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.     

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).     

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.     

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.     

17β-Estradiol and Vitamin E Modulates Oxidative Stress-Induced Kidney Toxicity in Diabetic Ovariectomized Rat

The aim of this study was to investigate the effects of vitamin E (alpha-tocopherol) and 17β-estradiol (E(2)) supplementation on malondialdehyde (MDA), glutathione (GSH), vitamin A, beta carotene, selenium-dependent glutathione peroxidase (GSH-Px), zinc-dependent superoxide dismutase (SOD), and copper/zinc-dependent catalase (CAT) values in the kidney of ovariectomized (OVX) diabetic rats. Forty-two female rats were randomly divided into seven equal groups as follows: group I, control; group II, OVX; group III, OVX+E(2); group IV, OVX+E(2)+alpha-tocopherol; group V, OVX+diabetic; group VI, OVX+diabetic+E(2); and group VII, OVX+diabetic+E(2)+alpha-tocopherol. E(2) (40?μg?kg(-1)/day) and alpha-tocopherol (100?μg?kg(-1)/day) were given. Bilateral ovariectomy was performed in all groups except group I. After 4?weeks, antioxidant and MDA levels in the kidney for all groups were analyzed. GSH-Px, CAT, SOD, GSH levels, vitamin A, and beta carotene levels were decreased in OVX group compared to those in the control group but MDA level was elevated via ovariectomy. However, E(2) and E(2)+alpha-tocopherol supplementations in OVX group was associated with an increase in the GSH-Px, GSH, CAT and Zn-SOD values, vitamin A, and beta carotene levels but a decrease in MDA levels in kidney. The MDA levels in the kidney of diabetic OVX rats were found higher than those in the control and OVX groups. However, GSH, GSH-Px, CAT, SOD, vitamin A, and beta carotene levels in kidney were lower in OVX diabetic rats. On the other hand, E(2) and E(2)+alpha-tocopherol supplementations to OVX diabetic rats have caused an increase in GSH-Px, CAT and SOD, GSH, vitamin A, and beta carotene levels but a decrease in MDA levels. In conclusion, the E(2) and E(2)+alpha-tocopherol supplementations to diabetic OVX and OVX rats may strengthen the antioxidant defense system by reducing lipid peroxidation, and therefore they may play a role in preventing renal disorders.     

Activity of Cassia auriculata leaf extract in rats with alcoholic liver injury

This study was undertaken to investigate the effect of Cassia auriculata leaf extract on tissue lipid peroxidation and antioxidant status in experimental hepatotoxicity. Administering ethanol to rats for 60 days resulted in significantly elevated levels of serum total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) as compared with those of the experimental control rats. Significantly elevated levels of tissue thiobarbituric acid reactive substances (TBARS), hydroperoxides and lowered activities of superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) were also observed on alcohol treatment as compared with those of experimental control rats. Concentration of serum non-enzymic antioxidants such as vitamin E and vitamin C were also significantly lowered on alcohol supplementation. Treatment with Cassia auriculata leaf extract at a dose of 250 mg kg(-1) body weight and 500 mg kg(-1) body weight to rats administered alcohol, lowered the levels of TBARS and hydroperoxides and elevated the activities of SOD and CAT and the levels of reduced GSH in the liver, brain, kidney and intestine significantly compared to unsupplemented alcohol treated rats. Cassia auriculata leaf extract treatment restored the serum vitamin E, and vitamin C levels also to near those of the experimental control animals. Our data indicate that supplementation with Cassia auriculata leaf extract can offer protection against free radical mediated oxidative stress in experimental hepatotoxicity. In addition, histopathological studies of the liver and brain confirmed the beneficial role of Cassia auriculata leaf extract.     

Effects of photodynamic treatment on biological antioxidant systems in rats

Effects of photodynamic treatments on inherent antioxidant metabolites and cellular defence enzymes have been investigated in rats. Wistar rats were grouped into untreated controls, light controls, hematoporphyrin derivative (Hpd) (treated with 5 and 10 mg Hpd/kg body weight and kept in dark) and sets treated with both Hpd and red light (dose 172 and 344 j/m2 ). After 2, 24, 48 and 72 hr of Hpd injection the rats sacrificed, livers quickly excised to analyze Hpd uptake, activities of enzymes like catalase, GSH-Px and antioxidants like GSH, vitamin A, vitamin E and vitamin C. The results showed that the loss of Hpd from liver as a function of post- injection time was non- linear. An increased generation of lipid radicals was observed in the groups treated with 5 mg Hpd and higher dose of light and in groups treated with 10 mg Hpd at both the doses of light. Combination of light and Hpd reduced hepatic GSH content with a concomitant reduction in GSH-Px. At higher doses of Hpd and light, there was a significant reduction in hepatic vitamin A levels. Combination of Hpd and light in all doses reduced vitamin E content in liver. The decreased biological antioxidant contents and GSH-Px may be attributed to their utilization for the scavenging of free radicals generated by Hpd and light in tissues. However, no change in catalase activity and vitamin C content in liver was noted in experimental rats. The results suggest that exposure to higher doses of Hpd with light alters oxidant stress system and TBARS content in rat.     

