Ethanol oxidation to acetaldehyde and next to acetate is accompanied by free radical generation. Free radicals can affect cell integrity when antioxidant mechanisms are no longer able to cope with the free radical generation observed in ethanol intoxication. Natural antioxidants are particularly useful in such a situation. The present study was designed to investigate the efficacy of green tea as a source of water-soluble antioxidants (catechins) on the liver and blood serum antioxidative potential of rats chronically (28 days) intoxicated with ethanol. Alcohol caused a decrease in liver superoxide dismutase, glutathione peroxidase and catalase activities and an increase in activity of glutathione reductase. Moreover, a decrease in the level of reduced glutathione, ascorbic acid, vitamins A and E and beta-carotene were observed. The activity of serum glutathione peroxidase decreased while glutathione reductase activity increased. The level of serum non-enzymatic antioxidants was also decreased in the liver. Alcohol administration caused an increase in the liver and serum lipid peroxidation products, measured as thiobarbituric acid-reactive substances. However, green tea prevents the changes observed after ethanol intoxication. Green tea also protects membrane phospholipids from enhanced peroxidation. These results indicate a beneficial effect of green tea in alcohol intoxication.

This paper reports data on the effect of green tea on the lipid peroxidation products formation and parameters of antioxidative system of the liver, blood serum and central nervous tissue of healthy young rats drinking green tea for five weeks. The rats were permitted free access to solubilized extract of green tea. Bioactive ingredients of green tea extract caused in the liver an increase in the activity of glutathione peroxidase and glutathione reductase and in the content of reduced glutathione as well as marked decrease in lipid hydroperoxides (LOOH), 4-hydroksynonenal (4-HNE) and malondialdehyde (MDA). The concentration of vitamin A increased by about 40%. Minor changes in the measured parameters were observed in the blood serum. GSH content increased slightly, whereas the index of the total antioxidant status increased significantly. In contrast, the lipid peroxidation products, particularly MDA was significantly diminished. In the central nervous tissue the activity of superoxide dismutase and glutathione peroxidase decreased while the activity od glutathione reductase and catalase increased after drinking green tea. Moreover the level of LOOH, 4-HNE and MDA significantly decreased. The use of green tea extract appeared to be beneficial to rats in reducing lipid peroxidation products. These results support and substantiate traditional consumption of green tea as protection against lipid peroxidation in the liver, blood serum, and central nervous tissue.

The effect of two compounds: N-acetylcysteine (NAC) and trolox derivative (U-83836E) on the methanol induced impairment of the antioxidant system of the rat brain was studied in male Wistar rats (approx. 250 g body weight). The animals were divided into six main groups: control group (0.5 ml of physiological saline intragastrically), NAC group (150 mg/kg intraperitoneally-i.p), U-83836E group (10 mg/kg i.p.), methanol group (3 g/kg intragastrically), NAC+methanol and U-83836E+methanol groups. In these particular groups the changes in antioxidant parameters were observed for 6,12,24,48 h and 5 and 7 days. The results proved that the use of methanol and N-acetylcysteine increased the activities of Cu,Zn-superoxide dismutase, glutathione peroxidase and glutathione reductase by about 15,15 and 41%, respectively, in comparison to the group of rats receiving methanol alone. Similarly, the level of GSH increased by about 17%, the concentration of ascorbate by 20%, while the thiobarbituric acid-reactive substances (TBA-rs) diminished to the values as in control group. The use of new antioxidant U8383E and methanol showed less beneficial effect in the measured parameters however, it serves as a better protector for the methanol induced decrease in GSH-content. These data suggest that NAC and U-83836E mitigate the toxic effects of methanol on the antioxidant system of the rat brain.

Methanol oxidation in the liver is accompanied by formation of formaldehyde and free radicals. These compounds can react with biologically active proteins, including proteolytic enzymes and their inhibitors. The activity of cathepsin G and elastase and their inhibitors such as alpha-1-antitrypsin and alpha-2-macroglobulin in plasma of rats given methanol orally in doses of 1.5, 3, and 6 g/kg was investigated for 7 days. The activity of cathepsin G and elastase was increased from 12 h to 5 d, proportionally to methanol dose. At the same time, activity of their inhibitors was reduced. Methanol ingestion in humans caused changes in activities of proteases and their inhibitors with similar direction as in rats. These changes in activity of proteases and their inhibitors produce significant disturbances in proteolytic-antiproteolytic balance after methanol administration.

