Copper serves as a limiting factor for multiple steps of tumour progression, including angiogenesis, growth and metastasis. High levels of copper have been found in a wide spectrum of human cancers. ...Antitumour activities of copper-chelating drugs have been reported in animal models. Organosulfur compounds (diallyl sulfide, DAS; diallyl disulfide, DADS; S-ethylcysteine, SEC; N-acetylcysteine, NAC) derived from garlic exhibit marked copper-chelating activity. We analysed a mixture of fifteen n-propyl polysulfides (DPPS) for potential antitumour activity against several murine tumour cell lines, including colon carcinoma (CT26), mammary carcinoma (4T1) and melanoma cell lines (B16F10), and compared the effects with the antiproliferative effect in highly proliferative murine mesenchymal stem cells (mMSCs). The effects of the mixture of n-propyl polysulfides (100%) on cell viability were determined using MTT assays. Cell apoptosis was analysed using Annexin V-FITC/PI assays.
The results of the MTT assays indicate that this standardized mixture of n-propyl polysulfides has a strong, dose-dependent cytotoxic effect against all three of the tested tumour cell lines (CT26, 4T1, B16F10). The cytotoxic effect of the n-propyl polysulfide mixture against the CT26 and B16F10 cell lines was much stronger than that of cisplatin and was significantly weaker in mMSCs, which are non-cancerous and highly proliferative cells, than in cancer cells. Flow cytometric analysis of CT26 and 4T1 cells revealed that apoptosis was not the dominant mechanism of cell death induced by the n-propyl polysulfide mixture. The n-propyl polysulfide mixture exerted highly cytotoxic activity against murine colon carcinoma and melanoma cell lines, but its antiproliferative activity against mMSCs was significantly lower than that of cisplatin.
Non-planar di-
-substituted PCB 153 (2,2’,4,4’,5,5’-hexachlorobiphenyl), one of the most abundant PCB congeners in the environment and in biological and human tissues, has been identified as ...potential endocrine disruptor affecting the reproductive and endocrine systems in rodents, wildlife, and humans. The aim of this study was to gain a deeper insight into its mode/mechanism of action in Chinese hamster ovary K1 cells (CHO-K1). PCB 153 (10–100 μmol/L) inhibited CHO-K1 cell proliferation, which was confirmed with four bioassays (Trypan Blue, Neutral Red, Kenacid Blue, and MTT), of which the MTT assay proved the most sensitive. PCB 153 also induced ROS formation in a dose-dependent manner. Apoptosis was seen after 6 h of exposure to PCB 153 doses ≥50 μmol/L, while prolonged exposure resulted in the activation of the necrotic pathway. PCB 153-induced disturbances in normal cell cycle progression were time-dependent, with the most significant effects occurring after 72 h.
U mnogim slučajevima indirektno prekrivanje pulpe (IPP) prihvatljiva je terapija za trajne zube u slučaju njezine reverzibilne upale. Za IPP koriste se različiti lijekovi – od kalcijeva hidroksida i ...staklenog ionomera do dentinskih adheziva. Svrha istraživanja: Svrha ovog istraživanja in vitro bila je izmjeriti citotoksičnost u staničnoj kulturi, uspoređujući četiri adheziva: Xeno® V (XE), Excite® F DSC (EX), Adhese® OneF (AD) i Prime & Bond NT (PB). Materijali i metode: Adhezivi su primijenjeni u skladu s uputama proizvođača. Nakon 24-satne izloženosti procijenjena je vijabilnost stanica s pomoću fotometrijskog testa (MTT test). Podatci su podvrgnuti analizi varijance (ANOVA). Rezultati: Adhezivi čija je glavna komponenta bila 2-hidroksietil metakrilat (HEMA) pokazali su se manje citotoksičnima, a oni koji su u svojem sastavu imali monomer uretan-dimetakrilat (UDMA) bili su najcitotoksičniji. Učinci na vijabilnost statistički su između adheziva značajno varirali. Zaključak: Rezultati pokazuju da je Adhese® OneF najmanje citotoksičan od ispitanih adheziva i može se koristiti kao sredstvo za indirektno prekrivanje pulpe. No Prime & Bond NT u istim je uvjetima pokazao smanjenu biokompatibilnost.
