Oxidative Stress In Aged Rats Research Articles

The effect of TEMPOL pretreatment on postoperative cognitive function, inflammatory response, and oxidative stress in aged rats under sevoflurane anesthesia.

The heterocyclic compound 4-hydroxy-(2,2,6,6-Tetramethylpiperidin-1-yl)oxyl (TEMPOL) has a protective effect on neurological function in brain tissues damaged by ischemia and hypoxia. This study explored the effects of TEMPOL pretreatment on postoperative cognitive function in aged rats under sevoflurane anesthesia, focusing on inflammatory response and oxidative stress. Sixty male rats were divided into normal control (C), sevoflurane anesthesia (S), TEMPOL pretreatment (T), and sevoflurane anesthesia + TEMPOL pretreatment (ST) groups (15 per group). Groups T and ST rats received continuous intraperitoneal TEMPOL (100 mg/kg) for 3 days, while groups C and S rats were injected with 0.9% saline. After pretreatment, groups S and ST received 3% sevoflurane anesthesia. Rats in group S exhibited a longer swimming distance, longer escape latency, lower frequency of platform crossing, and shorter dwell time in the targeted quadrant than those in groups C and T. Rats in group ST exhibited a shorter swimming distance, shorter escape latency, higher frequency of platform crossing, and longer dwell time in the targeted quadrant than those in group S. The expressions of interleukin-6, tumor necrosis factor-α, inducible nitric oxide synthase, and Ym1/2 messenger ribonucleic acid were higher in groups S and ST rats than in groups C and T rats and lower in group ST rats than in group S rat (p < .05). Superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) were lower, while malondialdehyde (MDA) was higher in groups S and ST rats than in groups C and T rats (p < .05). Group ST showed higher SOD, T-AOC, and GSH-Px, and lower MDA than group S (p < .05). TEMPOL pretreatment attenuated postoperative cognitive impairment induced by sevoflurane anesthesia in aged rats. This may be attributed to the downregulation of NR2B-CREB-BDNF pathway, reducing the inflammatory response and oxidative stress damage in hippocampal tissue.

Ameliorative Effect of Ellagic Acid on Aging in Rats with the Potential Mechanism Relying on the Gut Microbiota and Urolithin A-Producing Ability

Ellagic acid (EA) exhibits potential antiaging activity. Differences in individual ability to produce urolithins may result in large interindividual variability in the health effects of EA. Therefore, the effects and mechanism of EA on d-galactose-induced aging, considering urolithin A-producing ability, were investigated. Our results showed that EA improved cognitive impairment and hippocampal damage, increased the GABA (by 107.84-117.86%) and 5-HT (by 72.56-100.85%) levels, and suppressed the inflammatory and oxidative stress in aging rats. Thirteen plasma metabolites and 12 brain metabolites were improved by EA administration in aging rats. In particular, EA showed a better anti-aging effect in high-UroA-producing rats than in the low counterparts, while antibiotic intervention almost offset EA-alleviated aging induced by d-gal. Furthermore, the lower ratio of Firmicutes and Bacteroidota as well as the greater abundances of Akkermansia (by 139.21%), Bifidobacterium (by 88.04%), Clostridium_sensu_stricto_1 (by 183.47%), Lactobacillus (by 97.23%), and Turicibacter (by 83.06%) were observed in the high-UroA-producing group compared with the model group (p < 0.05). These findings provide novel insights into the anti-aging effects of EA and suggest that the ability of the gut microbiota responding to EA largely determines EA's anti-aging performance.

The Protective Effects of Protein-Enriched Fraction from Housefly (Musca domestica) against Aged-Related Brain Aging.

The Musca domestica larvae are well known for its multifunctions and great nutritional value. The present study aimed at investigating the beneficial effect of Musca domestica larvae extract (Mde) against memory impairment, structural damage and oxidative stress in aged rats. Twenty-month-old rats were gavaged with Mde for 2 mo. Morris Water Maze test indicated Mde prevented aging-induced spatial learning and memory dysfunction in the aged rats. Mde supply was also found to attenuate age-associated changes of brain histology that observed by light microscopy and transmission electron microscopy. Moreover, the increase of antioxidant capacity, glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, as well as the decreased methane dicarboxylic aldehyde (MDA) levels, were consistent with these results. Hence, we propose that oral administration of Mde could improve memory impairment via antioxidant action, and Mde has the potential to act as an excellent food supplement or medicine for the attenuation of brain aging.

