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Approaches for Identification and Validation of Antimicrobial Compounds of Plant Origin: A Long Way from the Field to the Market
Published in Mahendra Rai, Chistiane M. Feitosa, Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
Lívia Maria Batista Vilela, Carlos André dos Santos-Silva, Ricardo Salas Roldan-Filho, Pollyanna Michelle da Silva, Marx de Oliveira Lima, José Rafael da Silva Araújo, Wilson Dias de Oliveira, Suyane de Deus e Melo, Madson Allan de Luna Aragão, Thiago Henrique Napoleão, Patrícia Maria Guedes Paiva, Ana Christina Brasileiro-Vidal, Ana Maria Benko-Iseppon
After confirmation of the antimicrobial potential, preclinical tests should be conducted to detect the new compounds’ possible adverse effects at different concentrations on human health (Shegokar 2020). These tests provide information about in vivo and in vitro toxicology, including in vivo analysis of organ damage, individually and systemically, until cellular and DNA levels. If approved in preclinical trials, the new non-toxic compound can proceed to clinical trials in humans. The main preclinical tests based on current international legislation and their impacts on human health are explored here (Shegokar 2020).
In Vitro Alternatives to Animal Toxicity
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
The use of cell culture techniques in toxicological investigations is referred to as in vitro cytotoxicology or in vitro toxicology. The latter term also includes noncellular test systems, such as isolated organelles or high-throughput (HTP) microarrays. The reasons for the increasing interest in and success of these techniques in clinical and research toxicology testing are a consequence of the considerable advancements realized since the advent of the technology:1.Since the growth of the first mammalian cells in capillary glass tubes was described, cell culture technology has been extensively refined;2.The mechanism of toxicity of chemicals in humans and animals has been elucidated primarily through the use of in vitro toxicological methods;3.The necessity to determine the toxic effects of pharmaceuticals and industrial chemicals, which are developed and marketed at rapid and unprecedented rates, has made the development of fast, simple, and effective alternative test systems compulsory;4.Although the normal rate of progression of any scientific discipline is determined by the progress within the scientific community, some areas have received more encouragement than others.
Preclinical Characterization of Engineered Nanoparticles Intended for Cancer Therapeutics
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Anil K. Patri, Marina A. Dobrovolskaia, Stephan T. Stern, Scott E. McNeil
As is the case with any NCE, a thorough understanding of the properties that govern biocompatability is necessary to allow transition of nanomaterials to human clinical trials. Although in vitro toxicology studies can be informative, the obvious caveat is that phenomenon observed in vitro may not materialize in vivo due to differences in biological response or nanoparticle concentrations. Therefore, nanoparticle safety and therapeutic efficacy can only be definitively assessed by rigorous in vivo testing. This phase is guided in part by insights obtained from the physicochemical and in vitro characterization programs.
Evaluation of Calu-3 cell lines as an in vitro model to study the inhalation toxicity of flavoring extracts
Published in Toxicology Mechanisms and Methods, 2022
Xiaoli Ji, Yunhua Sheng, Ying Guan, Yinxia Li, Yuqiong Xu, Liming Tang
Long-term exposure to chemicals in smoke induces the development of many smoking-related diseases, including chronic obstructive pulmonary disease (COPD) (Simet et al. 2010). The US Food and Drug Administration (FDA) has authorized the Institute of Medicine (IOM) to develop ‘Scientific Standards for Studies on Modified Risk Tobacco Products’ (Institute of Medicine (U.S.). Committee on Scientific Standards for Studies on Modified Risk Tobacco Products 2012), in which in vitro toxicology testing was proposed as an important part of the evaluation process. Various in vitro assays have been used to assess the toxicity of tobacco and tobacco smoke (Li 2016). In recent years, the use of several devices (e.g. e-cigarettes) for recreational inhalation of non-flammable nicotine has emerged among teens and adults (Paumgartten et al. 2017). Although carcinogens appear to be reduced or eliminated in e-cigarettes, the health implications of e-cigarette aerosols containing flavoring chemicals including their enhancers are unclear based on toxicological effects on the lungs (Gonzalez-Suarez et al. 2016). Electronic liquids are available in many flavors (≈7000 are on the market), with menthol, sweet, and fruity electronic liquids being the most popular (Fetterman et al. 2018). The toxicological aspects of these flavoring additives are largely unknown; thus, developing alternative methods to assess the inhalation toxicity of flavoring chemicals is required.
Evaluation of the cytotoxic and genotoxic effects of mycotoxin fusaric acid
Published in Drug and Chemical Toxicology, 2020
Sevcan Mamur, Fatma Ünal, Serkan Yılmaz, Esra Erikel, Deniz Yüzbaşıoğlu
Cytotoxicity assays are widely used for the evaluation of cytotoxic effect on chemicals in in vitro toxicology studies. MTT assay is a cell viability assay often used to detect cytotoxicity following an exposure to toxic substances (Riss et al.2016) and this assay evaluates the mitochondrial function by determining the ability of living cells to reduce MTT into a blue formazon product (Ahmad et al.2016). The mitotic index (MI), replicative index (RI) and nuclear division index (NDI) are other methods of measuring the cellular proliferation and its kinetics. In this study, the results of the cytotoxicity assays (MTT in HeLa cell line and MI in human lymphocytes) showed that FA is a potential cytotoxic agent especially at higher concentrations. Moreover, the treatments over 25 μg/mL concentrations had cytotoxic effects and no dividing cells were observed in human lymphocytes with MI. The MI is used to characterize proliferating cells and to identify materials that inhibit or increase mitotic progression (Eroğlu et al.2007). The MI evaluation results in this study are consistent with the results of previous studies in which mycotoxin from Fusarium and/or other fungal species were significantly decreased the MI value (Lorenzi et al.2005, Çelik et al.2010). Unlike the results regarding MI in our study, RI and NDI indices did not confirm other cytotoxicity results. These results indicate that FA is most probably showed its action before DNA synthesis.
Co-delivery of a RanGTP inhibitory peptide and doxorubicin using dual-loaded liposomal carriers to combat chemotherapeutic resistance in breast cancer cells
Published in Expert Opinion on Drug Delivery, 2020
Yusuf Haggag, Bayan Abu Ras, Yahia El-Tanani, Murtaza M. Tambuwala, Paul McCarron, Mohammed Isreb, Mohamed El-Tanani
A cell viability assay was performed using an in vitro toxicology assay kit (MTT, 7H258, Sigma, Saint Louise, Missouri, USA) [38,39]. MCF-7, MDA-MB-231, and A549 cells (1.2–1.8 x104 cells/well in 100 µl media) were seeded in 96-well plates for 24 h before treatment. The following day, all cells were treated with 100 µl of each of the following formulations: blank liposome, free peptide (1 µM), free DOX (1 µM), peptide-loaded liposome (1 µM), DOX-loaded liposome (1 µM), combination of both peptide-loaded liposome (1 µM) and DOX-loaded liposome (1 µM), dual-loaded liposome at three different concentrations (0.25, 0.5 and 1 µM). All treatments were suspended in transfection Optimem® media. Untreated MCF-7, MDA-MB-231, and A549 cells were used as controls.