Significance of alterations in hepatic antioxidant enzymes. Primacy of glutathione peroxidase.
The relative contributions of catalase and the selenoenzyme glutathione peroxidase (GSH-Px) were elucidated in the rat liver by selectively modulating the activities of these enzymes using dietary selenium (Se) and the catalase inhibitor 3-amino-1,2,4-triazole (3-AT). Increased peroxidation occurred only in Se-deficient rats with markedly reduced cytosolic and mitochondrial GSH-Px activities. Although 3-AT treatment resulted in a 75% reduction of hepatic catalase activity and also a 20% reduction of both cytosolic and mitochondrial superoxide dismutase (SOD) activity, no incremental increase in peroxidation was observed over that associated with Se deficiency. In Se-deficient animals, treatment with 3-AT resulted in a doubling of cytosolic GSH-Px. This was associated with a 49% elevation in hepatic Se suggesting that increased Se may have contributed to the enhanced GSH-Px activity. These results suggest that GSH-Px plays the pivotal role in preventing hepatic peroxidation. Furthermore, the effects of 3-AT in vivo are not restricted to inhibition of catalase activity insofar as it also affects cytosolic GSH-Px activity and cytosolic and mitochondrial SOD activities.
Simmons
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TW
Biological Sciences and Toxicology Program, St. John's University, New York 112439.
Jamall
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IS
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D005979:Glutathione Peroxidase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D010545:Peroxides / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000172:deficiency / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism*
D010545:Peroxides; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D012643:Selenium; D000640:Amitrole