Oxidative Stress Defense System Research Articles

The manganese-salen compound EUK-134 and N-acetyl cysteine rescue from zinc- and paraquat-induced toxicity in rat polymorphonuclear leukocytes

Oxidative stress is implicated in toxicant-induced inflammation leading to chronic diseases. Polymorphonuclear leukocytes (PMNs) offer the first line of defense against infection in the mammals and protect against inflammation-mediated pathological anomalies. Conversely, activated PMNs contribute to the oxidative stress-mediated damage and inflammation. The study aimed to investigate the status of oxidative stress and antioxidant defense system in the PMNs of rats treated with/without zinc (Zn) and/or paraquat (PQ) in the presence or absence of a synthetic superoxide dismutase/catalase mimetic, a manganese-salen compound-EUK-134 and/or a glutathione precursor, N-acetyl cysteine (NAC). While Zn and/or PQ elevated the total free radical generation, lipid peroxidation (LPO) and catalytic activity of myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase alpha 4-4 (GSTA4-4), a pronounced decrease in reduced glutathione (GSH) and glutathione reductase (GR) activity was also observed. Zn and/or PQ augmented the expression of metallothionein-I and II and GSTA4-4. Pre-treatment of EUK-134 or NAC alone altered the level of total free radical generation, LPO, GSH content and catalytic activity of MPO, SOD, GR and GPx and the expression of metallothionein I and II towards normalcy. The alterations were more pronounced in the PMNs of rats treated with EUK-134 and NAC in combination. Catalytic activity/expression of GSTA4-4 remained unchanged in the PMNs of EUK-134 or NAC treated rats. The results demonstrate that EUK-134 and NAC protect PMNs from the toxic effects of Zn and PQ in rats and also suggest that metallothioneins I/II might contribute to antioxidant defense under GSH depleted conditions.

Candida glabrata candidemia.

Candida glabrata candidemia.

The influence of macro and trace elements on sperm quality

The aim of this study was to examine the association between combined concentrations of macro and trace elements and markers of oxidative stress and antioxidative defense system function together with selected cytokine levels. Based on the combined medians of the seminal plasma levels of calcium, magnesium, zinc, copper, iron, and selenium, the study subjects (88 fertile male volunteers) were divided into the following two subgroups: the Me-L group (low level of metals) and the Me-H group (high level of metals). There was a tendency toward reduced motility in the Me-H group compared to that in the Me-L group. The total protein, albumin, and total oxidation status (TOS) levels were significantly higher in the Me-H group than in the Me-L group. The total superoxide dismutase (SOD), Mn-SOD, and CuZn-SOD, activity in spermatozoa were significantly lower in the Me-H group than in the Me-L group. In seminal plasma, the Mn-SOD activity was significantly higher in the Me-H group, whereas the CuZn-SOD activity was significantly lower. Additionally, the activity levels of glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were lower in the Me-H group. The medians of IL-1β, IL-10, and IL-12 were significantly higher in the Me-H group than in the Me-L group, whereas the medians of IL-2, IL-5, and IL-13 were significantly lower. Higher levels of macro and trace elements in the seminal plasma of fertile males may be associated with decreased motility. Higher levels of the examined metals are associated with elevated oxidative stress accompanied by decreased activities of some of the antioxidant enzymes and increased pro-inflammatory cytokine levels.

Mechanistic basis for protection of differentiated SH-SY5Y cells by oryzanol-rich fraction against hydrogen peroxide-induced neurotoxicity.

