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Glutathione Peroxidase System and Microsomal Lipoperoxidation in Prenecrotic Stages of Dietary Hepatic Necrosis in Rats¹

Department of Pathology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96822

Simultaneous dietary deficiency of vitamin E and Se in weanling rats results in fatal hepatic necrosis. To investigate the possible relation between the state of hepatic cytosol glutathione peroxidase (GSH-Px) system (including glutathione reductase, GSH-Rd, and glucose-6-phosphate dehydrogenase, G-6-PD) and the hepatic microsomal lipoperoxidation (MLP), as well as the possible implications of these factors in the development of hepatic necrosis, weanling male rats were fed a basal diet low in Se and vitamin E, or were pair-fed with the same diet supplemented with either 3 mg/100 g diet of dl--tocopherol, with 0.36 mg/100 g diet of sodium selenite, or with both. Rats from the four groups were killed at 9, 20, and 26 days. At the late prenecrotic stage, GSH-Px activity in rats fed the basal diet alone was reduced by 97% and the in vitro MLP levels (malonaldehyde) were increased by seven-fold as compared with rats fed the diet supplemented with Se and vitamin E. However, in vivo MLP (diene conjugation) was only detected in the liver of one rat that already had foci of necrosis at the time of killing. The decrease in GSH-Px was completely prevented by Se, but vitamin E had no effect. Dietary vitamin E and/or Se had little effect on the activity of GSH-Rd, but both agents, singly or in combination, prevented the reduction of G-6-PD that occurred in rats deficient in vitamin E and Se. The increased in vitro MLP was only partially reduced by either Se or vitamin E, since in both cases there still were three-fold increases. These results suggest that: a) no clear-cut relation exists between the massive decline of cytosol GSH-Px and the development of hepatic necrosis; b) the state of GSH-Px is probably unrelated to MLP; and c) microsomes may not be the initial site of damage.

KEY WORDS: • dietary hepatic necrosis • Vitamin E • selenium GSH peroxidase • GSH reductase • G-6-PD • microsomal lipoperoxidation

¹ Presented in part at the American Institute of Nutrition meetings, Chicago, Illinois, April 1977. Abstract published in Federation Proc. 36, 1124.

Manuscript received 6 April 1977.