Electroacupuncture reduces astrocyte number and oxidative stress in aged rats with surgery-induced cognitive dysfunction

ObjectivesTo investigate the effects of electroacupuncture in regulating astrocytes and oxidative stress in a rat model of postoperative cognitive dysfunction (POCD).MethodsMale aged Sprague-Dawley rats were randomized to undergo left hepatic lobe resection to induce POCD, followed by either electroacupuncture or no treatment; or similar surgery without left lobe resection or electroacupuncture (sham). Postsurgical cognitive function, hippocampal astrocyte number and oxidative stress indicators were measured.ResultsAt days 1, 3 and 7 following surgery, escape latency was significantly shorter and platform crossing frequency was increased with electroacupuncture versus other groups. At postoperative day 1, the electroacupuncture group showed significantly fewer glial fibrillary acidic protein (GFAP)-positive hippocampal astrocytes versus the POCD model group. In POCD rats, electroacupuncture significantly decreased serum S100 calcium binding protein B and neuron-specific enolase levels, and increased brain-derived neurotrophic factor and glial cell-derived neurotrophic factor levels, at days 1, 3 and 7. Electroacupuncture significantly attenuated the hippocampal POCD-induced increase in malondialdehyde and decreased superoxide dismutase levels at day 1 following surgery.ConclusionElectroacupuncture may improve cognitive function in rats with POCD by reducing hippocampal GFAP-positive astrocyte number and suppressing oxidative stress.

OXIDATIVE CHANGES AND COGNITIVE FUNCTION DECLINE IN AGING RATS

Objective: This study aims to show that impairment of cognitive function occurred during aging is related to increased oxidative stress.&#x0D; Methods: A total of 36 Sprague Dawley rats were divided into four groups: Young (3 months), middle (14 months), and old age groups (18 and 23 months). Rats were killed and blood was collected for the measurement of oxidative stress which includes deoxyribonucleic acid (DNA) damage and lipid peroxidation (malondialdehyde [MDA] levels). Cognitive function of rats was measured through open-field experiments, Morris water maze (MWM), and object identification.&#x0D; Results: Increased DNA damage and MDA levels were found in middle age and old rats compared to young rats (3 months old, p&lt;0.05). There was an increase in anxiety with age as indicated by the increased production of fecal boli and decreased activity of grooming and rearing. For the navigation test, older rats took a long time to search for the hidden platform compared to young rats. In the probe test (spatial memory test 24 h after the last training), the middle- and old-age groups spent less time at the quadrant compared to the young age group.&#x0D; Conclusion: There is a decline in cognitive function with increased oxidative stress in aging rats.

Magnesium Lithospermate B from Salvia miltiorrhiza Bunge Ameliorates Aging-Induced Renal Inflammation and Senescence via NADPH Oxidase-Mediated Reactive Oxygen Generation.

The present study was conducted to examine whether magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix was renoprotective in pathways related to age-related oxidative stress in aged rats. Magnesium lithospermate B was orally administered at a dose of 2- or 8-mg/kg body weight for 16 consecutive days, and the effects were compared with those of vehicle in old and young rats. Magnesium lithospermate B administration to old rats ameliorated renal oxidative stress through reduction of reactive oxygen species. The old rats exhibited a dysregulation of the expression of proteins related to oxidative stress and inflammation in the kidneys, and MLB administration significantly reduced the protein expression of major subunits of nicotinamide adenine dinucleotide phosphate oxidase (Nox4 and p22phox ), phospho-p38, nuclear factor-kappa B p65, cyclooxygenase-2, and inducible nitric oxide synthase. In addition, MLB-treated old rats showed lower levels of senescence-related proteins such as p16, ADP-ribosylation factor 6, p53, and p21 through effects on the mitogen-activated protein kinase pathway. Magnesium lithospermate B administration also significantly attenuated the age-related increase in serum urea nitrogen, reflecting renal dysfunction, up-regulated podocyte structural proteins, and reduced renal structural injury. Our results provide important evidence that MLB reduces the renal damage of oxidative stress in old rats. Copyright © 2017 John Wiley & Sons, Ltd.

