Lipid peroxidation in liver tissue of ovariectomized and pinealectomized rats: effect of estradiol and progesterone supplementation

The present study aimed to determine the effect of estradiol-progesterone supplementation and pinealectomy on lipid peroxidation of liver tissue in ovariectomized rats. The study was carried out on 36 adult Sprague-Dawley female rats, which weighed 200-250 g. The rats were divided into 6 groups: Group 1: Sham Ovariectomy (Sham-Ovx), Group 2: Ovariectomy (Ovx), Group 3: Ovx + Estradiol-Progesterone supplementation (Ovx + H), Group 4: Sham Pinealectomy and Ovx (Sham Pnx -Ovx), Group 5: Ovx -Pnx, Group 6: Ovx -Pnx + H. Malondialdehyde (MDA), reduced form of glutathione (GSH) and glutathione peroxidase (GSH-Px) levels were determined in liver tissue of rats. The highest MDA levels and the lowest GSH-Px levels were determined in the ovariectomized-pinealectomized group, whereas the lowest MDA was in the Sham-Ovx group, and the highest GSH-Px levels were found in the Sham-Ovx and Ovx + Hormone supplemented group. Furthermore, the highest GSH levels were in group 1 and lowest levels were in group 5. The findings of this study demonstrate that ovariectomy led to lipid peroxidation in liver tissues of rats. Pinealectomy in addition to ovariectomy, increases lipid peroxidation, but, estradiol and progesterone supplementations to the ovariectomized-pinealectomized rats protect against lipid peroxidation to a significant extent.     

Effects of xylene and formaldehyde inhalations on oxidative stress in adult and developing rats livers.

In this study, it was aimed to demonstrate the possible oxidative stress caused by exposure of xylene and formaldehyde (HCHO) on liver tissue, and on body and liver weights in adult as well as developing rats. The rats (96 female Sprague-Dawley) were randomly divided into four groups: embryonic day 1 (Group 1), 1-day-old infantile rats (Group 2), 4-week-old rats (Group 3) and adult rats (Group 4). The animals were exposed to gases of technical xylene (300 ppm), HCHO (6 ppm) or technical xylene + HCHO (150 ppm + 3 ppm), 8 hours per day for 6 weeks. Superoxide dismutase (SOD) and catalase (CAT) activities, and glutathione (GSH) and malondialdehyde (MDA) levels were evaluated. In addition, body and liver weights were determinated. Compared to the control animals, body and liver weights were decreased in the embryonic day 1 group (P < 0.001, P < 0.01, respectively) and the 1-day-old infantile group (P < 0.001). Liver weight was increased in the 4-week-old group (P < 0.01). SOD activities were decreased in the 4-week-old rats exposed to HCHO (P < 0.01). CAT activities increased in the embryonic day 1 group (P < 0.05). GSH levels were decreased in the 1-day-old infantile group (P < 0.01), and MDA levels was increased in the embryonic day 1 group (P < 0.05) as compared with the respective control groups. As to GSH and MDA levels in adult and 4-week-old animals, no statistically significant differences were observed (P > 0.05). The present study indicates that exposures to xylene, HCHO and a mixture of them are toxic to liver tissue, and developing female rats are especially more adversely affected. Furthermore, the results of this study show that adult female rats could better tolerate the adverse effects of these toxic gases.     

Plasma and erythrocytes antioxidant status and trace element levels in proteinuric patients with moderate glomerular function.

The objective of the study was to investigate the effect of moderate glomerular dysfunction on oxidative stress. We determined the plasma and erythrocyte malondialdehyde (MDA) levels, as a marker of lipid peroxidation, erythrocyte glutathione (GSH) levels and activities of GSH-Px, GSH Red and SOD as an antioxidant enzymes, and plasma trace element levels containing Fe, Cu and Zn in twenty proteinuric patients (6.8 +/- 5.1 g/day) with moderate glomerular function and in 20 anemic control subjects. We found that the erythrocyte and plasma MDA levels and erythrocyte GSH-Px activities were significantly higher (p < 0.001, p < 0.001, p < 0.001, respectively) and the erythrocyte GSH levels and activities of GSH-Red and SOD activities were significantly lower (p < 0.001, p < 0.001, p < 0.001, respectively) in the patients than in the anemic subjects. Plasma Fe and Zn levels were not to be found significantly different in the patients compared to the anemic subjects. But plasma Cu levels were significantly higher in the patients (p < 0.05) when compared with the levels of anemic subjects. This study was concluded that cellular antioxidant activity decreases in proteinuric patients with moderate glomerular function. This may increase lipid peroxidation reactions by causing oxidative stress in erythrocyte membranes.     

