Parameters of dietary selenium and vitamin E deficiency in growing rabbits.

4 x 5 growing female rabbits (New Zealand White) with an initial live weight of 610 +/- 62 g were fed a torula yeast based semisynthetic diet low in selenium (<0.03 mg/kg diet) and containing <2 mg alpha-tocopherol per kg (group I). Group II received a vitamin E supplementation of 150 mg alpha-tocopherylacetate per kg diet, whereas for group III 0.40 mg Se as Na-selenite and for group IV both supplements were added. Selenium status and parameters of tissue damage were analyzed after 10 weeks on experiment (live weight 2,355 +/- 145 g). Selenium depletion of the Se deficient rabbits (groups I and II) was indicated by a significantly lower plasma Se content (group I: 38.3 +/- 6.23 microg Se/mL plasma, group II: 42.6 +/- 9.77, group III: 149 +/- 33.4, group IV: 126 +/- 6.45) and a significantly lower liver Se content (group I: 89.4 +/- 18.2 microg/kg fresh matter, group II: 111 +/- 26.2) as compared to the Se supplemented groups III (983 +/- 204) and IV (926 +/- 73.9). After 5 weeks on the experimental diets differences in the development of plasma glutathione peroxidase were observed. As compared to the initial status group (45.2 +/- 4.50) pGPx activity in mU/mg protein was decreased in group I (19.1 +/- 7.08), remained almost stable in the vitamin E supplemented group II (46.3 +/- 11.2) whereas an elevated enzyme activity was measured in the Se supplemented groups III (62.4 +/- 23.9) and IV (106 +/- 19.9). In the rabbit organs investigated 10 weeks of Se deficiency caused a significant loss of Se dependent cellular glutathione peroxidase activity (GPx1) of 94% (liver), 80% (kidney), 50% (heart muscle) and 60% (musculus longissimus dorsi) in comparison to Se supplemented control animals. Damage of cellular lipids and proteins in the liver was due to either Se or vitamin E deficiency. However damage was most severe under conditions of a combined Se and vitamin E deficiency. It can be concluded that the activity of plasma glutathione peroxidase is a sensitive indicator of Se deficiency in rabbits. The loss of GPx1 activity indicates the selenium depletion in various rabbit organs. Both selenium and vitamin E are essential and highly efficient antioxidants which protect rabbits against lipid and protein oxidation.     

Effects of dietary vitamin E and selenium on antioxidative defense mechanisms in the liver of rats treated with high doses of glucocorticoid

The aim of this work was to determine the effects of dietary intake vitamin E and selenium (Se) on lipid peroxidation as thiobarbituric acid reactive substances (TBARS) and on the antioxidative defense mechanisms in the liver of rats treated with high doses of prednisolone. Two hundred fifty adult male Wistar rats were randomly divided into five groups. The rats were fed a normal diet, but groups 3, 4, and 5 received a daily supplement in their drinking water of 20 mg vitamin E, 0.3 mg Se, and a combination of vitamin E and Se, respectively, for 30 d. For 3 d subsequently, the control group (group 1) was treated with a placebo, and the remaining four groups were injected intramuscularly with 100 mg/kg body weight (BW) prednisolone. After the last administration of prednisolone, 10 rats from each group were killed at 4, 8, 12, 24, and 48 h and the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) enzymes and the levels of glutathione (GSH) and TBARS in their livers were measured. GSH-Px, SOD, and CAT enzyme activities and GSH levels in prednisolone-treatment group (group 2) began to decrease gradually at 4 h, falling respectively to 38%, 55%, and 40% of the control levels by 24 h, and recovering to the control levels at 48 h. In contrast, prednisolone administration caused an increase in the hepatic TBARS, reaching up to four times the levels of the control at 24 h. However, supplementation with vitamin E and Se had a preventive effect on the elevation of the hepatic TBARS and improved the diminished activities of the antioxidative enzymes and the levels of GSH. Therefore, the present study demonstrates the effectiveness of vitamin E and Se in reducing hepatic damage in glucocorticoid-treated rats and suggests that reductions in increased TBARS as a result of prednisolone may be an important factor in the action of vitamin E and Se.     

