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TOXICOLOGICAL HIGHLIGHT |
Molecular Basis for Adaptive Responses during Chemically Induced Hepatotoxicity
Pharmacology Unit, School of Medicine and Pharmacology, the University of Western Australia, Nedlands, Western Australia 6009, Australia
1 To whom correspondence should be addressed at Pharmacology Unit, School of Medicine and Pharmacology, QEII Medical Centre, M-Block, Monash Ave, Nedlands, WA 6009, Australia. Fax: 61-8-9346 3469. E-mail: pburcham@meddent.uwa.edu.au.
Received November 28, 2005; accepted November 29, 2005
| The first 150 words of the full text of this article appear below. |
Prior exposure to toxic xenobiotics can elicit changes within liver that confer resistance upon subsequent reexposure—a phenomenon sometimes referred to as autoprotection (Dalhoff et al., 2001
; Thakore and Mehendale, 1991). Classically, the mechanisms underlying such responses have been assigned to either of two categories. First, so-called toxicodynamic alterations involve molecular changes within hepatocytes that counteract the deleterious biochemical events whereby hepatotoxicants induce toxicity. An example of this phenomenon is the induction of various antioxidant pathways in rodent liver on exposure to such diverse prooxidants as heavy metals, plasticizers, and hepatotoxic drugs (Bando et al., 2005; Nicholls-Grzemski et al., 2000; O'Brien, et al., 2000). Second, dispositional or toxicokinetic alterations decrease the delivery of chemicals to the liver or otherwise diminish the intracellular concentrations of xenobiotics attained in hepatocytes. In the past, the mechanisms underlying this second class of adaptive changes were often