Role In Antioxidant Defense System Research Articles

Association of Serum Gamma Glutamyl Transferase with Lipid Abnormalities in End Stage Renal Disease

Abstract Background End stage renal disease (ESRD) is characterized by high degree of mortality and cardiovascular complications. These complications occur due to many metabolic and endocrinal disturbances and dyslipidemia is the constant feature of ESRD. Oxidative stress is the final pathway mediating cardiovascular damage. There is evidence that GGT plays very important role in antioxidant defense system. Hence dyslipidemia and oxidative stress are predominant features of ESRD, which in long term predispose to cardiovascular complications. Objectives of our study were to estimate and to correlate lipid profile and GGT levels in ESRD patients on hemodialysis and healthy controls. Methods A case–control study was conducted in patients attending Nephrology unit of hospital. After obtaining informed consent, 45 patients who were clinically and biochemically diagnosed of ESRD between 25 and 60 years of age and undergoing hemodialysis were included as cases. Age of 70 and sex matched normal healthy volunteers from hospital staffs or patient attenders were included as controls. Serum lipid profile and GGT were estimated in all the study groups. Results Mean values of serum total cholesterol, triglycerides, LDL and GGT were significantly elevated in ESRD patients on hemodialysis. Serum HDL was significantly decreased in patients when compared to controls. We did not find any significant association of GGT with lipid parameters. Conclusion ESRD is associated with dyslipidemia and oxidative stress which predispose to adverse cardiovascular complications. However in our study no significant correlation between GGT levels and lipid parameters was observed.

Differential expression of CuZnSOD gene under low temperature stress in noble scallop Chlamys nobilis with different carotenoid content.

The noble scallop Chlamys nobilis belongs to a warm-water mollusk and has been cultured in the sea of southern China since 1980s'. However, accidents of massive mortality have often occurred during the winter, and one of the reasons could be accumulation of harmful reactive oxygen species caused by lower temperature. Carotenoids are well known for their anti-oxidant function. To investigate whether carotenoids do play a role in mollusks' antioxidant defense system under lower temperature stress, an acute lower temperature experiment was conducted by using two types of scallops: the orange with higher carotenoids content and the brown with lower carotenoids content. Their CuZnSOD gene was cloned, mRNA expression levels were determined, and SOD activity and carotenoids content were measured. The complete CuZnSOD cDNA consists of 1078 nucleotides with an open reading frame encoding 154 amino acid residues, which has high identity with that of its sister species Chlamys farreri. The mRNA expression levels in both the mantle and gill from the orange scallops were significantly higher (P<0.05) than that of the brown ones, but the result was the opposite in the blood. SOD activity in the mantle and gill from the orange scallops was significantly higher than (P<0.05) that from the brown ones. Further, significantly positive correlations were found among CuZnSOD gene transcript levels, SOD activity and total carotenoids content in the orange scallops. The present results suggested that carotenoids could play roles in antioxidant defense system by upregulating gene expression under lower temperature stress in the noble scallop.

Differential immune responses of a novel toll gene to Vibrio parahaemolyticus, LPS and poly I:C in noble scallop Chlamys nobilis with different carotenoid contents

