Zinc effects on glutathione metabolism relationship to zinc-induced protection from alkylating agents

Several aspects of the effects of zinc on the metabolism of glutathione were examined in the Chinese hamster cell (line CHO) and in three derived sublines which differ in their resistance to the thiol reactive heavy metal cadmium. In the parental CHO cell, which does not induce the synthesis of metallothionein in response to zinc, glutathione levels remained approximately constant during the first 6 hr of zinc exposure. In the resistant cell lines, which induce the synthesis of metallothionein in response to zinc, the glutathione levels dropped transiently during zinc exposure. In all cell lines except the most cadmium resistant line, the glutathione levels after 12 hr were increased up to 3-fold relative to pretreatment levels. Similarly, the glutathione S-transferase activity measured by the conjugation of 1-chloro-2,4-dinitrobenzene to glutathione was increased after 9-12 hr of zinc treatment in all except the most highly cadmium resistant cell line. Glutathione reductase was not affected consistently by zinc treatment; however, the level of activity of this enzyme in the most highly cadmium resistant line was two to three times greater than that observed in the other cell lines. These effects are considered in relation to the zinc-induced protection of these cells from the toxic effect of the alkylating agent melphalan.     

Relevance of NADPH depletion and mixed disulphide formation in rat lung to the mechanism of cell damage following paraquat administration

We have examined the possibility that the mechanism of paraquat toxicity in the lung involves both the formation of mixed disulphides (the amount of NPSH or GSH involved in protein disulphide formation) and the prolonged oxidation of NADPH, leading to NADPH depletion. We have compared the oxidation-reduction status of the lung, 2, 8 and 24 hr after dosing rats subcutaneously with 20 mg paraquat/kg (a dose which causes extensive lung damage 24 hr after dosing) or 20 mg diquat/kg (a chemically related bipyridyl which only causes very minimal lung damage 24 hr after dosing). Lung NADP⁺ levels were not affected 2, 8 or 24 hr after dosing with either bipyridyl. However, although NADPH levels were unchanged 2 hr after dosing with paraquat, and 2, 8 and 24 hr after dosing with diquat, there was a significant decrease in NADPH levels by 8 and 24 hr after dosing with paraquat. The changes in NADPH levels were coincident with the lung damage (characterized previously) caused by these treatments. In contrast with these effects on NADPH levels, there was an increase in NPSH and GSH levels in the lung by 8 and 24 hr after dosing with paraquat or diquat. Thus, there was no simple relationship between lung NADPH levels and lung sulphydryl levels.Lung mixed disulphide levels (the amounts of NPSH or GSH involved in disulphide formation) were increased 2, 8 and 24 hr after dosing with paraquat or diquat, although oxidized glutathione levels remained normal. Thus, an early and persistent biochemical effect of paraquat and diquat in the lung involves an increase in mixed disulphide levels, which is probably a consequence of the lungs' response to an increase in the oxidation of NADPH and GSH. As suggested previously, the increase in mixed disulphide levels appears to be a mechanism for regulating the normal redox state of the lung. However, despite this regulatory mechanism, NADPH depletion occurs 8 and 24 hr after dosing with paraquat, but not diquat, coincident with the development of lung damage.In conclusion, we suggest that mixed disulphide formation is not only a regulatory mechanism, but in some circumstances also may cause changes in essential biosynthetic and regulatory functions of the lung. This may ultimately lead to the drop in NADPH levels, which we propose is a critical biochemical event in the development of alveolar epithelial cell damage following the administration of paraquat.     

Effects of fasting,body weight,methylcellulose, and carboxymethylcellulose on hepatic glutathione levels in mice and hamsters

Male mice fasted overnight had only about half the hepatic reduced glutathione (GSH) concentration of fed mice. In contrast, fasted male hamsters had 68 per cent higher hepatic GSH levels than controls. No strong correlation of hepatic GSH concentration with body weight was found in either species. Single doses of 0.5% (w/v) methylcellulose (10 ml/kg, i.p.) decreased the hepatic GSH concentration 18–36 per cent in mice and hamsters. Multiple oral doses of 0.5% (w/v) methylcellulose (10 ml/kg once per day for 9 days) caused an initial doubling of the GSH level after two doses in hamsters, but after four doses the GSH level returned to normal. Chronic (60-day) oral administration of 0.5% (w/v) sodium carboxymethylcellulose (10 ml/kg twice daily) to hamsters caused a time-dependent depression of hepatic GSH concentration and a 4-fold increase in hepatic aniline hydroxylase activity after 45 days. No changes in the activities of aminopyrine N-demethylase and hexobarbital oxidase were found. It was concluded that hepatic glutathione levels in mice and hamsters are volatile and respond to relatively innocuous physiological (fasting, time of day) and pharmacological (methylcellulose, carboxymethylcellulose) stimuli.     