The effects of some antioxidant vitamin- and trace element-supplemented diets on activities of SOD, CAT, GSH-Px and LPO levels in chicken tissues

The effect of diets containing antioxidant vitamins and trace elements on chicken tissue activities of SOD, CAT, GSH-Px and of LPO levels was investigated. Chickens, 45 weeks of age were divided into six groups: control group, Cu group (13.2 mg Cu kg(-1) diet); Se group (0.07 mg Se kg(-l) diet); vitamin E group (70 mg DL-alpha-tocopherol acetate kg(-1) diet) and a constant level vitamin C, 200 mg kg(-1) diet); vitamin A group (240 mg retinol acetate kg(-1) diet) and vitamin C group (500 mg ascorbic acid kg(-1) diet). Significant variation of these antioxidant enzyme activities and LPO levels according to gender was demonstrated statistically. In the Cu group, CuZnSOD activity in the liver, erythrocyte, kidney and heart significantly increased by 75, 40, 12, 12% respectively (P<0.05). MnSOD activity in the heart, liver, kidney and brain of the vitamin C and in the heart of Cu group were found to be increased by approximately 15%, while in liver tissue of the Cu group it was reduced by 19% (P<0.05). GSH-Px activities in the Se, vitamin E and C groups were significantly increased, conversely LPO levels decreased (P<0.001). CAT activities in the liver and heart of the vitamin C group were significantly decreased (by 32%), but in kidney tissue only that of the Cu group was increased from 30.2 +/- 4.767 to 144.49 +/- 6.93 U mg(-1) P<0.001. The resistance to stress of the vitamin E and C groups, which had significantly increased activities of antioxidant enzymes and decreased lipid peroxide levels, were determined in 60% moisture medium at 45 degrees C.     

Influences of different stress models on the antioxidant status and lipid peroxidation in rat erythrocytes

The aim of this study was to investigate the influences of different stress models on the antioxidant status and lipid peroxidation (LPO) in erythrocytes of rats. Swiss-Albino female rats (3 months old) were used in this study. Rats were randomly divided into the following four groups; control group (C), cold stress group (CS), immobilization stress group (IS) and cold+immobilization stress group (CS+IS). Control group was kept in an animal laboratory (22 ±2°C). Rats in CS group were placed in cold room (5°C) for 15 min/day for 15 days. Rats in IS group were immobilized for 180 min/day for 15 days. Rats in CS+IS group were exposed to both cold and immobilization stresses for 15 days. At the end of experimental periods, the activities of glucose-6-phosphate dehydrogenase (G-6-PD), Cu,Zn-superoxide dismutase (Cu,Zn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and concentration of reduced glutathione (GSH) were measured. LPO was determined by measuring the contents of thiobarbituric acid-reactive substances (TBARS). Cu,Zn-SOD activity and TBARS concentration were increased after cold and immobilization stresses, but CAT and GSH-Px activities and GSH levels were decreased. Immobilization stress decreased the activity of G-6-PD. The activities of G-6-PD, CAT and GSH-Px, and the level of GSH were lower in CS+IS group than in the control group. Cu,Zn-SOD activity and TBARS levels were increased in CS+IS group when compared with the control group. From these findings, three stress models are thought to cause oxidative stress.     

