Endogenous Antioxidant Enzyme Activities Research Articles

Effects of D-003, a Mixture of Very Long Chain Saturated Fatty Acids, and Policosanol on in vivo Lipid Peroxidation in Rats

D-003 and policosanol (CAS 557-61-9), specific and distinct mixtures of high molecular weight primary aliphatic acids and alcohols, respectively, have shown to inhibit lipid peroxidation in vivo, but comparative studies between their effects on lipid peroxidation processes had not been conducted before. To compare the effects of D-003 and policosanol on markers of lipid peroxidation in vivo in rats. Male Wistar rats were distributed into 9 groups: a control group treated with acacia gum/water vehicle, 4 with policosanol and 4 with D-003, both treatments at 5, 25, 100 and 250 mg/kg. Treatments were administered during 4 weeks. Both treatments significantly and dose-dependently reduced plasma malondyaldehide (MDA) and total peroxides. Nevertheless, while D-003 was effective from 5 mg/kg, the lowest effective dose of policosanol was 25 mg/kg. The maximal effects of both treatments were obtained with 100 mg/kg, but greater in D-003 than in policosanol group, and the same occurred across all doses tested. MDA concentrations generated with the enzymatic system in liver homogenates were also significantly and dose-dependently inhibited with both treatments. The lowest effective doses of D-003 and policosanol were 5 and 100 mg/kg, respectively, and the highest inhibitions of about 80% (D-003) and 11% (policosanol). D-003 was more effective than policosanol in all comparisons. D-003 was also more effective than policosanol for lowering MDA concentrations generated with the no enzymatic system, but in these conditions policosanol was effective from 25 mg/kg and produced an inhibition somewhat greater (about 29%) than on MDA-generated by the enzymatic system. Both policosanol and D-003 did not modify the activity of endogenous antioxidant enzymes compared with the controls. D-003 (5-250 mg/kg) orally administered for 4 weeks was more effective than policosanol for lowering all the lipid peroxidation markers assessed, like plasma MDA and total peroxides, and MDA concentrations generated by the enzymatic and non-enzymatic oxidant systems of liver homogenates. The inhibitions with D-003 were marked and dose-dependent. Neither D-003 nor policosanol modified the activity of enzymes involved in the endogenic antioxidant defensive system.

Purple corn (Zea mays L.) phenolic compounds profile and its assessment as an agent against oxidative stress in isolated mouse organs.

This study was designed to determine the contents of total polyphenols, flavonoids, flavonols, flavanols, and anthocyanins of purple corn (Zea mays L.) extracts obtained with different methanol:water concentrations, acidified with 1% HCl (1 N). Another objective was to determine the antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and deoxyribose assay, individual phenolic compounds by high-performance liquid chromatography (HPLC), and endogenous antioxidant enzyme (superoxide dismutase [SOD], catalase [CAT], and total peroxidase [TPX]) activity and lipid peroxidation activity (thiobarbituric acid-reactive substances [TBARS] assay) in isolated mouse organs. Overall, the highest total content of polyphenols, anthocyanins, flavonoids, flavonols, and flavanols was obtained with the 80:20 methanol:water extract, acidified with 1% HCl (1 N). The 50% inhibitory concentration values obtained by the DPPH and ABTS assays with this extract were 66.3 μg/mL and 250 μg/mL, respectively. The antioxidant activity by the FRAP assay was 26.1 μM Trolox equivalents/g, whereas the deoxyribose assay presented 93.6% inhibition. Because of these results, the 80:20 methanol:water extract, acidified with 1% HCl (1 N), was used for the remaining tests. Eight phenolic compounds were identified by HPLC: chlorogenic acid, caffeic acid, rutin, ferulic acid, morin, quercetin, naringenin, and kaempferol. Furthermore, it was observed that the purple corn extract was capable of significantly reducing lipid peroxidation (lower malondialdehyde [MDA] concentrations by the TBARS assay) and at the same time increasing endogenous antioxidant enzyme (CAT, TPX, and SOD) activities in isolated mouse kidney, liver, and brain. On the basis of the results, it was concluded that the purple corn extract contained various bioactive phenolic compounds that exhibited considerable in vitro antioxidant activity, which correlated well with the decreased MDA formation and increase in activity of endogenous antioxidant enzymes observed in the isolated mouse organs. This warrants further in vivo studies with purple corn extracts to assess its antioxidant activity and other bioactivities.

