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Those haloge-nated solvents that produce selective and potent nephrotoxi-city have some features in common (Figure 7.7): (i) thenephrotoxicity is dependent on conjugation with glutathione(GSH); (ii) further metabolism to the cysteine conjugategenerates the penultimate, nephrotoxic species; and (iii) theportion of the cysteine conjugate derived from the parentmolecule provides a good leaving group for the subsequentreaction that generates the ultimate, nephrotoxic metabolite.GSH is an important component of cellular antioxidantdefense and is typically considered protective againstmost cytotoxic chemicals (e.g., see discussion later aboutApAp).

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