The noble scallop Chlamys nobilis, an important farming shellfish in the southern sea of China since 1980s, has suffered large-scale mortality problems in recent years. As efficient antioxidants, carotenoids have been reported to protect cells and tissues from oxidative damage due to adversity stress by eliminating the active oxygen free radicals. To investigate whether carotenoids have an immune influence to C. nobilis under pathogen stress, two stain scallops of orange and brown with different carotenoids content were used in this study. Carotenoids content in scallops’ muscle of the orange strain is significantly higher than that of the brown strain. The two strain scallops had the same age and been cultured the same environmental conditions. 300 scallops including 150 orange and 150 brown were firstly chosen from the field, then randomly divided into eight 500 L tanks (36 scallops each tank) for aerating culture. After 24 h acclimatization, scallops suffered from an acute challenge lasting 48 h of Vibrio parahaemolyticus, lipopolysaccharide (LPS), polyinosinic polycytidylic acid (Poly I:C), and PBS, respectively. Last, transcripts of a toll-like receptor called CnTLR-1, total carotenoids content (TCC), SOD activity, and CAT activity were measured. The full length cDNA of CnTLR-1 was 2982 bp with an open reading frame (ORF) of 1920 bp encoding 639 deduced amino acids, which contained five leucine-rich repeats (LRR), two LRR-C-terminal (LRRCT) motifs, a LRR-N-terminal (LRRNT) motif in the extracellular domain, a transmembrane domain and a Toll/Interleukin-1 Receptor (TIR) of 138 amino acids in the cytoplasmic region. CnTLR-1 was closely related to Crassostrea gigas and Mytilus galloprovincialis Tolls. CnTLR-1 transcripts from higher to lower in turn expressed in mantle, haemocytes, gill, kidney, gonad, hepatopancreas, intestines and adductor. Compared with PBS challenge, CnTLR-1 transcripts were all up-regulated by V. parahaemolyticus, LPS and Poly I:C, and transcripts were significantly higher in orange scallops than that of brown ones in all the immune challenges. TCC from the orange scallops were significantly higher than that from the brown ones in all tested tissues and first increased and then decreased. SOD enzymatic activities showed V-shapes and were lower in orange scallops than in brown ones, while CAT enzymatic activities displayed inverted V-shapes and were higher in orange scallops than in brown ones. The decrease of SOD and the increase of CAT were significantly higher in orange scallops than brown ones. The present results indicate that CnTLR-1 is an important factor involved in the immune defense against pathogens, and carotenoids can play roles in antioxidant defense system by up-regulating gene expression under pathogen stress in the noble scallop.

The food supplement coenzyme Q10 and suppression of antitubercular drug-induced hepatic injury in rats: the role of antioxidant defence system, anti-inflammatory cytokine IL-10.

Isoniazid (INH) and rifampicin (RIF), the most common anti-tubercular therapy, causes hepatotoxicity through a multi-step mechanism in certain individuals. The present study was an attempt to evaluate the hepatoprotective effect of coenzyme Q10 against INH + RIF-induced hepatotoxicity in Wistar albino rats. Hepatotoxicity was induced by the oral administration of INH + RIF (50mg/kg b.w. each/day) in normal saline water for 28days. The hepatoprotective effect of coenzyme Q10 (10mg/kg b.w./day) was compared with that of the standard drug silymarin (25mg/kg b.w./day). Animals were sacrificed at the end of the study period, and blood and liver were collected for biochemical, immunological and histological analyses. Evaluation of biochemical parameters showed that coenzyme Q10 treatment caused significant (P < 0.05) reduction in the elevated levels of serum liver function markers and restored normal levels of total protein, albumin and lipids in INH + RIF-treated rats. Also, it was observed that coenzyme Q10 was able to restore normal levels of enzymic antioxidants, reduced glutathione and lipid peroxidation in the INH + RIF-treated rats. Coenzyme Q10 was found to effectively reduce the extent of liver damage caused due to INH + RIF. In addition, the levels of IL-10 and IL-6 were significantly elevated in the INH + RIF-induced rats treated with CoQ10. Our study indicates the protective role of coenzyme Q10 in attenuating the hepatotoxic effects of INH + RIF in a rat model and that it could be used as a food supplement during anti-tubercular therapy.

Ferulic acid chronic treatment exerts antidepressant-like effect: role of antioxidant defense system.

Oxidative stress has been claimed a place in pathophysiology of depression; however, the details of the neurobiology of this condition remains incompletely understood. Recently, treatments employing antioxidants have been thoroughly researched. Ferulic acid (FA) is a phenolic compound with antioxidant and antidepressant-like effects. Herein, we investigated the involvement of the antioxidant activity of chronic oral FA treatment in its antidepressant-like effect using the tail suspension test (TST) and the forced swimming test (FST) in mice. The modulation of antioxidant system in blood, hippocampus and cerebral cortex was assessed after stress induction through TST and FST. Our results show that FA at the dose of 1 mg/kg has antidepressant-like effect without affecting locomotor activity. The stress induced by despair tests was able to decrease significantly the activities of superoxide dismutase (SOD) in the blood, catalase (CAT) in the blood and cerebral cortex and glutathione peroxidase (GSH-Px) in the cerebral cortex. Thiobarbituric acid-reactive substances (TBA-RS) levels were increased significantly in the cerebral cortex. Furthermore, the results show that FA was capable to increase SOD, CAT and GSH-Px activities and decrease TBA-RS levels in the blood, hippocampus and cerebral cortex. These findings demonstrated that FA treatment in low doses is capable to exert antidepressant-like effect with the involvement of the antioxidant defense system modulation.