BackgroundApoptosis is often the end result of oxidative damage to neurons. Due to shared pathways between oxidative stress, apoptosis and antioxidant defence systems, an oxidative insult could end up causing cellular apoptosis or survival depending on the severity of the insult and cellular responses. Plant bioresources have received close attention in recent years for their potential role in regulating the pathways involved in apoptosis and oxidative stress in favour of cell survival. Rice bran is a bioactive-rich by-product of rice milling process. It possesses antioxidant properties, making it a promising source of antioxidants that could potentially prevent oxidative stress-induced neurodegenerative diseases.MethodsThus, the present study investigated the neuroprotective properties of oryzanol-rich fraction (ORF) against hydrogen peroxide (H2O2)-induced neurotoxicity in differentiated human neuroblastoma SH-SY5Y cells. ORF was extracted from rice bran using a green technology platform, supercritical fluid extraction system. Furthermore, its effects on cell viability, morphological changes, cell cycle, and apoptosis were evaluated. The underlying transcriptomic changes involved in regulation of oxidative stress, apoptosis and antioxidant defence systems were equally studied.ResultsORF protected differentiated SH-SY5Y cells against H2O2-induced neurotoxicity through preserving the mitochondrial metabolic enzyme activities, thus reducing apoptosis. The mechanistic basis for the neuroprotective effects of ORF included upregulation of antioxidant genes (catalase, SOD 1 and SOD 2), downregulation of pro-apoptotic genes (JNK, TNF, ING3, BAK1, BAX, p21 and caspase-9), and upregulation of anti-apoptotic genes (ERK1/2, AKT1 and NF-Kβ).ConclusionThese findings suggest ORF may be an effective antioxidant that could prevent oxidative stress-induced neurodegenerative disorders.

Phenolic compounds oleuropein and hydroxytyrosol exert differential effects on glioma development via antioxidant defense systems

Oxidative stress is involved in many of the stages of tumorigenesis, and the administration of exogenous antioxidants seems to modulate them. Thus, it has been described that oleuropein and hydroxytyrosol exert important anti-cancer activities. We analyse in vivo the anti-tumor properties of both phenolic compounds in an animal model of glioma, and their effects on oxidative stress, enzymatic and non-enzymatic antioxidant defence systems and on several biochemical biomarkers. Hydroxytyrosol, but not oleuropein nor the mixture of both compounds, inhibits tumor growth through mechanisms that involve enzymatic and non-enzymatic antioxidant defences, as demonstrated by a decrease in lipid peroxidation and protein oxidation levels. Furthermore, hydroxytyrosol maintains the non-enzymatic antioxidants as in healthy animals, and positively modifies the enzymatic antioxidants. However, hydroxytyrosol probably acts not as an antioxidant, but through other mechanisms that only indirectly modify the redox status. Finally, these compounds yield few adverse effects related to changes in hepatic enzymes.

Ameliorative effect of pumpkin oil (Cucurbita pepo L.) against alcohol-induced hepatotoxicity and oxidative stress in albino rats

ObjectiveThe aim of the present study was to evaluate the protective role of pumpkin oil on experimental alcohol – induced hepatotoxicity. Materials and methodsRats are divided into three groups of 10 animals each. Group one (G1) was the control group is orally given distilled water for 4 weeks. Group two (G2) is given absolute ethyl alcohol (10%) in drinking water for 4 weeks. Group three (G3) alcohol– administered rats were pretreated with pumpkin oil (50 mg/kg body weight) three times per week for three weeks and alcohol (10%) three times per week (at the first two weeks of the experiment). ResultsAlcohol caused a marked rise in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (γGT) activities. Concerning oxidative stress and antioxidant defense system, the depleted hepatic glutathione content, glutathione-S-transferase and catalase activities of alcohol-administered rats were potentially increased above normal levels as a result of pretreatment with pumpkin oil. However, while elevated lipid peroxidation was noticed in alcohol treated rats, pretreatment with pumpkin oil produced a detectable decrease in lipid peroxidation level. ConclusionThe natural plant components found in pumpkin could improve the liver against alcohol-induced liver toxicity and oxidative stress. However, further clinical studies are required to assess the safety and benefits of pumpkin oil in human beings.

Erythrocyte superoxide dismutase, glutathione peroxidase, and catalase activities and risk of coronary heart disease in generally healthy women: a prospective study.

Erythrocyte antioxidant enzymes are major circulating antioxidant enzymes in the oxidative stress defense system. Few prospective studies have assessed the association between these enzymes and the risk of coronary heart disease (CHD) in generally healthy adults. We conducted a prospective nested case-control study of CHD among 32,826 women at baseline with 15 years of follow-up from 1989 to 2004 in the Nurses' Health Study. We investigated the association of baseline erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities with the risk of CHD. A total of 365 cases and 728 controls were included in the analysis. Overall, the relative risks of CHD associated with 1-standard deviation higher SOD, GPx, and CAT activities were 1.07 (95% confidence interval (CI): 0.94, 1.22), 1.04 (95% CI: 0.91, 1.18), and 1.04 (95% CI: 0.92, 1.17), respectively. Multivariable adjustments did not change the associations appreciably. Fasting status did not modify the associations, with the exception that SOD activity was positively associated with the risk of CHD among participants who provided blood samples within 12 hours of fasting. Overall, activities of SOD, GPx, and CAT were not associated with CHD among women who were generally healthy at the time of blood collection.