Impact of Hemidesmus indicus R.Br. extract on ethanol-mediated oxidative damage in rat kidney

The antioxidant effect of the ethanolic extract of Hemidesmus indicus R.Br. root (EHI), an indigenous Ayurvedic medicinal plant in India, was studied in rats with ethanol-induced nephrotoxicity. Administering 5 g/kg body weight/day of ethanol for 60 days to male Wistar rats resulted in significantly elevated levels of serum urea, creatinine and uric acid as well as kidney thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH) and conjugated dienes (CD) as compared to those of the experimental control rats. Decreased levels of kidney superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin C and vitamin E were also observed on alcohol administration as compared with those of the experimental control rats. EHI was administered at a dose of 500 mg/kg body weight/day for the last 30 days of the experiment to rats with ethanol-induced kidney injury, which significantly decreased the levels of serum urea, uric acid and creatinine as well as kidney TBARS, LOOH and CD and significantly elevated the activities of SOD, CAT, GPx, GSH, vitamin C and vitamin E in kidney as compared to that of untreated ethanol-administered rats. Histopathological observations also correlated with the biochemical parameters. Thus, the data indicate that treatment with EHI offers protection against free radical-mediated oxidative stress in kidney of animals with ethanol-induced nephrotoxicity.     

Enhanced testicular antioxidant capacity in streptozotocin-induced diabetic rats: protective role of vitamins C and E and selenium

Diabetes mellitus is associated with diabetic impairment of testicular function, ultimately leading to reduced fertility. Its etiology may involve oxidative damage by reactive oxygen substances, and protection against this damage can be offered by antioxidant supplementation. The aim of this study was to investigate the effects of intraperitoneal administration of vitamin C and E, selenium (Se), and vitamin E plus Se (COM) on concentrations of lipid peroxide (as malondialdehyde; MDA), reduced glutathione (GSH), and vitamin E concentrations and glutathione peroxidase (GSH-Px) activity in the testes of rats with diabetes induced by streptozotocin (STZ). Sixty groups were used (10 animals each) and these animals were initially allocated to two groups: control group and diabetic group. The diabetic group was subdivided into five groups as follows: diabetic control (DC), vitamin E, Se, COM, and vitamin C. Animals in the DC group and vitamin C, vitamin E, Se, and COM groups were made diabetic by the injection of STZ on 4 d after an injection of vitamins C and E, Se, and COM. Those vitamins and Se were also administered for 21 consecutive days. The MDA, vitamin E, GSH levels, and GSH-Px activities in testes were determined. Although the vitamin E concentration was higher in the control than in the DC group, the MDA levels were found to be lower in the control than in the DC group. The MDA levels in the testes samples of vitamin C, vitamin E, Se, and COM groups were lower than the DC group. However, GSH-Px activity and GSH levels in the testes were not significantly different between the control and DC groups. Vitamin E concentrations in the vitamin C, vitamin E, Se, and COM groups and GSH levels and GSH-Px activities in the Se, COM, and vitamin C groups were higher than either the control or DC group. The results indicate that reactive oxygen substances may be involved in possible testicular complications in diabetes of rats. Administration of vitamins C and E and Se reduced the testicular lipid peroxidation; these vitamins and Se had significant protective effects on testes of rats against oxidative damage in diabetes.     