Ganoderma lucidum total triterpenes prevent radiation-induced DNA damage and apoptosis in splenic lymphocytes in vitro

The development of radioprotective agents has been the subject of intense research, especially in the field of radiotherapy. In this study, we examined the radioprotective activity of the total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst in mouse splenic lymphocytes in vitro. Using the MTT assay, Ganoderma triterpenes were found to have no effect on cell viability, indicating that they are non-toxic to splenic lymphocytes. The effect of the total triterpenes on DNA damage and apoptosis induced by radiation was analyzed using the comet assay, DNA ladder assay and flow cytometric analysis. Total triterpenes were found to be highly effective in preventing DNA laddering, even at low concentrations (25μg/ml). The comet assay demonstrated that the G. triterpenes effectively prevented DNA damage, and flow cytometry revealed a reduction in apoptotic cells. The effect of the total triterpenes on intracellular reactive oxygen species (ROS) level and endogenous antioxidant enzyme activity in splenic lymphocytes were determined to elucidate possible radioprotective mechanisms. Total triterpenes successfully reduced the formation of intracellular ROS and enhanced endogenous antioxidant enzyme activity in splenic lymphocytes following irradiation. Thus, these findings indicate that the total triterpenes isolated from G. lucidum have a remarkable ability to protect normal cells from radiation-induced damage, which suggests therapeutic potential.

Decreased NADPH oxidase expression and antioxidant activity in cachectic skeletal muscle

BackgroundCancer cachexia is the progressive loss of skeletal muscle protein that contributes significantly to cancer morbidity and mortality. Evidence of antioxidant attenuation and the presence of oxidised proteins in patients with cancer cachexia indicate a role for oxidative stress. The level of oxidative stress in tissues is determined by an imbalance between reactive oxygen species production and antioxidant activity. This study aimed to investigate the superoxide generating NADPH oxidase (NOX) enzyme and antioxidant enzyme systems in murine adenocarcinoma tumour-bearing cachectic mice.MethodsSuperoxide levels, mRNA levels of NOX enzyme subunits and the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidise (GPx) and catalase was measured in the skeletal muscle of mice with cancer and cancer cachexia. Protein expression levels of NOX enzyme subunits and antioxidant enzyme activity was also measured in the same muscle samples.ResultsSuperoxide levels increased 1.4-fold in the muscle of mice with cancer cachexia, and this was associated with a decrease in mRNA of NOX enzyme subunits, NOX2, p40phox and p67phox along with the antioxidant enzymes SOD1, SOD2 and GPx. Cancer cachexia was also associated with a 1.3-fold decrease in SOD1 and 2.0-fold decrease in GPx enzyme activity.ConclusionDespite increased superoxide levels in cachectic skeletal muscle, NOX enzyme subunits, NOX2, p40phox and p67phox, were downregulated along with the expression and activity of the antioxidant enzymes. Therefore, the increased superoxide levels in cachectic skeletal muscle may be attributed to the reduction in the activity of endogenous antioxidant enzymes.

Terminalia arjuna Enhances Baroreflex Sensitivity and Myocardial Function in Isoproterenol-Induced Chronic Heart Failure Rats

Chronic heart failure (CHF) is characterized by left ventricular (LV) dysfunction along with impaired autonomic control functions. Herbal drugs are increasingly being used in the treatment of cardiovascular disorders. The present study was designed to examine the protective effect of Terminalia arjuna (T arjuna) bark extract on LV and baroreflex function in CHF and to elucidate the possible mechanistic clues in its cardioprotective action. The baroreflex was evaluated by measuring the changes in heart rate (HR) with changes in arterial blood pressure induced by bolus injections of phenylephrine (vasoconstrictor) and sodium nitroprusside (vasodilator). T arjuna bark extract and fluvastatin were tested/administered therapeutically and prophylactically in isoproterenol-induced rat model of CHF. Fifteen days after isoproterenol administration, rats exhibited cardiac dysfunction, hypertrophy, and LV remodeling along with reduced baroreflex sensitivity. Prophylactic and therapeutic treatment with T arjuna improved cardiac functions and baroreflex sensitivity. It also attenuated hypertrophy and fibrosis of the LV. Fluvastatin treatment exerted a similar protective effect against myocardial remodeling and heart failure. Further, T arjuna and fluvastatin significantly reduced oxidative stress and inflammatory cytokine level in CHF rats. In conclusion, T arjuna exerts beneficial effect on LV functions, myocardial remodeling, and autonomic control in CHF possibly through maintaining endogenous antioxidant enzyme activities, inhibiting lipid peroxidation and cytokine levels.