Age-related peculiarities of change in content of free radical oxidation products in muscle during stress

The age-dependent peculiarities of stimulation of free radical processes in subcellular fractions of skeletal muscle of rats subjected to long-term immobilization stress were studied in order to improve knowledge about changes of muscular tissue during ontogenesis. It is found that adult animals do not show accumulation of proteins carbonyls, TBA-reactive substances, and Schiff bases in subcellular fractions of the thigh muscle when immobilized. Long-term immobilization causes apparent manifestation of oxidative stress only in mitochondrial fraction in pubertal rats. Mitochondrial oxidative stress defense systems are sufficiently effective, however, direction of pathways of free radical oxidation carbonyl products catabolism alters in the cytoplasm of myocytes in old rats under long-term immobilization conditions.

Biomarkers of oxidative stress and antioxidant defense system among Guatemalan preschool children attending daycare centers with a common menu offering (639.2)

Objective: To describe and compare urine oxidative stress biomarkers and erythrocyte antioxidant enzymes activity, in preschoolers from 3 daycare centers in Guatemala Methods: 74 (2‐6 y/o) children (36 F / 38 M) attending 3 government‐subsidized daycare centers identified by location, coded as Center (C) and as to unique location: A (semi‐urban n=19); B (marginal‐urban n=23); and C (rural n=32) enrolled to measure oxidative damage to DNA (8‐hydroxydeoxyguanosine {8‐OHdG}) and lipid (15‐Isoprostane F2t {F2‐Iso}) and the erythrocyte activity of Catalase (CAT), Superoxide Dismutase (SOD), and Glutathione Reductase (GSHR) and Peroxidase (GPx) Results: 8‐OHdG and F2‐Iso median values were different between sexes (p=0.03 and p=0.04, respectively), even when calculating the total amount excreted per day and adjusting to weight. GPx also differed by sex (p=0.01). According to location 8‐OHdG and F2‐Iso were different between CA and CB (p<0.01 and p<0.01, respectively). CAT and GSHR were different in CB when compared to CA and CC (p<0.01 in both cases). SOD activity was different among all 3 centers (p<0.01), whereas GPx was different between CB and CC (p=0.02) Conclusion: Differences in oxidative biomarkers between sexes, especially those biomarkers that are involved in lipid oxidation (F2‐Iso and GPx), are seen.Funded by: Fundación Iberoamericana de Nutrición (FINUT), Spain and The Hildegard Grunow Foundation (HGF), GermanyGrant Funding Source: Supported by Fundación Iberoamericana de Nutrición (FINUT) and The Hildegard Grunow Foundation (HGF)

Influence of Azithromycin Treatment on Hepatic Lipid Peroxidation and Antioxidant Defence Systems of Rats

