Oxidative metabolites

In terrestrial animals, the excreted products of PAHs are mainly conjugates formed from oxidative metabolites. These include glutathione conjugates of epoxides, and sulfate and glucuronide conjugates of phenols and diols. 

Hauser, R., Meeker, J.D., and Singh, N.R et al. (2007). DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Human Reproduction 22, 688-695. 

KHACHIK F, BEECHER G R and SMITH J c (1995) Lutein, lycopene, and their oxidative metabolites in chemoprevention of cancer , J Cell Biochem Supp, 22, 236-46. 

Another study showed that a mixture of oxidative metabolites of P-carotene, but not P-carotene, was able to increase the binding of benzo[a]pyrene to DNA. Other mixtures of P-carotene cleavage products have been shown to induce oxidative stress in vitro,exert cytotoxic and genotoxic effects, and inhibit gap junction intercellular communications. It has been suggested that these detrimental effects could possibly occur in vivo following the intake of high doses of carotenoids. 

Bodor, N. Buchwald, P. (2006) Designing Safer (Soft) Drugs by Avoiding the Formation of Toxic and Oxidative Metabolites. Molecular Biotechnology, 26(2), 123-132. 

Prevents formation of hydroxylamine (oxidizing) metabolite of dapsone... 

Ring, B. J. et al. (1996). Identification of the human cytochromes P450 responsible for the in vitro formation of the major oxidative metabolites of the antipsychotic agent olanzapine. /. Pharmacol. Exp. Ther., 276, 658-66. 

Oxidative Metabolites of Lycopene and Their Biological Functions... 

Khachik, F., A. Steck, U.A. Niggli, and H. Pfander. 1998. Partial synthesis and structural elucidation of the oxidative metabolites of lycopene identified in tomato paste, tomato juice and human serum. J Agric Food Chem 46 4885 1890. 

Ferreira, ALA, KJ Yeum, RM Russell, NI Krinsky, and G Tang. 2004. Enzymatic and oxidative metabolites of lycopene. J Nutr Biochem 15 493-502. 

Hazai, E, Z Bikadi, F Zsila, and SF. Lockwood. 2006. Molecular modeling of the non-covalent binding of the dietary tomato carotenoids lycopene and lycophill, and selected oxidative metabolites with 5-lipoxygenase. Bio Med Chem 14 6859-6867. 

Screening is usually carried out with liver microsomes from humans, rats, mice, dogs and monkeys and liver S9 fraction from aroclor 1254-induced rats. The incubation is typically mn with a volume of 0.2-1. OmL in a microcentrifuge or a glass tube. Different incubation conditions are used for CYP and UGT reactions. The incubation mixture for formation of oxidative metabolites and/or GSH conjugates contains ... 

To prepare glucuronide conjugates of products formed from initial oxidation (to yield a hydroxyl or carboxylic acid group), the oxidative metabolite should be prepared first and used as a substrate in the incubation. Alternatively, an incubation with parent drug, NADPH and UDPGA may produce the desired glucuronide. 

Microbial oxidation of drug substrates occurs in a similar fashion to mammalian oxidative biotransformation. In contrast, microbial cultures rarely catalyze conjugations comparable to those in mammalian system (glucuronidation, sulfation and GSH conjugation). It is thus not surprising that microbial bioreactors are mainly used in the synthesis of oxidative metabolites. 

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