Salidroside Protects Against Hydrogen Peroxide-Induced Injury in Cardiac H9c2 Cells via PI3K-Akt Dependent Pathway

Oxidative stress induces serious tissue injury in cardiovascular diseases. Salidroside, with its strong antioxidative and cytoprotective actions, is of particular interest in the development of antioxidative therapies for oxidative injury in cardiac diseases. We examined the pharmacological effects of salidroside on H9c2 rat cardiomyoblast cells under conditions of oxidative stress induced by hydrogen peroxide (H2O2) challenge. Salidroside attenuated H2O2-impaired cell viability in a concentration-dependent manner, and effectively inhibited cellular malondialdehyde production, lethal sarcolemmal disruption, cell necrosis, and apoptosis induced by H2O2 insult. Salidroside significantly augmented Akt phosphorylation at Serine 473 in the absence or presence of H2O2 stimulation; wortmannin, a specific inhibitor of PI3K, abrogated salidroside protection. Salidroside increased the intracellular mRNA expression and activities of catalase and Mn-superoxide dismutases in a PI3K-dependent manner. Our results indicated that salidroside protected cardiomyocytes against oxidative injury through activating the PI3K/Akt pathway and increasing the expression and activities of endogenous PI3K dependent antioxidant enzymes.

Influence of aqueous extract of Arjuna (Terminalia arjuna) on growth and antioxidant defense system of human hepatoma cell line (HepG2)

Arjuna (Terminalia arjuna) is a common medicinal plant used in the ayurvedic system of medicine to treat various ailments and is one of the active ingredients in many polyherbal hepatoprotective formulations currently used in India. Despite its extensive usage, data on its ability to modulate basal oxidative markers in cell models are limited. Hence in the present study we have addressed whether aqueous extract of Arjuna possess the propensity to modulate endogenous oxidative markers in HepG2 cells. Cells were incubated with aqueous extract of Arjuna (1, 5, 10, 25 and 100 µg/ml) for varied time points (4, 8, 12, 16, 20 and 24 h) and biochemical markers of oxidative stress in cell lysate were determined. Cells incubated with Arjuna showed no significant effect in terms of cytotoxicity or cell proliferation upto 100 µg/ml concentrations. However, incubation with Arjuna for 24 h showed diminution in the levels of lipid hydroperoxide (18-42%) and reactive oxygen species (11-29%) in cell cytosol. The antioxidant capacity (19-31%) of cells and levels of reduced glutathione (18-32%) was also found to be significantly increased. Interestingly, aqueous extract of Arjuna also enhanced activities of endogenous antioxidant enzymes (superoxide dismutase, 25-41%; catalase, 39-50%; glutathione peroxidase, 20-35%; glutathione reductase, 26-35% and glutathione transferase, 12-30%). Taken together, these data suggest that Arjuna has the propensity to improve endogenous antioxidant levels and reduce basal oxidative stress in HepG2 cells and indicates its potential as antioxidant and hepatoprotective adjuvant to combat oxidative stress in vivo. Key words: Arjuna, Terminalia arjuna, oxidative stress, antioxidant, HepG2, Hepatoprotection

Anti‐ageing effects of protocatechuic acid from Alpinia on spleen and liver antioxidative system of senescent mice

The effects of Alpinia protocatechuic acid (PCA) on spleen and liver antioxidant system in aged rats have been studied. Alpinia PCA, a phenolic compound, was first isolated from the dried fruits of Alpinia Oxyphylla Miq. in our laboratory. Young and aged rats were injected intraperitoneally with Alpinia PCA at single doses of 5 mg kg(-1) (low dose) or 10 mg kg(-1) (high dose) per day for 7 days. The activities of endogenous antioxidants and the content of lipid peroxide in spleen and liver were assayed. Compared with young group, aged rats had significantly lower splenic weights, lower activities of glutathione peroxidase (GSH-PX) and catalase (CAT), higher level of malondialdehyde (MDA) in spleen and liver. The results proved that Alpinia PCA significantly elevated the splenic weights, increased the activities of GSH-PX and CAT and decreased the MDA level of aged rats. All these suggested that Alpinia PCA was a potential anti-ageing agent, and its effects on spleen and liver were achieved at least partly by promoting endogenous antioxidant enzymatic activities and normalizing age-associated alterations. It may be therapeutically useful to minimize age-associated disorders where oxidative damage is the major cause.