Hepatoprotective effect of kaempferol against alcoholic liver injury in mice.

Kaempferol is a biologically active component present in various plants. The hepatoprotective effect of kaempferol in drug-induced liver injury has been proven, while its effect against alcoholic liver injury (ALI) remains unclear. Hence, the present study aimed to evaluate the effect of kaempferol against ALI in mice. The experimental ALI mice model was developed and the mice were treated with different doses of kaempferol for 4 weeks. The liver functions were observed by monitoring the following parameters: Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) levels in serum; histopathological studies of liver tissue; oxidative stress by hydrogen peroxide (H2O2), superoxide dismutase (SOD) and glutathione (GSH); the lipid peroxidation status by malondialdehyde (MDA) and lipid accumulation by triglyceride (TG) level in serum; and the expression levels and activities of a key microsomal enzyme cytochrome 2E1 (CYP2E1), by both in vitro and in vivo methods. The ALI mice (untreated) showed clear symptoms of liver injury, such as significantly increased levels of oxidative stress, lipid peroxidation and excessive CYP2E1 expression and activity. The mice treated with different kaempferol dosages exhibited a significant decrease in the oxidative stress as well as lipid peroxidation, and increased anti-oxidative defense activity. The kaempferol treatment has significantly reduced the expression level and activity of hepatic CYP2E1, thus indicating that kaempferol could down regulate CYP2E1. These findings show the hepatoprotective properties of kaempferol against alcohol-induced liver injury by attenuating the activity and expression of CYP2E1 and by enhancing the protective role of anti-oxidative defense system.

A novel stress-associated protein SbSAP14 from Sorghum bicolor confers tolerance to salt stress in transgenic rice

We have characterized a member of the stress-associated protein (SAP) gene family from Sorghum bicolor (SbSAP14) with A20 and AN1 zinc-finger domains. Expression profiling revealed that SbSAP14 is specifically induced in response to dehydration, salt, and oxidative stress as well as abscisic acid treatment. During the early stage of salt stress, overexpression of SbSAP14 was able to prevent yellowing and withering of the leaf tip of rice plants. Measurements of malondialdehyde, ion leakage, and chlorophyll content demonstrated that transgenic rice had an enhanced tolerance to oxidative damage caused by salt stress. Under prolonged salt stress, transgenic rice plants had a higher seed germination rate and higher percentage seedling survival than wild-type (WT) plants. Importantly, in vivo and in situ assays revealed that the accumulation of reactive oxygen species in transgenic rice plants was significantly lower than that in WT plants. Among the six antioxidant genes tested, APX2, CatB, CatC, and SodA1 showed a higher expression level in transgenic rice than in WT rice. Based on these results, we propose that SbSAP14 may play a key role in antioxidant defense systems and possibly be involved in the induction of antioxidant genes in plants, suggesting a possible mechanism of the SAP gene family in stress defense response.

A study on the antioxidant defense system of psoriasis patients in the ethnic population of Kashmir-India

The study was designed to evaluate the role of antioxidant defense system in the etiology of psoriasis, a chronic skin disorder of complex etiology and pathology. Hospital-based case–control study was carried out in major referral hospital in Kashmir, North India. Cases (N = 40) were composed of patients with psoriasis vulgaris, and controls (N = 20) were healthy volunteers. Study included estimation in plasma of both patients and controls of glutathione (GSH) levels, superoxide dismutase (SOD) activity, and total antioxidant potential (AOP) as indices of antioxidant defense system and malondialdehyde (MDA) as a measure of lipid peroxidation (LP), an indicator of oxidative stress. The GSH levels, SOD activity, AOP, and malondialdehyde levels in plasma of psoriasis patients were 2.58 ± 0.22 μM/l, 5.24 ± 0.69 U/ml, 0.020 ± .011 nmol−1/ml h, and 0.88 ± 0.20 nmol/ml and were 4.76 ± 0.52 μM/l, 4.14 ± 0.56U/ml, 0.042 ± 0.018 nmol−1/ml h, and 0.53 ± 0.16 nmol/ml in healthy voluntary controls, respectively. A significant decrease in GSH levels (p < 0.005) and AOP (p < 0.005) and significant increase in SOD activity (p < 0.01) MDA levels (p < 0.005) as an indicator of LP was observed.