Skeletal muscle ischemia-reperfusion injury and cyclosporine A in the aging rat.

Old patients exhibit muscle impairments and increased perioperative risk during vascular surgery procedures. Although aging generally impairs protective mechanisms, data are lacking concerning skeletal muscle in elderly. We tested whether cyclosporine A (CsA), which protects skeletal muscle from ischemia-reperfusion (IR) in young rats, might reduce skeletal muscle mitochondrial dysfunction and oxidative stress in aging rats submitted to hindlimb IR. Wistar rats aged 71-73 weeks were randomized to IR (3 h unilateral tourniquet application and 2 h reperfusion) or IR + CsA (10 mg/kg cyclosporine IV before reperfusion). Maximal oxidative capacity (VM ax ), acceptor control ratio (ACR), and relative contribution of the mitochondrial respiratory chain complexes II, III, IV (VS ucc ), and IV (VTMPD /Asc ), together with calcium retention capacity (CRC) a marker of apoptosis, and tissue reactive oxygen species (ROS) production were determined in gastrocnemius muscles from both hindlimbs. Compared to the nonischemic hindlimb, IR significantly reduced mitochondrial coupling, VMax (from 7.34 ± 1.50 to 2.87 ± 1.22 μMO2 /min/g; P < 0.05; -70%), and VS ucc (from 6.14 ± 1.07 to 3.82 ± 0.83 μMO2 /min/g; P < 0.05; -42%) but not VTMPD /Asc . IR also decreased the CRC from 15.58 ± 3.85 to 6.19 ± 0.86 μMCa(2+) /min/g; P < 0.05; -42%). These alterations were not corrected by CsA (-77%, -49%, and -32% after IR for VM ax, VS ucc , and CRC, respectively). Further, CsA significantly increased ROS production in both hindlimbs (P < 0.05; +73%). In old rats, hindlimb IR impairs skeletal muscle mitochondrial function and increases oxidative stress. Cyclosporine A did not show protective effects.

Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats.

Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography–tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney.

Carnosine and vitamin E--a promising pair in the combat against testicular oxidative stress in aged rats.

Oxidative stress is considered to play a key role in ageing. Carnosine alone or together with vitamin E may prove to be helpful in dealing with problems of ageing through its antioxidant activity. Testis, by producing steroids and possessing a poor antioxidant system may become a strong target for the chronic oxidative stress generated during ageing. Therefore we investigated the in vivo effect of carnosine alone or together with vitamin E on testicular oxidative stress in aged rats. In this study, young (5 months) and aged (22 months) Wistar rats were used. Carnosine (250 mg kg(-1); i.p.; 5 days per week) and vitamin E (200 mg kg(-1); i.m.; twice per week) were given to aged rats for 2 months. Increased testicular lipid peroxidation and superoxide dismutase activity in aged rats were declined to the levels of young ones by both treatments. Decreased glutathione peroxidase and glutathione transferase activities returned to the level of young's only by carnosine plus vitamin E treatment. Histopathological evaluation described by Johnsen's score, also showed significant improvement with preserved spermatogenesis. Carnosine plus vitamin E treatment appears to stage a powerful performance by attenuating testicular oxidative stress and sparing the antioxidant system.

Mitochondria-targeted ROS scavenger improves post-ischemic recovery of cardiac function and attenuates mitochondrial abnormalities in aged rats

