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Models of Toxicity Screening Using Cultured Cells
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
Roberta L. Grant, Daniel Acosta
In vitro models commonly used in target organ toxicity testing include: perfused organ preparations, isolated tissue preparations, single cell suspensions, and tissue culture systems. Because these models are used as predictors of the human response, when applicable, all preparations should be derived from species that respond with fidelity to the toxic challenge.
Role of Herbal Medicines During Pregnancy and Labor
Published in Megh R. Goyal, Hafiz Ansar Rasul Suleria, Ademola Olabode Ayeleso, T. Jesse Joel, Sujogya Kumar Panda, The Therapeutic Properties of Medicinal Plants, 2019
Fanuel Lampiao, Ibrahim Chikowe, Mayeso Gwedela, Kondwani Katundu
Although herbs are widely accepted as safe and with few side effects because they are natural [22], yet data is very limited on their safety in pregnancy use [29]. In fact, most of the herbs circulating worldwide have unknown standardized active ingredients. Toxicity testing has, therefore, been a way of revealing and extrapolating some risks associated with them [22]. Research has shown that herbal medicines are associated with risk factors such as toxic potential, consumer-related factors (age, disease factors, and pregnancy), date of expiration, contamination, adulteration, and lack of regulation [27]. Primary risks associated with herbal use in pregnancy are toxicity to the mother with the potential to affect the fetus indirectly, fetotoxicity, teratogenesis, increased miscarriage risks, and poor neonatal health [22].
Introduction
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
In the academic or industrial arenas, the research toxicologist examines the broad issues in toxicology in the laboratory. Academic concerns include any of the public health areas where progress in understanding toxicological sciences is necessary. This includes the elucidation of mechanistic, clinical, or descriptive toxicological theories. In the pharmaceutical industry, research toxicologists are needed to conduct phase I trials—that is, preclinical testing of pharmaceuticals before clinical evaluation and marketing. Preclinical testing involves the toxicity testing of candidate compounds, which are chemically and biochemically screened as potentially useful therapeutic drugs. The toxicity testing procedures include both in vitro and animal protocols.
Three-dimensional (3D) cell culture studies: a review of the field of toxicology
Published in Drug and Chemical Toxicology, 2023
Seda İpek, Aylin Üstündağ, Benay Can Eke
The air–liquid interface (ALI) model (Figure 3), which is used in many organ toxicity studies, also comes into prominence with its use in respiratory toxicity studies. This model offers an opportunity to investigate the molecular mechanisms of action, modes of interaction, and physiological and pathophysiological responses by using different lung cells (Lacroix et al.2018). Ishikawa and Ito (2017) used a 3D co-culture model in an air–liquid interface to evaluate the effects of cigarette smoke exposure on the human bronchial epithelium. In this model, human bronchial tissue possessed a fibroblast layer and differentiated into epithelial cells. The results revealed that the number of ciliated cells decreased and the goblet cell differentiation was disturbed. Moreover, based on repeated cigarette smoke exposure, the secretion of inflammatory molecules increased in this model. This model can provide us with an in vitro model for toxicity testing that can be used for continuing exposures.
Development a high-throughput zebrafish embryo acute toxicity testing method based on OECD TG 236
Published in Toxicology Mechanisms and Methods, 2023
Shisan Xu, Fengyan Chen, Huan Zhang, Zhen-lie Huang, Jianjun Li, Desheng Wu, Xueping Chen
Predicting and assessing acute toxicity of industrial chemicals or consumables is crucial for human safety and environmental sustainability. Although conventional acute toxicity testing methods based on rodents and rabbits have been well documented and standardized by the United States government since the 1950s, there are still many disadvantages for these traditional methods, such as cost, time-consumption, as well as animal welfare concerns (Ducharme et al. 2015). Additionally, thousands of new chemicals including pesticides are introduced to the market and eventually dispersed into the environment every year (EPA 2011). Cell-line based in vitro testing methods are high throughput, less expensive and save time, but produce low predictability to vertebrates (Ali et al. 2011). There is increasingly demand to develop a new method to bridge the gap between in vivo animals and in vitro cell-lines, based on acute toxicity testing approaches. In that regard, zebrafish (Danio rerio) share approximately 70% gene sequence homology with humans and exhibit high structural similarities with vertebrates (Gunnarsson et al. 2008; Howe et al. 2013). Furthermore, biological consequences from zebrafish are translatable between conserved vertebrates (Behl et al. 2015; Nishimura et al. 2015). These reasons, together with the small body size, high fecundity, rapid embryonic development, ease of maintenance, and transparency of the embryos, make zebrafish an attractive model as an alternative animal toxicity testing paradigm (Ducharme et al. 2015; Teixidó et al. 2018, 2019).
Porcine cancer models: potential tools to enhance cancer drug trials
Published in Expert Opinion on Drug Discovery, 2020
Noah Robertson, Lawrence B. Schook, Kyle M. Schachtschneider
In order for new cancer drugs to pass FDA approval, these new chemical entities (NCE) are required to complete lengthy and expensive clinical trials to ensure their long-term safety, efficacy, and effectiveness in humans. This requires pharmaceutical companies to ‘jump’ from preclinical studies performed on suboptimal small animal models to investing significant time and money into clinical trials with a high probability of failure. In this review, we discuss issues with current animal cancer models and the clinical trial process, and how these limitations can hinder approval of new cancer drugs. The FDA follows the guidelines set forth by the International Committee on Harmonization for acceptable practices in drug development [5]. These guidelines require toxicity testing in two relevant animal species (Figure 1) [6]. Currently small animal rodent models, typically murine models, are used for initial in vivo testing of toxicity, pharmacodynamics, and pharmacokinetics of cancer drugs. Canines are commonly used as secondary relevant animal species for preclinical safety studies, and also play an important role in the clinical trial process through the NCI’s Comparative Oncology program [7,8].