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1.
Photochem Photobiol Sci ; 20(8): 1087-1098, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34398442

RESUMO

In this study, C-doped TiO2 nanoparticles (C-TiO2) were prepared and tested as a photosensitizer for visible-light-driven photodynamic therapy against cervical cancer cells (HeLa). X-ray diffraction and Transmission Electron Microscopy confirmed the anatase form of nanoparticles, spherical shape, and size distribution from 5 to 15 nm. Ultraviolet-visible light spectroscopy showed that C doping of TiO2 enhances the optical absorption in the visible light range caused by a bandgap narrowing. The photo-cytotoxic activity of C-TiO2 was investigated in vitro against HeLa cells. The lack of dark cytotoxicity indicates good biocompatibility of C-TiO2. In contrast, a combination with blue light significantly reduced the survival of HeLa cells: illumination only decreased cell viability by 30% (15 min of illumination, 120 µW power), and 60% when HeLa cells were preincubated with C-TiO2. We have also confirmed blue light-induced C-TiO2-catalyzed generation of reactive oxygen species in vitro and intracellularly. Oxidative stress triggered by C-TiO2/blue light was the leading cause of HeLa cell death. Fluorescent labeling of treated HeLa cells showed distinct morphological changes after the C-TiO2/blue light treatment. Unlike blue light illumination, which caused the appearance of large necrotic cells with deformed nuclei, cytoplasm swelling, and membrane blebbing, a combination of C-TiO2/blue light leads to controlled cell death, thus providing a better outcome of local anticancer therapy.


Assuntos
Carbono/química , Nanopartículas , Fototerapia , Titânio/química , Titânio/farmacologia , Neoplasias do Colo do Útero/patologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Terapia Combinada , Feminino , Células HeLa , Humanos
2.
Regul Toxicol Pharmacol ; 104: 21-28, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30844416

RESUMO

Long term exposure to oral smokeless tobacco may induce lesions in the oral cavity characterized by a hyperplastic epithelium. The possible role of nicotine and the physical properties of oral tobacco for developing these lesions, as well as of dysplasia and neoplasia is unclear. Low nitrosamine Swedish snus as well as non-genotoxic butylated hydroxyanisole induces increased cellular proliferation in the rat forestomach epithelia. Using this model, we report here on the effects of nicotine, pH, and particle size. Snus with different properties had no impact on oxidative stress as determined by 8-oxo-7,8-dihydro-2'-deoxyguanosine, or on interleukin IL-1b. Whereas BHA boosted IL-6, probably due to the presence of nicotine. there was no significant enhancement of cell divisions with increasing particle size, although in individual samples the variations in proliferation rates increased greatly with increasing particle size. Conforming to human experience, the enhanced cell proliferation caused by snus was found to be completely reversible. A cacao bean extract had a protective action similar to that previously found for blueberries. The main cause of the observed tobacco induced cell proliferation could be mechanical irritation, possibly in combination with nicotine, whereas within the studied range, pH did not affect the rate of cell division.


Assuntos
Hiperplasia/induzido quimicamente , Nicotina/toxicidade , Estômago/efeitos dos fármacos , Tabaco sem Fumaça/toxicidade , Administração Oral , Animais , Proliferação de Células/efeitos dos fármacos , Hiperplasia/patologia , Masculino , Nicotina/administração & dosagem , Ratos , Ratos Wistar , Estômago/patologia , Suécia
3.
Arh Hig Rada Toksikol ; 75(2): 137-146, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38963137

