Glutathione peroxidase and glutathione S-transferase activity of platelets

Abstract

A low Se intake in dietetically treated patients with phenylketonuria (PKU) or maple syrup urine disease (MSUD) leads to a marked reduction of the platelet glutathione peroxidase activity (GSHPx). The mean value amounted to 2.0 U/10(11) platelets with t-butyl hydroperoxidase (t-BOOH) (2.2 U/10(11) with H2O2) in patients and 5.8 U/10(11) with t-BOOH (5.4 U/10(11) with H2O2) in the control children. After Se supplementation with yeast rich in Se (dose: 135 micrograms Se/m2) the GSHPx activities rapidly increased. They reached a plateau after 2-3 weeks and remained there during the following 15-20 weeks of supplementation. After the cessation of supplementation there was a slow decrease, the values reached a low plateau after 24 weeks. In addition platelet glutathione S-transferase (GSHTf) was estimated with 1-chloro-2,4-dinitrobenzene. No significant difference between the values in healthy and dietetically treated patients in a low or normal Se state was observed. GSHTf did not exhibit peroxidase activity and did not show a compensatory increase when Se dependent GSHPx activity was low. The patients do not reveal clinical signs of disturbed platelet function. GSHPx may act in platelets via lipoxygenase on the prostaglandin pathway. The physiologic consequence of altered arachidonate metabolism, when GSHPx is deficient in platelets, remains to be elucidated.

Selenium and vitamin E status of healthy and institutionalized elderly subjects: analysis of plasma, erythrocytes and platelets

“…The institutionalized elderly, however, had significantly lower GSH-Px activity than the healthy elderly, despite both groups having similar levels of Se in their platelets. The same observation was reported by Kdsperek et al (1982) and Menzel et al (1983) in children receiving dietetic treatment for phenylketonuria and maple syrup urine disease.…”

Hyperphenylalaninemia Correlated with Global Decrease of Antioxidant Genes Expression in White Blood Cells of Adult Patients with Phenylketonuria

“…Figure 3 illustrates the results of our study compared with results of several studies on PKU patients, in vitro and in vivo models. As in the present study, several studies on PKU patients, adults and children with or without restrictive diet, highlighted a decrease of GPx enzyme in various (Menzel et al 1983;Reilly et al 1990;Sierra et al 1998;Sitta et al 2006;Sanayama et al 2011). The reduced expression of antioxidant systems that we observed could lead to an inefficient response to oxidative stress and by consequences to elevation of ROS levels (superoxide and hydroxyl anions especially) responsible for cellular damages previously highlighted in PKU (Ercal et al 2002;Sitta et al 2009;Sanayama et al 2011) and which may lead to brain injury observed in the disease.…”

“…3 Schematic representation of main results of the study (black arrows) compared with results of several studies on PKU patients, in vitro and in vivo models (grey arrows). As in this study, several studies highlighted a decrease of GPx enzyme in various tissues in PKU (Menzel et al 1983;Reilly et al 1990;Sierra et al 1998;Sitta et al 2006;Sanayama et al 2011). The combination of a decrease in expression of GPX and GSR may suggest a reduced activity of the GSH antioxidant system.…”

“…In PKU, accumulation of Phe and/or its metabolites may lead to a disturbance of redox homeostasis (Artuch et al 2004;Mazzola et al 2013). Some studies showed an increase of lipoperoxidation markers (Sanayama et al 2011) and DNA damages (Sitta et al 2009), or a reduction of various antioxidant compounds, especially selenium, coenzyme Q10, or antioxidant system of glutathione (Menzel et al 1983;Sitta et al 2006;Sanayama et al 2011). Decrease of antioxidant compounds was also observed in animal and in vitro models of PKU (Ercal et al 2002;Fernandes et al 2010;Mazzola et al 2011;Moraes et al 2014).…”

Selenium in Uremia: Culprit or Bystander?

“…Moreover, platelet GSHpx activity seems a sensitive and accurate index of Se nutrition [49], Platelet GSHpx has a general function in the protection against oxidative damage [43] and a specific function in the lipoxygenase pathway of fatly acids [50], A reduced GSH px activity has been observed in patients with myocardial infarction [51], and since a decreased activity may affect aggregation in vivo, this deficiency could play some role in human cardiovascular disease [II], Se deficiency also en hances production of platelet-activating factor, and this effect, such as the altered PG metabolism, involves an increase of phospholipase A2 [52], A correlation between Se deficiency and the decreased half-life of platelets in uremic patients has been suggested [35]. The authors investigated the platelet malondialdehyde (M DA) production as indices of thrombocyte membrane peroxidation in a group of dialy sis patients and in controls.…”