Influences of Different Stress Models on the Antioxidant Status and Lipid Peroxidation in Rat Erythrocytes

The aim of this study was to investigate the influences of different stress models on the antioxidant status and lipid peroxidation (LPO) in erythrocytes of rats. Swiss-Albino female rats (3 months old) were used in this study. Rats were randomly divided into the following four groups; control group (C), cold stress group (CS), immobilization stress group (IS) and cold+immobilization stress group (CS+IS). Control group was kept in an animal laboratory (22 &#45 2°C). Rats in CS group were placed in cold room (5°C) for 15 min/day for 15 days. Rats in IS group were immobilized for 180 min/day for 15 days. Rats in CS+IS group were exposed to both cold and immobilization stresses for 15 days. At the end of experimental periods, the activities of glucose-6-phosphate dehydrogenase (G-6-PD), Cu,Zn-superoxide dismutase (Cu,Zn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and concentration of reduced glutathione (GSH) were measured. LPO was determined by measuring the contents of thiobarbituric acid-reactive substances (TBARS). Cu,Zn-SOD activity and TBARS concentration were increased after cold and immobilization stresses, but CAT and GSH-Px activities and GSH levels were decreased. Immobilization stress decreased the activity of G-6-PD. The activities of G-6-PD, CAT and GSH-Px, and the level of GSH were lower in CS+IS group than in the control group. Cu,Zn-SOD activity and TBARS levels were increased in CS+IS group when compared with the control group. From these findings, three stress models are thought to cause oxidative stress.     

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.     

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.     

N-Acetylcysteine and Selenium Modulate Oxidative Stress,Antioxidant Vitamin and Cytokine Values in Traumatic Brain Injury-Induced Rats

It has been suggested that oxidative stress plays an important role in the pathophysiology of traumatic brain injury (TBI). N-acetylcysteine (NAC) and selenium (Se) display neuroprotective activities mediated at least in part by their antioxidant and anti-inflammatory properties although there is no report on oxidative stress, antioxidant vitamin, interleukin-1 beta (IL)-1β and IL-4 levels in brain and blood of TBI-induced rats. We investigated effects of NAC and Se administration on physical injury-induced brain toxicity in rats. Thirty-six male Sprague–Dawley rats were equally divided into four groups. First and second groups were used as control and TBI groups, respectively. NAC and Se were administrated to rats constituting third and forth groups at 1, 24, 48 and 72 h after TBI induction, respectively. At the end of 72 h, plasma, erythrocytes and brain cortex samples were taken. TBI resulted in significant increase in brain cortex, erythrocytes and plasma lipid peroxidation, total oxidant status (TOS) in brain cortex, and plasma IL-1β values although brain cortex vitamin A, β-carotene, vitamin C, vitamin E, reduced glutathione (GSH) and total antioxidant status (TAS) values, and plasma vitamin E concentrations, plasma IL-4 level and brain cortex and erythrocyte glutathione peroxidase (GSH-Px) activities decreased by TBI. The lipid peroxidation and IL-1β values were decreased by NAC and Se treatments. Plasma IL-4, brain cortex GSH, TAS, vitamin C and vitamin E values were increased by NAC and Se treatments although the brain cortex vitamin A and erythrocyte GSH-Px values were increased through NAC only. In conclusion, NAC and Se caused protective effects on the TBI-induced oxidative brain injury and interleukin production by inhibiting free radical production, regulation of cytokine-dependent processes and supporting antioxidant redox system.     

Effects of vitamin E supplementation in the extender on frozen-thawed bovine semen preservation

The maturing sperm cells discard the majority of their cytoplasm during the final stages of spermatogenesis and lose some of their defense enzymes. The purpose of this study was to investigate the effects of vitamin E supplementation on standard semen quality parameters and antioxidant activities of frozen-thawed bovine sperm. Vitamin E was added at concentrations of 0.5, 1.0, 1.5 and 2.0 mg/ml to bovine semen cryoprotective medium. The results showed that the sperm motility and VSL, STR values in the extender supplemented with 1.0 and 1.5 mg/ml of vitamin E, were significantly higher than that of other concentrations (P < 0.05). The percentages of acrosome-intact and membrane-intact sperm were significantly improved (P < 0.05) by supplementing with 1.5 mg/ml of vitamin E. In biochemical assays, the extender supplemented with vitamin E did not exhibit significant improvement in SOD (superoxide dismutase) levels, compared with the control (P > 0.05). Compared with other groups, CAT (catalase) levels were demonstrated to be greater with the supplementation of vitamin E at 1.0 and 1.5 mg/ml (P < 0.05). The extender supplemented with 1.5 mg/ml of vitamin E caused the highest levels of glutathione peroxidase (GSH-Px), compared with other groups (P < 0.05). The glutathione (GSH) activity was significantly higher with the supplementation of 0.5, 1.0 and 1.5 mg/ml of vitamin E, compared with 2.0 mg/ml in the vitamin E group and control (P < 0.05). Moreover, increasing the doses of vitamin E decreased sperm antioxidant activities, the extender supplemented with 2.0 mg/ml of vitamin E, caused the lowest levels of GSH-Px and GSH activities, compared with other treatment groups (P < 0.05). In conclusion, the beneficial effects of vitamin E noted in this study can be attributed to the antioxidant characteristics. Vitamin E supplementation in the extender reduced the lipid peroxidation potential and improved semen quality during freezing-thawing. More researches are needed to evaluate and understand the precise physiological role of vitamin E in reproduction.     