Mitochondria-generated reactive oxygen species (ROS) play a crucial role in the pathogenesis of aging and age-associated diseases. In this study, we evaluated the effects of XJB-5-131 (XJB), a mitochondria-targeted ROS and electron scavenger, on cardiac resistance to ischemia–reperfusion (IR)-induced oxidative stress in aged rats. Male adult (5-month old, n=17) and aged (29-month old, n=19) Fischer Brown Norway (F344/BN) rats were randomly assigned to the following groups: adult (A), adult+XJB (AX), aged (O), and aged+XJB (OX). XJB was administered 3 times per week (3mg/kg body weight, IP) for four weeks. At the end of the treatment period, cardiac function was continuously monitored in excised hearts using the Langendorff technique for 30min, followed by 20min of global ischemia, and 60-min reperfusion. XJB improved post-ischemic recovery of aged hearts, as evidenced by greater left ventricular developed-pressures and rate-pressure products than the untreated, aged-matched group. The state 3 respiration rates at complexes I, II and IV of mitochondria isolated from XJB-treated aged hearts were 57% (P<0.05), 25% (P<0.05) and 28% (P<0.05), respectively, higher than controls. Ca2+-induced swelling, an indicator of permeability transition pore opening, was reduced in the mitochondria of XJB-treated aged rats. In addition, XJB significantly attenuated the H2O2-induced depolarization of the mitochondrial inner membrane as well as the total and mitochondrial ROS levels in cultured cardiomyocytes. This study underlines the importance of mitochondrial ROS in aging-induced cardiac dysfunction and suggests that targeting mitochondrial ROS may be an effective therapeutic approach to protect the aged heart against IR injury.

Tocotrienol rich fraction reverses age-related deficits in spatial learning and memory in aged rats.

Little is known about the effect of vitamin E on brain function. Therefore, in this study we evaluated the effect of tocotrienol rich fraction (TRF) on behavioral impairment and oxidative stress in aged rats. Thirty-six male Wistar rats (young: 3-months-old; aged: 21-months-old) were treated with either the control (olive oil) or TRF (200 mg/kg) for 3 months. Behavioral studies were performed using the open field test and Morris water maze (MWM) task. Blood was taken for assessment of DNA damage, plasma malondialdehyde (MDA) and vitamin E, and erythrocyte antioxidant enzyme activity. Brains were also collected to measure vitamin E levels. Results showed that aged rats exhibited reduced exploratory activity, enhanced anxiety and decreased spatial learning and memory compared with young rats. DNA damage and plasma MDA were increased, and vitamin E levels in plasma and brain were reduced in aged rats. Aged rats supplemented with TRF showed a markedly reduced level of anxiety, improved spatial learning and memory, reduced amount and severity of DNA damage, a reduced level of MDA, and increased levels of antioxidant enzyme activity and plasma/brain vitamin E compared with age-matched controls. In conclusion, TRF supplementation reverses spatial learning and memory decline and decreases oxidative stress in aged rats.

Brain tissue hypoxia and oxidative stress induced by obstructive apneas is different in young and aged rats.

To test the hypotheses that brain oxygen partial pressure (PtO2) in response to obstructive apneas changes with age and that it might lead to different levels of cerebral tissue oxidative stress. Prospective controlled animal study. University laboratory. Sixty-four male Wistar rats: 32 young (3 mo old) and 32 aged (18 mo). Protocol 1: Twenty-four animals were subjected to obstructive apneas (50 apneas/h, lasting 15 sec each) or to sham procedure for 50 min. Protocol 2: Forty rats were subjected to obstructive apneas or sham procedure for 4 h. Protocol 1: Real-time PtO2 measurements were performed using a fast-response oxygen microelectrode. During successive apneas cerebral cortex PtO2 presented a different pattern in the two age groups; there was a fast increase in young rats, whereas it remained without significant changes between the beginning and the end of the protocol in the aged group. Protocol 2: Brain oxidative stress assessed by lipid peroxidation increased after apneas in young rats (1.34 ± 0.17 nmol/mg of protein) compared to old ones (0.63 ± 0.03 nmol/mg), where a higher expression of antioxidant enzymes was observed. The results suggest that brain oxidative stress in aged rats is lower than in young rats in response to recurrent apneas, mimicking obstructive sleep apnea. This could be due to the different PtO2 response observed between age groups and the increased antioxidant expression in aged rats. Dalmases M, Torres M, Márquez-Kisinousky L, Almendros I, Planas AM, Embid C, Martínez-Garcia MA, Navajas D, Farré R, Montserrat JM. Brain tissue hypoxia and oxidative stress induced by obstructive apneas is different in young and aged rats.