Protective role of intraperitoneally administered vitamin E and selenium on the antioxidative defense mechanisms in rats with diabetes induced by streptozotocin

The aim of this work was to determine the protective effects of intraperitoneally administered vitamin E and selenium (as Na₂SeO₃, Se) on the lipid peroxidation as thiobarbituric acid reactive substances (TBARS) and vitamin E levels, glutathione peroxidase (GSH-Px), reduced glutathione (GSH) activities in the plasma, red blood cell (RBC), liver, and muscle of rats with streptozotocin-induced diabetes. Fifty adult male Wistar rats were used and all rats were randomly divided into five groups. The first group was used as a control and the second group as a diabetic control. A placebo was given to first and second groups by injection. The third group was intraperitoneally administered with vitamin E (20 mg over 24 h), the fourth group with Se (0.3 mg over 24 h), and the fifth group with vitamin E and Se combination (COM) (20 mg vitamin E + 0.3 mg Se over 24 h). This administration was done for 25 days and the TBARS, vitamin E, GSH-Px, GSH levels in the plasma, RBC, liver, and muscle samples were determined. The vitamin E level in the plasma and liver was significantly (p < 0.05) higher in the control than in the diabetic control group. Also, the TBARS levels in the RBC, liver, and muscle were significantly (p < 0.05) lower in the control than in the diabetic control group. However, GSH-Px and GSH activities in RBC, liver, and muscle were not statistically different between the control and the diabetic control groups. The vitamin E levels in plasma and liver (p < 0.01 and p < 0.001) and GSH-Px activities (p < 0.01, p < 0.001) in RBC were significantly higher in vitamin E, Se, and COM groups than in both control and diabetic control groups. However, the TBARS levels of RBC, muscle, and liver in vitamin E and Se administered groups were significantly (p < 0.05-p < 0.001, respectively) decreased. These results indicate that intraperitoneally administered vitamin E and Se have significant protective effects on the blood, liver, and muscle against oxidative damage of diabetes. The abstract of this study was presented in Physiological Research 48(Suppl. 1), S99 (1999).     

Impact of Hemidesmus indicus R.Br. extract on ethanol-mediated oxidative damage in rat kidney

Abstract

The antioxidant effect of the ethanolic extract of Hemidesmus indicus R.Br. root (EHI), an indigenous Ayurvedic medicinal plant in India, was studied in rats with ethanol-induced nephrotoxicity. Administering 5 g/kg body weight/day of ethanol for 60 days to male Wistar rats resulted in significantly elevated levels of serum urea, creatinine and uric acid as well as kidney thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH) and conjugated dienes (CD) as compared to those of the experimental control rats. Decreased levels of kidney superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin C and vitamin E were also observed on alcohol administration as compared with those of the experimental control rats. EHI was administered at a dose of 500 mg/kg body weight/day for the last 30 days of the experiment to rats with ethanol-induced kidney injury, which significantly decreased the levels of serum urea, uric acid and creatinine as well as kidney TBARS, LOOH and CD and significantly elevated the activities of SOD, CAT, GPx, GSH, vitamin C and vitamin E in kidney as compared to that of untreated ethanol-administered rats. Histopathological observations also correlated with the biochemical parameters. Thus, the data indicate that treatment with EHI offers protection against free radical-mediated oxidative stress in kidney of animals with ethanol-induced nephtrotoxicity.     

Enhanced testicular antioxidant capacity in streptozotocin-induced diabetic rats

Diabetes mellitus is associated with diabetic impairment of testicular function, ultimately leading to reduced fertility. Its etiology may involve oxidative damage by reactive oxygen substances, and protection against this damage can be offered by antioxidant supplementation. The aim of this study was to investigate the effects of intraperitoneal administration of vitamin C and E, selenium (Se), and vitamin E plus Se (COM) on concentrations of lipid peroxide (as malondialdehyde; MDA), reduced glutathione (GSH), and vitamin E concentrations and glutathione peroxidase (GSH-Px) activity in the testes of rats with diabetes induced by streptozotocin (STZ). Sixty groups were used (10 animals each) and these animals were initially allocated to two groups: control group and diabetic group. The diabetic group was subdivided into five groups as follows: diabetic control (DC), vitamin E, Se, COM, and vitamin C. Animals in the DC group and vitamin C, vitamin E, Se, and COM groups were made diabetic by the injection of STZ on 4 d after an injection of vitamins C and E, Se, and COM. Those vitamins and Se were also administered for 21 consecutive days. The MDA, vitamin E, GSH levels, and GSH-Px activities in testes were determined. Although the vitamin E concentration was higher in the control than in the DC group, the MDA levels were found to be lower in the control than in the DC group. The MDA levels in the testes samples of vitamin C, vitamin E, Se, and COM groups were lower than the DC group. However, GSH-Px activity and GSH levels in the testes were not significantly different between the control and DC groups. Vitamin E concentrations in the vitamin C, vitamin E, Se, and COM groups and GSH levels and GSH-Px activities in the Se, COM, and vitamin C groups were higher than either the control or DC group. The results indicate that reactive oxygen substances may be involved in possible testicular complications in diabetes of rats. Administration of vitamins C and E and Se reduced the testicular lipid peroxidation; these vitamins and Se had significant protective effects on testes of rats against oxidative damage in diabetes. Abstract of the study was presented at the conference Trace Elements in Men and Animals-11. June 2–6, 2002; Dr. Naziroğlu has been awarded a TEMA11 Investigative Scientist Award.     

