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Nitrofurantoin-stimulated reactive oxygen species production and genotoxicity in digestive gland microsomes and cytosol of the common mussel (Mytilus edulis L.).
- Source :
-
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 1995 Apr; Vol. 131 (2), pp. 332-41. - Publication Year :
- 1995
-
Abstract
- 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 formation of superoxide anion radical (O2-) (measured as SOD-sensitive cytochrome c reduction or SOD-sensitive sensitive .OH production), H2O2 (effect of catalase), and hydroxyl radical (.OH) (iron/EDTA-mediated oxidation of KMBA to ethylene). Additionally, the genotoxic effects of NF were examined using the Salmonella typhimurium umu mutagenicity assay. Microsomal NAD(P)H-dependent oxygen consumption was stimulated by NF, leading to the formation of H2O2. Stimulation of microsomal O2- production by NF was evident for NADH but not NADPH, confirming redox cycling at least with the former coenzyme. No stimulation of O2- production was obvious for cytosolic fraction with either coenzyme. NF stimulated microsomal NAD(P)H-dependent .OH production; the rates of .OH production were greater for NADH than NADPH; and the .OH was indicated to be formed, at least in part, by an iron-catalyzed Haber-Weiss reaction. A role was indicated for a free radical driven Fenton reaction in the NF-stimulated microsomal production of .OH from NADPH. The production of mutagenic species from NF was observed for cytosol but not for microsomes, and the former effects were greater for NADH than NADPH. Overall, the NAD(P)H-dependent microsomal generation of ROS, and the lack of correlation of ROS production with mutagenicity, are considered indicative of the potential of digestive gland to metabolize NF by both one-electron and two-electron reductive pathways. From this and other studies, enhanced ROS production by NF and other redox cycling xenobiotics is indicated to be a widespread phenomenon in aquatic organisms and a potential mechanism of pollutant-mediated toxicity.
- Subjects :
- Animals
Bivalvia
Butyrates metabolism
Cytosol drug effects
Cytosol metabolism
Digestive System metabolism
Microbial Sensitivity Tests
Microsomes drug effects
Microsomes metabolism
Mutagenicity Tests
NAD pharmacology
NADP pharmacology
Oxidation-Reduction
Oxygen Consumption drug effects
Salmonella typhimurium drug effects
Sulfhydryl Compounds
Digestive System drug effects
Nitrofurantoin toxicity
Reactive Oxygen Species metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0041-008X
- Volume :
- 131
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Toxicology and applied pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 7716774
- Full Text :
- https://doi.org/10.1006/taap.1995.1076