacuolar degeneration. ΔΨm decreased when the concentration of scutellarein increased. Scutellarein effectively up-regulated the expression of mitochondrial Bax and caspase-3 and down-regulated the expression of Bcl-2. Scutellarein induces apoptosis of SAS human tongue cancer cells via activating mitochondrial signaling pathway.
2
Content available remote Vimentin cleavage in end-stage renal disease is not related to apoptosis
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EN
Anti-vimentin auto-antibodies contribute to chronic allograft nephropathy. They exist in sera of end-stage renal disease patients on hemodialysis (ESRD) already before renal transplantation. We found recently that a 49 kDa vimentin fragment is increased in lymphocytes of ESRD patients which is presented on the cell surface. In vitro studies showed that such a fragment is formed during apoptosis by active caspase-3. We hypothesized that vimentin degradation in leukocytes of ESRD patients correlates to caspase-3 activation in vivo. Lymphocytes and monocytes were isolated from ESRD patients and from healthy volunteers and analyzed for vimentin expression and caspase-3 activation. In addition, apoptosis was induced in vitro and quantified by flow cytometry. ESRD monocytes have shown only the full length 60 kDa vimentin isoform. ESRD lymphocytes, however, showed in addition a strongly increased expression of the 49 kDa vimentin in all samples. Caspase-3 activation was found in 60% of ESRD lymphocytes and 66% of ESRD monocytes but not in healthy volunteers. UV-mediated induction of apoptosis was not associated with vimentin degradation. These experiments could confirm increased vimentin degradation in ESRD lymphocytes. However, we could not validate any correlation to apoptosis.
EN
Mercury is among the heavy metals that have been reported to cause devastating health problems worldwide. The present work was aimed at investigating the effects of mercury chloride on the cytomorphology of the peritoneal macrophages of rat. The current study characterizes the mechanism by which mercury, a toxic metal, induces death in rat macrophages. In mercury treated group significant numbers of peritoneal macrophages were found to be pyknotic. The cellular death was confirmed by membrane blebbing and membrane rupture. Percentages of cells showing membrane blebbing was increased significantly after treatment. The result indicated mercury induced toxicity may affect macrophage mediated immunity. So macrophage activation during heavy metal mediated reaction is an interesting area to be explored in future researches.
4
Content available remote The effect of vitamin C on amiodarone-induced toxicity in rat thymocytes
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EN
Although, the antiarrhythmic effect of amiodarone (AMD) is well characterized, the mechanism of its toxicity on extracardiac tissues is still poorly understood. Several antioxidants have been shown to prevent AMD-induced toxicity by antioxidant and/or non-antioxidant mechanisms. In the current study, we evaluated the possible protective effect, in vitro, of vitamin C on AMD-induced toxicity in rat thymocytes. Rat thymocytes were cultured with increasing AMD concentrations (1–20 μM) with or without vitamin C (1000 μg/ml), for 24 hours. Cells treatment with AMD resulted in a concentration-dependent increase of hypodiploid cells and a significant decrease in cellular glutathione content. Vitamin C combined with AMD significantly decreased the proportion of hypodiploid cells and markedly increased the cellular glutathione content, compared with AMD treatment alone. These results suggest that treatment with vitamin C may prevent AMD-induced toxicity in rat thymocytes by restoring cellular glutathione content.
5
Content available remote Apoptosis quantification at the respiratory epithelium level in asthma
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EN
The „changes” occurring in the expression of the factors involved in the apoptotic chain at the level of the respiratory epithelium in asthma is still an unsolved issue. At this level an important role is played by the mitochondria and the factors that influence the membrane permeability, especially the Bcl-2 super family. The purpose of this study is to evaluate both the changes in the expression of the Bcl-2 and of the Bax proapoptotic factors at the respiratory epithelium level in 21 patients with bronchial asthma of different degrees of severity of disease (aaccording to GINA - Global Initiative For Asthma). To accomplish this, fragments of the bronchial mucosa were obtained through fiberbronchoscopy, being afterwords hystologically prepare in view of the immunomarking with anti Bcl-2 and anti-Bax antibodies. Microscopic examination revealed an important decrease in the level of proapoptotic factor Bcl-2 in patients with persistent severe forms of the disease and a significant decrease in the expression of the proapototic Bax factor at the respiratory epithelium level even in the early stages of the disease. Knowing all the factors involved in apoptosis at the respiratory epithelium level in bronchial asthma, as well as of their expression changes will be at the core of new therapeutical approaches to of this disease.