Chromium picolinate and chromium histidinate protects against renal dysfunction by modulation of NF-κB pathway in high-fat diet fed and Streptozotocin-induced diabetic rats

BackgroundDiabetic nephropathy is one of major complications of diabetes mellitus. Although chromium is an essential element for carbohydrate and lipid metabolism, its effects on diabetic nephropathy are not well understood. The present study was conducted to investigate the effects of chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-κB) and nuclear factor-E2-related factor-2 (Nrf2) pathway in the rat kidney.MethodsMale Wistar rats were divided into six groups. Group I received a standard diet (8% fat) and served as a control; Group II was fed with a standard diet and received CrPic; Group III was fed with a standard diet and received CrHis; Group IV received a high fat diet (HFD, 40% fat) for 2 weeks and then were injected with streptozotocin (STZ) (HFD/STZ); Group V was treated as group IV (HFD/STZ) but supplemented with CrPic for 12 weeks. Group VI was treated as group IV (HFD/STZ) but supplemented with CrHis.ResultsThe increased NF-κβ p65 in the HFD/STZ group was inhibited by CrPic and CrHis supplementation (P < 0.05). In STZ-treated rats, a significant decrease in levels of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) was found in kidney tissues when compared to control rats (P < 0.05). A significant increase in the levels of IκBα was observed in CrPic- and CrHis-treated rats when compared with STZ-treated rats. Renal Nrf2 levels were significantly decreased in diabetic rats compared with the control rats. There was a higher tendency for increase of kidney Nrf2 level and decrease in kidney NFκBp65 levels and 4- hydroxyl nonenal (4-HNE) protein adducts (P < 0.05) in diabetic rats.ConclusionOur result show that in kidney tissue CrHis/CrPic increases Nrf2 level, parallelly decreases NF-κB and partially restores IκBα levels in HFD/STZ group, suggesting that CrPic and CrHis may play a role in antioxidant defense system via the Nrf2 pathway by reducing inflammation through NF-κβ p65 inhibition. Moreover, a greater reduction in NF-κB expression and greater increases in expressions of IκBα and Nrf2 in diabetic rats supplemented with CrHis than rats supplemented with CrPic suggest that CrHis has more favorable effects than CrPic.

Combination of chemometrically assisted voltammetry, calorimetry, and circular dichroism as a new method for the study of bioinorganic substances: application to selenocystine metal complexes

Selenium-containing compounds play an important role in antioxidant defense systems, binding to toxic metals, preventing their uptake into cells, and thus protecting cells from metal-induced formation of reactive oxygen species. Here, we present a proposal for a relatively new method as a complement to the more usual methods used in selenium studies. A systematic study of the metal-binding properties of selenocystine (SeCyst) in the presence of divalent metal cations (Cd, Co, Hg, Ni, and Zn) is reported. Isothermal titration calorimetry provides thermodynamic parameters of the systems. Titrations produced curves that could be fit reasonably well to the one set of sites model. The data clearly demonstrate that one M(2+) binds one SeCyst molecule, and the stable M(SeCyst) complex is formed under these conditions. The order of the SeCyst binding constant for the metal ions is Hg(2+)>Cd(2+)~Zn(2+)>Ni(2+)>Co(2+). Cadmium ion was selected as a modulator for the behavior of SeCyst in the presence of a nonessential metal, and zinc was selected for the case of an essential element. These interactions of SeCyst with Cd(2+) and Zn(2+), either individually or combined, were studied in aqueous buffered solutions at physiological pH by differential pulse polarography and circular dichroism spectroscopy. Furthermore, recently developed chemometric tools were applied to differential pulse polarography data obtained in mixtures of SeCyst and glutathione in the presence of Cd(2+) at physiological pH.