Aim: Azithromycin is a semisynthetic macrolide antibiotic commonly indicated for use in middle ear, upper and lower respiratory tract infections, bronchitis, and communityacquired pneumonia with a well-established safety and efficacy profile. The antibiotic is usually well tolerated; however, it has been associated with rare cases of progressive cholestatic hepatitis and fulminant hepatic failure. This study was therefore designed to examine the effect of two doses of Azithromycin; 5.6 mg/kg body weight, (b.w.) and 11.2 mg/ kg b.w. on some hepatic and renal function indices, oxidative stress and antioxidant defense system in rats. Study Design: Toxicological, Histological and Biochemical study. Place and Duration of Study: Biochemistry Unit, Department of Chemical Sciences, Faculty of Natural Sciences, Ajayi Crowther University, Oyo, Nigeria between March 2012 and April 2012. Methodology: Thirty rats (Wistar strain) weighing between 180 – 200 g were randomly assigned into three treatment groups of ten animals each; Group I (Control) did not receive any drug, Group II received 5.6 mg/ kg b.w. and Group III received 11.2mg/ kg b.w. Azithromycin by oral gavage twice daily for seven days. Results: Urea, Creatinine and Bilirubin levels were significantly (p=0.05) elevated in the plasma of the rats that received 5.6 mg/ kg b.w. and 11.2mg/ kg b.w. by 20.0% and Original Research Article British Journal of Pharmaceutical Research, 4(2): 240-256, 2014 241 35.0%, 78.0% and 130.0%, and 14.0% and 47.4% respectively when compared to the control. Activities of some marker enzymes; aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and Gamma-glutamyl transferase (GGT) were also significantly increased (p=0.05) in the plasma of treated animals by 19.0% and 36.6%, 27.0% and 36.4%, 16.0% and 23.5%, and 43.9% and 80.5% respectively. Also, there was a significant increase (p=0.05) in plasma Triglycerides, Total cholesterol, HDLand LDL-cholesterol in the treated animals by 20% and 31.2%, 19% and 35.4%, 24% and 74.3%, and 33% and 35.2% respectively. Furthermore, the two doses of Azithromycin significantly (p=0.05) reduced the levels of hepatic Ascorbic acid, Glutathione (GSH) and activities of Glutathione-S-transferase (GST) by 35%, 66.3% and 34% and 56.1%, 45% and 50%, respectively. In addition, there was a significant decrease in the activities of hepatic Catalase (CAT), and Superoxide dismutase (SOD) by 67.4% and 43.0%, and 43% and 50% respectively in the two treated group. These were accompanied by a significant increase (p=0.05) in hepatic lipid peroxidation (LPO) by 81% and 91.6% respectively in the treated groups. The histology of the liver revealed sinusoidal and portal congestion and a mild periportal cellular infiltration by mononuclear cells, by Zithromax 500. Likewise, kidney histopathology revealed severe cortical congestion and hemorrhage and few tubules containing protein casts in the treated group. Conclusion: In conclusion, the administration of 5.6 mg/ kg b.w. and 11.2mg/ kg b.w. of Azithromycin induced marked renal and liver damage, oxidative stress and altered the antioxidant status in rats.

N-acetyl cysteine and selenium protects mercuric chloride-induced oxidative stress and antioxidant defense system in liver and kidney of rats: A histopathological approach

Mercury exposure is second-most common cause of metal poisoning which is quite stable and biotransformed to highly toxic metabolites thus eliciting biochemical alterations and oxidative stress. The aim of present study describes the protective effect of selenium either alone or in combination with N-acetyl cysteine (NAC) against acute mercuric chloride poisoning. The experiment was carried out in male albino Sprague Dawley rats (n=30) which was divided into five groups. Group 1 served as control. Groups 2–5 were administered mercuric chloride (HgCl2: 12mol/kg, i.p.) once only, group 2 served as experimental control. Animals of groups 3, 4 and 5 were received N-acetyl cysteine (NAC: 0.6mg/kg, i.p.) and selenium (Se: 0.5mg/kg, p.o.) and NAC with Se in combination. Acute HgCl2 toxicity caused significant rise in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, albumin, bilirubin, γ-glutamyl transpeptidase, cholesterol, triglycerides, protein, urea, creatinine, uric acid and blood urea nitrogen content. Animals also showed significantly higher mercury content in liver and kidney, significant rise in lipid peroxidation level with concomitant decrease in reduced glutathione content and the antioxidant enzyme activities of superoxide dismutase and catalase after HgCl2 exposure. Results of the present investigation clearly showed that combination therapy with NAC+Se provide maximum protection against mercury toxicity than monotherapy (alone treated groups) by preventing oxidative degradation of biological membrane from metal mediated free radical attacks.

Study of the Chemopreventive Effects of Zingiber Officinale Roots Against Aspartame Induced Testicular Toxicity in Rat Model

Infertility is one of the major health problems in life, and approximately 30% of this problem is due to male factors. Research carried out in last few decades has validated several such claims of use of traditional medicine plants. Zingiber officinale (Z. officinale) roots is commonly used as culinary spice and used medicinally for its antioxidant and androgenic activities. The aim of the present study was to evaluate the chemoprotective effect of Z. officinale roots against aspartame induced rat testicular toxicity. The chosen dose of aspartame was adjusted to 0.2ml/ 25g b.wt. and was given three times per week for 12 weeks. Ginger aqueous extract were adjusted to 500mg/kg and were given three times per week for 12 weeks. Aspartame caused a marked rise in serum testosterone, LH and FSH hormones level. Concerning oxidative stress and antioxidant defense system, aspartame group pretreated with ginger extract successfully ameliorated testes reduced glutathione level, glutathione-s-transferase and catalase activities compared to aspartame treated group which give inverse results. However, while elevated lipid peroxidation was noticed in aspartame treated rats, pretreatment with ginger extract produced a detectable decrease in lipid peroxidation level. The natural plant components may have chemopreventive effect against aspartame that may be cause testicular toxicity. However, further clinical studies are required to assess the safety and benefits of ginger root in human beings. ISSN:-2321-3485