Effects of additional vitamin E and selenium supply on antioxidative defence mechanisms in the kidney of rats treated with high doses of glucocorticoid

The aim of this work was to determine the effects of dietary vitamin E and selenium (Se) on lipid peroxidation as thiobarbituric acid reactive substances (TBARS) and on the antioxidative defence mechanisms in the kidney of rats treated with high-doses of prednisolone. Two hundred and fifty adult male Wistar rats were randomly divided into five groups. The rats were fed a normal diet, but groups 3, 4, and 5 received a daily supplement in their drinking water of 20 mg vitamin E, 0.3 mg Se, and a combination of vitamin E and Se, respectively, for 30 days. For 3 days subsequently, the control group (group 1) was treated with a placebo, and the remaining four groups were injected intramuscularly with 100 mg kg(-1) body weight (bw) prednisolone. After the last administration of prednisolone, 10 rats from each group were killed at 4, 8, 12, 24, and 48 h and the activities of glutathione peroxidase (GSH-Px) and catalase (CAT) enzymes, and the levels of glutathione (GSH) and TBARS in their kidneys were measured. GSH-Px and CAT enzyme activities and GSH levels in the prednisolone treatment group (group 2) began to decrease gradually at 4 h, falling respectively to 48 and 65% of the control levels by 24 h, and recovering to the control levels at 48 h. In contrast, prednisolone administration caused an increase in TBARS in the kidneys, reaching up to twice the levels of the control group at 24 h. However, supplementation with vitamin E and Se had a preventive effect on the elevation of kidney TBARS and improved the diminished activities of the antioxidative enzymes and the levels of GSH. Therefore, the present study demonstrates the effectiveness of vitamin E and Se in reducing kidney damage in glucocorticoid-treated rats and suggests that reductions in increased TBARS due to prednisolone may be an important factor in the action of vitamin E and Se.     

Effect of increasing selenite concentrations, vitamin E supplementation and different fetal calf serum content on GPx1 activity in primary cultured rabbit hepatocytes

Primary rabbit hepatocytes from 6 week old female New Zealand White rabbits (3.0 x 10(6) viable hepatocytes per treatment) were incubated for 24 h or 48 h with two basic variants of the selenium and vitamin E free DMEM/F12-HAM nutrition medium containing 2.5% or 10% fetal calf serum (FCS). Selenium and vitamin E concentrations of the media were varied by the addition of 0, 10, 50 and 100 ng Se/mL medium as sodium selenite and 100 microg alpha-tocopheryl acetate/mL. Lactic dehydrogenase (LDH) leakage of the hepatocytes was not influenced by the various selenium concentrations of the media, whereas vitamin E addition significantly inhibited LDH release. The activity of cellular glutathione peroxidase (GPx1) was markedly induced by increasing the selenium supplementation of the culture media. Vitamin E supply further enhanced GPx1 induction. In hepatocytes cultivated at the lower serum concentration (2.5% FCS), increasing the selenite concentration of the media raised GPx1 and reduced the intracellular levels of the reduced tripeptide glutathione (GSH). No vectored relation between the selenium concentration of the media and the activity of superoxide dismutase (SOD) could be observed. After both incubation periods (24 h and 48 h) SOD activity was significantly higher in the cytosol of hepatocytes grown in media containing 10% FCS as compared to cells incubated at the 2.5% FCS level. Furthermore, SOD activity was reduced by the addition of vitamin E to the media. In conclusion the results indicate an effective metabolism of rabbit hepatocytes for selenite even in amounts as low as nanograms. A general cytoprotective role for vitamin E can be shown by its ability to decrease LDH leakage and by the reduction of SOD activity.     

