Down-regulation of GPx1 mRNA and the loss of GPx1 activity causes cellular damage in the liver of selenium-deficient rabbits.
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.
Muller
A S
AS
Institute of Animal Nutrition and Nutrition Physiology, Justus Liebig University, Giessen, Germany.
Pallauf
J
J
D000821:Animal Feed / Q000032:analysis; D000818:Animals; D004032:Diet; D015536:Down-Regulation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005979:Glutathione Peroxidase / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D012643:Selenium / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood; D014811:Vitamin E Deficiency / Q000201:enzymology / Q000378:metabolism*
D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D012643:Selenium