Biochemical effects on radioprotective agents on the liver microsomal hydroxylating system: in vitro studies.
The action of two radioprotectors--cysteamine and cystamine--on the liver microsomal multi-enzyme hydroxylating system, a key stem in drug and biological compounds metabolism, has been studied. Their effects have been systematically analysed at the level of individual enzyme activities and global functions. The two compounds are quite inactive on NADPH and NADH cytochrome c reductase activities, but slightly denature the cytochrome P450 into cytochrome P420. Furthermore, they do inhibit to some extent (30 per cent at 10(-2) M) the rate of codeine hydroxylation and totally suppress ((at 10(-2) M) the NADPH-induced lipid peroxidation which occurs during enzymatic functioning. These results are discussed in the light of the toxicity of radioprotectors.
D000818:Animals; D003061:Codeine / Q000378:metabolism; D003538:Cystamine / Q000494:pharmacology*; D003543:Cysteamine / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003579:Cytochrome Reductases / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism*; D006900:Hydroxylation; D050356:Lipid Metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D051381:Rats
D003580:Cytochromes; D003543:Cysteamine; D003577:Cytochrome P-450 Enzyme System; D003579:Cytochrome Reductases; D009251:NADPH-Ferrihemoprotein Reductase; D003538:Cystamine; D003061:Codeine