[Influence of ethanol-metabolising systems on intensity of lipid peroxidation processes in gastrointestinal tract of rats].

The effects of some ethanol-metabolising systems (aldehyde dehydrogenase, catalase, cytochrome P450 2E1) on activation of lipid peroxidation (LPO) processes in gastrointestinal tract of rats have been studied using inhibitors of these systems. The intensity of LPO processes was evaluated by thiobarbituric acid-reactive products and chemiluminiscence intensity. It was found, that the acetadehyde metabolism play the main role in the indiction of lipid peroxidation in the gastrointestinal tract of rats.

[Effects of organic selenium substance, selenomethionine, in acute alcohol intoxication].

The effect of the preliminary saturation of rats with selenomethionine (50 g/kg, intragastrically, daily, 10 days) prior to acute alcohol intoxication (5 g/kg, 20% ethanol solution, intragastrically, singly on the 11th day with the exposure for 2 hours) was investigated. The activities of glutathione peroxidases (gastrointestinal mucosa, blood plasma, erythrocytes, liver), the levels of oxidized and reduced glutathione, LPO intensity and blood corticosterone level were studied.

Effect of Perftoran on free radical homeostasis during alcohol withdrawal syndrome.

We studied the effects of Perftoran on free radical processes in the liver of rats with withdrawal syndrome after chronic alcohol intoxication. Administration of Perftoran in the period of ethanol withdrawal eliminated the signs of oxidative stress and prevented elevation of enzyme activities in the blood, which reflects improvement of structural and functional characteristics of liver cell membranes.

[Effect of chronic morphine treatment on free radical state].

The state of an enzymatic component of the antioxidant system, intencity of lipid peroxidation (LPO) in the liver, nitric oxide level in blood plasma were investigated in rats subjected to chronic morphine intoxication. Male Wistar rats were treated with introperitoneal injections of 1% morphine hydrochloride twice a day. The daily dose of morphine was gradually increased trom 10 mg/kg (1-2 days) to 20 mg/kg (3-4 days), and up to 40 mg/kg starting at the fifth day. The first group of animals (n=8) received morphine injections for 14 and 21 days. Chronic morphine treatment was accompanied by marked inhibition of the peroxide-utilizing antioxidants in liver. This creates favourable conditions for H2O2 toxicity. Howewer, low level of thiobarbituric acid reactive products suggests involvement of some scavenger, which inhibits hydrogen-peroxide induced free radical processes. In vitro experiments suggests that morphine may be involved into reduction of H2O2 level, whereas administration of morphine to rats may also employ nitric oxide as the scavenger of reactive oxygen species.

[Interrupted alcohol treatment and liver: free radical homeostasis, nitric oxide, adaptive mechanisms].

Alcohol administration can result in liver damage. Reactive oxygen species (ROS), nitric oxide (NO) and their interaction are crucial factors in this process. The aim of work was to investigate, free radical state and mechanisms of adaptation of the antioxidant system (AOS) to stress, caused by interrupted alcohol intake. Repeated cycles of alcoholization caused an imbalance between production and utilization of various ROS. This imbalance was due to impairments in the system superoxide dismutase/catalase. Nevertheless, in most experimental groups there was clear reduction of lipid peroxidation (LPO) products evaluated by thiobarbituric acid reactive substances. This might be attributed to the antioxidant effect of NO. However, there was an increased level of transaminases in blood plasma. After 28 days of this experimental scheme all the parameters studied normalized.

[Antioxidant system activities and lipid peroxidation in nodal and non-nodal thyroid tissue of patients operated in connection with euthyroid nodular goiter].

The activities of the antioxidant systems (AOS) and lipid peroxidation (LP) were studied in the thyroid (operation material) of patients with euthyroid nodular goiter (in carcinoma, adenoma, colloid goiter tissues as well as in non-nodular adjacent thyroid tissue). Increased activities of superoxide dismutase (SOD, by 101.0 and 125.9%), catalase (by 76.6 and 71.2%), glutathione peroxidase (by 109.6 and 249.2%), glutathione reductase (by 84.6 and 195.9%) and LP aldehyde products (by 148.5 and 120.4%) were found in the adenoma and carcinoma tissues. The increased antioxidant system activity (SOD by 1.62-fold) and LP level by 1.62-1.65--fold in the non-goiter adjacent tissue from these patients indicate toxicity of malignant and non-malignant tumors for the adjacent normal thyroid tissues. Marked activation of oxidative stress (increased SOD activity (by 38.8-40.7%) reduced glutathione (52.4-90.0%) and TBARS concentrations (37.6-52.7%) in the nodal and non-nodal thyroid tissue in patients with multinodular colloid goiter suggest participation of free radical mechanisms in the disturbance of thyrocytes iodine metabolism and development of thyroid nodular pathology.