EN
Apoptosis is central to the biology of cutaneous malignant melanoma (CMM). The leucine zipper, down regulated in cancer 1 (LDOC-1) gene, is known to be a regulator of the nuclear factor kappa B (NF-kB) through inhibition of the same NF-kB. The poly (ADP-ribose) polymerase-1 (PARP1) gene plays an important role for the efficient maintenance of genome integrity. PARP-1 protein is required for the apoptosis-inducing factor (AIF) translocation from the mitochondria to the nucleus. We report here two interesting cases of family melanoma, a father and son 84 and 40 years old, respectively. The histological evaluation of the lesions of both men revealed diffused superficial melanoma with epithelioid cells. We evaluated the differential expression of LDOC-1 and PARP-1 mRNA in peripheral blood leukocytes of both the father and son. We found that both LDOC-1 and PARP-1 genes were down-regulated in both patients compared with those of controls. These data suggest that low levels of expression of LDOC-1 and PARP-1 mRNA may be associated with familial melanoma.
EN
Chromones are organic compounds reported to induce cytotoxic effect in an extensive variety of cells. Consequently, the synthesis and reorientation of the chromone molecules are of great interest for many researchers because of their miscellaneous biological activities. The present study was designed to assess the significant antitumor effects of C-(6-Methyl-4-oxo-4H-1-benzopyran-3-yl)-N-(p-tolyl) nitrone, a novel chromone linked nitrone derivative and to elucidate the mechanism of these effects on two human cancer cell lines HepG2 and HeLa. Cell proliferation was analysed by the MTT assay. Apoptosis was evaluated by DAPI staining and flow cytometric analysis and quantified by fluorometric assays for Caspase 3 and 9. Apaf-1 and cytochrome c expression were identified by means of Western Blot analysis. The derivative showed significant dose dependent cytotoxic effects in the cancer cells and induced the reactive oxygen species and endogenous nitric oxide production. Furthermore, mitochondrial membrane potential depolarization, translocation of mitochondrial cytochrome c to cytosol, induction of Apaf-1 and activation of caspases were observed during the derivative-mediated apoptosis. These findings proposed that the novel chromone linked nitrone derivative has significant antitumor effects on HepG2 and HeLa cells and have immense scope to develop as an anticancer agent.
EN
Objectives The aim of the study has been to investigate the effect of the Standard Reference Material of fine particulate matter (SRM 2786) on cytotoxicity and apoptosis in human lung bronchial epithelial cells (16HBE cells). Whether the lipopolysaccharide (LPS)-induced inflammation could further accelerate cell apoptosis induced by SRM 2786 stimulation has also been determined. Material and Methods 16HBE cells were exposed to various doses of SRM 2786 with or without LPS. The following parameters: cytotoxicity, apoptotic rate, Bax/Bcl-2 expression, nitric oxide (NO) production, and reactive oxygen species (ROS) generation were measured. Results The results have shown that SRM 2786 induces cell damage and apoptosis of 16HBE cells as demonstrated by significant decrease in expression of Bcl-2 and increase in expression of Bax. When compared with the control cells, the apoptotic rate of cells treated by 500 μg/ml of SRM 2786 increased from 2.43±0.21% to 43.96±2.95% (p < 0.01). Further, there was an elevated production of NO and ROS post SRM 2786 treatment. The level of NO in cells treated with 500 μg/ml of SRM 2786 was 18.33±1.02 μmol/l whereas that of control cells was 1.58±0.31 μmol/l (p < 0.01). When compared with the control group, the level of intracellular ROS increased by 24% after treatment with 500 μg/ml of SRM 2786 (p < 0.05). In addition, LPS pre-treatment may accelerate cell apoptosis by increasing generation of NO and ROS followed by SRM 2786 stimulation. When compared to cells treated with 125 μg/ml of SRM 2786 alone, the levels of NO and ROS in cells pretreated with LPS increased by 28% and 11.6%, respectively (p < 0.05), and the apoptotic rate increased from 34.62±4.44% to 54.11±3.34% (p < 0.01). Conclusions These findings have suggested that in vitro exposure to SRM 2786 could induce 16HBE cells apoptosis probably by means of the mechanism involving the generation of free radicals, while the degree of apoptosis would be further aggravated under inflammation condition. Int J Occup Med Environ Health 2018;31(2):173–183