Yellow gentian (
L.), a medicinal plant widely used in traditional medicine, displays multiple biological effects, ranging from beneficial to toxic. Since many promising applications have been ...reported so far, our aim was to evaluate its potential concentration- and time- dependent cytotoxic and genotoxic effects
. To that end we exposed human peripheral blood mononuclear cells to 0.5, 1, and 2 mg/mL of yellow gentian root extract (YGRE) to determine its effects on oxidative stress parameters pro/antioxidant balance (PAB) and lipid peroxidation, DNA damage (alkaline comet assay and chromosome aberrations), and cell viability (trypan blue exclusion test). Cell viability decreased with increasing concentrations and treatment duration. Only the lowest YGRE concentration (0.5 mg/mL) increased oxidative stress but produced minor DNA damage and cytotoxicity. At higher concentrations, redox parameters returned to near control values. The percentage of chromosome aberrations and percentage of DNA in the comet tail increased with increased YGRE concentration after 48 h and declined after 72 h of treatment. This points to the activation of DNA repair mechanism (homologous recombination), evidenced by the formation of chromosomal radial figures after 72 h of treatment with the highest YGRE concentration of 2 mg/mL. Our results suggest that YGRE, despite induction of cytotoxic and genotoxic effects, activates cell repair mechanisms that counter oxidative and DNA lesions and induce cell death in highly damaged cells. Therefore, observed protective effects of yellow gentian after longer exposure could be a result of activated repair and removal of cells with irreparable damage.
Herbal medicines have played an important role in treating different diseases since ancient times. Bioactive components of medicinal plants are a good starting point for discovering new drugs such as ...chemotherapeutics. Currently, there are four classes of plant-derived chemotherapeutic drugs used in clinical practice. However, to discover new potential cytotoxic molecules, the research effort on herbal extracts has not diminished. The aim of this review was to evaluate the chemical constituents of plants that possess cytotoxicity, the signalling pathways responsible for this effect, and the influence of solvent polarity on potential cytotoxic effect and to present the cytotoxic activity of selected herbal extracts. The polyphenolic, anthraquinon, diterpneoid, triterpenoid, flavonoid, betulinic acid and berberine content contributes to cytotoxicity of herbal extracts. The inhibitory effect on cancer cells viability could be a consequence of the non-apoptotic processes, such as cell cycle arrestment, and the apoptotic process in tumour cells through different signalling pathways. The influence of solvent polarity on potential cytotoxic effect of herbal extracts should not be ignored. In general, the best cytotoxic activity was found in nonpolar and moderately polar herbal extracts. The herbal extract with IC
below 30 μg/ml could be considered a very strong cytotoxic agent. Considering that many antitumor drugs have been discovered from natural products, further research on plants and plant-derived chemicals may result in the discovery of potent anticancer agents.
T-2 Toxin: Incidence and Toxicity in Poultry Sokolovic, Marijana; Garaj-Vrhovac, Verica; Simpraga, Borka
Arhiv za higijenu rada i toksikologiju,
03/2008, Letnik:
59, Številka:
1
Journal Article
Recenzirano
Odprti dostop
T-2 toxin is the most toxic type A trichothecene mycotoxin. It is the secondary metabolite of the Fusarium fungi, and is common in grain and animal feed. Toxic effects have been shown both in ...experimental animals and in livestock. It has been implicated in several outbreaks of human mycotoxicoses. Toxic effects in poultry include inhibition of protein, DNA, and RNA synthesis, cytotoxicity, immunomodulation, cell lesions in the digestive tract, organs and skin, neural disturbances and low performance in poultry production (decreased weight gain, egg production, and hatchability). Concentrations of T-2 toxin in feed are usually low, and its immunosuppressive effects and secondary infections often make diagnosis difficult. If at the onset of the disease, a change in diet leads to health and performance improvements in animals, this may point to mycotoxin poisoning. Regular control of grain and feed samples is a valuable preventive measure, and it is accurate only if representative samples are tested. This article reviews the incidence and toxic effects of T-2 toxin in poultry.