The role of antioxidant defense systems at differential salt tolerance of Hordeum marinum Huds. (sea barleygrass) and Hordeum vulgare L. (cultivated barley)

Barley ( Hordeum vulgare), one of the world's most extensively cultivated crops, is regarded as salt tolerant compared with other Triticeae members. There are also differences in salt tolerance between barley species. Hordeum marinum (sea barleygrass) inhabiting salt marshes is regarded as being markedly more salt tolerant than H. vulgare (cultivated barley). Moreover, it has been considered one of the most important wild species of barley in terms of having a source of genes for improvement of salt tolerance of wheat. The role of osmoregulation and ion homeostasis on salt tolerance of H. marinum has already been reported. However, the role of antioxidant defense system on salt tolerance of H. marinum has not been addressed yet. Therefore, in the present study, we investigated the changes in the lipid peroxidation, antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), ascorbate peroxidase (APX) and glutathione reductase (GR)] and isoenzymatic profiles of some antioxidant enzymes (SOD, APX, GR) in H. marinum and H. vulgare cv. Tokak 157/37, comparatively. H. marinum and H. vulgare were subjected to 0, 150 and 300 mM NaCl stress for 7 days. Shoot FW (fresh weight) and DW (dry weight) of both species were decreased at 300 mM NaCl, being more pronounced in H. vulgare. Shoot RGR (relative growth rate) of H. vulgare was more sensitive to NaCl than H. marinum. Similarly, stomatal conductance ( g s) was also reduced in both species by salt treatment, but it was more pronounced in H. vulgare. Salt treatment had no effects on chlorophyll fluorescence (Fv/Fm) in both species. Peroxidation of lipid membranes showed no change in H. marinum under salt stress while it increased by 60% in H. vulgare at 300 mM NaCl. At 150 mM NaCl, the activities of all antioxidant enzymes (except SOD) increased in both species. However, the activities of some antioxidant enzymes and their isoenzymes in H. vulgare either remained unchanged (CAT, POX and APX) or even decreased (SOD, GR) at 300 mM NaCl. Nevertheless, the activities of all antioxidant enzymes of H. marinum increased significantly at 300 mM NaCl. Moreover, while new isoenzymes (APX5, GR5) were identified in H. marinum, intensities of some isoenzymes (APX1, 2, 6, 7 and GR1, 3, 6, 7) increased at 300 mM NaCl. These findings possibly suggest that H. marinum has a better protection mechanism against salt-induced oxidative damage than H. vulgare, by inducing activity of antioxidant enzymes and their isoenzymes.

Involvement of thioredoxin reductase 1 in the regulation of redox balance and viability of rheumatoid synovial cells

Rheumatoid arthritis (RA), a chronic and systemic disease of unknown etiology, is characterized by hyperplasia of synovial cells, which ultimately lead to the destruction of cartilage and bone. To elucidate the molecular mechanisms that lead to RA, we analyzed synovial cells established from patients with RA by oligonucleotide microarrays. Gene expression profiles clearly suggested that oxidative stress is enhanced in RA synovial cells, which was confirmed by measuring cellular levels of reactive oxygen species. One of the highly up-regulated proteins in RA synovial cells was thioredoxin reductase 1 (TRXR1), a protein that plays an important role in antioxidant defense system. Subsequent analysis demonstrated that TRXR1 suppresses hydrogen peroxide and inhibits apoptosis of RA synovial cells. Thus, our results reveal a novel pathophysiologic function of RA synovial cells as a generator of oxidative stress, and a self-defense mechanism against self-generated oxidative stress.

Involvement of oxidative stress and role of antioxidative defense system in growing rice seedlings exposed to toxic concentrations of aluminum