Drug protein conjugates—VI. Role of glutathione in the metabolism of captopril and captopril plasma protein conjugates

Previous metabolic studies of captopril suggest that the rapid dissociation of captopril-plasma protein conjugates in vivo is dependent upon endogenous thiols such as glutathione and cysteine. Consistent with this hypothesis, we have found that cysteine (0.06–3 mM) and glutathione (0.02–1 mM) cleave ¹⁴C-captopril-plasma protein conjugates in vitro. Dissociation of the drug-protein conjugate was accompanied by formation of the corresponcling mixed disulphide which indicates that the reaction proceeds via a spontaneous thiol-disulphide interchange. Administration of high doses (50–300 mg/kg) of CP produced a time-dependent and dose-dependent decrease in hepatic glutathione concentrations in the mouse and the rat. The depletion of glutathione observed was similar to that produced by equimolar doses of D-penicillamine and paracetamol. Acute and chronic (7 days) administration of captopril (100 mg/kg) produces the same (11–12%) depletion of hepatic glutathione. However, changes in liver function as determined by elevation of serum glutamic-pyruvic transaminase was only observed at doses of 200 and 300 mg/kg. Thus, although thiol-disuiphide interactions between captopril and plasma proteins may contribute to the perturbation of hepatic glutathione concentrations, it is unlikely that this process will be of toxicological significance during therapeutic administration of captopril.     

Protective effect of lipoic acid against methotrexate-induced oxidative stress in liver mitochondria

Methotrexate (MTX) is a folic acid antagonist widely used as a cytotoxic chemotherapeutic agent for leukemia and other malignancies. The purpose of this study was to investigate the damage caused by MTX on liver mitochondria and its protection by using antioxidant properties of lipoic acid. MTX substantially affects mitochondrial function by reducing glutathione levels leading to disturbances in antioxidant enzyme defense system. Lipoic acid occurs naturally in mitochondria as a coenzyme. In various studies lipoic acid has been convincingly shown to exhibit an antioxidant role when supplemented exogenously. We studied the effect of lipoic acid pre-treatment on the toxicity of MTX in mouse liver mitochondria focusing specifically on the oxidative stress. MTX caused a significant rise in the mitochondrial lipid peroxidation (LPO), protein carbonyl (PC) content and superoxide radical generation. It also affected the mitochondrial thiol profile. Pre-treatment of mice with lipoic acid (35 mg/kg) markedly lowered mitochondrial LPO, PC content and superoxide radical generation. It also restored decreased enzymatic and non-enzymatic antioxidants of mitochondria. It is suggested that lipoic acid has a potential role in suppressing MTX-induced mitochondrial toxicity, and it affords protection either by reversing the decline of antioxidants or by the directly scavenging the free radicals.     

Cadmium retention increase: A probable key mechanism of the protective effect of zinc on cadmium-induced toxicity in the kidney

Zinc (Zn) reverses cadmium (Cd)-induced toxicity in kidneys although it increases Cd tissue burden, hence, the present study is designed to study the relationships between Cd, Zn and antioxidants in the kidneys of rats exposed to Cd orally. Male rats received either tap water, Cd or Cd + Zn in their drinking water during five weeks. Cd-induced increase in Cd and Zn accumulation was accompanied by a decrease in important variables (GSH, GSH/GSSG, CuZn SOD and GPx activities) and by an increase in others (Cd/Zn, GSSG and CuZn SOD/GPx). Zn supply intensified Cd retention and Cd/Zn; it amplified CuZn SOD activity, CuZn SOD/GPx and GSH/GSSG compared to normal values, but had no effect on Zn content increase. Besides, it ameliorated GPx activity and corrected GSSG level. High positive correlations were found between Cd concentrations and the majority of the studied variables suggesting a direct influence of Cd on them. Zn concentration had positive correlation with CuZn SOD/GPx, and negative one with GPx activity, which reflects an indirect protective effect of Zn. In conclusion, our results suggest that Zn increases Cd tissue retention in the kidney and that is probably the key mechanism of the protective effect of Zn.     

