In order to develop an understanding of the role of adjuvants in a popular glyphosate-based herbicide - Roundup® Concentrate Plus (RCP), on non-target organisms, the effects of pure glyphosate [N-(phosphonomethyl)-glycine], RCP and a non-ionic surfactant - polyethoxylated tallowamine (POEA) were studied in the fruit fly Drosophila melanogaster. Acute exposure to sub-lethal concentrations of RCP (15 μg/mL) and POEA (45 μg/mL) reduced (p < 0.001) lifespan of female flies compared to untreated controls or glyphosate (100 μg/mL). Negative geotaxis responses in female flies were reduced (p < 0.05) following acute exposure to sub-lethal concentrations of RCP and POEA whereas glyphosate did not significantly affect this response compared to untreated flies. Acute exposure to sub-lethal concentrations of RCP and POEA elevated (p < 0.05) protein carbonyl levels while markedly (p < 0.01) inhibiting carbonyl reductase activity whereas glyphosate treatment did not significantly affect protein carbonyl levels or carbonyl reductase activity. Fecundity was reduced (p < 0.05) following exposure to sub-lethal concentrations of RCP and POEA whereas glyphosate did not affect fecundity. In vitro treatment of ovarian stem sheath (OSS) cells with sub-lethal concentrations of RCP and POEA revealed decreased cell viability and enhanced caspase activity indicative of pro-apoptotic processes after 48 h compared to untreated controls. Glyphosate however was non-toxic at the concentration used. The results suggest that RCP and the surfactant POEA are more toxic than pure glyphosate and inhibit fecundity in Drosophila by impairing cell viability through enhanced apoptosis.
- MeSH
- adjuvancia farmaceutická toxicita MeSH
- apoptóza účinky léků MeSH
- buněčné linie MeSH
- dlouhověkost účinky léků MeSH
- Drosophila melanogaster účinky léků fyziologie MeSH
- fertilita účinky léků MeSH
- glycin analogy a deriváty toxicita MeSH
- herbicidy toxicita MeSH
- polyethylenglykoly toxicita MeSH
- povrchově aktivní látky toxicita MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The cytotoxicity of methacrylate-based biopolymers crosslinked by in situ photopolymerization has been attributed mainly to residual methacrylate monomers released due to incomplete polymerization. The residual monomers, primarily triethyleneglycol dimethacrylate or 2-hydroxyethyl methacrylate, may irritate adjacent tissue, or be released into the bloodstream and reach practically all tissues. Increased production of reactive oxygen species, which may be connected to concomitant glutathione depletion, has been the most noticeable effect observed in vitro following the exposure of cells to methacrylates. Radical scavengers such as glutathione or N-acetylcysteine represent the most important cellular strategy against methacrylate-induced toxicity by direct adduct formation, resulting in monomer detoxification. Reactive oxygen species may participate in methacrylate-induced genotoxic or pro-apoptotic effects and cell-cycle arrest via induction of corresponding molecular pathways in cells. A deeper understanding of the biological mechanisms and effects of methacrylates widely used in various bioapplications may enable a better estimation of potential risks and thus, selection of a more appropriate composition of polymer material to eliminate potentially harmful substances such as triethyleneglycol dimethacrylate.
- MeSH
- acetylcystein farmakologie MeSH
- biokompatibilní materiály chemie toxicita MeSH
- glutathion metabolismus MeSH
- kyseliny polymethakrylové chemie toxicita MeSH
- lidé MeSH
- methakryláty chemie toxicita MeSH
- polyethylenglykoly chemie toxicita MeSH
- reaktivní formy kyslíku metabolismus MeSH
- scavengery volných radikálů farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Several irritants were used in the in vitro irritation medical device round robin. The objective of this study was to verify their irritation potential using the human patch test (HPT), an in vitro assay, and in vivo data. The irritants were lactic acid (LA), heptanoic acid (HA), sodium dodecyl sulfate (SDS), Genapol® X-80 (GP), and Y-4 polymer. Dilute saline and sesame seed oil (SSO) solutions of each were evaluated using a 4 and 18 h HPT and the EpiDerm™ SIT-MD RhE assay; results were then compared to existing rabbit skin irritation test data. Results from the 4 h HPT were negative in most cases except for GP and SDS, while the 18 h HPT also identified some LA, HA, and GP samples as irritants. EpiDerm™ SIT-MD correctly identified all irritants except GP in SSO due to limited solubility. Data from cutaneous rabbit irritation tests were negative, while all intracutaneous results were strongly or weakly positive except for the most dilute GP solutions. These findings indicate that EpiDerm™ SIT-MD results correlate with those from the rabbit intracutaneous test and confirm that RhE assays are suitable replacements for animals in evaluating the tissue irritation potential of medical devices.