When seedlings of rice (Oryza sativa L.) cultivar Pant-12 were raised in sand cultures containing 80 and 160 muM Al(3+) in the medium for 5-20 days, a regular increase in Al(3+) uptake with a concomitant decrease in the length of roots as well as shoots was observed. Al(3+) treatment of 160 muM resulted in increased generation of superoxide anion (O(2) (-)) and hydrogen peroxide (H(2)O(2)), elevated amount of malondialdehyde, soluble protein and oxidized glutathione and decline in the concentrations of thiols (-SH) and ascorbic acid. Among antioxidative enzymes, activities of superoxide dismutase (SOD EC 1.15.1.1), guaiacol peroxidase (Guaiacol POX EC 1.11.1.7), ascorbate peroxidase (APX EC 1.11.1.11), monodehydroascorbate reductase (MDHAR EC 1.6.5.4), dehydroascorbate reductase (EC 1.8.5.1) and glutathione reductase (EC 1.6.4.2) increased significantly, whereas the activities of catalase (EC EC 1.11.1.6) and chloroplastic APX declined in 160 muM Al(3+ )stressed seedlings as compared to control seedlings. The results suggest that Al(3+) toxicity is associated with induction of oxidative stress in rice plants and among antioxidative enzymes SOD, Guaiacol POX and cytosolic APX appear to serve as important components of an antioxidative defense mechanism under Al(3+) toxicity. PAGE analysis confirmed the increased activity as well as appearance of new isoenzymes of APX in Al(3+) stressed seedlings. Immunoblot analysis revealed that changes in the activities of APX are due to changes in the amounts of enzyme protein. Similar findings were obtained when the experiments were repeated using another popular rice cv. Malviya-36.

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

Radiation pneumonitis is an unpredictable complication of radiotherapy for lung cancer and a condition which can cause significant morbidity. The ability to identify patients at a high risk of developing pneumonitis is critical, since it will enable the individualization of the treatment plan. Because the cytotoxic effect of radiation is propagated through reactive oxygen species (ROS) and ROS-driven oxidative stress, the role of antioxidant defense systems in radiation pneumonitis was investigated. Using the pneumonitis-sensitive C3H/HeN mice as a model, we demonstrated that the antioxidant response of the lung correlated well with that of red blood cells (RBC). We then proceeded to test whether differences of RBC antioxidant response would predict the pneumonitis development in patients. Superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) activities and glutathione in RBC were measured at baseline and then weekly for 6 weeks of treatment in 15 eligible patients receiving concurrent chemo-radiotherapy for unresectable stage III NSCLC. Striking differences were found in the antioxidant activities of RBC with respect to the pneumonitis development. Those who developed pneumonitis showed higher SOD and lower GPX activities at baseline compared to those who did not (3.7 vs 6.8 units/mg for median SOD, 16.5 vs 10.7 nmol/min/mg for median GPX). The functional imbalance of SOD and GPX was displayed consistently throughout the treatment period. The sensitivity and specificity of pneumonitis prediction were further increased when the GPX/SOD ratio was analyzed (pretreatment P = 0.0046). Our results provide a strong rationale to monitor SOD and GPX activities of RBC to identify patients who are at risk of developing pneumonitis, and to implement a strategy of increasing the GPX/SOD ratio in order to lower the risk.

Beneficial Effects of Selenium on Some Enzymes of Diabetic Rat Heart

It is known that selenium compounds can restore some metabolic parameters in experimental diabetes. However, as there are no clear data about their effects on the altered antioxidant defense system of the diabetic heart, we aimed to investigate whether these beneficial effects extend to the alterations of some enzyme activities, which play important roles in antioxidant defense system. Diabetes was induced by streptozotocin (50 mg/kg body weight) and rats were then treated with sodium selenite (5 micromol/kg/d) for 4 wk. Sodium selenite treatment of the diabetic rats significantly restored the altered activities of glutathione-S-transferase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase, which are involved in the glutathione metabolism of the heart, but slightly but significantly decreased the high blood glucose level. In summary, the present study suggests that the beneficial effects of sodium selenite treatment appears to be the result of the restoration altered activities of the antioxidant enzymes in diabetic heart tissue.

Expression of catalase and glutathione peroxidase in renal insufficiency

Chronic renal failure (CRF) is associated with oxidative stress, the precise mechanism of which is yet to be elucidated. The present study was undertaken to investigate in renal insufficiency the expression of catalase and glutathione peroxidase, which play a critical role in antioxidant defense system by catalyzing detoxification of hydrogen peroxide (H 2O 2) and organic hydroperoxides. Rats were randomly assigned to the CRF (5/6 nephrectomized) and sham-operated control groups and observed for 6 weeks. Renal and thoracic aortic catalase and glutathione peroxidase protein abundance was measured by Western blotting. The enzyme activities in the renal and aortic extracts, hepatic glutathione levels, blood pressure and urinary nitric oxide metabolites (NO x) excretion were also measured. Blood pressure and urinary nitric oxide metabolite (NO x ) excretion were also measured. The CRF group showed a significant down-regulation of both immunodetectable catalase and glutathione peroxidase proteins in the remnant kidney. Catalase activity was also significantly decreased in the remnant kidney whereas glutathione peroxidase activity was not significantly affected. Furthermore, the protein abundance of catalase was unchanged whereas the enzyme activity was significantly decreased in the thoracic aorta of CRF animals compared to the sham-operated controls. By contrast, both the protein abundance and the enzyme activity of glutathione peroxidase were not significantly affected in the aorta of CRF animals compared to the sham-operated controls. This was coupled with marked arterial hypertension, significant reduction of hepatic glutathione levels and urinary NO x excretion pointing to increased inactivation and sequestration of NO by superoxide. These events point to the role of impaired antioxidant defense system in the pathogenesis of oxidative stress in CRF.

