Effects of antioxidant stobadine on protein carbonylation, advanced oxidation protein products and reductive capacity of liver in streptozotocin-diabetic rats: role of oxidative/nitrosative stress

BACKGROUND: Increased oxidative/nitrosative stress is important in the pathogenesis of diabetic complications, and the protective effects of antioxidants are a topic of intense research. The purpose of this study was to investigate whether a pyridoindole antioxidant stobadine (STB) have a protective effect on tissue oxidative protein damage represented by the parameters such as protein carbonylation (PC), protein thiol (P-SH), total thiol (T-SH) and non-protein thiol (Np-SH), nitrotyrosine (3-NT), and advanced oxidation protein products (AOPP) in streptozotocin-diabetic rats. METHODS: Diabetes was induced in male Wistar rats by intraperitonal injection of streptozotocin (55 mg/kg). Some of the non-diabetic (control) and diabetic rats treated with STB (24.7 mg/kg/day) during 16 weeks, and the effects on blood glucose, PC, AOPP, 3-NT, P-SH, T-SH and Np-SH were studied. Biomarkers were assayed by enzyme-linked immunosorbent assay (ELISA) or by colorimetric methods. RESULTS: Administration of stobadine to diabetic animals lowered elevated blood glucose levels by approximately 16% relative to untreated diabetic rats. Although stobadine decreased blood glucose, poor glycemic control was maintained in stobadine treated diabetic rats during the treatment period. Biochemical analyses of liver proteins showed significant diminution of sulfhydryl groups, P-SH, T-SH, Np-SH, and elevation of carbonyl groups in diabetic animals in comparison to healthy controls. As a biomarker of nitrosative stress, 3-NT levels did not significantly change by diabetes induction or by stobadine treatment when compared to control animals. However, the treatment with stobadine resulted in a significant decrease in PC, AOPP levels and normalized P-SH, T-SH, Np-SH groups in liver of diabetic animals. CONCLUSIONS: The results are in accordance with the pro-oxidant role of chronic hyperglycemia, and the ability of stobadine to attenuate protein oxidation and improving tissue reductive capacity may account, at least partly for its observed beneficial effects on tissue function in diabetes.     

Postmitotic tissue selenium and manganese levels in alpha-lipoic acid-supplemented aged rats

Redistribution of selenium and manganese in postmitotic tissues of alpha-lipoic acid-supplemented aged rats has been proposed to contribute to metal-catalyzed protein oxidation. DL-Alpha-lipoic acid (LA) (100 mg/[kg body wt.day]) was administered intraperitoneally to the Sprague-Dawley rats for 14 days. Serum selenium levels were lowered in the aged rats with LA supplementation compared with those of the rats without LA supplementation. Similarly, the selenium levels of the heart, brain and muscle were found to be significantly lower in LA-supplemented rats when compared to control rats. On the other hand, serum manganese levels were not changed in the aged rats with LA supplementation compared with those of the rats without LA supplementation. The heart manganese levels detected in LA-supplemented rats were significantly lower than controls. Manganese levels of the brain and muscle tissues were increased in the aged rats with LA supplementation compared with those of the rats without LA supplementation. Based on the findings of our study, we conclude that LA may exhibit pro-oxidant effect depending on the altered selenium and manganese homeostasis. Thus, our results stress the importance of monitoring the dose of LA supplementation and serum selenium levels, duration of treatment and its potential harmful pro-oxidant effects in the postmitotic tissues of aged rats.     