- MeSH
- alternativy testů na zvířatech MeSH
- benchmarking MeSH
- dodecylsíran sodný toxicita MeSH
- dráždivé látky toxicita MeSH
- králíci MeSH
- kůže účinky léků MeSH
- kyselina mléčná toxicita MeSH
- kyseliny heptylové toxicita MeSH
- lidé MeSH
- náplasťové testy metody MeSH
- polyethylenglykoly toxicita MeSH
- polyvinylchlorid toxicita MeSH
- reprodukovatelnost výsledků MeSH
- testy kožní dráždivosti metody MeSH
- zdravotnické prostředky * MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Increased oxidative stress is indisputably an important mechanism of doxorubicin side effects, especially its cardiotoxicity. To prevent impairment of non-tumorous tissue and to improve the specificity in targeting the tumor tissue, new drug nanotransporters are developed. In many cases preclinical therapeutic advantage has been shown when compared with the administration of conventional drug solution. Three forms of doxorubicin--conventional (DOX), encapsulated in liposomes (lipoDOX) and in apoferritin (apoDOX) were applied to Wistar rats. After 24 h exposition, the plasma level of 4-hydroxy-2-nonenal (4-HNE) as a marker of lipoperoxidation and tissue gene expression of thioredoxin reductase 2 (TXNRD2) and aldehyde dehydrogenase 3A1 (ALDH3A1) as an important part of antioxidative system were determined. Only conventional DOX significantly increases the level of 4-HNE; encapsulated forms on the other hand show significant decrease in plasma levels of 4-HNE in comparison with DOX. They also cause significant decrease in gene expression of ALDH3A1 and TXNRD2 in liver as a main detoxification organ, and a mild influence on the expression of these enzymes in left heart ventricle as a potential target of toxicity. Thus, 4-HNE seems to be a good potential biomarker of oxidative stress induced by various forms of doxorubicin.
- MeSH
- aldehyddehydrogenasa genetika metabolismus MeSH
- aldehydy krev MeSH
- antibiotika antitumorózní aplikace a dávkování chemie toxicita MeSH
- apoferritiny aplikace a dávkování chemie toxicita MeSH
- biologické markery krev MeSH
- chemie farmaceutická MeSH
- down regulace MeSH
- doxorubicin aplikace a dávkování analogy a deriváty chemie toxicita MeSH
- játra účinky léků enzymologie MeSH
- oxidační stres účinky léků MeSH
- peroxidace lipidů účinky léků MeSH
- polyethylenglykoly aplikace a dávkování chemie toxicita MeSH
- potkani Wistar MeSH
- regulace genové exprese enzymů MeSH
- thioredoxinreduktasa 2 genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- MeSH
- antidota terapeutické užití MeSH
- chelátory terapeutické užití MeSH
- ibuprofen škodlivé účinky terapeutické užití toxicita MeSH
- kontinuální vzdělávání metody organizace a řízení trendy MeSH
- lidé MeSH
- otrava rtutí diagnóza farmakoterapie prevence a kontrola MeSH
- otrava diagnóza etiologie prevence a kontrola MeSH
- polyethylenglykoly škodlivé účinky toxicita MeSH
- toxikologie metody trendy výchova MeSH
- Check Tag
- lidé MeSH
- MeSH
- amfetamin aplikace a dávkování škodlivé účinky toxicita MeSH
- dekontaminace metody normy MeSH
- doxorubicin aplikace a dávkování terapeutické užití MeSH
- fysostigmin dějiny terapeutické užití MeSH
- lidé MeSH
- otrava diagnóza etiologie prevence a kontrola MeSH
- polyethylenglykoly škodlivé účinky toxicita MeSH
- toxikologie metody trendy MeSH
- Check Tag
- lidé MeSH