Oxidative stress and enzymic-non-enzymic antioxidant responses in children with acute pneumonia

In this article, oxidative stress and enzymic-non-enzymic antioxidants status were investigated in children with acute pneumonia. Our study included 28 children with acute pneumonia and 29 control subjects. The age ranged from 2 to 11 years (4.57+/-2.13 years) and 2 to 12 years (4.89+/-2.22 years) in the study and control groups, respectively. Whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum beta-carotene, retinol, vitamin C, vitamin E, catalase (CAT), ceruloplasmin (CLP), total bilirubin, erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were studied in all subjects. There was a statistically significant difference between the groups for all parameters except for serum CAT. Whole blood MDA, serum CLP and total bilirubin levels were higher in the study group than those of the control group. However, SOD, GPx, beta-carotene, retinol, vitamin C, vitamin E and GSH levels were lower in the study group compared with the control group. All antioxidant vitamin activities were decreased in children with acute pneumonia. Our study demonstrated that oxidative stress was increased whereas enzymic and non-enzymic antioxidant activities were significantly decreased in children with acute pneumonia.     

The chemopreventive effect of Ginkgo biloba and Silybum marianum extracts on hepatocarcinogenesis in rats

Background/objective

This study was designed to evaluate the potential chemopreventive activities of Ginkgo biloba extract (EGb) and Silybum marianum extract (silymarin) against hepatocarcinogenesis induced by N-nitrosodiethylamine (NDEA) in rats.

Methods

Rats were divided into 6 groups. Group 1 served as normal control rats. Group 2 animals were intragastrically administrated NDEA at a dose of 10 mg/kg five times a week for 12 weeks to induce hepatocellular carcinoma (HCC). Groups 3 and 4 animals were pretreated with silymarin and EGb respectively. Groups 5 and 6 animals were posttreated with silymarin and EGb respectively. The investigated parameters in serum are alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT) and vascular endothelial growth factor (VEGF). The investigated parameters in liver tissue are malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and comet assay parameters.

Results

In NDEA group, MDA level was elevated with subsequent decrease in GSH level and SOD, GPx and GR activities. In addition, NDEA group revealed a significant increase in serum ALT, AST and GGT activities and VEGF level. Furthermore, NDEA administrated animals showed a marked increase in comet assay parameters. These biochemical alterations induced by NDEA were confirmed by the histopathological examination of rat livers intoxicated with NDEA that showed an obvious cellular damage and well differentiated HCC. In contrast, silymarin+NDEA treated groups (3&;5) and EGb+NDEA treated groups (4&;6) showed a significant decrease in MDA level and a significant increase in GSH content and SOD, GPx and GR activities compared to NDEA group. Silymarin and EGb also beneficially down-regulated the increase in serum ALT, AST, GGT activities and VEGF level induced by NDEA. In addition, silymarin and EGb significantly decreased comet assay parameters. Histopathological examination of rat livers treated with either silymarin or EGb exhibited an improvement in the liver architecture compared to NDEA group.

Conclusions

The obtained findings suggested that silymarin and EGb may have beneficial chemopreventive roles against hepatocarcinogenesis through their antioxidant, antiangiogenic and antigenotoxic activities.     