Can we reduce oxidative stress with liver transplantation?

BackgroundThe aim of this study was to determine the levels of lipid peroxidation (MDA) and antioxidants such as reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in the blood serum of patients with cirrhosis and liver transplantation.MethodsIn this study, serum malondialdehyde acid (MDA) levels, superoxide dismutase (SOD), reduced glutathione (GSH), and catalase (CAT) activities were measured spectrophotometrically and compared to the results of the healthy control group.ResultsSOD, CAT and GSH activities were significantly decreased in the patient groups compared to the healthy control group (p<0.05). MDA levels were significantly higher in the patient group compared to the healthy control group (p <0.05).ConclusionsIn conclusion, this study demonstrated that oxidative stress may play an important role in the development of liver cirrhosis and in liver transplantation. This study is the first one to show how MDA, SOD, CAT and GSH levels change in liver cirrhosis and liver transplantation, while further studies are essential to investigate antioxidant enzymes and oxidative stress status in patients with cirrhosis and liver transplantation.     

Carnosine and taurine treatments decreased oxidative stress and tissue damage induced by d-galactose in rat liver

d-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of carnosine (CAR) or taurine (TAU), having antioxidant effects, on hepatic injury and oxidative stress in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days/week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days/week) or TAU (2.5 % w/w; in rat chow) for 2 months. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and hepatic malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-0050x), and glutathione transferase (GST) activities were determined. Hepatic expressions of B cell lymphoma-2 (Bcl-2), Bax and Ki-67 were evaluated. Serum ALT, AST, hepatic MDA, and PC levels were observed to increase in GAL-treated rats. Hepatic Bax expression, but not Bcl-2, increased, Ki-67 expression decreased. GAL treatment caused decreases in GSH levels, SOD and GSH-Px activities in the liver. Hepatic mRNA expressions of SOD, but not GSH-Px, also diminished. CAR or TAU treatments caused significant decreases in serum ALT and AST activities. These treatments decreased apoptosis and increased proliferation and ameliorated histopathological findings in the livers of GAL-treated rats. Both CAR and TAU reduced MDA and PC levels and elevated GSH levels, SOD and GSH-Px (non significant in TAU?+?GAL group) activities. These treatments did not alter hepatic mRNA expressions of SOD and GSH-Px enzymes. Our results indicate that CAR and TAU restored liver prooxidant status together with histopathological amelioration in GAL-induced liver damage.     

Effects of Bacillus thuringiensis toxin on hepatic lipid peroxidation and free-radical scavengers in rats given alpha-tocopherol or acetylsalicylate

The effect of Dipel (D), a Bacillus thuringiensis-based bioinsecticide, on hepatic antioxidant enzyme activities and lipid peroxidation in rat liver was investigated. Administration of D in a dose of 1 mg/100 g body mass for 4 successive days increased the activities of glutathione peroxidase (GPx), glutathione reductase (GR) and the level of malondialdehyde (MDA) in rat hepatocytes. The activity of superoxide dismutase (SOD) and glutathione (GSH) level were decreased. Administration of D in rats pretreated with alpha-tocopherol (alphaT) or acetylsalicylic acid (ASA) decreased the activities of GPx, GR and MDA levels, while the GSH level was increased compared with rats treated with D alone. The SOD activity was increased in rats pretreated with alphaT before D, but decreased on pretreatment with ASA, compared with rats treated with D alone. The results indicated that D induced oxidative stress in rat liver that has been protected by prior administration of alphaT or ASA.     

Lipid Peroxidation and Changes of Trace Elements in Mice Treated with Paradichlorobenzene