T-2 toksin je najtoksičniji predstavnik trikotecenskih mikotoksina tipa A. On je sekundarni produkt metabolizma plijesni roda Fusarium i često je prisutan u žitaricama i hrani za životinje. Štetni učinci uočeni su u eksperimentalnih životinja i životinja u uzgoju. On se povezuje s pojavom bolesti ljudi od mikotoksikoza. Učinci toksina u peradi su višestruki: inhibicija sinteze proteina, DNA i RNA, citotoksični učinak, imunomodulatorni učinak, oštećenje stanica probavnog sustava, organa i kože, živčani poremećaji te pad proizvodnih karakteristika u uzgoju peradi (slabiji prirast, pad nesivosti i valivosti). Koncentracije T-2 toksina u hrani redovito su vrlo malene, a zbog imunosupresivnog djelovanja toksina te istodobne sekundarne infekcije bolest se često teško dijagnosticira. Pri pojavi bolesti promjenom hrane može doći do poboljšanja zdravstvenog stanja, što također upućuje na moguće trovanje mikotoksinima. Redovita kontrola uzoraka žitarica i hrane za životinje jedna je od preventivnih mjera, a detekcija mikotoksina u žitaricama i hrani pouzdana je samo ako se ispituje reprezentativan uzorak. U radu su opisani učestalost i toksični učinci T-2 toksina u peradi.
In the era of nanoparticulate controlled and site specific drug delivery systems, use of solid lipids to produce first generation lipid nanoparticles, solid lipid nanoparticles (SLN), became a ...revolutionary approach in the early nineties. The present review is designed to provide an insight into how SLN are finding a niche as promising nanovectors and forms a sound basis to troubleshoot the existing problems associated with traditional systems. Herein, authors had tried to highlight the frontline aspects prominent to SLN. An updated list of lipids, advanced forms of SLN, methods of preparation, characterization parameters, and various routes of administration of SLN are explored in-depth. Stability, toxicity, stealthing, targeting efficiency and other prospectives of SLN are also discussed in detail. The present discussion embodies the potential of SLN, now being looked up by various research groups around the world for their utility in the core areas of pharmaceutical sciences, thereby urging pharmaceutical industries to foster their scale-up.
Pojava nanočestica za kontroliranu i ciljanu isporuku lijekova izrađenih iz čvrstih lipida (SLN) imala je ranih devedesetih godina revolucionarno značenje. U ovom preglednom radu opisani su SLN sustavi kao korisni nanovektori za isporuku lijekova. Autori ističu prednosti SLN sustava, daju pregled lipida za njihovu izradu, opisuju metode priprave, karakterizacijske parametre i različite načine primjene SLN-a. Osim toga, detaljno se raspravlja o njihovoj stabilnosti, toksičnosti te mogućnosti ciljane isporuke. Istaknute su mogućnosti koje pružaju SLNi u području farmaceutskih znanosti i njihova moguća primjena u farmaceutskoj industriji.
The purpose of this study was to evaluate the genotoxic potential of components leached from two conventional self-curing glass-ionomer cements (Fuji IX and Ketac Molar), and light-curing, resin ...modified glass-ionomer cements (Vitrebond, Fuji II LC). Evaluation was performed on human lymphocytes using alkaline and hOGG1 modified comet, and micronucleus assays. Each material, polymerised and unpolymerised, was eluted in extracellular saline (1 cm
mL
) for 1 h, 1 day, and 5 days. Cultures were treated with eluates using final dilutions of 10
, 10
, and 10
. Alkaline comet assay did not detect changes in DNA migration of treated cells regardless of the ionomer tested, polymerisation state, and elution duration. Glass ionomers failed to significantly influence micronucleus frequency. No oxidative DNA damage in treated lymphocytes was observed using hOGG1 modified comet assay. Obtained results indicate high biocompatibility of all tested materials used in the study under experimental conditions.
Svrha istraživanja bila je procijeniti genotoksični potencijal komponenata koje izlučuju dva konvencionalna samopolimerizirajuća stakleno-ionomerna cementa (Fuji IX i Ketac Molar) te svjetlosno polimerizirajući i smolom modificirani stakleno-ionomerni cementi (Vitrebond, Fuji II LC). Istraživanje je provedeno na ljudskim limfocitima primjenom alkalnog komet testa, komet testa modificiranog hOGG1 enzimom te mikronukleus testa. Svaki materijal, polimerizirani i nepolimerizirani, eluiran je u fiziološkoj otopini (1 cm
mL
) tijekom jednog sata, jednog dana i tijekom 5 dana. Kulture limfocita tretirane su eluatima u razrjeđenjima 10
, 10
i 10
. Alkalnim komet testom nisu zabilježene promjene u migraciji DNA iz tretiranih stanica bez obzira na ispitani ionomer, vrstu polimerizacije i trajanje elucije. Izloženost staklenim ionomerima nije značajno utjecala na učestalost mikronukleusa. Primjenom hOGG1 modificiranog komet testa nije zamijećeno oksidativno oštećenje DNA u tretiranim limfocitima. Dobiveni rezultati upućuju na visoki stupanj biokompatibilnosti svih testiranih materijala koji su se koristili u eksperimentalnim uvjetima.
