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Journal Article 2013; 34(5): 372-382 PubMed PMID: 23922044 Citation  Keywords:  Animals, Cell Line, Tumor, Cell Proliferation:drug effects, Dose-Response Relationship, Drug, Glucose:administration & dosage, Neurilemmoma:metabolism, Neurons:drug effects, Nitrosation:drug effects, Oxidative Stress:drug effects, Rats, Schwann Cells:drug.   

OBJECTIVE: One of the major complications during prolonged hyperglycemic condition is the onset of the so-called diabetic neuropathy, that can affect the peripheral nervous system. Evidence has reported that glucose-induced oxidative stress could be a key mediator in this process, impairing the cytoskeletal structures, such as microtubules. In general, much attention is paid to the possible nitrosative-induced changes of neurons during hyperglycemic conditions, while little is known of the Schwann cells.

METHODS: Using morphological examination, immunofluorescence staining and western blot analysis, the possible hyperglycemic oxidative-induced microtubular changes in the RT4 Schwannoma cell line was investigated.

RESULTS: After 72 hrs of 180 mM d-glucose exposure, a decrease of total, tyrosinated and detyrosinated α-tubulins was found, whereas a significant increase of the acetylated α-tubulin isotype and 3-nitro-l-tyrosine was present, both through western blot and immunofluorescence staining. Moreover a downregulation of catalase and deacetylase Sirt2 enzymes was detected.

CONCLUSION: Our data underline the importance of nitrosative-induced microtubular alterations in the PNS, during hyperglycemic conditions, highlighting that Schwann cells may be directly involved in the pathogenesis of diabetic neuropathy, through the impairment of their microtubular network....

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Journal Article 2013; 34(5): 418-425 PubMed PMID: 23922041 Citation  Keywords:  Animals, Glutathione Peroxidase:metabolism, Hippocampus:drug effects, Male, Malondialdehyde:metabolism, Melatonin:pharmacology, Oxidative Stress:drug effects, Pineal Gland:surgery, Rats, Rats, Wistar, Reactive Oxygen Species:metabolism, Superoxide Dismuta.   

OBJECTIVE: The effects of melatonin on antioxidant status were examined in pinealectomized rats using enzymatic, histological and immunohistochemical techniques. The aim of this study is to investigate the effects of melatonin on hippocampal apoptosis.

MATERIALS AND METHODS: Male Wistar rats (n=21) were divided into 3 groups: Group I and group II were designated as control (sham-pinealectomy) and pinealectomized rats, respectively. Rats in group III were pinealectomized and injected daily with melatonin (1 mg/kg) for 3 months beginning at day 7 after surgery. At the end of experimental period, all rats were killed by decapitation. The brains of the rats were removed and the hippocampus tissue was obtained from all brain specimens. The right hippocampal specimens of all rats were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels. The left hippocampus tissue specimens of all animals were used for immunohistochemical and histological evaluation.

RESULTS: The levels of SOD and GSH-Px were significantly decreased, and MDA levels were significantly increased in pinealectomized rats compared to the controls. In the histological and immunohistochemical evaluation of this group, increase of pyknotic cells, vacuolar degeneration and apoptosis were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels were detected in the rats administered melatonin after pinealectomy. Furthermore, histological and apoptotic changes in hippocampus caused by pinealectomy were lost in the rats treated with melatonin.

CONCLUSIONS: The results of our study revealed that pinealectomy-induced oxidative damage and morphological changes in the hippocampal tissue were suppressed by melatonin.

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Journal Article 2012; 33(Suppl 3): 183-189 PubMed PMID: 23353865 Citation  Keywords:  Animals, Antioxidants:metabolism, Basal Metabolism:drug effects, Biomarkers:metabolism, Caspases:metabolism, Female, Homeostasis:drug effects, Melatonin:metabolism, Mice, Mice, Inbred BALB C, Models, Animal, Oxidative Stress:drug effects, Thiobarbituric A.   

OBJECTIVES: Melatonin is a hormone with strong antioxidant activity. It is biosynthesized in the pineal gland and serves in the biological signaling and control of the circadian rhythm. Though there is evidence of beneficial effects of melatonin, the substance was not investigated in greater details associated with specific regulation of oxidative stress in organs and tissues.

DESIGN: The experiment is based on exposure of BALB/c mice to doses from 10 µg to 1mg of melatonin. Mice were euthanized after one and 24 hours, respectively. Biochemical markers in plasma, ferric reducing antioxidant power (FRAP), thiobarbituric acid reactive substances (TBARS) and activity of caspase-3 were examined in selected organs.