[Functional activity of blood and liver cells under formaldehyde intoxication via inhalation].

The influence of formaldehyde (of 5 and 10 mg/m3) on the state of the antioxidant system the blood and liver of rats, the activity of pentose phosphate pathway enzymes, and weight of immune organs was investigated. Formaldehyde intoxication led to activation of lipid peroxidation processes in red blood cells and hepatocytes. In the liver cells these changes were accompanied by activation of the antioxidant and detoxification systems. Formaldehyde depleted thiamine diphosphate in the liver, and this effect was not dose-dependent. The number of blood cells remained unchanged. Formaldehyde at the concentration of 10 mg/m3 exerted the negative effect on the thymus. This effect may be related to stimulation of lipid peroxidation.

Antioxidative effect of ursodeoxycholic acid in the liver of rats with oxidative stress caused by gamma-irradiation.

We studied effects of ursodeoxycholic acid (UDCA) (10 and 100 mg/kg b.w.) on the free radical generation, lipid peroxidation and the antioxidant defense system in the liver of rats with oxidative stress caused by gamma-irradiation. Both doses of UDCA normalized the liver parameters enhanced by gamma-irradiation: the content of superoxide anion and carbonyl-containing products of lipid peroxidation (alkanals, alkenals, alkadienals and ketones), the superoxide dismutase activity and the chemiluminescence enhanced by luminol. Only the highest dose of UDCA (100 mg/kg b.w.) decreased the chemiluminescence enhanced by lucigenin in liver microsomes and the hydroxyalkenals content in the liver. UDCA prevented reduced glutathione depletion caused by gamma-irradiation, whereas glutathione-related enzyme activities did not change under the influence of both the UDCA doses as well as gamma-irradiation. Thus, the data obtained suggest that UDCA is a metabolite having the sufficiently effective antioxidant properties.

Protection by pantothenol and beta-carotene against liver damage produced by low-dose gamma radiation.

Rats were exposed to a total dose of 0.75 Gy of gamma radiation from a 60Co source, receiving three doses of 0.25 Gy at weekly intervals. During two days before each irradiation, the animals received daily intragastric doses of 26 mg pantothenol or 15 mg beta-carotene per kg body mass. The animals were killed after the third irradiation session, and their blood and livers were analyzed. As found previously (Slyshenkov, V.S., Omelyanchik, S.N., Moiseenok, A.G., Trebukhina, R.V. & Wojtczak, L. (1998) Free Radical Biol. Med. 24, 894-899), in livers of animals not supplied with either pantothenol or beta-carotene and killed one hour after the irradiation, a large accumulation of lipid peroxidation products, as conjugated dienes, ketotrienes and thiobarbituric acid-reactive substances, could be observed. The contents of CoA, pantothenic acid, total phospholipids, total glutathione and GSH/GSSG ratio were considerably decreased, whereas the NAD/NADH ratio was increased. All these effects were alleviated in animals supplied with beta-carotene and were completely abolished in animals supplied with pantothenol. In the present paper, we extended our observations of irradiation effects over a period of up to 7 days after the last irradiation session. We found that most of these changes, with the exception of GSH/GSSG ratio, disappeared spontaneously, whereas supplementation with beta-carotene shortened the time required for the normalization of biochemical parameters. In addition, we found that the activities of glutathione reductase, glutathione peroxidase, catalase and NADP-dependent malate (decarboxylating) dehydrogenase ('malic enzyme') in liver were also significantly decreased one hour after irradiation but returned to the normal level within 7 days. Little or no decrease in these activities, already 1 h after the irradiation, could be seen in animals supplemented with either beta-carotene or pantothenol. It is concluded that pantothenol is an excellent radioprotective agent against low-dose gamma radiation.