Increased capillary vascularity in the femur of aged rats by exercise training

During aging, bone loss occurs in association with alteration of blood perfusion in the tissue. A number of studies have shown that repaired blood perfusion in various organs was improved by regular exercise, but the effect of exercise on bone microcirculation has not been studied fully yet. This study aimed to investigate the effect of exercise training on capillary vascularity in rat femur by directly observing the bone microcirculation under a laser scanning confocal microscope. Male Wistar rats were divided into three groups: sedentary-young (aged 4–6 months), sedentary-aged (aged 20–22 months) and trained-aged (aged 20–22 months). The exercise program included swimming training 5 days/week for 8 weeks. Using our newly devised window chamber, we directly observed the femur microcirculation of each group under a laser scanning confocal microscopic system. Based on the fluorescent image of microvasculature recorded at the surface of the femur, bone capillary vascularity (CV) was measured using computer software. Liver malondialdehyde (MDA) level was also measured to examine the relationship between CV and oxidative stress in aged rats. In the sedentary-aged group, the CV significantly decreased, but the MDA level significantly increased, compared with sedentary-young group. In the trained-aged group, CV was significantly higher, whereas the MDA level was significantly lower, compared with the sedentary-aged group. In both sedentary-young and sedentary-aged rats, the CV was linearly correlated with the MDA level. In conclusion, the swimming exercise could attenuate aged-induced suppression of CV, closely related to exercise-ameliorated oxidative stress in aged.

Protection of cochlear function from aminoglycosides ototoxicity by manganese superoxide dismutase gene in aging rat

determine the feasibility of manganese superoxide dismutase (MnSOD) gene therapy for protecting the cochlear function against aminoglycoside-induced oxidative stress in aging rats. The aging model of SD rats were obtained with 8 weeks daily of D-gal (150 mg/kg per day) hypodermic injection. In the 9th week, amikacin (500 mg/kg per day) were injected intramuscularly into some aging SD rats. The viral particles of recombinant adeno-associated viral vector II/MnSOD (6 microl, 5 x 10(11) vector genomes/ml) were injected into the perilymph through the round window membrane (RWM). The feasibility of MnSOD gene therapy against aminoglycoside-induced oxidative stress in aging rats was evaluated with the methods of caspase-3 protein analysis, apoptosis detection with immunohistochemical, the detection of MnSOD concentration, stretched preparation of basilar membrane and evaluation of hearing threshold with ABR-click. Compared with the control group, the concentration of MnSOD of cochlear tissue was increased (P < 0.05), and the active fragment expression of caspase-3, the numbers of apoptosis bodies and the hearing threshold were decreased (P < 0.05). MnSOD could play a partly role to treat cochlear aminoglycoside-induced oxidative damage in aging rats.

Protective effect of supercritical fluid rosemary extract, Rosmarinus officinalis, on antioxidants of major organs of aged rats

Rosemary leaves, “ Rosmarinus officinalis”, possess a variety of antioxidant, anti-tumoral and anti-inflammatory bioactivities. We hypothesized that rosemary extract could enhance antioxidant defenses and improve antioxidant status in aged rats. This work evaluates whether supplementing their diet with supercritical fluid (SFE) rosemary extract containing 20% antioxidant carnosic acid (CA) reduces oxidative stress in aged rats. Aged Wistar rats (20 months old) were included in the study. Rats were fed for 12 weeks with a standard kibble (80%) supplemented with turkey breast (20%) containing none or one of two different SFE rosemary concentrations (0.2% and 0.02%). After sacrifice, tissue samples were collected from heart and brain (cortex and hippocampus). Enzyme activities of catalase (CAT), glutathione peroxidase (GPX), superoxide dismutase (SOD) and nitric oxide synthase (NOS) were quantitatively analyzed. Lipid peroxidation and levels of reactive oxygen species (ROS) were also determined. Rosemary decreased lipid peroxidation in both brain tissues. The levels of catalase activities in heart and cortex were decreased in the rosemary-treated groups. The SFE rosemary-treated rats presented lower NOS levels in heart and lower ROS levels in hippocampus than the control rats. Supplementing the diet of aged rats with SFE rosemary extract produced a decrease in antioxidant enzyme activity, lipid peroxidation and ROS levels that was significant for catalase activity in heart and brain, NOS in heart, and LPO and ROS levels in different brain tissues. These observations suggest that the rosemary supplement improved the oxidative stress status in old rats.

