AD 5, a dehydroalanine derivative, decreases the amount of reactive oxygen species formed during nitrofurantion microsomal metabolism.
N-acyl dehydroalanines have been shown to react with and scavenge oxygen derived free radicals. One of those compounds, the AD-5 (N-(paramethoxyphenylacetyl) dehydroalanine) has been examined for its ability to decrease the amount of reactive oxygen species which appeared when liver microsomes (isolated from rats pretreated with phenobarbital) are incubated in the presence of Nitrofurantoin (NF). This molecule was used as a model compound in order to stimulate the production of superoxide anion and hydrogen peroxide, as well as to enhance the oxidation of NADPH and the oxygen uptake. These two later parameters were not modified when adding AD-5 to microsomes incubated in the presence of NF. However, in such conditions the amount of both and hydrogen peroxide was decreased. These effects were dose-dependent. These data suggest that AD 5 inhibits the building up of superoxide and consequently the production of hydrogen peroxide. We postulate that AD-5 acting as an oxygen derived free radical scavenger, can be used to inhibit the oxidative injury induced by nitrofurantoin and other redox cycling drugs.
Buc-Calderon
P
P
Unité de Biochimie Cancérologique et Toxicologique, Université Catholique de Louvain, Brussels, Belgium.
Roberfroid
M
M
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D009582:Nitrofurantoin / Q000378:metabolism*; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; C053274:AD 20; D009249:NADP; D009582:Nitrofurantoin; D006861:Hydrogen Peroxide; D000409:Alanine