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Adaptive Changes in Hepatic Glutathione Metabolism in Response to Excess Selenium in Rats^1,2,

Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, WI 53706

Experiments were conducted with rats to determine if administration of excess selenium (Se) alters hepatic glutathione (GSH) metabolism. Se was fed, 6 ppm as Na₂SeO₃, for 6 weeks in a 15% casein, tocopherol-free diet and compared to 0.1 ppm Se. High Se significantly increased the concentrations of hepatic nonprotein sulfhydryls (NPSH) and oxidized glutathione (GSSG) as well as the GSSG:NPSH ratio. Of the NPSH, 94.1 ± 1.7% was shown to be GSH. Similar increases in NPSH, GSSG and GSSG:NPSH due to high Se were seen when the diet was supplemented with methionine (0.3%) and/or vitamin E (100 IU/kg diet) although methionine independently increased NPSH and GSSG. Hepatic glucose-6-P dehydrogenase, glutathione reductase and -glutamyl-transpeptidase activities were significantly increased by high Se but cysteine dioxygenase activity was unaffected. An i.p. injection of Na₂SeO₃ (15 µmol Se/kg body weight) significantly increased hepatic GSSG, which was followed by an increase in NPSH(GSH) compared to saline controls. These results indicate that excess Se causes a shift in hepatic GSH toward a more oxidized state. Increases in NPSH(GSH) and in the enzyme activities observed appeared to be adaptive changes initiated in an attempt to maintain a normal GSSG:GSH ratio. Elevated GSSG or the increased GSSG:GSH ratio caused by Se may initiate these adaptations.

KEY WORDS: • selenium • glutathione

¹ A preliminary report of these experiments was presented at the meetings of the Federation of American Societies for Experimental Biology, New Orleans, LA; LeBoeuf, R. A. and Hoekstra, W. G. (1982) Fed. Proc 41: 286 (abs. 104).

² Research supported by the College of Agricultural and Life Sciences, University of Wisconsin-Madison and by U.S. Public Health Service Program Grant No. AM14881.

Manuscript received 30 July 1982.