The effects of delta-9-tetrahydrocannabinol on Krüppel-like factor-4 expression,redox homeostasis,and inflammation in the kidney of diabetic rat

Diabetes mellitus is a complex, multifactorial disorder that is attributed to pancreatic β cell dysfunction. Pancreatic β cell dysfunction results in declining utilization of glucose by peripheral tissues as kidney and it leads to nephropathy. Excessive production and accumulation of free radicals and incapable antioxidant defense system lead to impaired redox status. Macromolecular damage may occur due to impaired redox status and also immune imbalance. Δ9-Tetrahydrocannabinol (THC) is the main active ingredient in cannabis. THC acts as an immunomodulator and an antioxidant agent. Our aim was to evaluate the effects of THC in the diabetic kidney. We analyzed macromolecular damage biomarkers as protein carbonyl (PCO), lipid hydroperoxide (LHP), malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and antioxidant defense system biomarkers as thiol fractions (T-SH, NP-SH, P-SH) and Cu/Zn-superoxide dismutase activity for the antioxidative effects of THC. Furthermore, mRNA expression of Krüppel-like factor-4, secreted immunopositive cell number changes of interleukin-6, nuclear factor κβ (NF-κβ), and peroxisome proliferator-activated receptor-γ and tumor necrosis factor α (TNF-α) levels were analyzed for the immunomodulatory activity of THC. Diabetic rats showed significantly increased levels of PCO, LHP, MDA, and 8-OHdG when compared with controls (P < 0.05 for each parameter). THC significantly reduced the elevated levels of PCO and 8-OHdG (P < 0.05 for both parameters) and also LHP and MDA levels were insignificantly reduced by THC. Also, thiol fractions insignificantly increased in THC administered diabetic kidney when compared with diabetic rats. The NF-κβ cell number significantly decreased in the diabetic rats treated with THC compared with the diabetic group. According to our data, THC has ameliorative effects on the impaired redox status of diabetic kidney and also it acts as an immunomodulator. Therefore, THC might be used as a therapeutic agent for diabetic kidneys but its usage in the healthy kidney may show adverse effects.     

Oxidative stress in the aging rat heart is reversed by dietary supplementation with (R)-(alpha)-lipoic acid.

Oxidative stress has been implicated as a causal factor in the aging process of the heart and other tissues. To determine the extent of age-related myocardial oxidative stress, oxidant production, antioxidant status, and oxidative DNA damage were measured in hearts of young (2 months) and old (28 months) male Fischer 344 rats. Cardiac myocytes isolated from old rats showed a nearly threefold increase in the rate of oxidant production compared to young rats, as measured by the rates of 2,7-dichlorofluorescin diacetate oxidation. Determination of myocardial antioxidant status revealed a significant twofold decline in the levels of ascorbic acid (P = 0.03), but not alpha-tocopherol. A significant age-related increase (P = 0.05) in steady-state levels of oxidative DNA damage was observed, as monitored by 8-oxo-2'-deoxyguanosine levels. To investigate whether dietary supplementation with (R)-alpha-lipoic acid (LA) was effective at reducing oxidative stress, young and old rats were fed an AIN-93M diet with or without 0.2% (w/w) LA for 2 wk before death. Cardiac myocytes from old, LA-supplemented rats exhibited a markedly lower rate of oxidant production that was no longer significantly different from that in cells from unsupplemented, young rats. Lipoic acid supplementation also restored myocardial ascorbic acid levels and reduced oxidative DNA damage. Our data indicate that the aging rat heart is under increased mitochondrial-induced oxidative stress, which is significantly attenuated by lipoic acid supplementation.     

Intermittent hypobaric hypoxia-induced oxidative stress in rat erythrocytes: protective effects of vitamin E, vitamin C, and carnitine

