Interactions between paraquat and ferric complexes in the microsomal generation of oxygen radicals.
Transition metals may play a central role in the toxicity associated with paraquat. Studies were carried out to evaluate the interaction of paraquat with several ferric complexes in the promotion of oxygen radical generation by rat liver microsomes. In the absence of added iron, paraquat produced some increase in low level chemiluminescence by microsomes; there was a synergistic increase in light emission in the presence of paraquat plus ferric-ATP or ferric-citrate, but not paraquat plus either ferric-EDTA or ferric-diethylenetriamine pentaacetic acid (ferric-DETAPAC). Synergistic interactions could be observed at a paraquat concentration of 100 microM and a ferric-ATP concentration of 3 microM. In the absence or presence of paraquat, microsomal light emission was not affected by catalase or dimethyl sulfoxide (DMSO), indicating no significant role for hydroxyl radicals. Superoxide dismutase (SOD) did not affect chemiluminescence in the absence of paraquat but produced some inhibition in the presence of paraquat; this inhibition by SOD was most prominent in the absence of added iron and less pronounced in the presence of ferric-ATP or ferric-citrate. Although microsomal chemiluminescence is closely associated with lipid peroxidation, paraquat did not increase malondialdehyde production as reflected by production of thiobarbituric acid-reactive components. However, lipid peroxidation was sensitive to inhibition by SOD in the presence, but not in the absence, of paraquat, analogous to results with chemiluminescence. Paraquat synergistically increased microsomal hydroxyl radical production as measured by the production of ethylene from 2-keto-4-thiomethylbutyrate in the presence of ferric-EDTA or ferric-citrate. The interaction of paraquat with microsomes and ferric complexes resulted in an increase in oxygen radical generation. Various ferric complexes can increase the catalytic effectiveness of paraquat in promoting microsomal generation of oxygen radicals, although, depending on the reaction being investigated, the nature of the ferric complex is important.
Puntarulo
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Department of Biochemistry, Mount Sinai School of Medicine, New York, NY 10029.
Cederbaum
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D000818:Animals; D005290:Ferric Compounds / Q000378:metabolism*; D005609:Free Radicals; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008163:Luminescent Measurements; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010269:Paraquat / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D005290:Ferric Compounds; D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D009249:NADP; D010269:Paraquat; D010100:Oxygen