Oxidative Stress Parameters in Women with HIV and HIV/hepatitis B and/or C Co-infection

The pathogenesis of HIV/hepatitis B and/or C co-infection is far from being understood; yet, some studies have shown its relationship with oxidative stress. Because of oxidative stress (conjugated dienes and thiobarbituric acid reactants) and antioxidant defense systems (superoxide dismutase activity, α-tocopherol, reduced and oxidized glutathione) had different parameters in 26 women with HIV-monoinfection and 27 women with HIV/hepatitis B and/or C co-infection (with no signs of AIDS), they were evaluated. Spectral fluorofotometric methods were used. Statistical analysis was performed by parametric and non-parametric methods. The evaluation found that while conjugated dienes levels were significantly higher, superoxide dismutase (SOD) activity and α-tocopherol levels were significantly lower in women with HIV/hepatitis B and/or C co-infection than in those with HIV-monoinfection. Concurrently, during the highly active antiretroviral therapy (HAART), conjugated dienes, thiobarbituric acid reactants mean levels were lower; SOD activity and α-tocopherol levels were higher in HIV-monoinfected patients than in those with HIV/hepatitis B and/or C co-infection (with no signs of AIDS). This outcome was characterized by more expressed oxidative stress.

Changes induced by zinc toxicity in the 2-DE protein profile of sugar beet roots

Changes induced by three levels of Zn toxicity in the root proteome from Beta vulgaris were studied by two dimensional gel electrophoresis. 320 spots were consistently detected and 5, 5 and 11% of them showed significant changes in relative abundance as a result of the 50, 100 and 300μM Zn treatments, respectively, when compared to controls (1.2μM Zn). Forty-four spots had consistent changes between all treatments, and 93% were identified. At low and mild Zn excess, the complex I of the mitochondrial transport chain and the oxidative phosphorylation were mildly impaired, and an effort to compensate this effect by increasing glycolysis was observed. At high Zn excess, a general metabolism shutdown occurred, as denoted by decreases in the aerobic respiration and by an impairment of the defense systems against oxidative stress. Accordingly, lipid peroxidation increased as Zn supply increased. This study suggests that metabolic changes at high Zn supply reflect cell death, while changes at low and mild Zn supplies may rather explain the metabolic reprogramming occurring upon Zn toxicity. Results also suggest that Zn competition with divalent ions including Fe may contribute to many of the Zn toxicity symptoms, especially at low and moderate Zn supplies. Results in this work provide a comprehensive overview of the effects of Zn toxicity in roots of sugar beet plants. Effects at low and mild Zn excess are similar and reflect changes in the metabolism aimed to overcome this heavy metal stress, whereas effects at high Zn supply indicate a general shutdown of the metabolism and cell death. Our results indicate that Zn toxicity elicits major impairments in the oxidative stress defense systems, possibly due to Zn competition with divalent cations including Fe, in spite that Zn is not a redox active element by itself.

Nitric oxide alleviates arsenic-induced toxic effects in ridged Luffa seedlings

Hydroponic experiments were conducted to investigate whether exogenous addition of nitric oxide (NO) as sodium nitroprusside (SNP) alleviates arsenic (As) toxicity in Luffa acutangula (L.) Roxb. seedlings. Arsenic (5 and 50 μM) declined growth of Luffa seedlings which was accompanied by significant accumulation of As. SNP (100 μM) protected Luffa seedlings against As toxicity as it declined As accumulation significantly. The photosynthetic pigments and chlorophyll fluorescence parameters such as Fv/Fm, Fv/F0, Fm/F0 and qP were decreased while NPQ was raised by As. However, the toxic effects of As on photosynthesis were significantly ameliorated by SNP. The oxidative stress markers such as superoxide radical, hydrogen peroxide and malondialdehyde (lipid peroxidation) contents were enhanced by As, however, these oxidative indices were diminished significantly in the presence of SNP. As treatment stimulated the activities of SOD and CAT while the activities of APX and GST, and AsA content and AsA/DHA ratio were decreased. Upon SNP addition, along with further rise in SOD and CAT activity, APX and GST activity, and levels of AsA and AsA/DHA ratio were restored considerably. Overall results revealed that significant accumulation of As suppressed growth, photosynthesis, APX and GST activities and decreased AsA content, hence led to the oxidative stress. However, the addition of SNP protected seedlings against As stress by regulating As accumulation, oxidative stress and antioxidant defense system.