This study was aimed at determining the effect of vitamin E, vitamin C, and carnitine on intermittent hypobaric-hypoxia-induced oxidative stress (OS) in erythrocytes. For this purpose, male Wistar rats of 4 months of age were orally supplemented with one of the antioxidants prior to exposure to altitudes of 5700 m or 6300 m. Hemoglobin (Hb) and OS indices such as osmotic fragility and hemolysis were measured together with lipid peroxidation (LPO) and protein oxidation. The increase in Hb was accompanied by increase in activities of antioxidant enzymes, superoxide dismutase (SOD), and catalase (CAT) during exposure to both the altitudes without any further elevation by supplements. The extent of reduction in osmotic fragility and hemolysis by vitamin E and carnitine was greater at 6300 m than at 5700 m. Increase in LPO products, for example, malondialdehyde (MDA) and lipofuscin-like autofluorescent substances (AFS) was noticeable at both the altitudes, and vitamin E and carnitine were effective in reducing LPO. While protein oxidation products such as carbonyl content (PrC) and advanced oxidation protein products (AOPP) increased at 6300 m, protein sulphydryl (P-SH) content decreased. P-SH levels were restored on supplementation of antioxidants. Hence, our results indicate that vitamin E, vitamin C, and carnitine may be beneficial in overcoming OS and hemolysis under situations such as intermittent hypobaric hypoxia (IHH) and hypobarotherapy wherein hypoxia is used to correct many pathological situations in humans. Further, this study suggests that supplementation of vitamin E, vitamin C, and L-carnitine alone and not in combination can be beneficial in attenuating the OS associated with IHH compared to the unsupplemented rats exposed to two different altitudes.     

Antioxidant role of alpha-lipoic acid in lead toxicity.

The assumption of oxidative stress as a mechanism in lead toxicity suggests that antioxidants might play a role in the treatment of lead poisoning. The present study was designed to investigate the efficacy of lipoic acid (LA) in rebalancing the increased prooxidant/antioxidant ratio in lead-exposed Chinese hamster ovary (CHO) cells and Fischer 344 rats. Furthermore, LA's ability to decrease lead levels in the blood and tissues of lead-treated rats was examined. LA administration resulted in a significant improvement in the thiol capacity of cells via increasing glutathione levels and reducing malondialdehyde levels in the lead-exposed cells and animals, indicating a strong antioxidant shift on lead-induced oxidative stress. Furthermore, administration of LA after lead treatment significantly decreased catalase and red blood cell glucose-6-phosphate dehydrogenase activity. In vitro administration of LA to cultures of CHO cells significantly increased cell survival, that was inhibited by lead treatment in a concentration-dependent manner. Administration of LA was not effective in decreasing blood or tissue lead levels compared to a well-known chelator, succimer, that was able to reduce them to control levels. Hence, LA seems to be a good candidate for therapeutic intervention of lead poisoning, in combination with a chelator, rather than as a sole agent.     

Therapeutic Vitamin A Doses Increase the Levels of Markers of Oxidative Insult in <Emphasis Type="Italic">Substantia Nigra</Emphasis> and Decrease Locomotory and Exploratory Activity in Rats after Acute and Chronic Supplementation

Vitamin A is known to regulate some central nervous system (CNS)-associated functions. Vitamin A at high doses has been demonstrated to be beneficial in the treatment of some diseases, for instance acute promyelocytic leukemia. However, vitamin A and its naturally occurring metabolites (retinoids) are known to alter neuronal function, inducing behavioral disorders. Here we provide an evidence to indicate that vitamin A supplementation, at both therapeutic and excessive doses, induces oxidative stress in the rat substantia nigra. Vitamin A supplementation induced lipid peroxidation, protein carbonylation, and oxidation of protein thiol groups, as well as change in catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity. Surprisingly, locomotory and exploratory activity of rats were decreased after acute and chronic vitamin A supplementation. Therefore, we may conclude from our results that vitamin A supplementation is prooxidant to the rat substantia nigra and effective in altering behavior.     

Protection Against Oxidative Stress Caused by Intermittent Cold Exposure by Combined Supplementation with Vitamin E and C in the Aging Rat Hypothalamus