Paradichlorobenzene (pDCB) has been used as a space deodorant and moth repellant, as well as an intermediate in the chemical industry. Given its broad applications and high volatility, considerable concern exists regarding the adverse health effects of pDCB in the home and the workplace. In this study, changes in lipid peroxidation, antioxidants, and trace element levels in the liver and kidney of pDCB-treated mice were investigated to determine their roles in toxicity. Mice were orally gavaged once daily for seven consecutive days with pDCB (0 (corn oil control), 450, and 900 mg/kg). The level of malondialdehyde (MDA), an end product of lipid peroxidation, markedly increased in the high-dose pDCB group in both the liver and kidney compared with the control group. Changes in hepatic levels of reduced glutathione (GSH) in the pDCB groups were indistinguishable from the control group, while renal levels of reduced GSH in the high-dose pDCB group were significantly lowered in comparison to the control and the low-dose groups. Superoxide dismutase (SOD) activity in the liver of mice treated with pDCB showed a downward trend, whereas there was no consistent trend associated with changes in SOD activity in the kidney. Additionally, renal iron levels in the high-dose pDCB group were significantly decreased compared with the low-dose group and the controls, whereas hepatic iron content in the low-dose pDCB group was significantly lower compared with the controls. Selenium and zinc levels in the kidney were both significantly decreased in the high-dose pDCB group vs. the control and low-dose groups. There were no treatment-induced changes in copper levels in either the kidney or liver. However, a significant increase was found in the liver zinc/copper ratio in the high-dose pDCB group vs. the controls. In addition, blood zinc levels showed a downward trend with increased pDCB dosage. These results suggest that pDCB toxicity is mediated by oxidative damage and tissue-specific alterations in trace element levels both in the liver and the kidney of mice.     

Methionine challenge paradoxically induces a greater activation of the antioxidant defence in subjects with hyper- vs. normohomocysteinemia

To determine whether hyperhomocysteinemia induced post-methionine loading (PML) is associated with different response in the aminothiol redox state and oxidative stress vs. normohomocysteinemia, we assessed PML plasma thiols, vitamins, free malondialdehyde (MDA), and blood reduced glutathione (GSH) in 120 consecutive subjects (50 [35-56] years, 83 males), divided into two groups according to PML plasma total Hcy < 35 microM (Group 1, n = 65) or > or = 35 microM (Group 2, n = 55).In the group as a whole, plasma reduced cysteine and cysteinylglycine, blood reduced GSH (all p for time = 0.0001) and plasma total GSH (p for time = 0.001) increased from baseline to PML. MDA values were unchanged. Group 1 and 2 differed in blood reduced GSH (p for group = 0.004, higher in Group 2), and MDA levels (p for group = 0.024, lower in Group 2).The oxidative stress induced by methionine challenge seems to be opposed by scavenger molecules activation, namely GSH, and lipid peroxidation does not increase. This mechanism paradoxically appears to be more efficient in hyperhomocysteinemic subjects.     

Protective Effects of Erdosteine and Vitamins C and E Combination on Ischemia–Reperfusion-Induced Lung Oxidative Stress and Plasma Copper and Zinc Levels in a Rat Hind Limb Model

The aim of this study was to investigate the protective effects of erdosteine and vitamins C and E (VCE) on the lungs after performing hind limb ischemia–reperfusion (I/R) by assessing oxidative stress, plasma copper (Cu), and zinc (Zn) analysis. The animals were divided randomly into four groups as nine rats each as follows: control, I/R, I/R plus erdosteine, and I/R plus VCE combination. I/R period for 60 min was performed on the both hind limbs of all the rats in the groups of I/R, erdosteine with I/R, VCE with I/R allowing 120 min of reperfusion. The animals received orally erdosteine one time in a day and 3 days before I/R in the erdosteine group. In the VCE group, the animals VCE combination received one time in a day and 3 days before I/R, although placebo was given to control and I/R group animals. Lung lipid peroxidation (malondialdehyde [MDA]) level, superoxide dismutase (SOD), and catalase activities were increased, although lung glutathione (GSH) and plasma Zn levels decreased in I/R group in lung tissue compared with the control group. Serum MDA level, creatine kinase, and lactate dehydrogenase activities were increased in I/R group compared with the control. Lung MDA and plasma Zn levels and lung SOD activity were decreased by erdosteine administration, whereas lung GSH levels after I/R increased. The plasma Zn levels and lung SOD activity were decreased by VCE administration, although the plasma Cu and lung GSH levels increased after I/R. In conclusion, erdosteine has an antioxidant role on the values in the rat model, and it has more protective affect than in VCE in attenuating I/R-induced lung injury in rats.     

