NITROFURANTOIN-STIMULATED REACTIVE OXYGEN SPECIES PRODUCTION AND GENOTOXICITY IN DIGESTIVE GLAND MICROSOMES AND CYTOSOL OF THE COMMON MUSSEL (MYTILUS-EDULIS-L)

The ability of nitrofurantoin (NF) to produce reactive oxygen species (ROS) was investigated in subcellular fractions of digestive gland of the mussel Mytilus edulis in terms of oxygen consumption and the forma tion of superoxide anion radical (O-2(-)) (measured as SOD-sensitive c ytochrome c reduction or SOD-sensitive (OH)-O-. production), H2O2 (eff ects of catalase), and hydroxyl radical ((OH)-O-.) (iron/EDTA-mediated oxidation of KMBA to ethylene). Additionally, the genotoxic effects o f NF were examined using the Salmonella typhimurium umu mutagenicity a ssay. Microsomal NAD(P)H-dependent oxygen consumption was stimulated b y NF, leading to the formation of H2O2. Stimulation of microsomal O-2( -) production by NF was evident for NADH but not NADPH, confirming red ox cycling at least with the former coenzyme. No stimulation of O-2(-) production was obvious for cytosolic fraction with either coenzyme. N F stimulated microsomal NAD(P)H-dependent (OH)-O-. production; the rat es of (OH)-O-. production were greater for NADH than NADPH; and the (O H)-O-. was indicated to be formed, at least in part, by an iron-cataly zed Haber-Weiss reaction. A role was indicated for a free radical driv en Fenton reaction in the NF-stimulated microsomal production of (OH)- O-. from NADPH. The production of mutagenic species from NF was observ ed for cytosol but not for microsomes, and the former effects were gre ater for NADH than NADPH. Overall, the NAD(P)H-dependent microsomal ge neration of ROS, and the lack of correlation of ROS production with mu tagenicity, are considered indicative of the potential of digestive gl and to metabolize NF by both one-electron and two-electron reductive p athways. From this and other studies, enhanced ROS production by NF an d other redox cycling xenobiotics is indicated to be a widespread phen omenon in aquatic organisms and a potential mechanism of pollutant-med iated toxicity. (C) 1995 Academic Press,Inc.