This study investigated the effects of combined supplementation with vitamin E and C against oxidative stress (OS) caused by intermittent cold exposure (ICE) in the hypothalamus (HY) of aging male Wistar rats [adult (3-months), middle-aged (18-months) and old (24-months)]. Each age was divided into sub-groups: control (CON), cold-exposed at 10 °C (C10), cold-exposed at 5 °C (C5), supplemented control (CON+S) and supplemented cold-exposed at either 5 °C (C5+S) or 10 °C (C10+S). The supplement was a daily dose of 400 mg vitamin C and 50 IU of vitamin E/kg body weight. Cold exposure lasted 2 h/day for 4 weeks. All age groups exposed to cold showed increase in body mass and feeding efficiency. Feeding efficiency in the supplemented old group showed a statistically significant increase in the cold (p < 0.001). Age-related increases in levels of hydrogen peroxide (H₂O₂), protein carbonyl (PrC), advanced oxidation protein products and thiobarbituric acid reactive substances (TBARS) were further increased by cold in the HY. Cold reduced thiol(P-SH) levels and increased superoxide dismutase (SOD) and, catalase (CAT) activities as well as Hsp72 levels. However, supplementation lowered H₂O₂, PrC and TBARS with decreases in Hsp72 levels and in SOD and CAT activities. These changes were concomitant with elevations in P-SH, vitamin E and C levels. The results show that the OS caused by ICE in the HY and its subsequent protection following supplementation is related to the intensity of ICE as well as age of the animal. Immunohistochemical studies are underway to examine the findings on ICE-induced oxidative injury in the HY, and the prospects for vitamin E and C supplementation in the senescent.     

Alpha-lipoic acid does not alter stress protein response to acute exercise in diabetic brain

Heat shock proteins (HSPs) are molecular chaperones which may act protective in cerebrovascular insults and peripheral diabetic neuropathy. We hypothesized that alpha-lipoic acid (LA), a natural thiol antioxidant, may enhance brain HSP response in diabetes. Rats with or without streptozotocin-induced diabetes were treated with LA or saline for 8 weeks. Half of the rats were subjected to exhaustive exercise to investigate HSP induction, and the brain tissue was analyzed. Diabetes increased constitutive HSC70 mRNA, and decreased HSP90 and glucose-regulated protein 75 (GRP75) mRNA without affecting protein levels. Exercise increased HSP90 protein and mRNA, and also GRP75 and heme oxygenase-1 (HO-1) mRNA only in non-diabetic animals. LA had no significant effect on brain HSPs, although LA increased HSC70 and HO-1 mRNA in diabetic animals and decreased HSC70 mRNA in non-diabetic animals. Eukaryotic translation elongation factor-2, essential for protein synthesis, was decreased by diabetes and suggesting a mechanism for the impaired HSP response related to translocation of the nascent chain during protein synthesis. LA supplementation does not offset the adverse effects of diabetes on brain HSP mRNA expression. Diabetes may impair HSP translation through elongation factors related to nascent chain translocation and subsequent responses to acute stress.     

Dietary supplementation with (R)-alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex

Accumulation of divalent metal ions (e.g. iron and copper) has been proposed to contribute to heightened oxidative stress evident in aging and neurodegenerative disorders. To understand the extent of iron accumulation and its effect on antioxidant status, we monitored iron content in the cerebral cortex of F344 rats by inductively coupled plasma atomic emission spectrometry (ICP-AES) and found that the cerebral iron levels in 24-28-month-old rats were increased by 80% (p<0.01) relative to 3-month-old rats. Iron accumulation correlated with a decline in glutathione (GSH) and the GSH/GSSG ratio, indicating that iron accumulation altered antioxidant capacity and thiol redox state in aged animals. Because (R)-alpha-Lipoic acid (LA) is a potent chelator of divalent metal ions in vitro and also regenerates other antioxidants, we monitored whether feeding LA (0.2% [w/w]; 2 weeks) could lower cortical iron and improve antioxidant status. Results show that cerebral iron levels in old LA-fed animals were lower when compared to controls and were similar to levels seen in young rats. Antioxidant status and thiol redox state also improved markedly in old LA-fed rats versus controls. These results thus show that LA supplementation may be a means to modulate the age-related accumulation of cortical iron content, thereby lowering oxidative stress associated with aging.     

Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age

It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve these results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks.     

