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

Abstract

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.