The mitochondrial KATP channel does not mediate exercise preconditining against long duration ischemia

Exercise attenuates arrhythmias during the early moments of ischemia by mitochondrial ATP sensitive K+ (MKATP) channel activation. The purpose of this investigation was to evaluate whether the MKATP channel activation remains essential to exercise mediated arrhythmia prevention in response to extended duration IR (50min I, 120min R). The role of the sarcolemmal ATP sensitive K+ (SKATP) channel and endogenous antioxidant enzyme activities were also examined. 4 mo old rats were randomly assigned to either sham, sedentary, or exercise treatments (3 d × 60 min, ~70% VO2max). Exercised subgroups received MKATP inhibitor (″EXM″, 5HD, 10mg/kg) or SKATP inhibitor (″EXS″, HMR1098, 10mg/kg). ECGs recorded during surgical IR were examined for ventricular ectopy under blinded conditions. All treatment groups exhibited a similar rise in arrhythmias (SED 9.01±4.18, EX 7.19±4.62, EXM 8.02±2.99, & EXS 7.85±3.24) as compared to sham (0.98±0.97; p ≤ 0.001). In conclusion, these data demonstrate that exercise preconditioning affords a finite amount of arrhythmia protection against IR.

Diosgenin Ameliorates Cognition Deficit and Attenuates Oxidative Damage in Senescent Mice Induced by D-Galactose

This study attempted to access the neuroprotective effect of diosgenin on the senescent mice induced by d-galactose (D-gal). The mice in the experiments were orally administered with diosgenin (1, 5, 25 and 125 mg/kg), for four weeks from the sixth week. The learning and memory abilities of the mice in Morris water maze test and the mechanism involved in the neuroprotective effect of diosgenin on the mice brain tissue were investigated. Diosgenin (5, 25 and 125 mg/kg, p.o.) showed significantly improved learning and memory abilities in Morris water maze test compared to D-gal treated mice (200 mg/kg, ten weeks). Diosgenin also increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the malondialdehyde (MDA) level in the brain of D-gal treated mice. These results indicated that diosgenin has the potential to be a useful treatment for cognitive impairment. In addition, the memory enhancing effect of diosgenin may be partly mediated via enhancing endogenous antioxidant enzymatic activities.

Neuroprotective effects of Abacopterin E from Abacopteris penangiana against oxidative stress-induced neurotoxicity

Abacopterin E (AE) was isolated from Abacopteris penangiana (Hook.) Ching. This study was to elucidate its neuroprotective effects against hydrogen peroxide (H(2)O(2)) induced oxidative damage in PC12 cells and d-galactose (d-Gal) induced neurotoxicity in mice brain. In vitro, the protective effect of AE against H(2)O(2)-induced oxidative damage in the PC12 was investigated by the method of MTT (3,(4,5-dimethylthiazole-2-yl)2,5-diphenyl-tetrazolium bromide). In vivo, the protective effect of AE against d-Gal-induced neurotoxicity in mice was studied. The mice in the model group and the AE treatment groups were injected with the d-Gal 150 mg/(kg d) for 7 weeks while the mice in the control group were injected with the same volume of saline (0.9%). From the sixth week, the treatment groups were subcutaneously injected 4 or 8 mg/(kg d) of AE. In order to explore the potential mechanism of AE's action, the mice were assessed by behavioral and electrophysiological tests at the end of the administration. Then the mice brain tissues were measured for the levels of superoxide dismutases (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA). This study showed that AE lowered the H(2)O(2)-induced cytotoxicity, and AE significantly improved the learning and memory ability in behavioral performance. The biochemical examination revealed that AE restored the activities of SOD and GSH-Px, and attenuated the increase of MDA. Moreover, the electrophysiological analysis evidently showed that AE ameliorated the long-term potentiation (LTP). These results suggested that AE had neuroprotective effects, and its beneficial effects may be linked with inhibiting the generation of free radical and enhancing the activities of endogenous antioxidant enzymes.