Gut regulatory peptides bombesin and neurotensin reduce hepatic oxidative stress and histological alterations in bile duct ligated rats

Gut regulatory peptides bombesin (BBS) and neurotensin (NT) exert a wide spectrum of biological actions on gastrointestinal tissues and we have previously shown that they improve intestinal barrier function and oxidative stress in experimentally jaundiced rats. In the present study, we explored their potential action on liver histology and oxidative status in bile duct ligated rats. Seventy male Wistar rats were randomly divided into five groups: controls, sham operated, bile duct ligated (BDL), BDL+BBS (10 μg/kg, s.c. ×3), BDL+NT (300 μg/kg, i.p.). At the end of the experiment, on day 10, serum total bilirubin and alanine aminotransferase (ALT) levels were determined and endotoxin was measured in portal and aortic blood. Liver tissue samples were examined histologically for evaluation of the ratio of portal tracts presenting changes of obstructive cholangiopathy and neutrophils' number in portal tracts. In addition, hepatic oxidative status was estimated on liver homogenates by measurements of lipid peroxidation (malondialdehyde), protein oxidation (protein carbonyl groups) and thiol redox state [reduced glutathione (GSH), oxidized glutathione (GSSG), total non-protein mixed disulfides (NPSSR) and protein thiols (PSH)]. Administration of BBS or NT significantly reduced portal and aortic endotoxaemia observed in obstructive jaundice. Both agents significantly ameliorated liver injury, as demonstrated by improvement of obstructive cholangiopathy and reduction of ALT. This effect was accompanied by prevention of lipid peroxidation, protein oxidation and decrease of the oxidized forms GSSG and NPSSR. Moreover, neutrophil accumulation in portal tracts was significantly decreased. In conclusion, this study shows that gut regulatory peptides BBS and NT reduce cholestatic liver injury, exerting protective effects on portal tract architecture, neutrophil infiltration and hepatic oxidative stress in bile duct ligated rats.     

Dietary supplementation with (R)-α-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex

Abstract

Accumulation of divalent metal ions (e.g. iron and copper) has been proposed to contribute to heightened oxidative stress evident in aging and neurodegenerative disorders. To understand the extent of iron accumulation and its effect on antioxidant status, we monitored iron content in the cerebral cortex of F344 rats by inductively coupled plasma atomic emission spectrometry (ICP-AES) and found that the cerebral iron levels in 24–28-month-old rats were increased by 80% (p<0.01) relative to 3-month-old rats. Iron accumulation correlated with a decline in glutathione (GSH) and the GSH/GSSG ratio, indicating that iron accumulation altered antioxidant capacity and thiol redox state in aged animals. Because (R)-α-Lipoic acid (LA) is a potent chelator of divalent metal ions in vitro and also regenerates other antioxidants, we monitored whether feeding LA (0.2% [w/w]; 2 weeks) could lower cortical iron and improve antioxidant status. Results show that cerebral iron levels in old LA-fed animals were lower when compared to controls and were similar to levels seen in young rats. Antioxidant status and thiol redox state also improved markedly in old LA-fed rats versus controls. These results thus show that LA supplementation may be a means to modulate the age-related accumulation of cortical iron content, thereby lowering oxidative stress associated with aging.     

Alpha-lipoic acid supplementation: tissue glutathione homeostasis at rest and after exercise.

Antioxidant nutrients have demonstrated potential in protecting against exercise-induced oxidative stress. alpha-Lipoic acid (LA) is a proglutathione dietary supplement that is known to strengthen the antioxidant network. We studied the effect of intragastric LA supplementation (150 mg/kg, 8 wk) on tissue LA levels, glutathione metabolism, and lipid peroxidation in rats at rest and after exhaustive treadmill exercise. LA supplementation increased the level of free LA in the red gastrocnemius muscle and increased total glutathione levels in the liver and blood. The exercise-induced decrease in heart glutathione S-transferase activity was prevented by LA supplementation. Exhaustive exercise significantly increased thiobarbituric acid-reactive substance levels in the liver and red gastrocnemius muscle. LA supplementation protected against oxidative lipid damage in the heart, liver, and red gastrocnemius muscle. This study reports that orally supplemented LA is able to favorably influence tissue antioxidant defenses and counteract lipid peroxidation at rest and in response to exercise.     

Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress

In vitro studies have shown that alpha-lipoic acid (LA) is an antioxidant. There is a paucity of studies on LA supplementation in humans. Therefore, the aim of this study was to assess the effect of oral supplementation with LA alone and in combination with alpha-tocopherol (AT) on measures of oxidative stress. A total of 31 healthy adults were supplemented for 2 months either with LA (600 mg/d, n = 16), or with AT (400 IU/d, n = 15) alone, and then with the combination of both for 2 additional months. At baseline, after 2 and 4 months of supplementation, urine for F2-isoprostanes, plasma for protein carbonyl measurement and low-density lipoprotein (LDL) oxidative susceptibility was collected. Plasma oxidizability was assessed after incubation with 100 mM 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) for 4 h at 37 degrees C. LDL was subjected to copper- and AAPH-catalyzed oxidation at 37 degrees C over 5 h and the lag time was computed. LA significantly increased the lag time of LDL lipid peroxide formation for both copper-catalyzed and AAPH-induced LDL oxidalion (p < .05), decreased urinary F2-isoprostanes levels (p < .05), and plasma carbonyl levels after AAPH oxidation (p < .001). AT prolonged LDL lag time of lipid peroxide formation (p < .01 ) and conjugated dienes (p < .01) after copper-catalyzed LDL oxidation, decreased urinary F2-isoprostanes (p < .001), but had no effect on plasma carbonyls. The addition of LA to AT did not produce an additional significant improvement in the measures of oxidative stress. In conclusion, LA supplementation functions as an antioxidant, because it decreases plasma- and LDL-oxidation and urinary isoprostanes.     

Insinuation of exacerbated oxidative stress in sucrose-fed rats with a low dietary intake of magnesium: evidence of oxidative damage to proteins

High sucrose diets and low magnesium intake have been independently implicated in induction of oxidative stress in animal models. The aim of this study was to investigate whether low dietary magnesium intake exacerbates the prooxidant effects of high sucrose feeding. Rats were fed control (C), high sucrose (HS); low magnesium (LM) and high sucrose low magnesium (HSLM) diets for 90 days and oxidative stress evaluated in terms of formation of TBARS, advanced oxidation protein products and protein carbonyls. HS and LM rats showed evidence of lipid peroxidation and protein oxidation in plasma and liver. Enhanced oxidative injury to lipids and proteins after HSLM feeding was indicated by increased carbonyl content (p <0.01) and significantly (p <0.005) higher levels of TBARS in plasma and hepatic tissue relative to both HS and LM groups. Altogether, these results illustrate the potential detrimental and cumulative effects of low magnesium intake combined with high sucrose consumption on oxidative stress variables.     

Oxidative stress and protein oxidation in the brain of water drinking and alcohol drinking rats administered the HIV envelope protein, gp120

Possible roles of oxidative stress and protein oxidation on alcohol-induced augmentation of cerebral neuropathy in gp120 administered alcohol preferring rats drinking either pure water (W rats) or a free-choice ethanol and water (E rats) for 90 days. This study showed that peripherally administered gp120 accumulated into the brain, liver, and RBCs samples from water drinking – gp120 administered rats (Wg rats) and ethanol drinking – gp120 administered rats (Eg rats), although gp120 levels in samples from Eg rats were significantly greater than the levels in samples from Wg rats. The brain samples from ethanol drinking-saline administered (EC) and Wg rats exhibited comparable levels of free radicals that were significantly lower than the levels in Eg rats. Peroxiredoxin-I (PrxI) activity in the brain samples exhibited the following pattern: Wg ≫ ≫ WC ≫ EC > Eg. Total protein-carbonyl and carbonylated hippocampal cholinergic neurostimulating peptide precursor protein levels, but not N -acetylaspartate or N -acetyl aspartylglutamate or total protein-thiol levels, paralleled the free radical levels in the brain of all four groups. This suggests PrxI inhibition may be more sensitive indicator of oxidative stress than measuring free radicals or metabolites. As PrxI oxidation in WC, Wg, and EC rats was reversible, while PrxI oxidation in Eg rats was not, we suggest that alcohol drinking and gp120 together hyperoxidized and inactivated PrxI that suppressed free radical neutralization in the brain of Eg rats. In conclusion, chronic alcohol drinking, by carbonylating and hyperoxidizing free radical neutralization proteins, augmented the gp120-induced oxidative stress that may be associated with an increase in severity of the brain neuropathy.     