Effects of the AMPA receptor modulator S 18986 on measures of cognition and oxidative stress in aged rats

Development of cognitive-enhancing drugs that delay or halt mild cognitive impairment progression to Alzheimer's disease would be of great benefit. The aim of this study was to examine the ability of (S)-2,3-dihydro-[3,4]-cyclopentano-1,2,4-benzothiadiazine-1,1-dioxide (S 18986), a positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, to improve behavioral performance and alleviate age-related deficits in oxidative stress status in the prelimbic cortex and hippocampus. Daily administration of S 18986 (0.1, 0.3, and 1.0 mg/kg) or vehicle was given to separate groups of male rats starting at 12 months of age. Additionally, daily vehicle administration was given to a group of rats starting at 3 months of age. Four months after initiation of drug administration, rats were trained and tested in an operant-delayed alternation task and a reinforcer devaluation task. Upon completion of testing, oxidative stress status was assessed in the prelimbic cortex and hippocampus. S 18986 dose-dependently altered responses in the reinforcer devaluation task such that aged rats came to resemble young rats. There were no age or drug effects in the operant-delayed alternation task. Levels of the lipid peroxidation product 4-hydroxy-nonenal (HNE) were increased, and Cu/Zn-superoxide dismutase (SOD) levels were decreased in prelimbic cortex in aged rats, changes that were reversed by S 18986. Similarly, age-related increases in hippocampal HNE levels were prevented by S 18986. Positive modulation of AMPA receptor activity may be a therapeutic approach to halt or slow progression of mild cognitive impairment via improvement in oxidative stress status in the hippocampus and prelimbic cortex.

Suppression of age-related renal changes in NF-κB and its target gene expression by dietary ferulate

Ferulate is a well-described natural antioxidant found in plants. It protects against cellular redox disruption and several oxidative stress-related diseases, including inflammation in animal studies. In this study, we examined ferulate for its ability to suppress redox-sensitive, proinflammatory NF-κB activation via NF-κB-inducing kinase (NIK)/IkappaB kinase (IKK) and mitogen-activated protein kinases (MAPKs) by reducing oxidative stress in aged rats. The experimental design was set as follows: Sprague–Dawley rats, ages 7 months (young) and 20 months (old) were used in this study, and dietary ferulate (0.01% or 0.02%) was fed to the old rats for 10 days. Data show that in aged kidney tissue, ferulate exhibited its antioxidative action by maintaining redox regulation, suppressing NF-κB activation and modulating the expression of NF-κB-induced, proinflammatory COX-2, iNOS, VCAM-1 and ICAM-1. Next, we examined cultured YPEN-1 endothelial cells and show that ferulate protected YPEN-1 cells against tert-butylhydroperoxide-induced oxidative stress. The molecular modulation of NF-κB by ferulate was further revealed in endothelial YPEN-1 cells through ferulate's ability to suppress the activation of NIK/IKK and MAPKs. Based on these results, we conclude that ferulate's antioxidative capacity suppressed the age-related increase in NF-κB activity through inhibition of NIK/IKK and MAPKs in vivo. This study may also suggest the potentiality of ferulate as a developable supplement against chronic inflammatory disease as well as aging.

PROTECTIVE EFFECT OF FOLIC ACID AGAINST H2O2 INDUCED-HEPATIC OXIDATIVE STRESS IN AGED RATS

The protective effect of folic acid (FA) on he-patic oxidative stress in aged rats exposed to oxi-dative stress by supply drinking water with 1% H2O2 (v/v) was studied. Rats were divided into two groups, the first group was considered as standard one (F1) which was fed on basal diet and administrated 1 mg FA/ Kg body weight (BW) daily by stomach tube without addition H2O2 in drinking water. The second group was divided into five subgroups, the first subgroup was the control (F2) which fed on basal diet free from folic acid (FF) with 1 % H2O2 in the drinking water, while other groups from F3 to F6 were adminis-trated different concentrations of folic acid (1, 20, 40 and 80 mg FA/ Kg BW), respectively. Weight gain, total feed intake, feed efficiency, liver weight and its relative weight were estimated. Bi-ochemical assay: activity of antioxidant enzymes system such as superoxide dismutase (SOD), cata-lase (CAT); lipid peroxidation level as malondial-dehyde (MDA), hydrogen peroxidase (H2O2); and liver functions [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phos-phatase (ALP) and gamma glutamyl transferase (γ-GT), and lactate dehydrogenase (LDH)], were determined. Additionally, total protein (TP), al-bumin, globulin, A/G ratio, total bilirubin, direct bilirubin, indirect bilirubin; and kidney functions [creatinine, urea, and uric acid]; and lipid profile as [total cholesterol, HDL-cholesterol and LDL-cholesterol, and triglycerides] were also, carried out. The obtained results showed accumulated weight gain which significantly increased in rats group administrated 40 and 80 mg/ Kg BW/d folic acid. No changes in relative liver weight among tested rat groups were recorded. No significant difference was observed in lipid profile, LDH and SOD between groups (F1 and F6). Data also indi-cated that F1 group recorded the best one which was low in MDA and high in CAT, followed by F6. Folic acid showed no effect on kidney func-tions. No histopathological changes were observed in liver of rat groups administered 40 or 80 mg folic acid / Kg BW/d, thus indicating that supple-mentation with high doses of FA had a protective effect from the hepatic oxidative stress in liver of tested rats.

