Modulation of Thiols and Other Low-Molecular-Weight Cofactors

Effects on Drug Metabolism and Disease Susceptibility
  • Charles V. Smith
Part of the Methods in Pharmacology and Toxicology book series (MIPT)


A brief summary of the pioneering work of Brodie, Gillette, and coworkers on the discovery and development of the concept of chemically reactive intermediates serves as the backdrop for this chapter on approaches to studying how chemicals modify thiols and other cellular nucleophiles. As examples, work is presented on classic hepatotoxicants such as acetaminophen, bromobenzene, carbon tetrachloride, and diquat. Discussion focuses on illustrations of key data and methods to assess lipid peroxidation, oxidant stress, chemically induced depletion of glutathione and protein thiols, and oxidative modification of proteins. Further adaptation of the methodologies and approaches that are discussed to relevant human and live animal models of toxicant action and physiological responses are needed. These strategies and the data that the applications can provide are important, not only for characterization of specific human exposures and toxicities, but also for the evolution of important fundamental principles, concepts, and experimental approaches.

Key Words

Acetaminophen: overdose acetaminophen: hepatic necrosis induced by acetaminophen: protein adducts acetaminophen: thioether conjugates; N-acetyl-p-benzoquinone imine antioxidant defense mechanisms bromobenzene carbon tetrachloride free radicals glutathione glutathione disulfide glutathione reductase hyperoxic lung injury lipid peroxidation oxidant stress polyunsaturated fatty acids protein thiols reactive intermediates reactive nitrogen species thiol oxidation 


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Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  • Charles V. Smith
    • 1
    • 2
  1. 1.Center for Developmental Toxicology, Columbus Children’s Research InstituteColumbus Children’s HospitalColumbus
  2. 2.Department of PediatricsThe Ohio State UniversityColumbus

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