Drug-induced lipid peroxidation in mice—I Modulation by monooxegenase activity,glutathione and selenium status

Feeding male mice for 2 days with sucrose leads to a decrease of total liver glutathione by more than 50 per cent when compared to controls. Such animals were intoxicated with 300 mg/kg paracetamol and upon administration of inducers of the drug-metabolizing system, in vivo and vitro lipid peroxidation in these animals was largely increased as well as the susceptibility to the drug. Pretreatment of the mice with methylcholanthrene led to a 28-fold, with benzo(α)pyrene to a 22-fold, and with phenobarbital to a tenfold increase in ethane exhalation. In vivo administration of various monooxygenase inhibitors showed that all agents effectively inhibit paracetamol-induced lipid peroxidation. It is concluded that phase I metabolism of paracetamol is a prerequisite for the manifestation of drug-induced lipid peroxidation.Selenium deficiency in mice neither affected hepatic levels of glutathione nor its decrease following sucrose feeding, nor glutathione transferase, superoxide dismutase, catalase and glutathione reductase activity. Selenium-dependent glutathione peroxidase activity of selenium-deficient mice, reactive with H₂O₂ as well as with t-butylhydroperoxide, decreased to 5 per cent of the supplemented controls. A glutathione peroxidase activity, which utilized cumenehydroperoxide as a substrate but insensitive to selenium deficiency, was found. Selenium-deficient diethylmaleate-pretreated animals were much more susceptible to paracetamol-induced lipid peroxidation than controls. Supplemented diethylmaleate-pretreated animals showed no signs of lipid peroxidation if treated with 100 mg/kg aminopyrine or ethylmorphine. However, deficient animals exhibited high ethane exhalation rates, drastically increased serum transaminases, loss of hepatic glutathione and mortality upon administration of these drugs. Qualitatively similar results with lower ethane exhalation rates were observed when 125 mg/kg furosemide was administered to diethylmaleate-pretreated selenium-deficient or -adequate mice. Even administration of 200 mg/kg ethoxycoumarin in combination with diethylmaleate lead to significant lipid peroxidation in phenobarbital-induced mice.The results demonstrate that in vivo selenium-dependent glutathione peroxidase plays a predominant role within the glutathione redox couple system. The enzyme protects the liver from peroxidative damage evoked by phase I metabolism of various drug types, as long as sufficient glutathione is available. It is suggested that activated oxygen released from the microsomal monooxygenase is the species responsible for the observed lipid peroxidation accompanied by severe acute liver lesions.     

Intestinal glutathione: determinant of mucosal peroxide transport, metabolism, and oxidative susceptibility

The intestine is a primary site of nutrient absorption and a critical defense barrier against dietary-derived mutagens, carcinogens, and oxidants. Accumulation of oxidants like peroxidized lipids in the gut lumen can contribute to impairment of mucosal metabolic pathways, enterocyte dysfunction independent of cell injury, and development of gut pathologies, such as inflammation and cancer. Despite this recognition, we know little of the pathways of intestinal transport, metabolism, and luminal disposition of dietary peroxides in vivo or of the underlying mechanisms of lipid peroxide-induced genesis of intestinal disease processes. This chapter summarizes our current understanding of the determinants of intestinal absorption and metabolism of peroxidized lipids. I will review experimental evidence from our laboratory and others (Table 1) supporting the pivotal role that glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) play in mucosal transport and metabolism of lipid hydroperoxides and how reductant availability can be compromised under chronic stress such as hypoxia, and the influence of GSH on oxidative susceptibility, and redox contribution to genesis of gut disorders. The discussion is pertinent to understanding dietary lipid peroxides and GSH redox balance in intestinal physiology and pathophysiology and the significance of luminal GSH in preserving the integrity of the intestinal epithelium.     

Extension of the blood half-life of glyceryl trinitrate. Inhibition of glutathione organic nitrate ester reductase activity in the rat and guinea pig

Cephalothin, penicillin G and probenecid inhibited GSH organic nitrate ester reductase (ONER) and several other enzymatic activities of GSH-S-transferases (EC 2.5.1.18) from rat and guinea pig liver. Erythrityl tetranitrate, a substrate for ONER, inhibited the aryl and alkyl transferase activities of two guinea pig liver GSH-S-transferases. These findings support the concept that ONER is one of the several activities possessed by the GSH-S-transferases. In an examination of possible in vivo action, parenteral administration of these inhibitors 2–30 min prior to i.v. administration of [¹⁴C]glyceryl trinitrate resulted in a 50–100 per cent increase in the half-time of the metabolism phase of [¹⁴C]glyceryl trinitrate clearance from the blood and postponed the appearance of metabolites. This presumably occurs through the in vivo inhibition of GSH-ONER activity of the GSH-S-transferases and suggests a possible means of prolonging the pharmacologie action of nitrate esters.     