Role of antioxidant defense system and biochemical adaptation on stress tolerance of high mountain and steppe plants

Abstract Eleven species were collected from Northwest Anatolian mountains (1500–2000 m) and 18 species were collected from the Central Anatolian steppes (850–1000 m) in June 1998 and 1999. In all the species investigated, the water and dry matter percentages and solute contents were measured. The chlorophyll, β-carotene, ascorbate and α-tocopherol contents and catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR) enzyme activities of the plants were also determined. The steppe plants had lower water content compared with alpine plants. The chlorophyll contents of the plants investigated did not change with altitude. However, the carotenoid/chlorophyll ratio of alpine plants was found to be significantly higher. The antioxidant/chlorophyll ratio of the trees and shrubs was higher than that of herbaceous plants. Carotenoid concentrations and SOD activity were higher in alpine plants than in steppe plants. Proline and soluble protein concentrations were significantly higher in alpine plants than in steppe plants. There was a significant difference between the plants as regards to antioxidant capacity at the family level. Though there was a high antioxidant capacity in alpine Poaceae, Lamiaceae species from steppe had very low concentrations of antioxidants. In conclusion, it was shown that although antioxidant protection was important in alpine plants, there were significant differences among the plant species. In addition to antioxidant protection, the higher soluble protein and proline contents have a very important role in the stress resistance of the alpine plants.

Antioxidants, NFκB Activation, and Diabetogenesis

Although many risk factors can trigger the development of insulin-dependent diabetes (IDDM), it is likely that reactive oxygen species (ROS) play a central role in beta-cell death and disease progression. This review will focus on the role of antioxidant defense systems in the susceptibility to IDDM and on ROS as cellular messengers that regulate the expression of genes leading to beta-cell death. Accumulating evidence indicates that increased antioxidant defense systems reduce the susceptibility to IDDM in animal models or in human study. It is suggested that pancreas-specific ROS productions play a critical role in signaling the cellular autoimmune/inflammatory response by activating the transcription factor, NFkappaB. Various diabetogenic factors may lead to an increase in ROS production, which activates the redox-sensitive NFkappaB. This may be the initial event for the expression of cytokines and chemotactic agents involved in the autoimmune/inflammatory response. It is believed that this cascade results in a cyclic amplification of ROS and eventually leads to apoptosis and/or necrosis of beta cells. The specificity of antioxidants to inhibit NFkappaB activation and the hyperglycemic response emphasizes the importance of selectivity in antioxidant therapy. Research in this area will contribute significantly to our understanding of the cellular and mechanistic role of ROS in the etiology of IDDM and will lead to the development of better prevention strategies.

Modes of action of the plant-derived phototoxin α-terthienyl in mosquito larvae

The mode of action of the plant-derived phototoxic insecticide α-terthienyl (α-T), was examined in larvae of the mosquito Aedes aegypti (Linn.) (Diptera: Culicidae). Exposure of larvae to the toxin in the presence of near-ultraviolet light resulted in increased tissue levels of fluorescent breakdown products resulting from lipid peroxidation (LPO_. Control experiments confirmed that the fluorescent activity of α-T did not interfere with fluorometric determination of LPO products. Photosensitization by α-T had no significant effect on tissue levels of either total or reduced glutathione (GSH). However, levels of oxidized glutathione (glutathione disulfide) increased almost twofold as a result of α-T treatment in the presence of near-uv light. The role of LPO and GSH oxidation as indicators of mode of action of α-T and the possible role of antioxidant defense systems are discussed.