The aim of the present study was to evaluate superoxide dismutase (Cu,Zn-SOD) activity in the principal layers of polyester grafts implanted into the abdominal aorta of dogs. The grafts were examined 7 days and 1, 4 and 12 months after the operation, It was found that SOD activity occurred in all polyester graft layers during the whole experiment. The neointima activity was 1.5-fold lower during the Ist month; with the passage of time, it became 2-fold lower than in the normal aorta (p < 0.01). SOD activity in the medial and outer graft layers behaved similarly: it was lowest after 7 days, increased after I month and significantly decreased after 4 and 12 months (p < 0.01). Our study shows that the activity of SOD is low in polyester grafts and it can thus be inferred that protection against the superoxide anion is inadequate.

OBJECTIVE:Non-enzymatic low-molecular antioxidants are one of the important mechanisms which protect cells against the toxic effect of oxygen. The aim of the present study was to determine the content of glutathione, glutathione reductase, and ascorbic acid in the principal layers of polyester grafts. INTERVENTIONS AND MEASURES: The experiments were carried out on 24 mongrel dogs, in which polyester double velour DALLON grafts were implanted. Seven days, 1, 4, and 12 months after the operation the grafts were excised. The following were determined: glutathione content by use of a GSH-400 system, glutathione reductase activity by the method of Langdon and Mize, and ascorbic acid content by the Kyaw method.RESULTS:It was found that the glutathione content in the graft neointima was 33% lower, in the graft neomedia higher during the first 4 months, in the neoadventitia 50% lower after 4 months than in the corresponding layers of the aorta (p < 0.01). The activity of glutathione reductase was significantly higher in all the graft layers during 12 months' observation than in the normal aorta layers. The ascorbic acid content of the graft layers was lowest 7 days after the implantation, and then in time increased so that 12 months after the operation it reaches its highest values.CONCLUSIONS:Our study shows that low non-enzymatic antioxidative potential is not capable of proteoting the newly forming graft layers, particularly the neointima, against oxygen toxicity. Thus, it would be beneficial to administer antioxidants (vitamin C, vitamin E, and N-acetylcysteine).

SOD, CAT, GSH-Px, GSSG-R, ascorbic acid, α-tocopherol, nonprotein- and protein-bound sulfhydryl compounds, and TBA-rs content in the liver, erythrocytes, and blood serum of rats treated with methanol after 6, 12, and 24 h and 2, 5, and 7 days were investigated. Furthermore, hematological parameters of erythrocytes were analysed. GSH-Px, GSSG-R, sulfhydryl compounds, and ascorbic acid in the liver, erythrocytes, and in blood serum were significantly decreased. In addition, Cu,Zn-SOD and tocopherol in erythrocytes were diminished, whereas TBA-rs in the three biological materials was enhanced. Simultaneously, erythrocytes amount, hemoglobin level, hematocrit, and MCV were reduced. These results indicate that methanol in rats leads to the impairment of antioxidant mechanisms in the liver, erythrocytes, and blood serum.

Activities of the antioxidant enzymes such as superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) as well as the level of reduced glutathione and the concentration of thiobarbituric acid—reactive substance (TBARS) in brain regions in transiently hypoperfused rat brain with or without intravenous infusion of spermine were evaluated. Cerebral hypoperfusion was induced by temporary occlusion of common carotid arteries for 30 min and subsequently, by reperfusion for 60 min. Infusion of spermine reversed the decrease in SOD activity in the cerebral cortex, striatum, hippocampus, hypothalamus and midbrain, and amounted to 50.1 U, 61.5 U, 50.3 U, 30.0 U, 38.0 U, respectively, while GSH-Px restored to normal values only in the cerebral cortex and striatum and amounted to 100 u and 110 U, respectively. During hypoperfusion/reperfusion and after use of spermine no changes in GSSG-R were seen in the hypothalamus and midbrain. The activity of GSSG-R was in accordance with the control for the striatum and amounted to 39.0 IU after using spermine. GSH content returned to normal values in the striatum and midbrain after i.v. use of spermine and amounted to 210 and 240 nmol/g of wet tissue, respectively. In addition, the production of TBARS dropped markedly (P<0.05) in the hippocampus and midbrain and amounted to 100 and 105 μmol/g of wet tissue, respectively. Partially beneficial effect of spermine could result from the inhibition of free radical generation and capability of chelate formation with iron ions.

The antioxidant enzymatic system in brain hypoperfusion/reperfusion model in rats after spermine administration was evaluated. Incomplete cerebral ischemia/reperfusion induced by temporal occlusion of common carotid arteries caused a decrease in the activities of superoxide dismutase and glutathione reductase as well as total and free sulfhydryl groups, while thiobarbituric acid-reactive substances became elevated. Administration of spermine after the reperfusion led to restoring all above parameters to normal values. Protective effect of spermine in transiently hypoperfused and subsequently reperfused rat brain is briefly discussed.

