Biomarkers of toxicity

Cytotoxicity Evaluated for confounding interpretation of in vitro efficacy assays, for predicting potential for human toxicity especially in liver but also if warranted by other safety assessments in bone marrow, kidney, neurons, immu-nocytes and so on. Also used for developing understanding of biochemical mechanisms of toxicity. HCA has been repeatedly demonstrated to be an effective tool in predictive toxicology. May also be used for certain translational safety biomarkers of toxicity [37]... 

Mendrick, D.L. (2008) Genomic and genetic biomarkers of toxicity. Toxicology, 245, 175-181. 

Effects seen, target organs in the mother, target organs of dys-morphology in fetuses, biomarkers of toxicity, no effect level, lowest effect level, etc. 

Continue basic research into areas that may provide enhanced endpoints such as biomarkers of toxicity or developmental signaling patterns cell fate molecular endpoints (genetic or proteins) cell identity (different cell populations, such as neural crest) markers to detect events not shown by morphology during the culture period (e.g., markers of limb pattern formation). 

De Coen WM, Janssen CR. 2003. The missing biomarker link relationships between effects on the cellular energy allocation biomarker of toxicant-stressed Daphnia magna and corresponding population characteristics. Environ Toxicol Chem 22 1632-1641. 

Kennedy S (2002) The role of proteomics in toxicology identification of biomarkers of toxicity by protein expression analysis. Biomarkers 7 269-290 Li J, Zhang Z, Rosenzweig J, Wang YY, Chan DW (2002) Proteomics and bioinformatics approaches for identification of serum biomarkers to detect breast cancer. Clinical Chemistry 48 1296-1304... 

Kavanaugh, T. J. University of Washington Glutathione biosynthesis as a biomarker of toxic exposure NIEHS... 

Clinical diagnosis is relatively simple and is based on medical history, circumstances of exposure, and the presence of clinical symptoms of poisoning. Confirmation of diagnosis can be made by measurement of red blood cell AChE or plasma ChE. Activities of these enzymes are accepted as biomarkers of exposure and/or toxicity of OPs and carbamates. Red blood cell AChE is identical to the enzyme present in the target synapses and its levels are assumed to reflect the effects in target organs. Thus, red blood cell AChE is regarded as a biomarker of toxicity of these compounds. However, it must be kept in mind that the above assumption is only correct when the inhibitor has equal access to blood and synapses. It is difficult to know... 

Identification of novel biomarkers of toxicity Previously, the detection of novel biomarkers of toxic effect has mainly been serendipitous. However, it is now possible to use a combined NMR-expert systems approach to systematically explore the relationships between biofluid composition and toxicity and to generate novel combination biomarkers of toxicity. Pattern recognition maps can be examined for evidence of clustering of data according to site and type of toxic lesion. 

There are obvious limitations in terms of choice of biofluid for instance, urine might not be as appropriate as cerebrospinal fluid for studying neuropathology. There is also the potential for confusion with mixed-toxicity drugs that, for example, affect both liver and kidney, as the biomarkers of toxicity will be a complex combination that relates to both sites and possibly to the multiple mechanisms. However, this offset by the fact that mixed toxicities often have different timescales and such effects can therefore be deconvoluted by making repeated sequential measurements in individual animals. 

Kennedy S (2002) The role of proteomics in toxicology Identification of biomarkers of toxicity by protein expression analysis. Biomarkers 7(4) 269-290. 

Kammenga, J.E., Arts, M.S.J. and OudeBreuil, W.J.M. (1998) HSP60 as a potential biomarker of toxic stress in the nematode Plectus acuminatus. Archives of Environmental Contamination and Toxicology, 34, 253-258. 

In conclusion, glycosylation of specific serum glycoproteins has been shown to change under different pathological conditions. Because chronic exposures to xenobiotics often lead to disease, it can be expected to find that the glycan compositions of selected glycoproteins serve as sensitive, reliable and easy to analyze biomarkers of toxic exposures. 

The integration of such data streams allows the characterization of the molecular pathways involved in the response of the cells to chemical insult. The apical endpoints of these pathways represent potential biomarkers of toxicity in vivo and in the clinics as well as new avenues for high-throughput screening tests. 

Blaauboer BJ, Boekelheide K, Clewell HJ, Daneshian M, Dingemans MML, Goldberg AM, Heneweer M, Jaworska J, Kramer NI, Leist M, Seibert H, Testai E, Vandebriel RJ, Yager JD, Zurlo J (2012) The use of biomarkers of toxicity for integrating in vitro hazard estimates into risk assessment for humans. ALTEX 29(4) 411-425... 

IV. ANTI-ChE-INDUCED HYPOTHERMIA AS A BIOMARKER OF TOXICITY IN RODENTS... 

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