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Natural Products from the Amazon Region as Potential Antimicrobials
Published in Mahendra Rai, Chistiane M. Feitosa, Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
Josiane E. A. Silva, Iasmin L. D. Paranatinga, Elaine C. P. Oliveira, Silvia K. S. Escher, Ananda S. Antonio, Leandro S. Nascimento, Patricia P. Orlandi, Valdir F. Veiga-Júnior
When a bioassay is performed and an active substance is found, several aspects of the research must be evaluated next. The sustainability of the continuity of studies is one of these aspects. If the substance isolated from a natural product already has an economically viable synthetic route, it is likely that its price in the market will be low, making the choice to extract this substance from the plant in question unfeasible. Obviously, if the choice is to use a cheaper biological source, without needing isolation, then the isolated synthetic derivative, probably with more side effects, will not be the first choice. The isolated substance may be available not only by synthetic routes, but sometimes as a by-product of the bioindustry. In that case, they also become viable to being purchased commercially.
Marine Natural Products for Human Health Care
Published in Hafiz Ansar Rasul Suleria, Megh R. Goyal, Health Benefits of Secondary Phytocompounds from Plant and Marine Sources, 2021
In the systematic attempt to identify bioactive crude extracts or fractions, selected biochemical and/or phenotypical targets are assayed in an HTS manner as part of the bioassay-guided isolation process. The bioassays constituting an HTS program are chosen based on the research area of interest for the individual bioprospecting laboratories. An HTS program may consist of bioassays devoted to detecting bioactivity within one area of interest, for example anticancer agents. For this purpose, cell-based anticancer assays, as well as kinase and caspase inhibition assays may be used. It may also consist of bioassays for detecting a variety of activities towards a range of diseases or interest areas.
Quick Methods: Structure-Activity Relationships and Short-Term Bioassay
Published in Samuel C. Morris, Cancer Risk Assessment, 2020
Short-term bioassays, primarily in vitro, provide valuable tools for research and prescreening of potential carcinogens. Their quick turnaround and relatively low cost make possible studies which simply could not be done with long-term animal bioassay such as detailed analysis of complex mixtures. They are not designed for amateur use, however. They are complex, technically and professionally demanding procedures, and require skilled scientists to perform them properly and to interpret results. They cannot provide the final determination of the question of carcinogenicity nor have they been acceptable for quantitative dose-response functions, although many short-term tests can provide quantitative results. They do provide additional information that can be used in conjunction with animal or epidemiological results in both qualitative and quantitative interpretation (see Chap. 12). As an example, they can aid in determining whether an agent causes cancer by directly affecting genetic material, or if it has a more peripheral role.
Assessing chemical carcinogenicity: hazard identification, classification, and risk assessment. Insight from a Toxicology Forum state-of-the-science workshop
Published in Critical Reviews in Toxicology, 2021
Susan P. Felter, Virunya S. Bhat, Philip A. Botham, David A. Bussard, Warren Casey, A. Wallace Hayes, Gina M. Hilton, Kelly A. Magurany, Ursula G. Sauer, Edward V. Ohanian
If the test-animal MoA is determined to be potentially relevant to humans and dose-response information is available, dose-response assessments are performed to establish the PoD for the subsequent risk assessment. Some of the aforementioned IATAs consider that assessments based on a PoD for a non-genotoxic precursor key event related to a carcinogenic outcome will be protective of carcinogenic risk. WoE evaluation of intended use and potential exposure, mechanistic and/or short-term animal tests, and chemical read-across information are primed to reduce the use of a rodent chronic bioassay. Eventually, evidence based on in vitro NAMs may reduce or eliminate the need for animal testing. NAMs may also provide the opportunity to develop a more health protective safety assessment through more precise PoDs for the definition of reference doses or for use in dose-response extrapolations.
Critical evaluation of the human relevance of the mode of action for rodent liver tumor formation by activators of the constitutive androstane receptor (CAR)
Published in Critical Reviews in Toxicology, 2021
Tomoya Yamada, Samuel M. Cohen, Brian G. Lake
Currently, long-term bioassays in the mouse and rat are employed to screen for chemicals which may be carcinogenic to humans. Analysis of tumor data demonstrates that the liver is the most common site of tumor formation in both the mouse and rat (Huff et al. 1991; Gold et al. 2001; Thoolen et al. 2010). The potential usefulness and difficulties of such long-term bioassays for human risk assessment have been evaluated in many publications (Cohen 2004, 2010, 2017; Cohen and Arnold 2011; Osimitz et al. 2013; Goodman 2018; Cohen et al. 2019; Doe et al. 2019; Heusinkveld et al. 2020; Luijten et al. 2020). Such bioassays have two fundamental assumptions: first, rodent carcinogens are human carcinogens (i.e. interspecies extrapolation); and second, results obtained in rodents at high dose levels will be indicative of potential effects in humans at environmentally relevant exposure levels (i.e. dose extrapolation) (Cohen 2010, 2017; Goodman 2018). Certainly for most nongenotoxic rodent carcinogens, one or both of these assumptions are not correct. Moreover, such long-term bioassays are expensive, time consuming and require large numbers of animals. Short-term screens have been proposed based on evaluation of MOA to avoid the use of the long-term bioassays (Cohen 2010; Cohen et al. 2019).
Peptidomic analysis in the discovery of therapeutically valuable peptides in amphibian skin secretions
Published in Expert Review of Proteomics, 2019
J. Michael Conlon, Milena Mechkarska, Jérôme Leprince
The major disadvantage of methods that involve detection of active components by using bioassays is their low sensitivity. Thus, peptides with antimicrobial activity that may be potentially therapeutically valuable but are present in chromatographic fractions in low concentrations that are below the minimum inhibitory concentration (MIC) will not be detected. Similarly, insulin-releasing peptides that are present in concentrations below the threshold concentration (minimum concentration producing a significant increase in the rate of release) will be missed. This limitation is of particular relevance in investigations involving very small frogs or in the case of rare species when often only a single individual is available for study. In addition, microbiological assays generally require a dedicated laboratory as they cannot be performed in facilities that employ mammalian cell lines due to the high probability of contamination. The use of ELISA kits to detect peptides that stimulate the release of anti-inflammatory cytokines and/or insulin may be prohibitively expensive. Similarly, methods involving radioimmunoassay may be precluded because of prohibition of the use of radioactivity in the investigator’s laboratory.