Chemopreventive potential of luteolin during colon carcinogenesis induced by 1,2-dimethylhydrazine

We investigated the chemopreventive potential of luteolin on hepatic and circulatory lipid peroxidation and antioxidant status during 1,2-dimethylhydrazine induced colon carcinogenesis in rats. Rats were given a weekly subcutaneous injection of DMH at a dose of 20 mg/kg body weight for 15 weeks. Luteolin (0.2 mg/kg body weight/everyday p.o.) was given at the initiation and also at the postinitiation stages of carcinogenesis to DMH treated rats. The animals were sacrificed at the end of 30 weeks. Enhanced lipid peroxidation in the liver and circulation of tumor bearing rats was accompanied by a significant decrease in the levels of plasma and hepatic reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), vitamin C, vitamin E and beta-carotene in DMH treated rats as compared to the control rats. Intragastric administration of luteolin (0.2mg/kg body weight) to DMH-treated rats significantly reduced the incidence and size of tumor in the colon, reduced lipid peroxidation levels and enhanced the plasma and hepatic activities of GSH, GPx, GST, GR, SOD, CAT, vitamin C, vitamin E and beta-carotene. Thus the chemopreventive efficacy of luteolin against colon carcinogenesis is evidenced by our preliminary studies which showed decreased incidence of tumors and the antiperoxidative and antioxidant effect of luteolin. Further study on the exact mechanism of action of luteolin in preventing colon carcinogenesis is yet to be elucidated.     

Effects of intraperitoneally injected selenium and vitamin E in rats anesthetized with halothane.

Halothane, commonly used for anesthetizing humans and animals, is one of the most important volatile anesthetics and may cause the formation of free radicals during its biotransformation. Free radicals may lead to degeneration of liver cells. Vitamin E and glutathione peroxidase (GSH-Px) containing selenium are two natural antioxidants, and these may protect the cellular lipid and lipoproteins against oxidative damage caused by free radicals. Therefore, the purposes of the present study were to investigate the probable protective effects of intraperitoneally administered Se and vitamin E on liver enzymes and to determine some other hematological parameters in the halothane anesthesia of rats. All rats were randomly divided into five groups. The first group was used as a control, and physiological saline (0.9%) was intraperitoneally injected into these animals as a placebo. The second group was used as an anesthesia control group and was only anesthetized with halothane for two hours. The third group received intraperitoneally administered Se (Na2SeO3, 0.3 mg/200 g body weight), the fourth group vitamin E (dl-alpha-tocopheryl acetate, 100 mg/kg body weight), and the fifth group a Se plus vitamin E combination (Na2SeO3, 0.3 mg/200 g body weight + dl-alpha-tocopheryl acetate, 100 mg/kg body weight). The activities of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, triglycerides, erythrocyte counts, the packet-cell volume, hemoglobin concentrations and neutrophyle rates significantly increased (p < 0.05 to p < 0.01) after halothane anesthesia and returned to near control levels after Se, vitamin E and Se plus vitamin E injections. The values of cholesterol, total protein, white blood cell counts and lymphocyte rates significantly decreased (p < 0.05 to p < 0.01) in the anesthesia control group. However, the levels of albumin, total bilirubin, creatinine, the mean corpuscular volume, the mean corpuscular hemoglobin, and the mean corpuscular hemoglobin concentration were not statistically influenced. In conclusion, we have determined that halothane anesthesia affected some liver enzymes and some other biochemical and hematological parameters. Se, vitamin E and their combination may prevent the increase of liver enzymes after halothane anesthesia. Based upon these results, Se and vitamin E may play an important role in the indication of hepatic cellular injury produced by halothane.     

