Plasma selenium in patients with cirrhosis

Abstract

Plasma selenium concentration is decreased in patients with cirrhosis and, based on this finding, it has been suggested that patients with cirrhosis are selenium deficient. We measured plasma selenium concentration and the two plasma selenoproteins, glutathione peroxidase (GSHPx-3) and selenoprotein P, in the plasma of patients with cirrhosis of Child classes A, B, and C and in control subjects. Plasma selenium declined in proportion to the severity of the cirrhotic condition, as indicated by the Child class. Selenoprotein P, which originates largely in the liver, declined in a similar manner. Plasma glutathione peroxidase activity increased, and GSHPx-3 originates in the kidney. Selenium in the non-selenoprotein pool, shown by others to be largely selenomethionine in albumin, declined. Thus, although plasma selenium is decreased in patients with cirrhosis, the increase in plasma glutathione peroxidase activity, which occurs in them, suggests that patients with cirrhosis do not have selenium deficiency. (HEPATOL-OGY 1998;27:794-798.) Selenium exerts biological effects as an essential constituent of selenoproteins. 1 Pathological conditions, such as selenium deficiency and organ damage, which are severe enough to alter selenium metabolism, can be expected to affect the concentrations of selenoproteins and to have biochemical and pathological consequences. Several groups have reported that patients with cirrhosis have plasma selenium concentrations lower than those of healthy controls. [2][3][4][5][6] The pathogenesis of those depressed selenium levels is unknown; therefore it is not known whether a remediable state of selenium deficiency exists in cirrhotics.Virtually all the selenium in plasma is present in the form of seleno-amino acids in the primary structure of proteins. One of these amino acids is selenocysteine, the physiologically active form of the element, which is synthesized in animal cells and is present in stoichiometric amounts in selenoproteins. Glutathione peroxidase (isoform GSHPx-3) and selenoprotein P are the only selenoproteins that have been identified in plasma. 7,8 The other amino acid form of selenium in plasma is selenomethionine, 9 an amino acid that is synthesized by plants and is incorporated randomly into animal proteins as a constituent of the methionine pool.Proteins that contain selenomethionine do not contain the element in stoichiometric amounts and are often referred to as selenium-containing proteins to distinguish them from true selenoproteins. Small molecule forms of uncharacterized selenium are involved in homeostasis of the element. Those forms account for approximately 3% of plasma selenium under steady state conditions. 10

High selenium intake and increased diabetes risk: experimental evidence for interplay between selenium and carbohydrate metabolism

“…(64–67) Human plasma contains selenium in form of the selenoenzyme GPx3, a low-molecular-weight selenium pool and most notably the selenium transporter selenoprotein P (SeP), which accounts for 50–60% of circulating selenium. (68) Compared to GPx activity, both SeP and the remaining non-selenoprotein plasma selenium pool require a higher dietary selenium intake for their optimization and saturation. (64–67) It is tempting to speculate that SeP and/or low-molecular-weight selenium compounds may affect insulin-induced signalling pathways related to carbohydrate and lipid metabolism.…”

“…The major fraction of total selenium in human plasma is present as SeP, which is mainly secreted by the liver and supplies peripheral tissues with selenium. (68,69) SeP represents a suitable biomarker for selenium status, because its plasma concentration increases in response to different dietary forms and to a wide range of doses in selenium supplementation studies. (64–67) This obvious importance of SeP for selenium homeostasis prompted us to investigate the regulation of hepatic SeP production by factors related to carbohydrate metabolism.…”

Selenium, an Antioxidant Nutrient

“…The bars represent the following: A, healthy individual in the United States with average selenium intake (approximately 100 μg selenium per day); B, healthy individual with lower, but adequate, intake (approximately 55 μg per day); C, healthy individual with very high selenium intake as selenomethionine (approximately 400 μg per day); D, healthy but selenium‐deficient individual from China (intake approximately 10 μg per day); and E, patient with cirrhosis and adequate selenium intake (approximately 100 μg per day). Values are representations derived from several clinical studies 15,17,18 …”

“…Patients with cirrhosis have been reported to have “low” plasma selenium concentrations by several investigators. We carried out a detailed analysis of plasma selenium in patients with cirrhosis 17 . Cirrhosis caused a decrease in plasma selenium that could be traced to a fall in selenoprotein P and selenium in albumin (Figure 1, compare bars A and E).…”

Delaying of insulin signal transduction in skeletal muscle cells by selenium compounds

“…Depending on the content and the chemical form of Se in the diet, Se concentrations in human plasma can vary considerably, ranging from 20 μg/L (0.25 μM) to 95 μg/L (1.2 μM) in Chinese subjects and from 79 μg/L (1.0 μM) to 147 μg/L (1.86 μM) in US-Americans [4]. Se is present in human plasma in the form of two selenoproteins, SeP and GPx3, as well as in a non-selenoprotein Se pool bound to albumin [5]. A daily intake of 30-85 μg Se is recommended for adequate Se supply, based on dietary requirements for saturation of plasma GPx3 activity, whereas the optimization of plasma SeP levels requires a higher intake of 90-100 μg Se/day [6][7][8].…”