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Toxicology- From Cells to Man - Proceedings of the 1995 EUROTOX Congress Meeting Held in Prague, Czech Republic, August 27-l30, 1995 (Paperback, Softcover reprint of the original 1st ed. 1996)
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Toxicology- From Cells to Man - Proceedings of the 1995 EUROTOX Congress Meeting Held in Prague, Czech Republic, August 27-l30, 1995 (Paperback, Softcover reprint of the original 1st ed. 1996)
Series: Archives of Toxicology, 18
Expected to ship within 10 - 15 working days
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Renal transport and xenobiotic metabolism play an important role in
the detoxication and excretion of potentially toxic xenobiotics.
However, recent experimental evidence has demonstrated that renal
xenobiotic metabolism and renal transport processes also play an
important role in the nephrotoxicity of xenobiotics and xenobiotic
metabolites. The high blood flow to the kidney combined with its
ability to concentrate solutes may expose the kidney to high
concentrations of xenobiotics and xenobiotics metabolites present
in the systemic circulation. Recently, it has been demonstrated
that xenobiotic metabolites formed in the liver and other organs
may be targeted to the kidney by selective transport systems~ many
xenobiotics require enzymatic transformation to proximate reactive
metabolites to elicit their toxic and carcinogenic effects. The
enzymatic formation of reactive metabolites is termed
bioactivation. The bioactivation mechanisms for many
nephrotoxicants have, at least in part, been elucidated in the past
15 years. Many ultimate toxicants formed in the kidney are
electrophiles whose interaction with cellular macromolecules may
cause a perturbation of normal cell function resulting in necrosis
and/or cancer (Anders 1988). Electrophilic metabolites may bind to
nucleophilic sites in cellular macromolecules~ the importance of
covalent modification of protein and DNA in cell killing and in the
induction of tumors is established (Miller and Miller 1981~ Nelson
and Pearson 1990~ Hinson and Roberts 1992). The objective of this
review is to summarize new information about renal transport, renal
bioactivation and their relation to nephrotoxicity using two
relevant example for the basic mechanisms outlined above.
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