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Fetal pharmacotherapy generally relies on nonspecific biodistribution of therapeutic agents to the unborn child following drug administration into the maternal circulation system. Physiologically, transfer of polar, high-molecular weight solutes across the placenta ...

The MTT colorimetric assay is an established method of determining viable cell number in proliferation and cytotoxicity studies. This assay is based on the cleavage of the yellow tetrazolium salt, MTT, to form a soluble blue formazan product by mitochondrial enzymes, and the amount of formaz ...

Biologically reactive intermediates are formed following metabolism of xenobiotics, and during normal oxidative metabolism. These reactive species are electrophilic in nature and are capable of forming stable adducts with target proteins. These covalent protein modific ...

Biological reactive intermediates can be created via metabolism of xenobiotics during the process of chemical elimination. They can also be formed as by-products of cellular metabolism, which produces reactive oxygen and nitrogen species. These reactive intermediates tend to be e ...

Xenobiotics, including therapeutic agents, can produce a variety of beneficial, as well as adverse, effects in mammals. One potential source of drug-mediated toxicity stems from metabolic activation of the parent compound, typically catalyzed by one or more members of the cytochrome P ...

The embryonic zebrafish model offers the power of whole-animal investigations (e.g., intact organism, functional homeostatic feedback mechanisms, and intercellular signaling) with the convenience of cell culture (e.g., cost- and time-efficient, minimal infrastructure, sm ...

The Frog Embryo Teratogenesis Assay Xenopus (FETAX) test is a development toxicity screening test. Due to the small amount of compound needed and the capability to study organogenesis in a short period of time (96 h), FETAX test constitutes an efficient development toxicity alert test when per ...

Mitochondrial dysfunction is a major mechanism whereby drugs can induce liver injury and other serious side effects, such as lactic acidosis and rhabdomyolysis, in some patients. Several in vitro and in vivo investigations can be performed in order to determine if drugs can disturb mitoch ...

Real-time reverse transcription polymerase chain reaction (RT-PCR) represents a benchmark technology in the detection and quantification of mRNA. Yet, accurate results cannot be realized without proper statistical analysis of RT-PCR data. Here, we examine some of the issues conce ...

Numerous xenobiotics are toxic to human and animal cells by interacting with their metabolism, but the precise metabolic step affected and the biochemical mechanism behind such a toxicity often remain unknown. In an attempt to reduce the ignorance in this field, we have developed a new approa ...

In recent years, several global omics technologies have been increasingly used to better understand the molecular mechanisms of drug toxicity. Two-dimensional difference gel electrophoresis (2D-DIGE) is a large-scale proteomics high-resolution gel-based quantitative m ...

Transcript profiling (“Transcriptomics”) is a widely used technique that obtains information on the abundance of multiple mRNA transcripts within a biological sample simultaneously. Therefore, when a number of such samples are analysed, as in a scientific experiment, large and com ...

Delayed ventricular repolarization, as measured by a prolongation of the QT interval on the electrocardiogram, is a major safety issue in the drug development process. It is now recognized that most cases of drug-induced QT prolongation arise from direct pharmacological inhibition of t ...

The comet assay is a sensitive electrophoretic method for measuring DNA breaks at the level of single cells, used widely in genotoxicity experiments, biomonitoring, and in fundamental research. Its sensitivity and range of application are increased by the incorporation of an extra step, ...

The cytokinesis-block micronucleus (CBMN) assay has since many years been applied for in vitro genotoxicity testing and biomonitoring of human populations. The standard in vitro/ex vivo micronucleus test is usually performed on human lymphocytes and has become a comprehensive met ...

Tissue microarrays (TMAs) have recently emerged as very valuable tools for high-throughput pathological assessment, especially in the cancer research arena. This important technology, however, has yet to fully penetrate into the area of toxicology. Here, we describe the creation of T ...

Immunohistochemical techniques detect antigens in tissue sections by means of immunological and chemical reactions. This technique is highly sensitive and specific and can detect a wide variety of antigens in multiple animal species. This chapter reviews common immunohistoch ...

Histological procedures aim to provide good quality sections that can be used for a light microscopic evaluation of human or animal tissue changes in either spontaneous or induced diseases. Routinely, tissues are fixed with neutral formalin 10%, embedded in paraffin, and then manually se ...

Necropsy is a major step of most studies using laboratory animals. During necropsy, tissue and organ changes noticeable grossly can be recorded, and important tissue samples can be stored for subsequent evaluation. It is therefore important that the personnel in charge of this key experime ...

A pediatric assessment is now a required component of every New Drug Application in North America or Marketing Authorization Application in Europe, unless a waiver has been granted previously. Nonclinical juvenile toxicity studies are usually required as part of this assessment. The p ...