title: Nitrofurantoin-stimulated superoxide production by channel catfish (Ictalurus punctatus) hepatic microsomal and soluble fractions.
abstract: Nitroaromatic compounds, which frequently contaminate the environment, are known to be reduced to corresponding aromatic amines by fish as well as mammals under anaerobic conditions. Although amine products are not generally formed aerobically, "nitroreductase"-mediated redox cycling of nitroaromatics may occur under these conditions, leading to enhanced production of a potentially toxic oxygen species, superoxide (O-2). In this study, we have investigated the ability of channel catfish (Ictalurus punctatus) hepatic microsomal and soluble fractions to stimulate O-2) production upon exposure to a model redox cycling nitroaromatic compound, nitrofurantoin (NF). Two assays for O-2 production, cytochrome c reduction and cyanide-insensitive oxygen consumption, were stimulated by NF exposure to both hepatic fractions. These reactions were partially inhibited by superoxide dismutase (SOD), and by SOD and catalase in the oxygen consumption assay, providing specific evidence for the involvement of O-2 in the stimulatory effect by NF. Furthermore, results of cofactor requirement and inhibition studies suggest that NF enhancement of O-2 production was mediated by NADPH-cytochrome P-450 (c) reductase in the microsomal fraction and xanthine oxidase in the soluble fraction. These findings comprehensively suggest that the in vitro stimulation of O-2 production by nitroaromatics as indicated in mammals may also occur in fish and, therefore, suggests a similar potential for oxyradical-mediated toxicities in these species.
authors.affiliation: Ecotoxicology Laboratory, School of Forestry and Environmental Studies, Duke University, Durham, North Carolina 27706.
authors.forename: P C
authors.initials: PC
authors.lastname: Washburn
authors.forename: R T
authors.initials: RT
authors.lastname: Di Giulio
mesh_terms: D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002397:Catfishes / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D007059:Ictaluridae / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000494:pharmacology; D009582:Nitrofurantoin / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D013481:Superoxides; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D009582:Nitrofurantoin; D002374:Catalase; D013482:Superoxide Dismutase