The role of oxidative stress in zearalenone-mediated toxicity in Hep G2 cells: oxidative DNA damage, gluthatione depletion and stress proteins induction

Zearalenone (ZEN) is a fusarial mycotoxin with several adverse effects in laboratory and domestic animals including mainly estrogenicity. While most ZEN toxic effects have been quite well investigated, little is known regarding its mechanism of toxicity. Our previous investigations have shown the involvement of cytotoxicity, inhibition of macromolecules synthesis as well as genotoxicity. However, there are no available data regarding the involvement of the oxidative stress pathway in ZEN toxicity. In this context, the aim of this study was to find out whether ZEN induces oxidative cell damage. Using human hepatocytes Hep G2 cells, ZEN-induced stress response is monitored at several levels in these cells. ZEN mediated induction of oxidative DNA damage (comet assay using the repair enzymes), modulation of gluthatione (GSH), cytotoxicity (growth inhibition) and the oxidative stress responsive gene Hsp 70 and Hsp 90 were investigated with respect to concentration and time dependency. Hep G2 cells respond to ZEN exposure by loss of cell viability, induction of oxidative DNA damage, GSH depletion and Hsp 70 and Hsp 90 induction already at concentrations, which are not yet cytotoxic. The perturbation of the oxidative status was further confirmed by the significant reduction of the induced oxidative DNA damage as well as stress protein induction when cells were pre-treated with Vitamin E prior to exposure to ZEN. Our study clearly demonstrates that oxidative damage is likely to be evoked as one of the main pathway of ZEN toxicity. This oxidative damage may therefore be an initiating event and contribute, at least in part, to the mechanism of ZEN different genotoxic and cytotoxic effects.     

Ameliorating effect of curcumin on sodium arsenite-induced oxidative damage and lipid peroxidation in different rat organs

The present study was conducted to investigate the antioxidative effect of curcumin against sodium arsenite-induced oxidative damage in rat. Animals were divided into four groups, the first group was used as control. Groups 2, 3 and 4 were orally treated with curcumin (15 mg/kg BW), sodium arsenite (Sa, 5 mg/kg BW) and sodium arsenite plus curcumin, respectively. Rats were orally administered their respective doses daily for 30 days. Results showed that Sa increased thiobarbituric acid-reactive substances (TBARS) in plasma, liver, kidney, lung, testes and brain. While, the activities of glutathione S-transferase, superoxide dismutase and catalase and the content of sulfhydryl groups (SH-groups) were significantly decreased in plasma and tissues compared to control. Treatment with curcumin alone reduced the levels of TBARS, while induced the activities of the antioxidant enzymes, and the levels of SH-groups. The presence of curcumin with Sa reduced the induction in the levels of TBARS and induced the decrease in the activities of antioxidant enzymes and the levels of SH-groups. Results indicated that treatment with Sa decreased body weight and increased liver weight compared to control. The presence of curcumin with Sa alleviated its toxic effects. It can be concluded that curcumin has beneficial influences and could be able to antagonize Sa toxicity.     

Effect of nitroheterocyclic drugs on lipid peroxidation and glutathione content in rat liver extracts

Incubation of rat liver cell-free extracts with an NADPH-generating system and with nifurtimox or benznidazole (two nitroheterocyclic drugs used in the treatment of Chagas' disease) produced oxidation of reduced glutathione (GSH) and increased lipid peroxidation, as shown by the generation of thiobarbituric-acid-reacting intermediates. Nifurtimox and benznidazole inhibited GSSG-reductase, but not GSH-peroxidase, the former inhibition contributing to GSH depletion. In every case, nifurtimox was more effective than benznidazole. Addition of GSH or free-radical scavengers (catalase, superoxide dismutase, mannitol, sodium benzoate or L-histidine) prevented the effect of nifurtimox on lipid peroxidation reactions. These results support the assumption [M. Dubin, S. N. J. Moreno, E. E. Martino, R. Docampo and A. O. M. Dubin, Biochem. Pharmac.32, 483 (1983)] that, in the rat liver, GSH exerts a protective action against oxygen radicals generated by the nitroheterocyclic drugs.     

