Antioxidant Redox System Research Articles

WITHDRAWN: Tenoxicam modulates antioxidant redox system and lipid peroxidation in rat brain

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Topiramate and Vitamin E Modulate Antioxidant Enzyme Activities, Nitric Oxide and Lipid Peroxidation Levels in Pentylenetetrazol‐Induced Nephrotoxicity in Rats

Previous studies have shown that generation of free radicals is increased following pentylenetetrazol kindling, due to increased cytosolic Ca2+ concentrations. Topiramate, a voltage-gated calcium channel inhibitor, has an evident effect in the treatment of childhood epilepsy; however, topiramate may cause nephrotoxicity. We investigated the effects of topiramate and vitamin E administration on pentylenetetrazol-induced nephrotoxicity in rats by evaluation of lipid peroxidation, nitric oxide, glutathione peroxidase, catalase and superoxide dismutase values. Forty male Wistar rats were randomly divided into five equal groups. Group 1 was used as control and group II received a single dose of pentylenetetrazol. Fifty and 100 mg/kg topiramate daily were intragastrically administered to rats in groups III and IV for 7 days, respectively. Intragastric 100 mg topiramate (daily for 7 days) and intraperitoneal vitamin E (150 mg/kg, daily for 3 days) combination were given to animals in group V before a single-dose pentylenetetrazol administration. Serum and kidney samples were taken after 3 hr of pentylenetetrazol administration. Pentylenetetrazol resulted in a significant increase in nitric oxide levels of serum and kidney, and lipid peroxidation levels of kidney although superoxide dismutase and catalase activities in the kidney was reduced by pentylenetetrazol administration. The lipid peroxidation levels in serum and kidneys and the nitric oxide levels in kidneys of groups III, IV and V were decreased by topiramate although the superoxide dismutase and catalase activities in the kidneys were increased. Lipid peroxidation and nitric oxide levels were reduced by the topiramate and vitamin E combination compared to only topiramate. Glutathione peroxidase activity was not affect by pentylenetetrazol, topiramate and vitamin E administrations. In conclusion, topiramate and vitamin E have protective effects on pentylenetetrazol-induced nephrotoxicity by inhibition of free radicals and by support of the antioxidant redox system.

Tenoxicam Modulates Antioxidant Redox System and Lipid Peroxidation in Rat Brain

We investigated effects of two doses of Tenoxicam, a type 2 cyclooxygenase inhibitor, administration on lipid peroxidation and antioxidant redox system in cortex of the brain in rats. Twenty-two male Wistar rats were randomly divided into three groups. First group was used as control. 10 and 20 mg/kg body weight Tenoxicam were intramuscularly administrated to rats constituting the second and third groups for 10 days, respectively. Both dose of Tenoxicam administration resulted in significant increase in the glutathione peroxidase activity, reduced glutathione and vitamins C and E of cortex of the brain. The lipid peroxidation levels in the cortex of the brain were significantly decreased by the administration. Vitamin A and beta-carotene concentration was not affected by the administration. There was no statistical difference in all values between 10 and 20 mg Tenoxicam administrated groups. In conclusion, treatment of brain with 10 and 20 mg Tenoxicam has protective effects on the oxidative stress by inhibiting free radical and supporting antioxidant redox system.

Glutathione metabolism and antioxidant responses during Eleutherococcus senticosus somatic embryo development in a bioreactor

Compared to non-embryogenic callus, proembryonic mass, globular, and heart-shaped embryos of Eleutherococcus senticosus had higher levels of endogenous reduced glutathione (GSH). GSH content declined during the course of the embryo development (torpedo and cotyledon). Similarly, glutathione reductase that is involved in the recycling of GSH providing a constant intracellular level of GSH was also higher in globular and heart-shaped embryos. The transient increase in GSH contents also correlated with the changes in measured γ-glutamylcysteine synthetase activity over the same period. The endogenous levels of oxidized glutathione showed similar trend during development of the somatic embryos, whereas it declined in maturing somatic embryos. A pronounced increase in glutathione-S-transferase, glutathione peroxidase, catalase, and guaiacol peroxidase activity was observed during somatic embryo maturation. Ascorbate-glutathione cycle enzymes (ascorbate peroxidase; dehydroascorbate reductase and monodehydroascorbate reductase) activities also induced indicated that antioxidant enzymes played an important role during embryo development. These results suggested that the coordinated up-regulations of the antioxidant enzymes and glutathione redox system provide protection during somatic embryo development in E. senticosus. Antioxidant responses through alterations of the glutathione redox systems, have been described in the present studies have a significant role in somatic embryo development.

Acetyl-L-Carnitine Prevents Selenite-Induced Cataractogenesis in an Experimental Animal Model

Purpose: To investigate whether acetyl-L-carnitine (ALCAR) retards selenite-induced cataractogenesis in vivo. Methods: On postpartum day 10, group I pups received intraperitoneal saline and group II and group III pups received subcutaneous sodium selenite; Group III pups also received intraperitoneal ALCAR once daily on postpartum days 9–14. Both eyes of each pup were examined up to postpartum day 30. After sacrifice, extricated pup lenses were analyzed for antioxidant and redox system components. Results: There was dense lenticular opacification in all group II pups, minimal opacification in 33% of group III pups, and no opacification in 67% of group III and in all group I pups. Group II lenses exhibited significantly lower values of antioxidant and redox system components and higher malondialdehyde concentrations than group I or group III lenses. Conclusion: ALCAR prevents selenite-induced cataractogenesis in Wistar rat pups, possibly by inhibiting depletion of antioxidant enzyme and redox system components and inhibiting lipid peroxidation.

