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  • Title: Metabolism and disposition of N-(4-(5-nitro-2-furyl)-(2-14-C)thiazolyl)acetamide in the rat.
    Author: Wang CY, Chiu CW, Bryan GT.
    Journal: Drug Metab Dispos; 1975; 3(2):89-95. PubMed ID: 236164.
    Abstract:
    The metabolism of N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide (NFTA), a carcinogen for the mouse, rat, dog, and hamster, was investigated in the rat. Radioactive NFTA administered ip to young and lactating female rats was rapidly absorbed through the peritoneum and deposited in the urine, intestinal contents, and feces. Less than 0.5% of the radioactivity was expired as CO2 during the first 24 hr. Two yellow metabolites, accounting for 5 and 27% of the radioactivity in the urine, were found by paper chromatography. One metabolite retained the 2-amino-4-(5-nitro-2-furyl)thiazole moiety. Less than 0.5% of the radioactivity in the urine was due to unchanged 14-C-NFTA. The radioactivity level in the visceral organs reached a maximum 2 hr after dosing and then gradually decreased. Liver contained considerably more radioactivity than did other visceral organs; this was mainly distributed in the cytosol and 900g pellets. Fifty per cent of the radioactivity in the liver was bound to the hot trichloroacetic acid (TCA)-insoluble fraction; that bound to the cold TCA-insoluble fraction increased gradually from 66.9% at 2 hr to 82.6% at 24 hr. The radioactivity bound to the cold and hot TCA-insoluble fractions in kidney remained at 30% and 20%, respectively. Nitroreduction of 14-C-NFTA by microsomes, as a prerequisite of the binding of metabolite to microsomal protein, was demonstrated. Addition of L-cysteine or reduced glutathione to the incubation mixture did not alter the nitroreductase activity of the microsomes; however, binding of radioactivity to protein was significantly decreased. Addition of other amino acids did not significantly decrease the nitroreductase activity or binding to protein. These results suggest that reduced NFTA binds to the protein sulfhydryl groups. Since 14-C-NFTA binds to macromolecules in vivo,nitroreductionmay be important for the metabolism of 5-nitrofurans.
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