Age-related changes in the glutathione redox system

The effect of aging on the glutathione redox system was evaluated in this study. For this purpose, we determined reduced glutathione (GSH) and oxidized glutathione (GSSG) in whole blood, glutathione peroxidase (GPx) and glutathione reductase (GSSGR) in erythrocytes and selenium (Se) in plasma in 176 healthy individuals. We also calculated GSH/GSSG molar ratios. These subjects were divided into five groups: group 1 (n=25; 0.2-1 years old); group 2 (n=28; 2-11 years old); group 3 (n=23; 12-24 years old); group 4 (n=40; 25-40 years old); group 5 (n=60; 41-69 years old). GSH levels in groups 1 and 5 were significantly lower than the other groups (p<0.001). Conversely, GSSG levels were significantly high in these periods (p<0.001). The GSH/GSSG molar ratio was found to be low both in the first year of life and in the oldest group (p<0.001, respectively). GPx activity in group 5 was increased as compared to the other groups (p<0.001). GSSGR activity was significantly lower in the oldest groups than in the other groups (p<0.001). Se levels were found to be low in the oldest group (p<0.001). Selenium levels of women in group 5 were significantly high as compared to the men (p<0.01). We found negative correlations between age and GSH levels (r=0.402; p<0.001), selenium levels (r=0.454; p<0.001), GSH/GSSG molar ratio (r=0.557; p<0.001) and GSSGR activity (r=0.556; p<0.001). There were positive correlations between age and GPx (r=0.538; p<0.001) and GSSG level (r=0.551; p<0.001). In conclusion, our findings show that the glutathione redox system is affected by age. Oxidative stress increases during the aging process. There is no effect of aging on the glutathione redox system according to sex except for the Se level.     

Protective effects of ascorbic acid, dl-alpha-tocopherol acetate, and sodium selenate on ethanol-induced liver damage of rats

In this study, the effect of a combination of vitamin C (ascorbic acid), vitamin E (dl-alpha-tocopherol acetate), and selenium (sodium selenate) on ethanol-induced liver damage in rats was investigated, morphologically and biochemically. The ethanol-induced injury was produced by the administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and selenium (0.5 mg/kg) (ViCESe) for 3 d 1 h prior to the administration of absolute ethanol. In the liver of the animals given ethanol, the degenerative changes such as extreme hyperemia, vacuolization in cells of portal areas, a dilation in sinusoids, mononuclear cell infiltration, a swelling in cisternae of granular endoplasmic reticulum and in mitochondrial cristae, an increase in smooth endoplasmic reticulum, many lipid vacuoles were observed both light and electron microscopically. A similar structure was usually distinguished when compared with control animals, in rats given ethanol + ViCESe. In this group, the findings indicating cellular damage were either not observed at all or were decreased. In the group administered ethanol, a reduction of the blood glutathione (GSH) level and increases in serum values of alanine aminotranserase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) activities were observed, whereas in the control group, the reverse was found to occur. On the other hand, in the group in which ethanol + ViCESe was administered, it was observed that the blood GSH value and serum ALP and ALT activities increased and serum AST, LDH, and GGT activities decreased. As a result, the present study indicates that ViCESe because of their antioxidant activity against ethanol damage have a protective effect on the liver.     

The effects of isosorbide dinitrate on methemoglobin reductase enzyme activity and antioxidant states

Isosorbide dinitrate (ISDN) has been used in the treatment of ischaemic cardiovascular diseases for many years. ISDN is the most popular nitric oxide donor and causes methemoglobinemia as an important side-effect. The purpose of this study was to examine antioxidant states and methemoglobin reductase activity after giving ISDN and ISDN plus vitamin E. Rats were divided into three groups according to the treatment: control group, ISDN group and ISDN plus vit. E group. We measured reduced glutathione in blood (GSH), plasma malondialdehyde (MDA), erythrocyte superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and NADH-dependent methemoglobin reductase activities. In the ISDN group, plasma MDA levels were significantly high compared to the control and ISDN + vit. E groups (p < 0.001). In the ISDN and ISDN + vit. E groups, blood GSH levels were higher than those of the control group (p < 0.05). Changes of SOD and GPx activities were not significant. In the ISDN and ISDN + vit. E groups the erythrocyte catalase and NADH-dependent methemoglobin reductase activities were significantly higher than that in the control group (p < 0.001). We conclude that oxidant drugs such as ISDN need to be carefully used because of lipid peroxidation and methemoglobinemia. These findings support the notion that vitamine E protects tissues against oxidative stress.     