Effect of Cerium Oxide Nanoparticles on Rice: A Study Involving the Antioxidant Defense System and In Vivo Fluorescence Imaging

Previous studies have reported the uptake of cerium oxide nanoparticles (nCeO2) by plants, but their physiological impacts are not yet well understood. This research was aimed to study the impact of nCeO2 on the oxidative stress and antioxidant defense system in germinating rice seeds. The seeds were germinated for 10 days in nCeO2 suspension at 62.5, 125, 250, and 500 mg L(-1) concentrations. The Ce uptake, growth performance, stress levels, membrane damage, and antioxidant responses in seedlings were analyzed. Ce in tissues increased with increased nCeO2 concentrations, but the seedlings showed no visible signs of toxicity. Biochemical assays and in vivo imaging of H2O2 revealed that, relative to the control, the 62.5 and 125 mg nCeO2 L(-1) treatments significantly reduced the H2O2 generation in both shoots and roots. Enhanced electrolyte leakage and lipid peroxidation were found in the shoots of seedlings grown at 500 mg nCeO2 L(-1). Altered enzyme activities and levels of ascorbate and free thiols resulting in enhanced membrane damage and photosynthetic stress in the shoots were observed at 500 mg nCeO2 L(-1). These findings demonstrate a nCeO2 concentration-dependent modification of oxidative stress and antioxidant defense system in rice seedlings.

Extra virgin olive oil (EVOO) consumption and antioxidant status in healthy institutionalized elderly humans

Recent studies show that the elderly have increased oxidative stress and impaired antioxidant defense systems. Our study aims to evaluate the effects of daily consumption of EVOO in the healthy institutionalized elderly. We studied anthropometric, biochemical and antioxidant parameters in 62 subjects aged 65–96 years after a 6-week daily intake of polyphenol-rich EVOO with high oleuropein derivative contents. Subjects were divided into a control group (CG) who maintained their dietary habits (n=39) and an olive group (OG) who consumed EVOO as the only added fat, plus a daily dose of 50ml (n=23). We found a significant reduction of total cholesterol (TC), HDL, LDL and TGs in OG subjects and a significant increase of HDL levels. There was no significant variation in the CG parameters. In OG the total antioxidant capacity (TAC) in plasma increased with significant differences over CG. Plasma hydroxytyrosol (OH-Tyr) concentration showed a significant increase after EVOO intervention. Daily consumption of EVOO was found to have positive effects on lipid profiles, OH-Tyr levels and TAC. The results also show a significant increase of catalase (CAT) in erythrocytes and a decrease (p<0.05) in superoxide dismutase (SOD) and glutathione peroxidase (GH-PX) activity after EVOO intake. To our knowledge, no other study has examined the effects of EVOO consumption on biochemical parameters, antioxidant capacity and antioxidant enzyme activity in healthy elderly subjects. In conclusion, our results show that nutritional intervention with EVOO improves antioxidant status in healthy elderly people.

Impaired Mitochondrial Dynamics and Nrf2 Signaling Contribute to Compromised Responses to Oxidative Stress in Striatal Cells Expressing Full-Length Mutant Huntingtin

