Production of reactive oxygen species by peritoneal macrophages and hepatic mitochondria and microsomes from endrin-treated rats.
Recent studies have shown that the administration of endrin to rodents induces lipid peroxidation in various tissues and decreases glutathione content. These results suggest that endrin produces reactive oxygen species and/or free radicals. We have therefore examined the effect of endrin (4.5 mg/kg) on the production of reactive oxygen species by peritoneal macrophages and hepatic mitochondria and microsomes in rats. The effects of endrin on hepatic mitochondrial and microsomal lipid peroxidation and membrane fluidity as well as the incidence of hepatic nuclear DNA damage were also examined. Twenty-four hours after endrin administration, significant increases in the production of chemiluminescence by the three tissue fractions were observed. Furthermore, peritoneal macrophages from endrin-treated animals resulted in 3.0- and 2.8-fold increases in cytochrome c and iodonitrotetrazolium (INT) reduction, indicating enhanced production of superoxide anion. Endrin administration also resulted in significant increases in lipid peroxidation of mitochondrial and microsomal membranes as well as decreases in the fluidity of these two membranous fractions. A significant increase in hepatic nuclear DNA single-strand breaks also occurred in response to endrin administration. The results indicate that macrophage, mitochondria, and microsomes produce reactive oxygen species following endrin administration, and these reactive oxygen species may contribute to the toxic manifestations of endrin.
Department of Pharmaceutical Sciences and Pharmacology, Creighton University Health Sciences Center, Omaha, NE 68178.
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M
Bagchi
E A
EA
Hassoun
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D
Bagchi
S J
SJ
Stohs
D000818:Animals; D004249:DNA Damage / Q000187:drug effects; D004732:Endrin / Q000494:pharmacology*; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D008163:Luminescent Measurements; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008560:Membrane Fluidity / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D017382:Reactive Oxygen Species; D013481:Superoxides; D004732:Endrin