242GLUTATHIONE CONTENT AND EXPRESSION OF ANTIOXIDANT ENZYME MRNAS IN SHEEP OOCYTES

Reactive oxygen species (ROS) are normal products of embryo metabolism;; however, oxidative injury may negatively impact development if ROS production exeeds antioxidant defense mechanisms. Protection of the embryo against ROS is dependent, in part, upon the pool of antioxidant enzyme mRNA and products stored in the oocyte. Previous work has demonstrated that retinol administration to superovulated ewes, followed by natural service, resulted in embryos with improved competence to develop in vitro. In other cell systems, retinoids have been shown to participate in the antioxidant network and redox system. The objectives of this study were to analyze glutathione content and characterize antioxidant enzyme mRNA expression in mature ovine oocytes and test the hypothesis that retinol administration affects levels of these products. Ewes were superovulated and administered retinol on the first and last day of FSH injection. Oocytes were collected from oviducts 60h later and either prepared for glutathione (GSH) analysis or subjected to RNA isolation. Glutathione was quantified by the recycling assay of the enzyme 5,5-dithiobis-(2-nitrobenzoic acid)-glutathione reductase using a total of more than 260 oocytes. Transcripts encoding for manganese superoxide dismutase (Mn-SOD), copper zinc superoxide dismutase (Cu-Zn SOD), glutathione synthetase (GS) and glutathione transferase pi (GSTp) were analyzed in a total of 86 single oocytes by semi-quantitative RT-PCR using a histone H2a transcript as the internal control. Chi-square analysis was performed to detect differences due to treatments. Glutathione content did not differ significantly between oocytes collected from retinol-treated (6.78±3.81pmol/oocyte) and control (6.38±1.58pmol/oocyte) ewes. Transcripts encoding for Mn-SOD, Cu-Zn SOD, GS and GSTp were detected in greater than 95% of the oocytes analyzed. Relative abundance of these transcripts did not differ between treatments. For the first time, glutathione content and antioxidant enzyme mRNA expression has been analyzed in in vivo-matured sheep oocytes. Retinol treatment did not appear to affect the expression of these products. Results demonstrate the existence of endogenous antioxidant defense products, stored as mRNA and protein, in sheep oocytes.

Role of nerve growth factor in oxidant homeostasis: glutathione metabolism.

Free radicals are generated in the CNS by ongoing oxygen metabolism and biological events associated with injury and inflammation. Increased free radical levels may also persist in some chronic neurological diseases and in the aged. Nerve growth factor (NGF) is a member of the neurotrophin family of proteins that can regulate neuronal development, maintenance, and recovery from injury. NGF protected rat pheochromocytoma PC12 cells, an adrenal chromaffin-like NGF-responsive cell line, from the oxidant stress accompanying hydrogen peroxide treatment by stimulating GSH levels and enzymes in the GSH metabolism cycle and in the GSH/GSH peroxidase antioxidant redox system, a ubiquitous cellular antioxidant system. Specifically, NGF increased gamma-glutamylcysteine synthetase (GCS) activity, the rate-limiting enzyme for GSH synthesis, by 50% after 9 h and GSH levels by 100% after 24 h of treatment. NGF stimulated GSH peroxidase by 30% after 3 days and glucose 6-phosphate dehydrogenase by 50% after 2 days. Treatment with NGF and cycloheximide, or actinomycin D, which inhibit protein and RNA synthesis, respectively, blocked the NGF stimulation of GCS and glucose 6-phosphate dehydrogenase. Increased GSH levels due to NGF treatment were responsible for the significant protection of PC12 cells from hydrogen peroxide-induced stress. Pretreatment of PC12 cells with NGF for 24 h rescued cells from the toxic effects of the extracellular hydrogen peroxide generated by the glucose/glucose oxidase system but did not rescue cells that were subjected to GSH deprivation due to treatment with 10 microM L-buthionine-(S,R)-sulfoximine, an inhibitor of GCS.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of reactive oxygen species in cell toxicity

Several types of compound exert their cytotoxicity by generating reactive oxygen species, notably the superoxide anion radical. These include quinoid and nitroaromatic compounds serving as redox cyclers i.e. producing superoxide at the expense of NADPH and oxygen catalyzed by cellular reductases. In specialized cell-types employed in defense such as granulocytes, eosinophils and macrophages, myeloperoxidase, NADPH oxidase and nitric oxide synthase have been identified as major sources of reactive oxygen species in cell toxicity. These include hypochlorite, singlet oxygen, Superoxide, nitric oxide and hydrogen peroxide. The interaction of superoxide and nitric oxide generates further oxidants such as peroxynitrite. Lumino-amplified Chemiluminescence generated by Kupffer cells is partially sensitive to inhibitors of NO synthase. Superoxide dismutase has been found to catalyze a novel reaction, the reversible conversion of nitric oxide to the nitroxyl anion, the latter being viewed as another form of EDRF. In the defense against oxidative damage, there are enzymatic and nonenzymatic antioxidants. Regarding compounds used pharmacologically, we have been interested in ebselen, a seleno-organic compound exhibiting GSH peroxidase activity, which protects against reactive oxygen species generated, for example, at reoxygenation following a period of hypoxia. Further, we have studied lipoate and dihydrolipoate as antioxidant redox system and as singlet oxygen quencher e.g. protecting against damage of deoxyguanosines in plasmid DNA generated by singlet oxygen.