Beneficial effect of succinic acid monoethyl ester on erythrocyte membrane bound enzymes and antioxidant status in streptozotocin-nicotinamide induced type 2 diabetes

Succinic acid monoethyl ester (EMS) was recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. In the present study the effect of EMS and metformin on erythrocyte membrane bound enzymes and antioxidants activity in plasma and erythrocytes of streptozotocin-nicotinamide induced type 2 diabeteic model was investigated. Succinic acid monoethyl ester was administered intraperitonially for 30 days to control and diabetic rats. The effect of EMS on glucose, insulin, hemoglobin, glycosylated hemoglobin, TBARS, hydroperoxide, superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (Gpx), glutathione-S-transferase (GST), vitamins C and E, reduced glutathione (GSH) and membrane bound enzymes were studied. The effect of EMS was compared with metformin, a reference drug. The levels of glucose, glycosylated hemoglobin, TBARS, hyderoperoxide, and vitamin E were increased significantly whereas the level of insulin and hemoglobin, as well as antioxidants (SOD, CAT, Gpx, GST, vitamin C and GSH) membrane bound total ATPase, Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase were decreased significantly in streptozotocin-nicotinamide diabetic rats. Administration of EMS to diabetic rats showed a decrease in the levels of glucose, glycosylated hemoglobin, lipid peroxidation markers and vitamin E. In addition the levels of insulin, hemoglobin, enzymic antioxidants, vitamin C, and GSH and the activities of membrane bound enzymes also were increased in EMS and metformin treated diabetic rats. The present study indicates that the EMS possesses a significant beneficial effect on erythrocyte membrane bound enzymes and antioxidants defense system in addition to its antidiabetic effect.     

Melatonin controls oxidative stress and modulates iron, ferritin, and transferrin levels in adriamycin treated rats

AIM: Chemotherapy with adriamycin (ADR) is limited by its iron-mediated pro-oxidant toxicity. Because melatonin (MLT) is a broad spectrum antioxidant, we investigated the ability of MLT to control iron, its binding proteins, and the oxidative damage induced by ADR. MAIN METHODS: ADR was given as single i.p. dose of 10 mg kg(-1) body weight into male rats. MLT at a dose of 15 mg kg(-1) was injected daily for 5 days before ADR treatment followed by another injection for 5 days. Biochemical methods were used for this investigation. KEY FINDINGS: ADR injection caused elevations in plasma creatine kinase isoenzyme, lactic dehydrogenase, and aminotransferases, iron, ferritin, and transferrin. These changes were associated with increases in lipid peroxidation and protein oxidation as well as decreases in glutathione (GSH) levels and glutathione-S-transferase (GST) activity, while glutathione peroxidase (GSH-Px), and catalase (CAT) activity were elevated in the heart and liver of ADR treated rats. In the MLT+ADR group, the cardiac and hepatic function parameters and the levels of iron, transferrin and ferritin in plasma were normalized to control levels. The rats that were subjected to MLT+ADR had normalized CAT and GSH-Px activity and decreased TBARS and protein carbonyl levels compared the group only treated with ADR. GST activity and GSH concentration in the heart and liver were normalized when MLT accompanied ADR treatment. SIGNIFICANCE: MLT ameliorated oxidative stress by controlling iron, and binding protein levels in ADR treated rats demonstrating the usefulness of adriamycin in cancer chemotherapy and allowing a better management of iron levels.     

Simvastatin and vitamin E effects on cardiac and hepatic oxidative stress in rats fed on high fat diet

High fat diet (HFD) is a common cause of metabolic syndrome and type 2 diabetes mellitus. Published data showed that HFD and subsequent dyslipidemia are major triggers for oxidative stress. Forty-eight male Sprague–Dawley rats, weighing 170–200 g, were divided into six groups: control, control with vitamin E (100 mg/kg/day, i.p.), control with simvastatin (SIM) (10 mg/kg of body weight/day), HFD, HFD with vitamin E, and HFD with SIM. Standard and high cholesterol diets were given for 15 weeks and SIM and vitamin E were added in the last 4 weeks. In all rats, serum vitamin E, total cholesterol (TC), triglycerides (TG), low (LDL) and high (HDL) density lipoproteins, alanine (ALT) and aspartate (AST) transaminases, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT) as well as cardiac and hepatic thiobarbituric acid-reactive substances (TBARS) and antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)) were measured. Also, electrocardiogram (ECG) was recorded. HFD significantly increased QTc interval, heart rate (HR), serum TC, TG, LDL, ALT, AST, ALP, GGT, liver TG, and cardiac and hepatic TBARS but decreased antioxidants and HDL, while SIM decreased HR, liver TG, serum TC, TG, and LDL and increased HDL in HFD rats. Vitamin E had no effect. Moreover, SIM and vitamin E decreased QTc interval, serum ALT, AST, ALP, GGT, and cardiac and hepatic TBARS and increased antioxidants in HFD rats. Histopathological observations confirm the biochemical parameters. SIM and vitamin E slow progression of hypercholesterolemia-induced oxidative stress in liver and heart and improve their functions.