Mechanistic Clues in the Cardioprotective Effect of Terminalia Arjuna Bark Extract in Isoproterenol-Induced Chronic Heart Failure in Rats

The present study demonstrated prophylactic and therapeutic potential of Terminalia arjuna bark extract in isoproterenol (ISO)-induced chronic heart failure (CHF). Fifteen days after injection of ISO (85 mg/kg twice at an interval of 24 h, s.c), rats showed decline in maximal rate of rise and fall of left ventricular pressure (LV (dP/dt)(max) and LV (dP/dt)(min)), cardiac contractility index (LV (dP/dt)(max)/LVP), cardiac output and rise in LV end-diastolic pressure. CHF rats showed a significant increase in serum creatine kinase isoenzyme-MB (CK-MB) and malondialdehyde levels, as well as fall in the activities of superoxide dismutase, reduced glutathione. Altered lipid profile and increased level of cytokine tumour necrosis factor-α (TNF-α) along with histological changes in heart were also observed in CHF rats. T. arjuna bark extract (500 mg/kg, p.o) treatment prior and 15 days after ISO injection significantly attenuated cardiac dysfunction and myocardial injury in CHF rats. Cardioprotective action of T. arjuna was comparable to fluvastatin, a synthetic drug. The results suggest that T. arjuna bark extract has a significant prophylactic and therapeutic beneficial effect on protection of heart against ISO-induced CHF possibly through maintaining endogenous antioxidant enzyme activities, inhibiting lipid peroxidation and cytokine levels.

Neuropsychopharmacological effect of sesamol in unpredictable chronic mild stress model of depression: behavioral and biochemical evidences

A complex relationship exists among stressful situations, body's reaction to stress, and the onset of clinical depression. Chronic unpredictable stressors can produce a situation similar to clinical depression, and such animal models can be used for the preclinical evaluation of antidepressants. Many findings have shown that the levels of proinflammatory cytokines (e.g., TNF-α) and oxidative stress (increased lipid peroxidation, decreased glutathione levels, and endogenous antioxidant enzyme activities) are increased in patients with depression. Sesamol, a phenolic derivative with a methylenedioxy group, is a potent inhibitor of cytokine production as well as an antioxidant. The present study was designed to investigate the effect of sesamol on unpredictable chronic stress-induced behavioral and biochemical alterations in mice. Animals were subjected to different stress paradigms daily for a period of 21days to induce depressive-like behavior. The sucrose preference, immobility period, locomotor activity, memory acquisition, and retention were evaluated. Chronic treatment with sesamol significantly reversed the unpredictable chronic stress-induced behavioral (increased immobility period, reduced sucrose preference), biochemical (increased lipid peroxidation and nitrite levels; decreased glutathione levels, superoxide dismutase and catalase activities), and inflammation surge (serum TNF-α) in stressed mice. The study revealed that sesamol exerted antidepressant-like effects in behavioral despair paradigm in chronically stressed mice, specifically by modulating central oxidative-nitrosative stress and inflammation.

Triptolide Alleviates Hepatic Ischemia/Reperfusion Injury by Attenuating Oxidative Stress and Inhibiting NF-κB Activity in Mice

Hepatic I/R injury is unavoidable in liver transplantation and surgery. This remains a significant problem in surgical procedures. The purpose of this study was to investigate the effects of triptolide on liver ischemia/reperfusion (I/R) injury and related mechanisms in mice. Male C57BL/6 mice were randomized into four groups: (1) sham group; (2) sham-triptolide group; (3) I/R group; and (4) I-R/triptolide group. Ninety minutes of warm ischemia was induced and flow by 24 h reperfusion. Serum alanine aminotransferase and aspartate aminotransferase were assayed, pathologic alterations and (NF)-κB p65 immunohistochemistry were observed. Liver malondialdehyde (MDA) level, activity of endogenous antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, and activity of neutrophil accumulation marker myeloperoxidase (MPO) were measured. TNF-α, IL-6, and IL-1β mRNA were detected by RT-PCR, whereas nuclear factor (NF)-κB p65 and IκBα were assessed with Western blotting. Plasma aminotransferase activity was higher in the I/R group than in the I/R-triptolide group. MDA level and neutrophil infiltration were also markedly reduced, while SOD, CAT, and GSH-Px levels increased in I/R-triptolide group compared with I/R group. In group 4, histopathologic changes were significantly attenuated in triptolide-treated livers. In comparison with group 3, triptolide reduced NF-κB p65 nuclear and IκBα expression, and effectively suppressed pro-inflammatory cytokine level during the I/R. These results suggest that triptolide has protective effects against hepatic I/R injury. Its mechanisms might be related to reduction of oxidative stress and neutrophil infiltration and inhibition NF-κB p65 activity.