EN
Objectives Perfluorooctane sulfonate (PFOS) and zinc oxide nanoparticles (ZnO-NPs) are frequently detected in the environment but few studies have assessed the joint toxicity of them. Oxidative stress and apoptosis to zebrafish (Danio rerio) embryos induced by the PFOS and ZnO-NPs were investigated in this study. Material and Methods The embryos were exposed to the PFOS (0, 0.4, 0.8 and 1.6 mg/l), ZnO-NPs (12.5, 25, 50 mg/l) and PFOS plus ZnO-NPs (0.4+12.5, 0.8+25 and 1.6+50 mg/l) mixture solutions until 96 h post-fertilization. Activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx) and malondialdehyde (MDA) content were measured in zebrafish embryos after exposure lasting for 96 h. At the same time, the genes expression related to reactive oxygen species (ROS) generation, oxidative damage and apoptosis were also measured. Results A significant induction of the ROS accompanied by the increase in the activity of the Gpx and MDA contents were found in co-treatment groups. Furthermore, several apoptosis pathway related genes such as Bax, p53, caspase-3 and caspase-9 were significantly up-regulated in the PFOS plus ZnO-NPs exposure groups, while anti-apoptotic gene Bcl-2 was significantly down-regulated in the PFOS plus ZnO-NPs exposure groups. In addition, some oxidative stress-related genes such as Cat, GSH peroxidase 1 (Gpx1a) and superoxide dismutase 1 (Sod1) were also significantly down-regulated after the PFOS plus ZnO-NPs co-treatments. Conclusions The results demonstrated that the PFOS plus ZnO-NPs co-exposure could cause more serious oxidative stress and apoptosis than the PFOS and ZnO-NPs exposure alone at the exposure concentrations above. The synergistic effects of the PFOS and ZnO-NPs may be the important mechanisms of their toxicity to zebrafish embryos. Int J Occup Med Environ Health 2017;30(2):213–229
EN
Objectives To study any possible correlation between arsenic toxicity and the development of oral carcinoma in West Bengal population. Material and Methods Ethical clearance for this study was obtained from the Vivekananda Institute of Medical Sciences. Out of 30 785 patients attending our hospital from November 2012 to July 2015, 107 cases and 50 control individuals were selected. The hair and buccal smear samples were obtained upon their consent for the purpose of the analysis of arsenic count and cytogenetic damage, respectively. Results Ninety-six percent of cases came from the highly arsenic affected districts and 81.3% showed their arsenic count above the safe limit (0.8 μg/g) whereas 96% of the controls’ arsenic count was within the safe limit. The study showed a significant difference of the micronuclei and apoptosis frequency between the cases and controls. Conclusions The difference of micronuclei and apoptosis frequency between cases and controls was significant. The maximum number of cases came from highly arsenic affected areas and a higher percentage of cases showed elevated arsenic count, as compared to controls, which may indicate a possible link between arsenic toxicity and this disease. However, a larger sample size is required for a proper correlation. Int J Occup Med Environ Health 2017;30(2):271–279
EN
Molluscs represent a simple and significant model system to test how specific metals can simultaneously affect development and putative mechanisms of defense and/or cell death. Lamellidens marginalis (Bivalvia: Eulamellibranchiata) are the molluscs of Indian freshwater ecosystem and important biological resources. Lead (Pb) is widespread heavy metal that is released into the environment from different sources. Their accumulation in the soils can become dangerous to all kinds of organisms, including plants, animals and human life, causing many adverse effects. Lamellidens are used as reliable markers and bioindicators highly sensitive to environmental changes. The aim of the present work was to determine the toxic effect of lead on the cytomorphology of hemocytes of Lamellidens marginalis and to evaluate its potential as a bio monitor for detecting a heavy-metal polluted environment. Treated cells showed apoptosis and paraptosis (vacuolation) like features. Morphological analyses suggested an irretrievable destruction of normal morphology of hemocyte. However further studies are needed to investigate this topic, particularly in relation to the pollutants reported in this paper.