Copper Intoxication; Antioxidant Defenses and Oxidative Damage in Rat Brain

Copper (Cu) is an integral part of many important enzymes involved in a number of vital biological processes. Even though Cu is essential to life, it can become toxic to cells, at elevated tissue concentrations. Oxidative damage due to Cu has been reported in recent studies in various tissues. In this study, we aimed to determine the effect of excess Cu on oxidative and anti-oxidative substances in brain tissue in a rat model. Sixteen male Wistar albino rats were divided into two groups: the control group, which was given normal tap water, and the experimental group, which received water containing Cu in a dose of 1 g/l. All rats were sacrificed at the end of 4 wk, under ether anesthesia. Cu concentration in the liver and in plasma alanine aminotransferase (ALT) and aspartate transaminase (AST) activities were determined. There were multiparameter changes with significant ALT and AST activity elevation and increased liver Cu concentration. In brain tissue, Cu concentration, superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels and glutathione (GSH) concentrations were determined. Brain Cu concentration was significantly higher in rats receiving excess Cu, compared with control rats (p < 0.05). Our results showed that SOD activities and GSH levels in brain tissue of the Cu-intoxicated animals were significantly lower than in the control group (p < 0.01 and p < 0,001, respectively). The brain MDA levels were found to be significantly higher in the experimental group than in the control group (p < 0.001). The present results indicate that excessive Cu accumulation in the brain depressed SOD activities and GSH levels and resulted in high MDA levels in brain homogenate due to the lipid peroxidation induced by the Cu overload.     

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.     

Evaluation of trace elements and oxidative stress levels in the liver and kidney of streptozotocin-induced experimental diabetic rat model

In this study, we aimed to investigate the relationship among trace elements (Cu, Fe, Zn and Mg) on oxidative and anti-oxidative substances in liver and kidneys tissues in streptozotocin (STZ) diabetic rat model. The mean levels of Fe and Cu were found significantly higher in the liver and kidneys of the diabetic rats, in comparison to the control rats. On the other hand, the mean levels of Zn and Mg in the liver and kidneys of the diabetic rats were significantly lower than in the control rats. The liver and kidneys malonaldehyde (MDA) levels of the experimental group were found to be higher than in the control group (p < 0.001; p < 0.01, respectively) after 4 weeks of the experimental period. Superoxide dismutase (SOD) activities and glutathione (GSH) levels in the liver tissue of STZ-induced diabetic rats were found to be lower in the experimental group than in the control group (p < 0.01). SOD activity and GSH concentration in kidneys of the diabetic rats were significantly diminished with respect to the control group (p < 0.01). In conclusion, the present results indicate that the increase of Fe and Cu together with decreas of Zn and Mg concentration in liver and kidney of STZ-induced diabetic rats may be involved in disturbances of oxidative balance in both the tissues. Therefore, these findings may contribute to explain the role of impaired ion metabolism of some elements in the progression of diabetic oxidative complications.     

Effect of Selenium Supplementation on Lipid Peroxidation,Antioxidant Enzymes,and Lactate Levels in Rats Immediately After Acute Swimming Exercise

The present study aims to evaluate the effect of selenium supplementation on lipid peroxidation and lactate levels in rats subjected to acute swimming exercise. Thirty-two adult male rats of Sprague–Dawley type were divided into four groups. Group 1, control; group 2, selenium-supplemented; group 3, swimming control; group 4, selenium-supplemented swimming group. The animals in groups 2 and 4 were supplemented with (i.p.) 6 mg/kg/day sodium selenite for 4 weeks. The blood samples taken from the animals by decapitation method were analyzed in terms of erythrocyte-reduced glutathione (GSH), serum glutathione peroxidase (GPx) and superoxide dismutase (SOD), and plasma malondialdehyde (MDA) and lactate using the colorimetric method, and serum selenium values using an atomic emission device. In the study, the highest MDA and lactate values were found in group 3, while the highest GSH, GPx and SOD values were obtained in group 4 (p < 0,001). Group 2 had the highest and group 3 had the lowest selenium levels (p < 0,001). Results of the study indicate that the increase in free radical production and lactate levels due to acute swimming exercise in rats might be offset by selenium supplementation. Selenium supplementation may be important in that it supports the antioxidant system in physical activity.     

