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Influence of bipyridylium compounds on microsomal mixed-function oxidation activities
L Zychlinski1, P Raska-Emery, M R Montgomery
1University of South Florida, College of Public Health and Medical Research Service, Tampa.
Journal of Biochemical Toxicology
|January 1, 1988
Summary
Paraquat and diquat herbicides inhibit mixed-function oxidation (MFO) and stimulate NADPH oxidation in lung, liver, and kidney microsomes. This suggests a role in bipyridyl herbicide toxicity.
Area of Science:
- Biochemistry
- Toxicology
- Pharmacology
Background:
- Bipyridyl herbicides, paraquat and diquat, are widely used.
- Their effects on xenobiotic metabolism and cellular processes require detailed investigation.
Purpose of the Study:
- To investigate the influence of paraquat and diquat on microsomal mixed-function oxidation (MFO) and NADPH oxidation rates.
- To elucidate the mechanism of enzyme inhibition and the role of NADPH oxidation in bipyridyl toxicity.
Main Methods:
- Incubation of lung, liver, and kidney microsomal preparations with paraquat and diquat.
- Assay of MFO activities (benzphetamine N-demethylation, ethylmorphine N-demethylation) and NADPH oxidation rates.
- Kinetic analysis to determine the type of enzyme inhibition.
Main Results:
- Paraquat and diquat inhibited MFO activities in lung and liver microsomes but not in kidney preparations.
- Enzyme inhibition was noncompetitive, affecting only Vmax.
- Both herbicides significantly stimulated NADPH oxidation in all tested microsomal preparations.
- The degree of NADPH oxidation stimulation varied depending on the organ and presence of MFO substrates.
Conclusions:
- Bipyridyl herbicides are potent stimulators of in vitro NADPH oxidation.
- NADPH oxidation stimulation appears to be a key factor in the inhibition of xenobiotic metabolism by these compounds.
- Further research is needed to determine the role of these effects in overall bipyridyl toxicity.