Relationship Between Plasma Carotenoids, Fruit and Vegetable Intake, and Plasma Extracellular Superoxide Dismutase Activity in Women: Different in Health and Disease?

Abstract Exogenous antioxidants may influence endogenous antioxidant enzyme activity. We observed in healthy women (n = 95) that higher plasma α-carotene, β-carotene, β-cryptoxanthin, sum of plasma carotenoids, and fruit and vegetable intake were associated with lower plasma extracellular-superoxide dismutase activity. In women with a history of cardiovascular disease, diabetes, or cancer (n = 62), we observed no associations. Our observation that plasma extracellular-superoxide dismutase activity was inversely associated with plasma carotenoids and fruit and vegetable intake in healthy women, but not in women with a history of cardiovascular disease, diabetes, or cancer, suggests that the associations between exogenous and endogenous antioxidants may differ in health and disease.

Therapeutic effects of SMND-309, a new metabolite of salvianolic acid B, on experimental liver fibrosis

(2E)-2-{6-[(E)-2-carboxylvinyl]-2,3-dihydroxyphenyl}-3-(3,4-dihydroxyphenyl) propenoic acid, a novel compound designated SMND-309, is a new metabolite of salvianolic acid B. The present study was carried out to investigate the effects of SMND-309 on experimental liver fibrosis in rats induced by subcutaneous injection of carbon tetrachloride and explore its possible mechanisms on the basis of biochemical, histopathologic and immunohistochemical studies. The results showed that intragastrical treatment with SMND-309 ameliorated liver function and decreased the elevation of serum hyaluronic acid, laminin, procollagen type III levels and hydroxyproline content in liver tissue. It also decreased the elevation in the malondialdehyde level and restored the decrease in superoxide dismutase and glutathione peroxidase activities. Upon histopathologic examination, the SMND-309-treated rats reduced the liver damage and the liver fibrosis grade. Moreover, the results of immunohistochemical examination showed that SMND-309 powerfully down-regulated the expression of connective tissue growth factor (CTGF) rather than transforming growth factor-beta1 (TGF-β1) in serum and liver. Meanwhile, SMND-309 exhibits significantly higher potency compared with salvianolic acid B (Sal B) at the same dose. The antifibrotic mechanisms of SMND-309 might be associated with its ability to suppress the expression of CTGF as well as scavenge lipid peroxidation products and increase endogenous antioxidant enzyme activity.

Effect of feeding blended and interesterified vegetable oils on antioxidant enzymes in rats

The present study was undertaken to evaluate the effect of feeding blended and interesterified oils prepared using coconut oil (CNO) with rice bran oil (RBO) or sesame oil (SESO), with a polyunsaturated/saturated (P/S) ratio of 0.8–1.0, on oxidative stress and endogenous antioxidant system. Feeding blended oils resulted in significantly increased hepatic lipid peroxide levels in rats given blended oil CNO+RBO or CNO+SESO by 1.3 and 1.6-fold, respectively compared to rats fed diet containing CNO. The lipid peroxide level in erythrocyte membrane also increased in rats fed blended oil compared to rats fed with CNO. Rats fed interesterified oils prepared from these blended oils also showed increased lipid peroxide level compared to rats given CNO diet, however it was not significantly different from rats fed with their respective blends. There was a significant increase in the activity of endogenous antioxidant enzymes super oxide dismutase, catalase, glutathione peroxidase and glutathione-s-transferase after feeding blended and interesterified oils. The activities of Na+/K+-ATPase and Ca2+/Mg2+-ATPase were increased in rats fed blended and interesterified oils. These results indicated that the P/S ratio of dietary fat is an important factor in determining the oxidative stress, activity of endogenous antioxidant enzymes and activity of membrane bound enzymes.