Protective effect of glycine supplementation on the levels of lipid peroxidation and antioxidant enzymes in the erythrocyte of rats with alcohol-induced liver injury

We studied the effect of glycine supplementation on lipid peroxidation and antioxidants in the erythrocyte membrane, plasma and hepatocytes of rats with alcohol-induced hepatotoxicity. Administering ethanol (20%) for 60 days to male Wistar rats resulted in significantly elevated levels of erythrocyte membrane, plasma and hepatocyte thiobarbituric acid reactive substances (TBARS) as compared with those of the experimental control rats. Decreased activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx) and glutathione reductase (GR) were also observed on alcohol supplementation as compared with those of the experimental control rats. Glycine was administered at a dose of 0.6 g kg(-1) body weight to rats with alcohol-induced liver injury, which significantly decreased the levels of TBARS and significantly elevated the activities of SOD, CAT, GSH, GPx and GR in the erythrocyte membrane, plasma and hepatocytes as compared to that of untreated alcohol supplemented rats. Thus, our data indicate that supplementation with glycine offers protection against free radical-mediated oxidative stress in the erythrocyte membrane, plasma and hepatocytes of animals with alcohol-induced liver injury.     

L-malate reverses oxidative stress and antioxidative defenses in liver and heart of aged rats

The intracellular levels of antioxidant and free radical scavenging enzymes are gradually altered during the aging process. An age-dependent increase of oxidative stress occurring throughout the lifetime is hypothesized to be the major cause of aging. The current study examined the effects of L-malate on oxidative stress and antioxidative defenses in the liver and heart of aged rats. Sprague-Dawley male rats were randomly divided into four groups, each group consisting of 6 animals. Group Ia and Group IIa were young and aged control rats. Group Ib and Group IIb were young and aged rats treated with L-malate (210 mg/kg body weight per day). L-malate was orally administrated via intragastric canula for 30 days, then the rats were sacrificed and the liver and heart were removed to determine the oxidant production, lipid peroxidation and antioxidative defenses of young and aged rats. Dietary L-malate reduced the accumulation of reactive oxygen species (ROS) and significantly decreased the level of lipid peroxidation in the liver and heart of the aged rats. Accordingly, L-malate was found to enhance the antioxidative defense system with an increased activity of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) and increased glutathione (GSH) levels in the liver of aged rats, a phenomenon not observed in the heart of aged rats. Our data indicate that oxidative stress was reversed and the antioxidative defense system was strengthened by dietary supplementation with L-malate.     

Lipid peroxidation in ovariectomized and pinealectomized rats: the effects of estradiol and progesterone supplementation

In the present study, we investigated the effect of estradiol and progesterone supplementation on oxidant and antioxidant parameters of renal tissue in ovariectomized and pinealectomized rats. The study was carried out on 36 adult, Sprague-Dawley strain female rats, 6 months of age and weighing 200-250 g. The rats were divided into six groups, each group included six rats: Group 1: Sham-ovariectomized (Sham-Ovx); Group 2: Ovariectomized (Ovx); Group 3: Ovx and estradiol (E) and progesterone (P) supplemented (Ovx+E-P); Group 4: Ovariectomized and sham pinealectomy (Ovx+sham Pnx); Group 5: Ovariectomized+Pinealectomized (Ovx+Pnx); Group 6: Ovariectomized+Pinealectomized+Hormone Supplemented group (Ovx+Pnx+E-P). The levels of malondialdehyde (MDA), reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) were analysed in renal tissues of rats. The highest and the lowest levels of MDA were determined in Groups 5 and 1 respectively (p < 0.001). However, GSH and GSH-Px levels demonstrated statistically important decreases in groups 2, 4, 5 (p < 0.001). The findings of this study demonstrate that ovariectomy leads to oxidative damage in renal tissue. Pinealectomy in addition to ovariectomy greatly increases the oxidative damage. However, female sex hormones supplementations to the Ovx and/or Ovx+Pnx rats protected against lipid peroxidation by activating the antioxidant system.     

Protective effect of silymarin on oxidative stress in rat brain

Brain is susceptible to oxidative stress and it is associated with age-related brain dysfunction. Previously, we have pointed out a dramatic decrease of glutathione levels in the rat brain after acetaminophen (APAP) oral administration overdose. Silymarin (SM) is a mixture of bioactive flavonolignans isolated from Silybum marianum (L.) Gaertn., employed usually in the treatment of alcoholic liver disease and as anti-hepatotoxic agent in humans. In this study, we have evaluated the effect of SM on enzymatic and non enzymatic antioxidant defensive systems in rat brain after APAP-induced damage. Male albino Wistar rats were treated with SM (200 mg/kg/die orally) for three days, or with APAP single oral administration (3 g/kg) or with SM (200 mg/kg/die orally) for 3 days and APAP single oral administration (3 g/kg) at third day. Successively the following parameters were measured: reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), enzymatic activity variations of superoxide dismutase (SOD) and malondialdehyde levels (MDA). Our results showed a significant decrease of GSH levels, AA levels and SOD activity and an increase of MDA and GSSG levels after APAP administration. After SM administration GSH and AA significantly increase and SOD activity was significantly enhanced. In the SM+APAP group, GSH values significantly increase and the others parameters remained unchanged respect to control values. These results suggest that SM may to protect the SNC by oxidative damage for its ability to prevent lipid peroxidation and replenishing the GSH levels.     

