Prevention by Se-cysteine precursors of disturbances in glutathione pool in simulating endogenous intoxication

Endogenous intoxication (EI) accompanied by oxidative stress (OS) is most frequently simulated by parenteral administration of bacterial lipopolysaccharide (LPS). The glutathione (G-SH) system impairments, which follow EI, are polyorganic and represent a characteristic manifestation of OS. Prevention of OS by modulation of Se-cysteine-containing proteins and antioxidant protection enzymes (glutathione peroxidase, thioredoxine reductase, selenoprotein P, etc) is a rational approach enabling to substantiate new technologies for prevention of oxidative stress and stress-induced pathology. The experiments were carried out on 40 Wistar CRL:(WI) WUBR female albino adult rats subdivided into 5 groups and treated with Se-containing substances (intragastrically, 250 mikrog Se/kg body weight in a 2% starch solution) in the following order: group 1- control, 2- selenite, 3- dimethyldipyrasolylselenide, 4- Se-pyrane, 5- Se-methionine. The Se-consumption with feed was 0.14 ppm. On day 10, half of the animals from each group were administered subcutaneously with E. coli LPS (Sigma, L-2630) at a dose of 400 mikrog/kg body weight, and development of EI and OS was observed by measuring colonic temperature as well as OS product accumulation in blood plasma and erythrocytes. EI was found to be followed by Se mobilization from blood plasma, decreased plasma and liver GSH level and glutathione-S-transferase (GT) activity, GSH/ G-SS-G ratio and total glutathione in liver, with liver glutathione reductase (GR) activity being unchanged. The 10-day selenite and Se-methionine administration caused selenemia enhancement, decreasing in group 2 and being unchanged in group 5 with EI. The administration of Se-substance (with the exception of Se-pyrane) prevented a reduction of plasma and liver G-SH (with the exception of selenite). The protective selenite effect was also absent in studying the G-SH/G-SS-G ratio and total glutathione. The highest liver glutathione redox state level was observed in experimental group 5 (Se-methionine administration) where it was above the control values, but was not followed by GR activation. The activity of the latter was diminished in selenite-treated animals. The group 2- 5 animals had increased liver GT activity, and no LPS-caused decrease was observed after the dimethydipyrasolylselenide and Se-methionine administration.vokMyynti MTT Tietopalvelut 31600 Jokioine

Changes in glutathione peroxidase activities and glutathione system indices in rat liver and intestine in endogenous intoxication intiation under controlled selenium consumtion

We studied the content and the ratio of the glutathione oxidized and reduced forms (GSSG, GSH, total G) as well as glutathione reductase and glutathione peroxidase activities (t-BOOH and H2O2 substrates) in the liver, duodenal, small and large intestines of albino rats (Wistar CRL:(WI) WUBR) consuming a low selenium diet supplemented with sodium selenite (SS) in drinking water or the organic preparation Sedimethyldipyrasolyl selenide (DPS) (both at a dose of 0,1 mikrog Se/ml water). The Se-consumption with feed was 0,14 ppm. Some animals were administered intraperitoneally with E. coli lipopolysaccharide (Sigma, L-2630) at a dose of 400 mikrog LPS/kg body weight to provoke endogenous intoxication (EI, endotoxemia). The development of hyperthermia was monitored by measuring colonic temperature, increasing blood plasma oxidative stress indices and their slackening in SS and DPS consumption. EI elevated the GSSG concentration and reduced the liver GSH/GSSG ratio, which was not found in the SS- and DPS - supplemented animals. Glutathione peroxidase activity turned out to be considerably increased in consuming Secontaining preparations, however, the greatest increase was after the SS administration. The EI development in the duodenal, small and large intestinal mucosa was accompanied by an identical decrease of GSH amount, the GSH/GSSG ratio and total G. The SS consumption elevated the GSH/GSSG ratio in all the intestinal regions and the total G in the large intestine as well as activated glutathione reductase in the small intestine. Both the Se-containing compounds stabilized the mucosal G system (probably, synthesis of G) in EI, which was pronounced in the large intestine. The results obtained indicate considerable variations in formation of Se-cysteine liver and intestinal stores in consumption of organic and inorganic selenium forms and enables to optimize the schemes for prevention and pathogenetic treatment of oxidative stress- induced pathologic processes in hepatology and gastroenterology.vokMyynti MTT Tietopalvelut 31600 Jokioine