Initiating Treadmill Training In Late Middle Aged Rats Exacerbates Skeletal Muscle Protein Carbonyl Accumulation In Senescence

Age-related loss of muscle mass and function exhibits a marked acceleration from late middle age to senescence and may in part be due to an increase in oxidative damage. Exercise training is one method that may slow this process. PURPOSE: This study was carried out to test the hypothesis that long term exercise training initiated at late middle age would attenuate the age related increase in oxidative damage in senescence via an increase in endogenous antioxidant enzyme activity. METHODS: 29 mo old male F344BN rats were treadmill trained 5 d/wk for 2 mo and then 4 d/wk for the last 3-5 mo for 1 h each day (35T), while another group remained cage bound (35C). A young sedentary cage bound group (7C) was also included. Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities were measured spectrophotometrically in the mixed vastus lateralis muscle. Cross sections from the gastrocnemius muscle were fluorescently labelled for slow myosin heavy chain, dystrophin and carbonyls. RESULTS: SOD, CAT, and GPX activities all increased with age. SOD activity had a further ∼25% increase with training. Fiber area was smaller in 35C and 35T compared to 7C across all fiber types. Type IIa fiber area was lower in 35T compared to 35C (825±102 μm2 vs 1579±175 μm2) as were type IIb/x fibers (35T: 1468±266 μm2 vs 35C: 2488±348 μm2). Type I fiber area was similar between 35T and 35C (35T: 1528±179 μm2, 35C: 1619±191 μm2). 35T had a greater percentage of small fibers (CSA≤1000 μm2) than 35C and small fibers were virtually non existent in 7C. Carbonyl intensity was 50% greater in 35C than 7C, and 150% and 25% greater in 35T than 7C and 35C, respectively. Carbonyl intensity was higher in smaller muscle fibers across all muscle phenotypes. CONCLUSION: Although exercise training initiated at late middle age was able to increase antioxidant defences, contrary to our hypothesis there was a greater accumulation of oxidative damage in response to exercise training in senescence. Supported by NSERC, CIHR, AHFMR

Whole body radioprotective activity of an acetone–water extract from the seedpod of Nelumbo nucifera Gaertn. seedpod

Procyanidins extracted with acetone–water from lotus ( Nelumbo nucifera Gaertn.) seedpod (LSPCs) were evaluated for in vivo radioprotective activity against whole body gamma irradiation in Swiss albino mice. Pretreated with LSPCs 200 mg/kg by intragastric ( i.g.) for 15 days was found to be the most effective dose in preventing radiation sickness, reducing radiation-induced mortality, increasing mean survival time and elevating radiation median lethal dose (LD 50) from 8.9 to 10.5 Gy, indicating a dose modifying factor (DMF) of 1.18. Further, administered LSPCs at a dose of 200 mg/kg could effectively maintain spleen index close to normal, stimulate endogenous spleen colony forming units, promote the levels of red blood cells (RBC), white blood cells (WBC), platelets and hemoglobin in peripheral blood, and prevent spleen and skin damage in irradiated mice, reduce the level of radiation-induced micronucleated polychromatic erythrocytes in bone marrow, maintain the polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) ratio ( P/ N ratio) and significantly decrease bone marrow chromosomal damage. Alternatively, pretreated with LSPCs (200 mg/kg) significantly decreased the lipid peroxidation (LPO) level, and elevated the activities of endogenous antioxidant enzymes in liver after irradiation. Thus LSPCs possess a strong whole body radioprotective activity, and it may be used as a radioprotector.

Beneficial effects of hydrogen gas in a rat model of traumatic brain injury via reducing oxidative stress

Traumatic brain injury (TBI) is a leading cause of mortality and disability among the young population. It has been shown that hydrogen gas (H 2) exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radical ( OH, the most cytotoxic ROS). Recently, we have found that H 2 inhalation significantly improved the survival rate and organ damage of septic mice. In the present study, we investigated the effectiveness of H 2 therapy on brain edema, blood–brain barrier (BBB) breakdown, neurological dysfunction and injury volume in TBI-challenged rats. In addition, we investigated the effects of H 2 treatment on the changes of oxidative products and antioxidant enzymes in brain tissue of TBI-challenged rats. Hydrogen treatment was given by exposure to 2% H 2 from 5 min to 5 h after sham or TBI operation, respectively. Here, we found that TBI-challenged rats showed significant brain injuries characterized by the increase of BBB permeability, brain edema and lesion volume as well as neurological dysfunction, which was significantly attenuated by 2% H 2 treatment. In addition, we found that the decrease of oxidative products and the increase of endogenous antioxidant enzymatic activities in the brain tissue may be associated with the protective effects of H 2 treatment in TBI-challenged rats. The present study supports that H 2 inhalation may be a more effective therapeutic strategy for patients with TBI.