Huntington disease (HD) is an inherited neurodegenerative disease resulting from an abnormal expansion of polyglutamine in huntingtin (Htt). Compromised oxidative stress defense systems have emerged as a contributing factor to the pathogenesis of HD. Indeed activation of the Nrf2 pathway, which plays a prominent role in mediating antioxidant responses, has been considered as a therapeutic strategy for the treatment of HD. Given the fact that there is an interrelationship between impairments in mitochondrial dynamics and increased oxidative stress, in this present study we examined the effect of mutant Htt (mHtt) on these two parameters. STHdhQ111/Q111 cells, striatal cells expressing mHtt, display more fragmented mitochondria compared to STHdhQ7/Q7 cells, striatal cells expressing wild type Htt, concurrent with alterations in the expression levels of Drp1 and Opa1, key regulators of mitochondrial fission and fusion, respectively. Studies of mitochondrial dynamics using cell fusion and mitochondrial targeted photo-switchable Dendra revealed that mitochondrial fusion is significantly decreased in STHdhQ111/Q111 cells. Oxidative stress leads to dramatic increases in the number of STHdhQ111/Q111 cells containing swollen mitochondria, while STHdhQ7/Q7 cells just show increases in the number of fragmented mitochondria. mHtt expression results in reduced activity of Nrf2, and activation of the Nrf2 pathway by the oxidant tBHQ is significantly impaired in STHdhQ111/Q111 cells. Nrf2 expression does not differ between the two cell types, but STHdhQ111/Q111 cells show reduced expression of Keap1 and p62, key modulators of Nrf2 signaling. In addition, STHdhQ111/Q111 cells exhibit increases in autophagy, whereas the basal level of autophagy activation is low in STHdhQ7/Q7 cells. These results suggest that mHtt disrupts Nrf2 signaling which contributes to impaired mitochondrial dynamics and may enhance susceptibility to oxidative stress in STHdhQ111/Q111 cells.

Silicon mediates arsenic tolerance in rice (Oryza sativa L.) through lowering of arsenic uptake and improved antioxidant defence system

Arsenic (As) contamination of paddy rice in South and South-East Asia has raised much concern as rice is the subsidence diet for millions. Two contrasting rice (Oryza sativa L.) cultivars i.e. Triguna (As tolerant) and IET-4786 (As sensitive) were grown hydroponically to study the effect of silicon (Si) supplementation on As accumulation, growth, oxidative stress and antioxidative defence system in shoots during arsenite [As(III)] stress. Rice seedlings were exposed to three As(III) levels (0, 10 and 25μM) and three silicic acid levels (0, 0.5 and 1mM Si) in solution culture experiments. Addition of 1mM Si during As(III) exposure significantly lowers shoot As accumulation in both the cultivar, but more prominently in Triguna (P≤0.01) than IET-4786 (P≤0.05). However, addition of Si during As(III) stress had no significant effect on shoot length and dry weight (P<0.01) of both the cultivars, compared to their As(III) treated plants. In contrast to IET-4786 (P≤0.05), Triguna tolerated As induced oxidative stress through elevated level of cysteine, enhanced antioxidant enzymes activities and their isozymes. Upon Si supplementation lower conglomeration of oxidative stress parameters viz., superoxide and peroxide radicals, lipid peroxidation and electrolyte leakage coincides with increased antioxidants activities and enhanced level of thiols, more effectively in shoots of Triguna than IET-4786 during As(III) stress (P≤0.05). In conclusion, 1mM Si addition, significantly ameliorates As induced oxidative stress in Triguna cultivar by lowering the As accumulation and improving antioxidant and thiolic system compared to IET-4786, implying genotypic differences with Triguna being less susceptible to stress dependent membrane lipid peroxidation.

Alloxan Induced Oxidative Stress and Impairment of Oxidative Defense System in rats

Objective: To study the activity of statins and alloxan induced oxidative stress and oxidative defense system in rats. Method and Materials: Either sex of Wistar rats were used for studying the activity of statins (Atorvastatin) and oxidative stress is induced by the induction of alloxan (100mg/kg) and statins acts as antioxidants which suppressed the oxidative stress. Animals were divided into five groups and each groups having six animals. Freshly prepared alloxan (100 mg/kg) i.p. were given to third group at first day and forth group at first day then followed by statin (30mg/kg), orally, up to seven day and fifth group at last day of treatment to produced oxidative stress. And investigate the defense mechanism of statins which suppressed the oxidative stress produced by the alloxan. Result: With the help of investigation of biochemical parameters of different groups of animals we found out that atorvastatin showed significantly suppressed the oxidative stress produced by the alloxan and impaired the oxidative defense system in rats. Conclusion: From the investigation it was found that alloxan produced the oxidative stress and statins impaired the oxidative defense system in rats.