SOD activity and -SH compounds in the liver and RBCs, and some hematological parameters were investigated in control rats and in those submitted to chronic (3 months) intoxication with ethanol. We found significantly lower SOD activity and a decrease in -SH groups in the liver and RBCs of ethanol-treated rats in comparison with the control group. The hemoglobin content and mean corpuscular hemoglobin concentration were reduced, while mean corpuscular volume of RBCs was increased when compared with the control group.

The ammonia concentration and changes in the activity of ammonia metabolizing enzymes in the brain tissue during ischemia/reperfusion were investigated in rats. During ischemia (0.5 h) we found a statistically significant increase in brain ammonia concentration and a significant decrease in glutamate dehydrogenase activity. After 1 h of reperfusion, a further accumulation of ammonia concentration was observed. Furthermore, the brain glutamine syntethase and glutamate dehydrogenase were decreased, whereas the brain glutaminase activity was increased. The causes for the changed activities of some ammonia metabolizing enzymes in brain after ischemia/reperfusion have been discussed.

The antioxidant enzymatic system in the ischemia/reperfusion induced brain injury in rats after U-74389G administration was evaluated. Ischemia/reperfusion caused a decrease in the activities of superoxide dismutase and glutathione reductase, as well as of total and free sulfhydryl groups, while thiobarbituric acid-reactive substances became elevated. Administration of U-74389G lead to restoring to normal values of all above parameters. Protective effect of the drug in ischemia/reperfusion induced brain injury has been suggested.

SOD, CAT, GSH-Px, and sulfhydryl compounds MDA contents in liver of rats treated with heparegen for 7, 14, and 21 days after alcoholic liver injury have been investigated. After use of this drug, we found beneficial effects on GSH-Px activity, sulfhydryl compounds (total and nonprotein), and MDA content and a partially beneficial effect on SOD and CAT activities. These enzyme activities after 21 days of drug administration were restored. Furthermore, heparegen shortens the time necessary for the return of AIAT and GGTP to normal value. This enzymatic data are supported by histological studies in light microscopy.

The effect of acetaldehyde administration for 4 weeks on antioxidant protection systems was investigated in liver of rats. Liver SOD activity was decreased from control value 542.4 U/g of tissue to 411.2 U/g of tissue in experimental group (24% decrease). GSH-Px activity was practically unchanged and liver CAT activity was significantly decreased (35%). Sulfhydryl compounds in liver non-proteins following ACH treatment were decreased from 4.22 mumol/g of tissue in control group to 2.86 mumol/g of tissue (23%). Furthermore acetaldehyde treatment caused significant increase in MDA level in liver (78% increase).

This paper reports data on the effect of two drugs: Heparegen (thiazalidine-4-carboxylic acid) and D-penicillamine on the blood ammonia concentration and on some ammonia metabolizing enzymes in liver and brain of rats intoxicated with ethanol. It seems, that both drugs decrease ammonia concentration and simultaneously elevate liver and brain glutamine synthetase activity. The effect of D-penicillamine on the nitrogen metabolism in the damaged liver appears to be more favourable than that of Heparegen.

Sulfhydryl compounds in plasma, liver and brain of rats treated with two immunostimulant drugs, isoprinosine and levamisole, after alcoholic liver injury have been investigated. After use of both drugs for 6 days we found partially beneficial effect on the SH-groups in plasma and liver. No changes in nonprotein SH compounds were observed in rat brain after treatment with isoprinosine, levamisole or ethanol. Furthermore, levamisole shortens the time necessary for the return of AlAT activity to normal value.

There appears to be increasing evidence that ethanol toxicity may be associated with an increased production of reactive oxygen intermediates. In rats we studied the effect of 4 weeks of ethanol ingestion on the liver cytosolic defense system against active oxygen species. Compared with the control rats, the ethanol-fed animals had a significantly higher liver malondialdehyde content and significantly lower reduced glutathione level. Moreover, ethanol feeding resulted in a decrease of Superoxide dismutase and catalase activities while glutathione peroxidase activity was only slightly diminished. Thus, prolonged ethanol administration profoundly modified the hepatic status of the enzymatic defense system leading to lipid peroxidation that may disrupt vital functions of liver cells.

Morphological examination of the liver and biochemical studies of the serum were carried out on rats fed: a) ethanol p.o. in the daily dose of 6 g/kg for 4 weeks and maintained on standard diet (Et-OH) and b) ethanol in the same doses but fed the BCAA enriched diet (to amount of 1.174 mM/day/rat) were carried out. It can be concluded that BCAA enriched diet given simultaneously with ethanol prevent in part the morphological and ultrastructural changes in liver and improve positive body weight gain of experimental animals.