RESULTS: We confirmed significant alteration in high-density lipoprotein and total cholesterols and glucose. After one day, levels of glucose and high-density lipoprotein cholesterol were decreased, while total cholesterol increased in a dose dependent manner. FRAP values increased in spleen, liver, kidney, heart, and brain indicating a growing potential of low molecular weight antioxidants 24 hours after exposure. However, TBARS values indicating oxidative stress were elevated in heart, kidney, and liver.

CONCLUSIONS: Despite the antioxidant properties of melatonin, its effect on the organism is more complicated. It influences not only the oxidative homeostasis but also the basal metabolism, as represented by, e.g., cholesterol and glucose. This substance could thus be used for therapeutical purposes such as amelioration of pathologies associated with generation of reactive species or some metabolic dysfunctions....

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Journal Article 2012; 33(Suppl 3): 130-135 PubMed PMID: 23353856 Citation  Keywords:  Animals, Antioxidants:metabolism, Biomarkers:metabolism, Carps:embryology, Catalase:metabolism, Czech Republic, Embryo, Nonmammalian:drug effects, Female, Glutathione Reductase:metabolism, Herbicides:toxicity, Male, Oxidative Stress:drug effects, Prometry.   

OBJECTIVES: The aim of the study was to investigate effects of the triazine herbicide prometryne on early life stages of common carp Cyprinus carpio as indicated by oxidative stress and antioxidant indices.

DESIGN: Toxicity tests were performed according to OECD 210 methodologies. Common carp larvae and embryos exposed for 35 days to prometryne at three concentrations, 0.51 (reported concentration in Czech rivers), 80 (1% 96 h LC50), and 1200 (15% 96 h LC50) μg/l, were compared to carp in a non-treated control group. Activity of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR), as well as levels of thiobarbituric acid reactive substances (TBARS) were assessed.

RESULTS: Chronic exposure of early life stages of carp to prometryne showed no effect on growth and mortality rates. Levels of oxidative damage in fish test groups showed no significant differences from the controls. Glutathione reductase activity at exposure 0.51 μg/l was significantly increase (p<0.01) compared with controls and other exposures.

CONCLUSION: The chronic exposure to prometryne showed no influence on oxidative stress. Differences from control fish was observed in GR activity in exposure prometryne 0.51 μg/l....

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Journal Article 2012; 33(Suppl 3): 124-129 PubMed PMID: 23353855 Citation  Keywords:  Animals, Biomarkers:metabolism, Carps:embryology, Dose-Response Relationship, Drug, Embryo, Nonmammalian:drug effects, Free Radicals:metabolism, Herbicides:toxicity, Lipid Peroxidation:drug effects, Oxidative Stress:drug effects, Phenols:metabolism, Plant.   

OBJECTIVES: This work assessed the subchronic effects of the triazine compounds terbuthylazine and metribuzin on embryo-larval stages of common carp (Cyprinus carpio L.) using biotransformation enzyme and selected oxidative stress parameters.

DESIGN: Early developmental stages of fish, from embryo to larvae, were exposed to terbuthylazine at concentrations of 0.9, 160, 520, and 820 μg/L, and metribuzin at concentrations of 0.9, 4, 14, and 32 mg/L for 30 days and compared to the non-treated control group. For assessment of free radical defence the activities of glutathione S-transferase (GST) and glutathione reductase (GR) were measured; the lipid peroxidation (TBARS) level was determined as a marker of free radical damage.

RESULTS: Terbuthylazine had no significant effect (p>0.05) at any tested concentrations on GST activity. Terbuthylazine caused an increase (p<0.05) in GR activity at the concentration of 520 μg/L. We found a non-significant (p>0.05) effect of terbuthylazine exposure on TBARS level. In metribuzin treated groups, the activity of GST was increased (p<0.05) in all experimental groups, with the highest at the concentration of 32 mg/L. GR activity was increased in the 0.9, 4, and 14 mg/L groups and the TBARS levels were the highest in the 0.9 mg/L group.

CONCLUSION: Our results suggest that terbuthylazine and metribuzin induced oxidative stress in embryo-larval stages of common carp. Increased activities of biotransformation enzymes or antioxidant defence enzymes were markers of free radical attack. There was low lipid peroxidation in early developed fish after triazine exposure....