Melatonin reduces oxidative stress induced by ochratoxin A in rat liver and kidney

Melatonin (MEL) displays antioxidant and free radical scavenger properties. In the present study, the effect of MEL on the oxidative stress induced by ochratoxin A (OTA) administration in rats was investigated. Four groups of 15 rats each were used: controls, MEL-treated rats (5 mg/kg body mass), OTA-treated rats (250 μg/kg) and MEL+OTA-treated rats. After 4 weeks of treatment, the levels of malondialdehyde (MDA), a lipid peroxidation product (LPO) were measured in serum and homogenates of liver and kidney. Also, the levels of glutathione (GSH), and activities of glutathione reductase (GR), glutathione peroxidase (GSPx), superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) in liver and kidney were determined. In OTA-treated rats, the levels of LPO in serum and in both liver and kidney were significantly increased compared to levels in controls. Concomitantly, the levels of GSH and enzyme activities of SOD, CAT, GSPx and GR in both liver and kidney were significantly decreased in comparison with controls. In rats received MEL+OTA, the changes in the levels of LPO in serum and in liver and kidney were not statistically significant compared to controls. Concomitantly, the levels of GSPx, GR and GST activities in both liver and kidney tissues were significantly increased in comparison with controls. Similar increases in GSPx, GR and GST activities were also observed in MEL-treated rats when compared with controls. In conclusion, the oxidative stress may be a major mechanism for the toxicity of OTA. MEL has a protective effect against OTA toxicity through an inhibition of the oxidative damage and stimulation of GST activities. Thus, clinical application of melatonin as therapy should be considered in cases of ochratoxicosis.     

Protective effects of garlic oil on hepatocarcinoma induced by N-nitrosodiethylamine in rats

To investigate the protective effects and the possible mechanisms of garlic oil (GO) against N-nitrosodiethylamine (NDEA)-induced hepatocarcinoma in rats, Wistar rats were gavaged with GO (20 or 40 mg/kg) for 1 week, and then were gavaged with GO and NDEA (10 mg/kg) for the next 20 weeks. The changes of morphology, histology, the biochemical indices of serum, and DNA oxidative damage of liver were examined to assess the protective effects. Lipid peroxidation (LPO), antioxidant defense system, and apoptosis-related proteins were measured to investigate potential mechanisms. At the end of the study (21 weeks), GO administration significantly inhibited the increase of the nodule incidence and average nodule number per nodule-bearing liver induced by NDEA, improved hepatocellular architecture, and dramatically inhibited NDEA-induced elevation of serum biochemical indices (alanine aminotransferase , aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase) and hepatic 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in a dose-dependent manner. The mechanistic studies demonstrated that GO counteracted NDEA-induced oxidative stress in rats illustrated by the restoration of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) levels, and the reduction of the malondialdehyde (MDA) levels in liver. Furthermore, the mRNA and protein levels of Bcl-2, Bcl-xl, andβ-arrestin-2 were significantly decreased whereas those of Bax and caspase-3 were significantly increased. These data suggest that GO exhibited significant protection against NDEA-induced hepatocarcinogenesis, which might be related with the enhancement of the antioxidant activity and the induction of apoptosis.     

Antioxidant tolerance of kidney after irradiation

Different doses of irradiation were performed in which group 1 (non-irradiated), group 2 (8 Gy/single dose/whole body) and group 3 (15 Gy/single dose/whole body) were formed of guinea pigs. After 24 hr of radiation exposure the levels of lipid peroxidation product, malondialdehyde, (MDA), glutathione (GSH) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured in the whole kidney. The MDA content increased in animals irradiated with 8 and 15 Gy. And group 3 showed an increase the level of MDA. GSH contents of kidney in group 2 and 3 increased. The activity of SOD decreased markedly in group 3 when compared with control group. The activity of GSH-Px decreased significantly in group 2 and group 3 in comparison to controls. It may be concluded that a high dose of ionizing irradiation cause excessive oxidative stress in kidney.