12
Content available remote Protein Disulfide Isomerase Superfamily in Disease and the Regulation of Apoptosis
63%
EN
Cellular homeostasis requires the balance of a multitude of signaling cascades that are contingent upon the essential proteins being properly synthesized, folded and delivered to appropriate subcellular locations. In eukaryotic cells the endoplasmic reticulum (ER) is a specialized organelle that is the central site of synthesis and folding of secretory, membrane and a number of organelletargeted proteins. The integrity of protein folding is enabled by the presence of ATP, Ca++, molecular chaperones, as well as an oxidizing redox environment. The imbalance between the load and capacity of protein folding results in a cellular condition known as ER stress. Failure of these pathways to restore ER homeostasis results in the activation of apoptotic pathways. Protein disulfide isomerases (PDI) compose a superfamily of oxidoreductases that have diverse sequences and are localized in the ER, nucleus, cytosol, mitochondria and cell membrane. The PDI superfamily has multiple functions including, acting as molecular chaperones, protein-binding partners, and hormone reservoirs. Recently , PDI family members have been implicated in the regulation of apoptotic signaling events. The complexities underlying the molecular mechanisms that define the switch from pro-survival to pro-death response are evidenced by recent studies that reveal the roles of specific chaperone proteins as integration points in signaling pathways that determine cell fate. The following review discusses the dual role of PDI in cell death and survival during ER stress.
PL
Wstęp Chloropiryfos (CPF), środek owadobójczy szeroko stosowany w rolnictwie, może powodować zatrucia u ludzi. Z tego powodu prowadzi się wiele badań dotyczących możliwości leczenia zatrucia chloropiryfosem. Celem pracy była ocena wpływu estru fenetylowego kwasu kawowego (caffeic acid phenethyl ester – CAPE) i intralipidu (IL) na uszkodzenia wątroby u szczurów wywołane przez chloropiryfos. Materiał i metody Szczurom podawano CPF (10 mg/kg masy ciała (mc.), doustnie), CAPE (10 μmol/kg mc., dootrzewnowo), IL (18,6 ml/kg mc., doustnie), CPF+CAPE, CPF+IL oraz CPF+CAPE+IL. Zmierzono całkowitą zdolność utleniającą (total oxidant capacity – TOC) i całkowitą zdolność przeciwutleniającą (total antioxidant capacity – TAC) osocza krwi i obliczono wskaźnik stresu oksydacyjnego (oxidative stress index – OSI). U zwierząt wykonano także badanie histopatologiczne i barwienie immunohistochemiczne tkanek wątroby. Wyniki Chloropiryfos istotnie zmniejszał u badanych szczurów TAC osocza, a zwiększał apoptozę, TOC i OSI. Natomiast CAPE i CAPE+IL istotnie zmniejszały OSI osocza i apoptozę, a zwiększały TAC osocza u szczurów z uszkodzeniami wątroby wywołanymi przez chloropiryfos. Wnioski Badanie wykazało, że CAPE i CAPE+IL poprzez zmniejszenie stresu oksydacyjnego i apoptozy redukują u szczurów uszkodzenia wątroby wywołane przez chloropiryfos. Med. Pr. 2016;67(6):743–749
EN
Background Chlorpyrifos (CPF), insecticide widely used in agriculture, may cause poisonings in the case of humans. As a result, there is a large amount of treatment research underway to focus on the possibility of chlorpyrifos induced poisonings. The aim of this study has been to evaluate the effects of caffeic acid phenethyl ester (CAPE) and intralipid (IL) on hepatotoxicity induced by chlorpyrifos in the case of rats. Material and Methods The rats in this study were treated with CPF (10 mg/kg body weight (b.w.), orally), CAPE (10 μmol/kg b.w., intraperitoneally), IL (18.6 ml/kg b.w., orally), CPF+CAPE, CPF+IL, and CPF+CAPE+IL. The plasma total oxidant capacity (TOC), total antioxidant capacity (TAC) were measured and the oxidative stress index (OSI) was calculated. Liver histopathology and immunohistochemical staining were performed. Results Chlorpyrifos statistically significantly decreased the TAC levels in the rats’ plasma and increased the apoptosis and the TOC and OSI levels. In the chlorpyrifos induced liver injury, CAPE and CAPE+IL significantly decreased the plasma OSI levels and the apoptosis, and significantly increased the plasma TAC levels. Conclusions This study revealed that CAPE and CAPE+IL attenuate chlorpyrifos induced liver injuries by decreasing oxidative stress and apoptosis. Med Pr 2016;67(6):743–749
EN