Effects of Antioxidant Supplementation and Repetitive Loading on Biomarkers of Oxidative Stress in Aged Rats

PURPOSE: The purpose of this study was to characterize the effects of two different dietary antioxidant supplementations and chronic repetitive loading exercise on biomarkers of oxidative stress in aged rats. METHODS: Aged Fischer 344 Brown × Norway rats (30 months) were randomly assigned to either a diet supplemented with Vitamin C (2% by weight) and Vitamin E (30,000 I. U.) (N = 4), curcumin (1% by weight) (N = 5) or normal (unsupplemented) rat chow (N=4). The dorsiflexors of one limb in all animals was loaded 3 times per week for 4.5 weeks. The contralateral limb served as the intra-animal control. Additional control aged (30 months, N=4) and young adult rats (6 weeks of age, N=6) underwent the training protocol, but received the non-supplemented diet. The tibialis anterior muscle (TA) was removed and assayed for biomarkers of oxidative stress that included: the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG), which is a measure of redox status, malondialdehyde (MDA) which is a biomarker for lipid peroxidation, 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is a marker of oxidative damage to DNA, catalase concentration, and cytosolic hydrogen peroxide (HO) levels. RESULTS: The data indicate that compared to control muscles, repetitive loading significantly increased catalase activity and lowered MDA levels in the TA. Non-supplemented chronic exercise significantly increased cytosolic H2O2 levels in the TA of old rats, but decreased the cytosolic H2O2 levels in the TA of young adult rats. Supplementation with Vitamin E & C significantly increased the GSH/GSSG ratio and decreased cytosolic HO levels in muscles of old rats. Supplementation with either Vitamins E & C or curcumin attenuated the increase H2O2 levels in the exercised TA muscle of old rats. Supplementation had no effect on catalase concentration. CONCLUSION: The results suggest that both antioxidant supplementation and repetitive loading exercise can improve the pro-oxidant status in muscles of old rats, but that they may work via different mechanisms.

Green Tea Protection Against Age-Dependent Ethanol-Induced Oxidative Stress

Ethanol intoxication leads to oxidative stress, which may be additionally enhanced by aging. The aim of this study was to investigate the influence of green tea as a source of water-soluble antioxidants on the ability to prevent oxidative stress in aged rats sub-chronically intoxicated with ethanol. Two-, 12-, and 24-mo-old male Wistar rats were divided into 4 experimental groups: (1) control, (2) green tea, (3) ethanol, and (4) ethanol and green tea. Ethanol intoxication produced age-dependent decrease in the activity of serum superoxide dismutase, glutathione peroxidase, and reductase and in levels of glutathione (GSH), vitamins C, E, and A, and βcarotene. Changes in the serum antioxidative ability were accompanied by enhanced oxidative modification of lipid (increase in lipid hydroperoxides, malondiadehyde, and 4-hydroxynonenal levels) and protein (rise in carbonyl group levels). Green tea partially protected against changes in antioxidant enzymatic as well as nonenzymatic parameters produced by ethanol and enhanced by aging. Administration of green tea significantly protects cellular components such as lipids and proteins against oxidative modification. Results indicate that green tea effectively protects blood serum against oxidative stress produced by ethanol as well as aging.