This study investigated possible growth-inhibiting effects of bee venom applied alone or in combination with a cytotoxic drug bleomycin on HeLa and V79 cells in vitro based on clone formation, cell ...counting, and apoptosis. Melittin, the key component of bee venom, is a potent inhibitor of calmodulin activity, and also a potent inhibitor cell growth and clonogenicity. Intracellular accumulation of melittin correlates with the cytotoxicity of antitumour agents. Previous studies indicated that some calcium antagonists and calmodulin inhibitors enhanced intracellular levels of antitumor agents by inhibiting their outward transport. In this study, treatment of exponentially growing HeLa and V79 cells with bleomycin caused a dose-dependent decrease in cell survival due to DNA damage. This lethal effect was potentiated by adding a non-lethal dose of the bee venom. By preventing repair of damaged DNA, bee venom inhibited recovery from potentially lethal damage induced by bleomycin in V79 and HeLa cells. Apoptosis, necrosis, and lysis were presumed as possible mechanisms by which bee venom inhibited growth and clonogenicity of V79 cells. HeLa cells, on the other hand, showed greater resistance to bee venom. Our findings suggest that bee venom might find a therapeutic use in enhancing cytotoxicity of antitumour agent bleomycin.
U uvjetima in vitro istražen je inhibitorni u _inak p _elinjeg otrova, samog ili združenog s citostatikom bleomicinom, na rast stanica HeLa i V79. Rabljene su sljedeće metode: brojenje stanica, metoda klonskog rasta i apoptoza. Poznato je da neki antagonisti kalcija i kalmodulinski inhibitori povisuju unutarstani _nu razinu protutumorskih lijekova inhibirajući njihov prijenos iz stanice. Unutarstani _na akumulacija melitina izravno povećava citotoksi _ni u _inak protutumorskog lijeka. Obrada stanica HeLa i V79 u eksponencijalnoj fazi rasta bleomicinom uzrokuje oštećenje DNA ovisno o dozi te smanjenje broja živih stanica. Uo _eno je da se letalni u _inak bleomicina može poja _ati dodatkom neletalne doze p _elinjeg otrova. P _elinji otrov pritom inhibira popravak nastalih oštećenja u stanicama HeLa i V79 te sprje _ava oporavak stanica tretiranih bleomicinom. Apoptoza, nekroza i liza mogući su mehanizmi kojima p _elinji otrov inhibira rast i stvaranje kolonija stanica V79, dok HeLa-stanice pokazuju poja _anu otpornost na p _elinji otrov. Istraživanje također potvrđuje mogućnost uporabe p _elinjeg otrova u povećanju citotoksi _nosti bleomicina.
The mechanism of aluminium-induced cytotoxicity has not yet been defined. This study investigated possible changes in essential elements in workers occupationally exposed to Al fumes. It included 60 ...exposed workers and a matching control group of 60 employees not occupationally exposed to Al. Mean serum copper, calcium, zinc and iron were significantly lower in the exposed group than in controls. In addition, mean plasma and urine levels of Al were significantly higher in the exposed employees than in the controls. A statistically significant negative correlation was found between plasma and urinary Al and the studied essential elements. These findings corroborate the hypothesis that Al exposure has an adverse effect on essential elements in humans, with subsequent impact on the cellular enzymatic and metabolic processes.
Dosada nije razjašnjen mehanizam citotoksičnoga djelovanja aluminija. U ovome ispitivanju pokušalo se ustanoviti dolazi li do promjena u sadržaju esencijalnih elemenata u skupini radnika koji su bili profesionalno izloženi aluminijskim parama. Ispitivanje je obuhvatilo 60 izloženih radnika i odgovarajuću kontrolnu skupinu od 60 zaposlenika koji nisu bili profesionalno izloženi aluminijskim parama. Rezultati su pokazali značajno niže srednje razina bakra, kalcija, cinka i željeza u serumu izloženih radnika u odnosu na kontrolu. Usto su iskazali značajno više razine Al u plazmi i mokraći. Utvrđena je statistički značajna negativna korelacija između Al u plazmi/mokraći i ispitanih esencijalnih elemenata. Ovi rezultati upućuju na pretpostavku da izloženost aluminiju nepovoljno djeluje na razine esencijalnih elemenata u ljudi, a time i na lučenje enzima i stanični metabolizam.
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