Phloroglucinol: Antioxidant properties and effects on cellular oxidative markers in human HepG2 cell line

Phloroglucinol is an ubiquitous secondary metabolite encountered in a free state or polymerised as phlorotannins in brown macroalgae, and present in higher plants. FRAP and TEAC assays measured the antioxidant properties of phloroglucinol in non-biological conditions. Additionally, the biological effects of phloroglucinol (4–400 μM) were scrutinised using cellular oxidative stress markers, such as the generation of ROS, antioxidant defences (concentration of GSH and activities of GPx, GR and GST), and levels of MDA as a marker for lipid peroxidation. The direct effect was assessed immediately after an incubation period, whereas for the protective effect, the incubation period was followed by 3-h treatment with the pro-oxidant t-BOOH. The results indicated that despite having a higher radical scavenging capacity than Trolox after 30 min, phloroglucinol was not a suitable antioxidant standard for phlorotannins. Regarding the biological effects, phloroglucinol had no impact on cell viability, reduced levels of ROS and increased antioxidant defences in the direct treatment for most concentrations. The results of the protective effect were mitigated as phloroglucinol failed to protect from ROS generation but evoked a significant recovery of the stress-altered cellular antioxidant defences to restful conditions. Additionally, MDA levels were greatly reduced, preventing a radical chain oxidation.     

Effects of polysaccharide peptides from COV-1 strain of Coriolus versicolor on glutathione and glutathione-related enzymes in the mouse.

The effects of polysaccharide peptide (PSP), an immunomodulator isolated from Coriolus versicolor COV-1, on glutathione (GSH) and GSH-related enzymes was investigated in C57 mouse. Administration of PSP (1-4 micromole/kg, i.p.) produced a transient, dose-dependent depletion (10-37%) of hepatic GSH, with no effect on serum glutamic-pyruvic transaminase (SGPT) activity. Blood GSH was depleted (6-25%) at 3 h, followed by a rebound increase above the control GSH level (20%) at 18 h. The GSSG/GSH ratio, a measure of oxidative stress, was increased 3 h after PSP treatment but returned to normal levels at 24 h. Sub-chronic treatment of PSP (1-4 micromole/kg/day, i.p.) for seven days did not produce any significant changes in hepatic GSH levels and the GSSG/GSH ratio when measured 24 h after the final dose of PSP. PSP had little effect on glutathione transferase (GST), glutathione reductase (GSSG reductase) and glutathione peroxidase (GPX) activities in the liver. However, a dose-dependent increase in blood GPX activity (30-48%) was observed at 3h, which coincided with the increase in the GSSG/GSH ratio. The increase in blood GPX activity may be a responsive measure to deal with the transient oxidative stress induced by PSP treatment. The results showed that PSP only caused a transient perturbation on hepatic glutathione without affecting the GSH-related enzymes such as GST, GSSG reductase and GPX. The observed changes in blood GSH simply reflected the intra-organ translocation of glutathione, as the glutathione-related enzymes were not significantly affected by PSP treatment.     

Immortalized hepatocytes as in vitro model systems for toxicity testing: the comparative toxicity of menadione in immortalized cells, primary cultures of hepatocytes and HTC hepatoma cells

Immortalized differentiated liver cell lines capable of continuous proliferation, and expressing stable liver-specific functions, would be valuable for in vitro toxicity testing in the pharmaceutical, chemical, food and cosmetics industries. Immortalized rat hepatocyte cell lines have been produced by transfection of SV40 DNA by electroporation or calcium phosphate precipitation. Their utility has been assessed by studying the toxicity of a model compound, menadione, and by measuring the activities of DT-diaphorase and NADPH cytochrome c reductase. Enzyme activities and toxicity were compared in freshly isolated hepatocytes, the immortalized cell lines and dedifferentiated HTC hepatoma cells. In HTC cells DT-diaphorase activity was 100-fold elevated compared with freshly isolated hepatocytes. In only one cell line, C2.1.2. (produced by calcium phosphate precipitation), was DT-diaphorase activity increased (twofold) compared with freshly isolated hepatocytes. Menadione caused loss of viability at similar concentrations (40–80 μ ) in the immortalized cell lines and 24-hr primary cultures of hepatocytes, whereas HTC cells showed loss of viability only with menadione concentrations above 200 μ . The immortalized lines therefore appear to have potential for predicting toxicity and for menadione this can be correlated with the expression of DT-diaphorase.     