Both ethylene and propylene glycol alkyl ethers (EGAEs and PGAEs, respectively) are widely used, mainly as solvents, in industrial and household products. Some EGAEs demonstrate gonadotoxic, embriotoxic, fetotoxic and teratogenic effects in both humans and experimental animals. Due to the noxious impact of these ethers on reproduction and development of organisms EGAEs are replaced for considerably less toxic PGAEs. The data on the mechanisms of testicular, embriotoxic, fetotoxic and teratogenic effects of EGAEs are presented in this paper. Our particular attention was focused on the metabolism of some EGAEs and their organ-specific toxicities, apoptosis of spermatocytes associated with changes in the expression of various genes that code for oxidative stress factors, protein kinases and nuclear hormone receptors. Med Pr 2015;66(5):725–737
PL
Etery alkilowe glikolu etylenowego (ethylene glycol alkyl ethers – EGAE) i propylenowego (propylene glycol alkyl ethers – PGAE) są szeroko stosowane w przemyśle i gospodarstwie domowym, głównie jako rozpuszczalniki. Niektóre EGAE wykazują działanie gonadotoksyczne, embriotoksyczne, fetotoksyczne i teratogenne zarówno u ludzi, jak i zwierząt doświadczalnych. Ze względu na szkodliwe działanie tych eterów na rozrodczość i rozwój organizmu EGAE są zastępowane znacznie mniej toksycznymi PGAE. W niniejszej pracy przedstawiono dane na temat mechanizmów toksycznego działania EGAE na komórki rozrodcze, zarodek i płód. Szczególną uwagę zwrócono na metabolizm niektórych EGAEs i ich toksyczność narządową, a także na apoptozę spermatocytów związaną ze zmianami ekspresji genów, które kodują czynniki stresu oksydacyjnego, kinazy białkowe i jądrowe receptory hormonów. Med. Pr. 2015;66(5):725–737
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Content available Arsen – trucizna czy lek?
51%
EN
Arsenic (As) is commonly known as a poison. Only a few people know that As has also been widely used in medicine. In the past years As and its compounds were used as a medicine for the treatment of such diseases as diabetes, psoriasis, syphilis, skin ulcers and joint diseases. Nowadays As is also used especially in the treatment of patients with acute promyelocytic leukemia. The International Agency for Research on Cancer (IARC) has recognized arsenic as an element with carcinogenic effect evidenced by epidemiological studies, but as previously mentioned it is also used in the treatment of neoplastic diseases. This underlines the specificity of the arsenic effects. Arsenic occurs widely in the natural environment, for example, it is present in soil and water, which contributes to its migration to food products. Long exposure to this element may lead to liver damages and also to changes in myocardium. Bearing in mind that such serious health problems can occur, monitoring of the As presence in the environmental media plays a very important role. In addition, the occupational risk of As exposure in the workplace should be identified and checked. Also the standards for As presence in food should be established. This paper presents a review of the 2015 publications based on the Medical database like PubMed and Polish Medical Bibliography. It includes the most important information about arsenic in both forms, poison and medicine. Med Pr 2016;67(1):89–96
PL
Arsen to pierwiastek kojarzony głównie z działaniem toksycznym. Należy jednak podkreślić, że mimo toksyczności jest on stosowany w medycynie. W przeszłości arsen i jego związki wykorzystywano w leczeniu m.in. cukrzycy, łuszczycy, kiły, owrzodzeń skóry i chorób stawów. Obecnie stosowany jest w onkologii, głównie u pacjentów z ostrą białaczką promielocytową. Z jednej strony więc arsen został uznany przez Międzynarodową Agencję Badań nad Rakiem (International Agency for Research on Cancer – IARC) za pierwiastek o udowodnionym epidemiologicznie rakotwórczym działaniu, a z drugiej – jest wykorzystywany w terapii chorób onkologicznych. Na działanie arsenu człowiek jest narażony także w codziennym życiu, ponieważ jest to substancja szeroko rozpowszechniona w przyrodzie. Występuje w glebie i wodzie, co skutkuje przedostawaniem się tego związku do pożywienia. Długotrwała ekspozycja na arsen i jego związki może doprowadzić np. do zmian w mięśniu sercowym lub uszkodzenia wątroby. Z tego powodu ważne jest prowadzenie monitoringu zawartości tej substancji w glebie, wodzie i pożywieniu, a także możliwości narażenia zawodowego. Niezbędne jest także ustalenie norm zawartości tego pierwiastka (zarówno zawartości całkowitej, jak i jego nieorganicznej formy) w pożywieniu. Niniejszy artykuł jest przeglądem publikacji znajdujących się w bazach medycznych PubMed oraz Polskiej Bibliografii Lekarskiej, które ukazały się do 2015 r. oraz dotyczyły arsenu i jego związków. W artykule przedstawiono najważniejsze informacje dotyczące arsenu – zarówno jako trucizny, jak i leku. Med. Pr. 2016;67(1):89–96
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