Protective effect of green tea on lead-induced oxidative damage in rat’s blood and brain tissue homogenates

Recent studies have shown that lead (Pb) could disrupt tissue prooxidant/antioxidant balance which lead to physiological dysfunction. Natural antioxidants are particularly useful in such situation. Current study was designed to investigate efficacy of green tea extract (GTE), on oxidative status in brain tissue and blood caused by chronic oral Pb administration in rats. Four groups of adult male rats (each 15 rats) were utilized: control group; GTE-group (oral 1.5% w/v GTE for 6 weeks); Pb-group (oral 0.4% lead acetate for 6 weeks), and Pb+GTE-group (1.5% GTE and 0.4% lead acetate for 6 weeks). Levels of prooxidant/antioxidant parameters [lipid peroxides (LPO), nitric oxides (NO), total antioxidant capacity (TAC), glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD)] in plasma, erythrocytes, and brain tissue homogenate were measured using colorimetric methods. Pb concentrations in whole blood and brain tissue homogenate were measured by atomic absorption. In Pb-group, levels of LPO were higher while NO and GSH were lower in plasma, erythrocytes, and brain tissue than controls. TAC in plasma, SOD in erythrocytes, and GST in brain tissue homogenate were lower in Pb-group versus control. GTE co-administrated with Pb-reduced Pb contents, increased antioxidant status than Pb-group. In erythrocytes, Pb correlated positively with LPO and negatively with NO, GSH, SOD, and Hb. In brain tissue homogenate, Pb correlated positively with LPO and negatively with GSH. This study suggests that lead induce toxicity by interfering balance between prooxidant/antioxidant. Treatment of rats with GTE combined with Pb enhances antioxidant/ detoxification system which reduced oxidative stress. These observations suggest that GTE is a potential complementary agent in treatment of chronic lead intoxication.     

The hydroalcoholic extract of watercress attenuates protein oxidation,oxidative stress,and liver damage after bile duct ligation in rats

Cholestatic liver disease is recognized by extreme collagen formation and deposition, which is mediated by free radicals. The aim of the current study was to investigate the probable hepatoprotective effects of hydroalcoholic extract of watercress (WC) against oxidative stress and liver injury in bile duct ligation (BDL)- induced cholestatic rats. A total of 32 male Wistar rats were divided into four groups; sham control (SC), BDL, SC + hydroalcoholic extract of WC and BDL + hydroalcoholic extract of WC. WC-treated rats received daily WC 500 mg/kg/day for 10 days. Biochemical tests, hepatic oxidative stress markers, and antioxidant enzymes activity were estimated. Further, liver hydroxyproline content was assayed and histological analysis was made. The BDL model markedly elevated the protein carbonyl (PCO) and hydroxyproline contents and decreased the glutathione peroxidase (GPx) activity. Hydroalcoholic extract of WC significantly decreased the surge in liver PCO and hydroxyproline levels and increased the reduced GPx enzyme activity contents in the hepatic tissue. As determined by hematoxylin and eosin staining, BDL considerably induced hepatocyte necrosis. Moreover, these changes were significantly attenuated by the hydroalcoholic extract of WC treatment. Our data indicate that the hydroalcoholic extract of WC extract attenuated liver damage in BDL rats by decreasing the hydroxyproline content and histopathological indexes. Also, it reduced oxidative stress by preventing the hepatic protein oxidation and enhancing the activity of the GPx enzyme via antioxidative effect and free-radical scavenging. Our findings suggest that hydroalcoholic extract of WC could be a beneficial new curative agent for cholestatic liver damage.