Effect of taurine supplementation on cytochrome P450 2E1 and oxidative stress in the liver and kidneys of rats with streptozotocin-induced diabetes

To investigate whether diabetes-induced alterations of CYP2E1 and oxidative stress can be modulated by dietary taurine supplementation, male Wistar rats were divided into non-diabetic, diabetic, and diabetic taurine-supplemented groups (administered at 2% in the drinking water). Increased levels of CYP2E1-catalyzed p-nitrophenol hydroxylation were found in liver and kidney microsomes of rats with STZ-induced diabetes compared to those of non-diabetic control rats. Immunoblot and RT-PCR analyses of CYP2E1 protein and mRNA levels in the liver and kidneys showed the same trend as with enzyme activities. Taurine supplementation significantly decreased the enzyme activity and expression (protein and mRNA) of CYP2E1 in diabetic rat kidneys. Plasma β-hydroxybutyrate concentration was significantly reduced in taurine-treated diabetic rats. The induction of heme oxygenase-1 mRNA was suppressed by taurine treatment in diabetic rat kidneys. An increase in reduced glutathione (GSH) and a higher ratio of reduced to oxidized glutathione (GSH/GSSG) together with lower values of thiobarbituric acid-reactive substances (TBARS) were observed in the kidneys of taurine-treated diabetic rats. However, taurine supplementation caused only a slight or insignificant effect on these alternations in the liver of diabetic rats. Our results show dietary taurine may reduce CYP2E1 expression and activity, and oxidative stress in kidneys of diabetic rats.     

Evaluation of the potential protective effects of ad libitum black grape juice against liver oxidative damage in whole-body acute X-irradiated rats

Aims

The aim of this study was to evaluate the potential protective effects of ad libitum black grape (Vitis labrusca) juice against liver oxidative damage in whole-body acute X-irradiated rats.

Main methods

Animals were fed ad libitum and drank voluntarily black grape juice or placebo (isocaloric glucose and fructose solution) for 6 days before and 15 days following a 6 Gy X-irradiation from a 200 kV machine.

Key findings

Irradiated animals receiving placebo showed a significant increase in the concentration of thiobarbituric acid-reactive substances (TBARS), a marker of lipid peroxidation, as well as a significant decrease in both Cu/Zn superoxide dismutase (Cu/ZnSOD) and glutathione peroxidase (GPx) activity and reduced glutathione concentration (GSH). Black grape juice supplementation resulted in a reversal of lipid peroxidation, Cu/ZnSOD activity, and GSH concentration, towards values not significantly differing from those in non-irradiated, placebo-supplemented rats. Poly(ADP-ribose) polymerase (PARP-1) and Cu/ZnSOD changes in protein expression were observed for irradiated rats. No change in p53 expression or DNA fragmentation was found.

Significance

Ad libitum black grape juice intake is able to restore the liver primary antioxidant system against adverse effects due to whole-body acute X-irradiation in rats after 15 days post-irradiation. The results support using antioxidant supplements as a preventive tool against radiation-induced harm.     

Effect of sweet grass extract against oxidative stress in rat liver and serum

Ethanol metabolism is accompanied by generation of free radicals which can damage the cell components. However, sweet grass is a source of coumarin and its derivatives have emerged as a promising group of antioxidant compounds. The aim of this study has been to investigate the influence of sweet grass on oxidative stress formation in the liver and serum of rats intoxicated with ethanol. Alcohol intoxication led to a decrease in the superoxide dismutase, catalase, glutathione peroxidase and reductase activity in the blood serum as well as in the liver, but not in the glutathione reductase activity. The decrease in the antioxidant abilities of the examined tissues after ethanol intoxication resulted in enhanced lipid peroxidation measured as malondialdehyde and 4-hydroxynonenal levels. The metabolic consequence of oxidative modifications of lipids was damage of the liver cells membrane and an increase in its permeability appeared as a leakage of alanine aminotransferase and aspartate aminotransferase into the blood. Administration of sweet grass to the ethanol-intoxicated rats remarkably prevented the significant increase in concentrations of all measured lipid peroxidation products as well as the damage of the liver cell membrane. These results indicate beneficial antioxidant effect of the sweet grass on the liver of rats intoxicated with ethanol.