Photodynamic therapy is an alternative treatment mainly for cancer but also for bacterial infections. This treatment dates back to 1900 when a German medical school graduate Oscar Raab found a photodynamic effect while doing research for his doctoral dissertation with Professor Hermann von Tappeiner. Unexpectedly, Raab revealed that the toxicity of acridine on paramecium depends on the intensity of light in his laboratory. Photodynamic therapy is therefore based on the administration of a photosensitizer with subsequent light irradiation within the absorption maxima of this substance followed by reactive oxygen species formation and finally cell death. Although this treatment is not a novelty, there is an endeavor for various modifications to the therapy. For example, selectivity and efficiency of the photosensitizer, as well as irradiation with various types of light sources are still being modified to improve final results of the photodynamic therapy. The main aim of this review is to summarize anticancer and antibacterial modifications, namely various compounds, approaches, and techniques, to enhance the effectiveness of photodynamic therapy.
Photodynamic therapy (PDT) uses photosensitive substance to provoke a cytotoxic reaction causing a cell damage or cell death. The substances, photosensitizers, are usually derivates of porphyrine or phtalocyanine. Photosensitizers must be activated by light in order to produce reactive oxygen species, mainly singlet oxygen. Sonodynamic therapy (SDT) utilizes ultrasound to enhance a cytotoxic effects of compounds called sonosensitizers. In this study we investigated photodynamic and sonodynamic effect of chloraluminium phtalocyanine disulfonate (ClAlPcS(2)) on HeLa cells. DNA damage, cell viability and reactive oxygen species (ROS) production were assessed to find whether the combination of PDT and SDT inflicts HeLa cells more than PDT alone. We found that the combined therapy increases DNA fragmentation, enhances ROS production and decreases cell survival. Our results indicate that ClAlPcS(2) can act as a sonosentitiser and combined with PDT causes more irreversible changes to the cells resulting in cell death than PDT alone.
Growing worldwide efforts to replace (reduce) animal testing and to improve alternative in vitro tests which may be more efficient in terms of both time, cost and scientific validity include also genotoxicity/mutagenicity endpoints. The aim of the review article was to summarize currently available in vitro testing approaches in this field, their regulatory acceptance and recommended combinations for classification of chemicals. A study using the combination of Comet Assay performed on two cell lines and the Chromosomal Aberration test on human peripheral lymphocytes was performed with the aim to predict the genotoxic potential of selected paraben esters, serving as a model chemical group. Parabens are widely used in consumer products as preservatives and have been reported to exhibit inconclusive results in numerous genotoxicity studies. The Comet Assay identified Ethylparaben and Benzylparaben as potentially genotoxic. The Chromosomal Aberration test revealed weak genotoxic potential in case of Ethylparaben and positive genotoxicity in case of Butylparaben, Propylparaben and Isopropylparaben. The main reasons for variability seem to be limited water solubility of parabens, determining their bioavailability at the cellular level, and absence of metabolic activation in the Comet Assay. The results confirmed that the Comet Assay should serve as a screening test and should not be used as a stand-alone method for classification of genotoxicity. The weight of evidence approach in risk assessment should be supported with data generated with the use of human relevant in vitro methods based on cells / tissues of human origin.
Animal testing has been prohibited for the safety assessment of cosmetic ingredients or finished products. Thus, alternative non-animal methods, followed by confirmatory clinical studies on human volunteers, should be used as the sole legally acceptable approach within the EU. The safety assessment of cosmetic products requires the involvement of multiple scientific disciplines, including analytical chemistry and biomedicine, as well as in chemico, in vitro and in silico toxicology. Recent data suggest that fragrance components may exert multiple adverse biological effects, e.g. cytotoxicity, skin sensitisation, (photo)genotoxicity, mutagenicity, reprotoxicity and endocrine disruption. Therefore, a pilot study was conducted with selected samples of fragrance-based products, such as deodorant, eau de toilette and eau de parfum, with the aim of integrating results from a number of alternative non-animal methods suitable for the detection of the following toxicological endpoints: cytotoxicity (with 3T3 Balb/c fibroblasts); skin sensitisation potential ( in chemico method, DPRA); skin sensitisation potential (LuSens in vitro method, based on human keratinocytes); genotoxicity potential ( in vitro Comet assay with 3T3 Balb/c cells); and endocrine disruption ( in vitro YES/YAS assay). The presence of twenty-four specific known allergens in the products was determined by using GC-MS/MS. The strategies for estimation of the NOAEL of a mixture of allergens, which were proposed by the Scientific Committee on Consumer Products in their ‘Opinion on Tea tree oil’ document and by the Norwegian Food Safety Authority in their 'Risk Profile of Tea tree oil' report, were used as models for the NOAEL estimation of the mixtures of allergens that were identified in the individual samples tested in this study.
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