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Journal Article 2012; 33(Suppl 3): 72-76 PubMed PMID: 23353847 Citation  Keywords:  Animals, Anti-Inflammatory Agents, Non-Steroidal:toxicity, Aspirin:toxicity, Dose-Response Relationship, Drug, Embryo, Nonmammalian:drug effects, Inactivation, Metabolic:physiology, Lethal Dose 50, Oxidative Stress:drug effects, Toxicity Tests, Acute, Wat.   

OBJECTIVES: The aim of this study was to compare the acute toxicity of acetylsalicylic acid to embryonic and juvenile stages of aquarium fish - zebrafish (Danio rerio), oxidative stress parameters and detoxifying enzyme.

METHODS: Tests were performed according to OECD No. 203 (Fish, acute toxicity test) and OECD No. 212 (Fish, short-term toxicity test on embryo and sac-fry stages) methodology.

RESULTS: The results showed the mean acetylsalicylic acid LC50 value to be 567.7 mg/L in juvenile zebrafish. The acute toxicity of acetylsalicylic acid for zebrafish embryos was 274.6 mg/L. Statistically significantly higher activity of GST was found in concentrations 340, 380 and 420 mg/L of acetylsalicylic acid. TBARS, GPx and GST didn't show statistically significant activity in tested concentrations of acetylsalicylic acid.

CONCLUSIONS: The results revealed a statistically significantly higher degree of sensitivity in the embryonic stages of zebrafish compared to its juveniles. Acetylsalicylic acid did not cause statistically significantly higher antioxidative defence in zebrafish....

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Journal Article 2012; 33(5): 530-535 PubMed PMID: 23090272 Citation  Keywords:  Age Factors, Animals, Animals, Newborn, Antioxidants:pharmacology, Ascorbic Acid:pharmacology, Cerebral Cortex:drug effects, Epilepsy:drug therapy, Evoked Potentials:drug effects, Female, Hypoxia, Brain:drug therapy, Male, Oxidative Stress:drug effects, P.   

OBJECTIVES: The effects of ascorbic acid and α-tocopherol pre-treatment on hypoxia induced changes in brain cortex excitability were tested in immature rats exposed chronically to simulated altitude of 7 000 m.

METHODS: Rat pups were kept together with their mothers for 8 hours a day in hypobaric chamber since the day of the birth till the postnatal day 11 or 17. Each day immediately before placing to hypobaric chamber pups were pretreated intraperitoneally either with ascorbic acid (100 mg/kg) or α-tocopherol (1 500 mg/kg). Cortical afterdischarges were elicited by repeated stimulation of the right sensorimotor cortex. The duration of evoked cortical afterdischarges was analyzed.

RESULTS: Duration of cortical afterdischarges progressively declines with age. Hypoxia prolonged the duration of afterdischarges in 12-, 18- and 25-day-old animals. Pretratment with ascorbic acid or α-tocopherol shorted afterdischarges duration in youngest experimental group when compared with animals exposed to hypoxia only.

CONCLUSION: Hypoxia significantly affects the brain cortex excitability by prolonging afterdischarges duration. This effect differs with age. Antioxidant pre-treatment brought about shorter duration of cortical afterdischarges only in the youngest experimental group. The antioxidant effect is therefore age dependent....

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Journal Article 2012; 33(3): 279-284 PubMed PMID: 22635084 Citation  Keywords:  Animals, Catalase:metabolism, Cell Line, Tumor, Cell Proliferation:drug effects, Cell Survival:drug effects, Diabetic Neuropathies:metabolism, Glucose:pharmacology, Hyperglycemia:metabolism, Neurilemmoma:metabolism, Oxidative Stress:drug effects, Rats, Re.   

OBJECTIVES: Schwann cells may be involved in the pathogenesis of several neuropathies, such as those linked to an excess of d-glucose. Indeed, hyperglicemic condition can often result in the production of high reactive/nitrosative oxygen species concentration and possible damage of several cell structures. In the present work attention has been focused on the possible nitrosative effect of hyperglycemia on RT4 Schwannoma cell lines.

METHODS: Cells were cultured for 72hrs in the presence of 180 mM D-glucose. Morphology, growth rate, cell viability, catalase evaluation and Western blot were performed.

RESULTS: In D-glucose-exposed cells, 3-Nitrotyrosine increase and subsequent modifications in cell morphology, growth rate, viability and catalase activity were found.

CONCLUSION: Our findings suggested a possible primary role played by Schwann cells in the hyperglicemic neuropathy pathogenesis, through the excessive production of RNS and a decrease in antioxidant defense systems, bearing out the importance of the "nitrosative hypothesis" in the hyperglicemic-induced nervous system complications....

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