硒酸精氨酸对小鼠酒精性肝损伤的保护作用

目的探讨硒酸精氨酸对小鼠酒精性肝损伤的保护作用。方法用连续灌服酒精的方法建立小鼠酒精性肝损伤模型。将60只雄性小鼠随机分为四组：对照组,模型组,硒酸精氨酸处理组和二氧化硒处理组。连续灌胃8周后,测定小鼠血清中天冬氨酸氨基转移酶（AST）,丙氨酸转移酶（ALT）,肝匀浆中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）、谷胱甘肽（GSH）的含量。对肝脏切片做HE染色和Masson染色,在光镜下观察肝脏病理学变化。结果硒酸精氨酸能显著降低酒精性肝损伤引起的AST的升高（P〈0．01）,有效保持了肝脏中GPx和SOD的活性（P〈0．01）。病理学观察结果与酶学变化相一致,硒酸精氨酸对肝脏的保护作用明显优于二氧化硒。结论硒酸精氨酸对小鼠酒精性肝损伤具有显著的保护作用,效果也优于二氧化硒。     

Protective effects of ascorbic acid, Dl-α-tocopherol acetate, and sodium selenate on ethanol-induced gastric mucosal injury of rats

In this study, the effect of ascorbic acid (vitamin C), Dl-α-tocopherol acetate (vitamin E), and sodium selenate (selenium) on ethanol-induced gastric mucosal injury in rats was investigated morphologically and biochemically. The gastric mucosal injury was produced by administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and selenium (0.5 mg/kg) for 3 d 1 h prior to the administration of absolute ethanol. In gastric mucosa of rats given ethanol according to control groups, neuronal nitric oxide expression decreased. This immunoreactivity was much lower in the group given ethanol+vitamin C+vitamin E+selenium than the control group and the ethanol-induced group. Scanning electron microscopic evaluation of the ethanol-induced group, when compared to control groups, revealed degenerative changes in gastric mucosa, whereas a good arrangement in surface topography of gastric mucosa in the group given ethanol + vitamin C+vitamin E + selenium was observed. In the group administered ethanol, a reduction of the stomach glutathione (GSH) and serum total protein levels and increases in serum sialic acid, triglycerides, and stomach lipid peroxidation (LPO) levels were observed. Vitamin C+vitamin E+Se administration to alcohol-treated rats significantly increased the serum total protein, triglyceride levels, and stomach GSH levels and significantly lowered the levels of serum sialic acid and stomach LPO compared to untreated alcohol-supplemented rats. As a result of these findings, we can say that the combination of vitamin C, vitamin E, and selenium has a protective effect on ethanol-induced gastric mucosal injury of rats.     

Protective effects of ascorbic acid, dl-α-tocopherol acetate, and sodium selenate on ethanol-induced liver damage of rats

In this study, the effect of a combination of vitamin C (ascorbic acid), vitamin E (dl-α-tocopherol acetate), and selenium (sodium selenate) on ethanol-induced liver damage in rats was investigated, morphologically and biochemically. The ethanol-induced injury was produced by the administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and selenium (0.5 mg/kg) (ViCESe) for 3 d 1 h prior to the administration of absolute ethanol. In the liver of the animals given ethanol, the degenerative changes such as extreme hyperemia, vacuolization in cells of portal areas, a dilation in sinusoids, mononuclear cell infiltration, a swelling in cisternae of granular endoplasmic reticulum and in mitochondrial cristae, an increase in smooth endoplasmic reticulum, many lipid vacuoles were observed both light and electron microscopically. A similar structure was usually distinguished when compared with control animals, in rats given ethanol+ViCESe. In this group, the findings indicating cellular damage were either not observed at all or were decreased. In the group administered ethanol, a reduction of the blood glutathione (GSH) level and increases in serum values of alanine aminotranserase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) activities were observed, whereas in the control group, the reverse was found to occur. On the other hand, in the group in which ethanol+ViCESe was administered, it was observed that the blood GSH value and serum ALP and ALT activities increased and serum AST, LDH, and GGT activities decreased. As a result, the present study indicates that ViCESe because of their antioxidant activity against ethanol damage have a protective effect on the liver.     