RESUMO

Traditional medicine has used sage (Salvia officinalis L.) preparations for centuries to prevent and treat various inflammatory and oxidative stress-induced conditions. The aim of this in vitro study was to determine the bioactive properties of a sage leave extract obtained with environmentally friendly aqueous extraction and lyophilisation in primary human peripheral blood cells. To that end we measured the total phenolic and flavonoid content (TPC and TFC, respectively) with gas chromatography-mass spectrometry (GC-MS). Non-cytotoxic concentrations determined with the trypan blue assay were used to assess the antioxidant (DPPH, ABTS, and PAB assay), antigenotoxic (CBMN assay), immunomodulatory (IL-1ß and TNF-α), and neuroprotective effects (AChE inhibition). The extract contained high TPC (162 mg GAE/g of dry extract) and TFC (39.47 mg QE/g of dry extract) concentrations, while ß-thujone content was unexpectedly low (below 0.9 %). Strong radical-scavenging activity combined with glutathione reductase activation led to a decrease in basal and H2O2-induced oxidative stress and DNA damage. A decrease in TNF-α and increase in IL-1ß levels suggest complex immunomodulatory response that could contribute to antioxidant and, together with mild AChE inhibition, neuroprotective effects. Overall, this study has demonstrated that aqueous sage leave extract reduces the levels of thujone, 1,8-cineole, pinene, and terpene ketones that could be toxic in high concentrations, while maintaining high concentrations of biologically active protective compounds which have a potential to prevent and/or treat inflammatory and oxidative stress-related conditions.


Assuntos
Inflamação , Leucócitos Mononucleares , Estresse Oxidativo , Extratos Vegetais , Salvia officinalis , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Leucócitos Mononucleares/efeitos dos fármacos , Salvia officinalis/química , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Dano ao DNA/efeitos dos fármacos , Folhas de Planta/química
4.
Arh Hig Rada Toksikol ; 73(1): 23-30, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35390241

RESUMO

Ionising radiation damages DNA directly and indirectly through increased production of reactive oxygen species. Although telomeres have been reported as indicators of radiosensitivity, their maintenance in response to occupational exposure to low radiation doses is still a matter of debate. In this work we aimed to investigate telomere length and structure in hospital workers occupationally exposed to X-rays and to relate these findings to oxidation of biomolecules and chromosome aberrations. Blood samples of exposed participants and matching controls were taken during periodical check-ups. Chromosome aberrations and telomere length and structure were analysed in peripheral blood lymphocytes using Q-FISH, whereas oxidative stress parameters [pro/antioxidant balance (PAB), lipid peroxidation, and 8-oxo-dG] were measured in plasma samples. Based on the CA findings we divided the exposed group into two subgroups, of which one had chromosome aberrations in the first division metaphases and the other did not. There was no significant difference in telomere length between any of the groups. However, both subgroups showed significantly higher rate of fragile telomeres and higher lipid peroxidation product and 8-oxo-dG levels than controls. The rate of fragile telomeres significantly correlated with plasma levels of 8-oxo-dG, which suggests that continuous exposure to low radiation doses induces oxidative base damage of guanine resulting in telomere fragility.


Assuntos
Exposição Ocupacional , Radiologia , 8-Hidroxi-2'-Desoxiguanosina , Aberrações Cromossômicas , Humanos , Exposição Ocupacional/efeitos adversos , Radiação Ionizante , Telômero
5.
Arh Hig Rada Toksikol ; 71(4): 320-328, 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33410776

RESUMO

Yellow gentian (Gentiana lutea 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 in vitro. 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.


Assuntos
Gentiana , Leucócitos Mononucleares , Extratos Vegetais , Ensaio Cometa , Dano ao DNA , Humanos , Extratos Vegetais/farmacologia
6.
Curr Pharm Des ; 25(18): 2071-2076, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31538881

RESUMO

BACKGROUND: Obesity, diabetes, and associated diseases are increasing all over the world, and pose a great burden on public health. According to the latest reports, 440 million people are suffering from diabetes. Diabetes is caused by impaired ability to produce or respond to the hormone insulin consequently resulting in hyperglycemia. METHODS: Data used for this review was obtained by using PUBMED/MEDLINE (1987-2018). The main data search terms were: Gentiana lutea, Gentiana lutea extract, Gentiana lutea constituents, obesity, diabetes mellitus, diabetic complications. RESULTS: In the present review, we describe the potential of root powder of yellow gentian (Gentiana lutea) for the prevention of obesity and diabetes including complications related to this disease. CONCLUSION: Reasonably effective, low-cost alternatives could fulfill an important role for a large part of the human population and could be of great value for the food market. Even a modest reduction of morbidity and mortality with respect to this disease translates into millions of lives saved.


Assuntos
Gentiana/química , Obesidade/tratamento farmacológico , Fitoterapia , Diabetes Mellitus/tratamento farmacológico , Humanos , Raízes de Plantas/química
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