Bioactivation of xenobiotics

Mulder GJ. Drug metabolism inactivation and bioactivation of xenobiotics. In Mulder GJ, Dencker L, eds. Pharmaceutical Toxicology. London, UK Pharmaceutical Press, 2006. 

Glatt H. Sulphotransferases in the bioactivation of xenobiotics. Chem Biol Interact 2000 129 141-170. 

Dekant W, Vamvakas S. Glutathione-dependent bioactivation of xenobiotics. Xenobiotica 1993 23 873-887. 

It has been shown that the renal bioactivation of xenobiotics such as the herbicides paraquat and diquat [10, 111, 112], and of p-lactams such as cephaloridine and cefsulodin [10, 40, 41] or the antitumor agent adriamycin [113, 114] can induce the generation of reactive oxygen species (oxidative stress) which can be involved in alterations of the structure and functions of cell membranes, cytoskeletal injury, mutagenicity, carcinogenicity, and cell necrosis [115-117]. 

Clewell HJ, 3rd, Andersen ME. Physiologically-based pharmacokinetic modehng and bioactivation of xenobiotics. Toxicol Ind Health 1994 10 1-24. 

CAPEN, C.C. (1996) Toxic responses of the endocrine system. In Cassarett and Doull s Toxicology, The Basic Science of Toxicology, edited by C.D.Klaassen, 5th edition (New York McGrawHill). COULSON, C.J. (1994) Molecular Mechanisms of Drug Action, (London Taylor Francis). DEKANT, W. and VAMVAKAS, S. (1993) Glutathione-dependent bioactivation of xenobiotics. 

Fig. 10 Bioactivation of xenobiotics via the prostaglandin H synthase (PHS) and lipoxygenase (LPO) pathways-postuiated role in teratogenesis. The hydroperoxidase component of embryonic and fetal PHSs, and hydroperoxidases associated with LPOs, can oxidize xenobiotics to free radical intermediates that initiate the formation of reactive oxygen species causing oxidative stress (modified from Yu and Wells 1995)...

All of the following statements r atding liver bioactivation of xenobiotics to a more toxic fbtm are true exc f ... 

Hepatic bioactivation of xenobiotics decreases Kver microsafiial proteins and reduces liver weight... 

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