Dimethoate Induces Kidney Dysfunction, Disrupts Membrane-Bound ATPases and Confers Cytotoxicity Through DNA Damage. Protective Effects of Vitamin E and Selenium

Dimethoate (DM) is an organophosphate insecticide widely used in agriculture and industry and has toxic effects on non-target organisms especially mammalian. However, we still know little about DM-induced kidney injury and its alleviation by natural antioxidants. In the present study, selenium (Se), vitamin E, DM, Se+DM, vitamin E+DM, Se+vitamin E+DM were given to adult rats for 4 weeks. Plasma creatinine and uric acid, kidney MDA, PC, H₂O₂ and AOPP levels were higher, while Na⁺-K⁺-ATPase and LDH values were lower in the DM group than those of controls. A smear without ladder formation on agarose gel was shown in the DM group, indicating random DNA degradation and DM-induced genotoxicity. A decrease in kidney GSH, NPSH and plasma urea levels and an increase in GPx, SOD and catalase activities were observed in the DM group when compared to those of controls. Plasma cystatin C levels increased, indicating a decrease in glomerular filtration rate. When Se or vitamin E was added through diet, the biochemical parameters cited above were partially restored in Se+DM and vitamin E+DM than DM group. The joint effect of Se and vitamin E was more powerful against DM-induced oxidative stress and kidney dysfunction. The changes in biochemical parameters were substantiated by histological data. In conclusion, our results indicated a possible mechanism of DM-induced nephrotoxicity, where renal genotoxicity was noted, membrane-bound ATPases and plasma biomarkers were disturbed. Se and vitamin E ameliorated the toxic effects of this pesticide in renal tissue suggesting their role as potential antioxidants.     

Effects of X-ray radiation on lipid peroxidation and antioxidant systems in rabbits treated with antioxidant compounds

The aim of this study was to investigate the effects of supplemental antioxidant vitamins and minerals on lipid peroxidation and on the antioxidant systems in rabbits exposed to X-rays. The rabbits were divided into two experimental groups and one control group, each group containing seven rabbits. The first group (VG) received daily oral doses of vitamin E (460 mg/kg live weight) and vitamin C (100 mg/kg live weight). The second group (MG) was fed a mineral-enriched diet that contained 60 mg manganese chloride, 40 mg zinc sulfate, and 5 mg copper sulfate per kilogram of feed. The third group served as controls and received only a standard diet. Blood samples were obtained before and after the supplementation with vitamins or minerals, as well as before and after irradiation with a total dose of 550-rad X-rays. The blood samples were analyzed for their content of malondialdehyde (MDA), plasma vitamins C and E, retinol, reduced glutathione (GSH), and glutathione peroxidase activity (GPx). After irradiation, the control group showed increased levels of MDA and activity of GPx (p<0.05), whereas the levels of GSH, vitamin C, and vitamin E were decreased. In the VG, the concentration of MDA was lower (p<0.05), and the concentration of GSH and vitamins C and E were higher (p<0.05) when compared to controls. In the MG, the concentrations of MDA, GSH, vitamin C, and retinol were not affected by the mineral administration and radiation. The level of vitamin E in the MG increased with mineral administration (p<0.05), but decreased after irradiation (p<0.05). For the control group, the level of GSH was higher than in the two experimental groups. After irradiation, the VG animals had vitamin E and C levels that were higher than in MG and control groups (p<0.05). The activity of GPx was not affected by vitamin or mineral supplementation or by irradiation. We conclude that the supplementation with antioxidant vitamins and minerals may serve to reinforce the antioxidant systems, thus having a protective effect against cell damage by X-rays.