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.
Even though the endocrine-disrupting potential of perfluorooctanoic acid (PFOA) is well known, the mechanisms underlying its cellular and epigenetic toxicity at the critical stage of hypothalamic ...development are poorly understood. This is why we studied its effects on the embryonic mouse hypothalamic cell line N46 (mHypoE-N46) with a hope to shed more light on the mechanisms through which PFOA causes embryonic hypothalamic cell damage. To do that, we studied cell viability, global DNA methylation, and gene expression in cells exposed to PFOA. As the PFOA dose increased, cell viability decreased, while global DNA methylation increased. PFOA also significantly altered the expression of genes related to the apoptosis and cell cycle, neurotrophic genes, and the
,
, and
genes. Our findings suggest that exposure to PFOA affects cell survival through the reprogramming of embryonic hypothalamic DNA methylation patterns and altering cell homeostasis genes. DNA methylation and changes in the
gene expression induced by PFOA also imply wider ramifications, as they alter genes of other major mechanisms of the embryonic hypothalamus. Our study may therefore serve as a good starting point for further research into the mechanisms of PFOA effect of hypothalamic development.
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.
Isoniazid is one of the most commonly used drugs to treat tuberculosis. Its administration is associated with a high incidence of hepatotoxicity. The aim of this study was to establish the protective ...effects of taurine against cytotoxicity induced by isoniazid and its suspected toxic metabolite hydrazine in isolated rat hepatocytes by measuring reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial depolarisation, reduced glutathione (GSH), and oxidised glutathione (GSSG). Isoniazid caused no significant ROS formation in normal hepatocytes, but in glutathione-depleted cells it was considerable. Hydrazine caused ROS formation and lipid peroxidation in both intact and glutathione-depleted cells. Both isoniazid and hydrazine caused mitochondrial membrane depolarisation. Hydrazine lowered cellular GSH reserve and increased GSSG. Taurine (200 μmol L
) and N-acetylcysteine (200 μmol L-1) effectively countered the toxic effects of isoniazid and/or hydrazine by decreasing ROS formation, lipid peroxidation, and mitochondrial damage. Taurine prevented depletion of GSH and lowered GSSG levels in hydrazine-treated cells. This study suggests that the protective effects of taurine against isoniazid and its intermediary metabolite hydrazine cytotoxicity in rat hepatocytes could be attributed to antioxidative action.
Izoniazid je jedan od najčešćih lijekova za tuberkulozu, ali se njegova primjena povezuje s veoma učestalom hepatotoksičnosti. Cilj je ovog istraživanja bio ocijeniti djelotvornost taurina u zaštiti izoliranih hepatocita štakora od citotoksičnosti izazvane izoniazidom i njegovim toksičnim metabolitom hidrazinom. U tu smo svrhu utvrdili razine reaktivnih kisikovih spojeva (ROS), lipidnu peroksidaciju, depolarizaciju mitohondrija, reducirani glutation (GSH) te oksidirani glutation (GSSG). Izoniazid nije doveo do značajnoga nastanka ROS-a u normalnih hepatocita, ali je zato bio značajan u stanica osiromašenih glutationom. I izoniazid i hidrazine doveli su do depolarizacije membrane mitohondrija. Hidrazin je smanjio staničnu rezervu GSH i povećao razinu GSSG. Taurin (200 μmol L-1) i N-acetilcistein (200 μmol L
) uspješno su zaštitili od toksičnoga djelovanja izoniazida i/ili hidrazina, smanjivši nastanak ROS-a, lipidnu peroksidaciju i oštećenje mitohondrija. Taurin je spriječio potpuni gubitak GSH-a te snizio razine GSSG-a u stanica tretiranih hidrazinom. Rezultati našeg istraživanje upućuju na to da se zaštitno djelovanje taurina od stanične toksičnosti izoniazida i hidrazina može pripisati njegovu andioksidacijskome djelovanju.
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.