Down‐regulation of GPx1 mRNA and the loss of GPx1 activity causes cellular damage in the liver of selenium‐deficient rabbits

Abstract

The effects of 10 weeks of dietary selenium and/or vitamin E deficiency (< 0.03 mg Se and 1.5 mg vitamin E per kg diet) on body Se and vitamin E stores and on the down-regulation of liver cellular glutathione peroxidase (GPx1) and plasma glutathione peroxidase (GPx3) were examined in growing female New Zealand White rabbits in comparison to Se (+ 0.40 mg Se/kg diet) and/or vitamin E (+ 150 I.U./kg diet) supplemented controls. Additionally plasma lactate dehydrogenase (LDH) activity, liver thiobarbituric acid-reactive substances (TBA-RS) and liver protein carbonyls were measured to assess the development of oxidative stress during an alimentary Se and/or vitamin E deficiency. Significantly decreased concentrations of Se and vitamin E in plasma (Se: - 70%; vitamin E: - 87%) and liver (Se: - 90%; vitamin E: - 95%) indicated an efficacious Se and vitamin E depletion of the rabbits within 10 weeks. GPx1 messenger RNA levels (GPx1 mRNA) in the livers of Se-depleted rabbits were down-regulated to 1/3-1/8 of the Se supplemented controls. GPx1 enzyme activity in the livers of Se-deficient rabbits declined to 10% of the Se-supplied control rabbits. A significantly elevated LDH activity in the blood plasma of Se- and vitamin E-deficient rabbits indicated a general impairment of tissues. Markedly increased TBA-RS concentrations and protein carbonyl contents in the livers of Se- and vitamin E-deficient rabbits gave further evidence for severe oxidative damage of cellular lipids and proteins during an alimentary Se and/or vitamin E deficiency. Both a full expresssion of GPx1 attained by dietary Se supplementation and dietary vitamin E supply effected an almost complete protection against oxidative cellular damage of the liver.

Selenium-deficient diet enhances protein oxidation and affects methionine sulfoxide reductase (MsrB) protein level in certain mouse tissues

“…The observation that selenium deficiency leads to substantial elevations in the carbonyl content of proteins in various mouse tissues (Fig. 4) is in agreement with results of a recent study showing that there is a marked increase in the protein carbonyl content in livers of SD rabbits (32). Because the activities of TR and MsrB are reduced significantly in selenium-depleted liver and kidney, compared with brain, it is reasonable to suggest that the lowered expression of these proteins in liver and kidney may contribute greatly to the observed enhanced protein carbonylation (Fig.…”

Dietary selenium variation-induced oxidative stress modulates CDC2/cyclin B1 expression and apoptosis of germ cells in mice testis

“…A decrease in GSH-Px activity, as observed in Se-deficient (group I) animals, confirms lowered Se levels and induction of oxidative stress in the testes [5,7]. Recently, a number of workers have reported Se-deficiency-dependent down-regulation of GSH-Px activity [42]. In the Se-excess group (Group III), an increase in GSH-Px activity was observed, as compared to the Se-adequate group (Group II).…”

Gene Expression Profile at the G1/S Transition of Liver Regeneration after Partial Hepatectomy in Mice

“…28,29 In our analysis we found downregulation of Ces1 and Ces3, the essential enzymes participate in the hydrolysis and detoxification of numerous toxic compounds and Gsta2, Gsta4, Gstm6 and Gstt1, the polymorphic Glutathione S-transferase (GST) enzymes responsible for the metabolism of a broad range of xenobiotics including carcinogens and endogenous compounds. 28 In contrast GPx3, a major antioxidant enzyme in reducing lipid hydroperoxides and hydrogen peroxide in plasma 30 and nicotinamide N-methyltransferase (NNMT), the primary catabolic enzyme of nicotinamide 31 are upregulated. It might be possible that the amount of metabolic activity there by the amount of toxic waste produced in the remnant liver after PH is less compared to normal liver which in turn determines the expression of genes involved in xenobiotic metabolism.…”