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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 2010; 31(Suppl 2): 101-104 PubMed PMID: 21187839 Citation  Keywords:  Antioxidants:pharmacology, Ascorbic Acid:pharmacology, Copper:pharmacology, Cysteamine:pharmacology, Dose-Response Relationship, Drug, Glutathione:pharmacology, Hyaluronic Acid:metabolism, Hydrogen Peroxide:metabolism, Hydroxides:metabolism, Oxidation-Red.   

OBJECTIVE: This study presents the results of antioxidative and pro-oxidative efficacy of cysteamine and D-penicillamine (D-pen) in comparison to L-glutathione (L-GSH) on high-molar-mass hyaluronan (HA) degradation by cupric ions plus ascorbic acid.

METHODS: The substance tested was applied in the degradative system cupric ions plus ascorbate: (i) before the reaction onset or also (ii) 1 h after the reaction started. The results obtained were compared with that one recorded by using the degradative system in the absence of the substance tested. To monitor HA degradation kinetics, rotational viscometry was applied. Moreover, the standard ABTS and DPPH assays were used.

RESULTS: By using the method of rotational viscometry, D-pen showed dual effect: initial inhibitory effect on •OH radicals was changed to a pro-oxidative one in the dose and time dependent manner. Both L-GSH and cysteamine were recorded to be more effective scavengers of •OH radicals than D-pen. Cysteamine demonstrated to be an excellent scavenger also of alkoxyl- and peroxyl- type radicals. Based on IC50 values, gained by ABTS assay, it is evident that D-pen showed higher radical scavenging capacity compared to cysteamine. Similar results were observed also in DPPH assay, although in this assay less effective radical scavenging capacities of both substances tested were recorded.

CONCLUSIONS: On the basis of the results obtained, it can be stated that D-pen can produce hydrogen peroxide or •OH radicals and can inhibit the production of these oxidants. Our results showed that both L-GSH and cysteamine are similarly effective in inhibiting of HA degradation. Moreover, cysteamine demonstrated to be a significant inhibitor of alkoxyl- and peroxyl- type radicals generated from C-type macroradical of HA....

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Journal Article 2010; 31(Suppl 2): 96-100 PubMed PMID: 21187837 Citation  Keywords:  Animals, Antioxidants:pharmacology, Antirheumatic Agents:pharmacology, Arthritis, Experimental:drug therapy, Carnosine:pharmacology, Disease Models, Animal, Free Radicals, Glutathione:metabolism, Hyaluronic Acid:metabolism, In Vitro Techniques, Male, Meth.   

OBJECTIVE: New ways of supplementary or combinatory therapy of rheumatoid arthritis (RA) are of great importance. The aim is to find an additive to classical RA therapy with natural molecules without side effects possessing anti-inflammatory and anti-oxidative properties. In this study we investigated the anti-oxidative and anti-inflammatory properties of the endogenous natural compound carnosine (CARN) in vitro and in vivo. Moreover, we tested also the inhibitory properties of the drug methotrexate (MTX) on dynamic viscosity of hyaluronan (HA) solutions in the same manner.

METHODS: For in vitro testing of the inhibitory properties of CARN against degradation of HA solutions, we used the model of degradation of hyaluronan (HA) induced by free radicals. Both substances, CARN and MTX, were compared to glutathione (GSH). Rotational viscometry was used in evaluation of protective properties of compounds studied. The ability of CARN to restore the redox imbalance occurring in adjuvant arthritis (AA) of rats was also tested. We monitored the effect of CARN on hind paw volume (HPV) and on the levels of protein carbonyls, and thiobarbituric acid reacting substances (TBARS) in AA.

RESULTS: In the reaction system with the prevalence of •OH and/or peroxy-type radicals, CARN in 200 μmol/L concentration tested was shown to exert a protective action on HA degradation. MTX was less effective than CARN in preventing HA degradation. Its ability to protect HA against radical degradation was evident only at the highest concentration of 400 μmol/L. In AA, carnosine significantly reduced TBARS and protein carbonyls in plasma, and also decreased the HPV of animals most effectively on the day 14.

CONCLUSIONS: CARN proved its inhibitory properties against degradation of HA solutions at experimental conditions in vitro and showed its beneficial efficiency in vivo. Moreover, it reduced also HPV, the clinical marker of inflammation in AA....

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Journal Article 2010; 31(Suppl 2): 79-83 PubMed PMID: 21187828 Citation  Keywords:  Animals, Antioxidants:pharmacology, Antirheumatic Agents:therapeutic use, Arthritis, Experimental:drug therapy, Cell Line, Disease Models, Animal, Drug Therapy, Combination, Macrophages:cytology, Male, Methotrexate:therapeutic use, Neutrophils:drug effect.   

OBJECTIVE: Formation of reactive oxygen species in neutrophils of rats with adjuvant arthritis and generation of nitric oxide in RAW 264.7 macrophages were analysed in the presence of pinosylvin.

METHODS AND RESULTS: The method of chemiluminescence was used for the detection of reactive oxygen species in blood of rats with adjuvant arthritis. Pinosylvin (50 mg/kg, daily, p.o.) and methotrexate (0.4 mg/kg, twice a week, p.o.) were applied separately or in a combination over a period of 28 days from the day of immunisation. Adjuvant arthritis was accompanied by a significantly increased number of neutrophils, by elevated concentration of oxidants in blood and by excessive responsiveness of neutrophils to stimulation with PMA. In rats treated with methotrexate, all these changes were significantly reduced and the inhibition became more pronounced when methotrexate was applied in the combination with pinosylvin; the monotherapy with pinosylvin did not induce any detectable changes in the parameters tested. Under in vitro conditions, pinosylvin inhibited formation of nitric oxide (NO) in macrophages, as demonstrated by the decreased concentration of nitrite - the end-product of NO metabolism (assessed by Griess' method), by the reduced expression of inducible NO synthase (detected by Western blot), and by the failure of pinosylvin to scavenge nitric oxide (measured amperometrically in cell-free system).

CONCLUSION: The observed ability of pinosylvin to decrease concentration of reactive oxygen and nitrogen species, along with its capacity to enhance the efficacy of methotrexate in arthritis treatment may shed more light into the pharmacological potential of this prospective natural substance....

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Journal Article 2010; 31(Suppl 2): 91-95 PubMed PMID: 21187826 Citation  Keywords:  Animals, Anti-Inflammatory Agents:pharmacology, Antioxidants:pharmacology, Arthritis, Experimental:drug therapy, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Therapy, Combination, Male, Oxidative Stress:drug effects, Peroxidase:metabolis.   

OBJECTIVE: The aim of this study was to evaluate the effects of pinosylvin (PIN) and pterostilbene (PTE), natural substances from the stilbenoid group, on the development of adjuvant arthritis in rats.

METHODS: Adjuvant arthritis (AA) was induced by a single intradermal injection of Mycobacterium butyricum in incomplete Freund's adjuvant in male Lewis rats. Our experiments included healthy intact animals as reference controls, arthritic animals without any drug administration, and arthritic animals with administration of PIN and PTE in the oral daily dose of 30 mg/kg b.w. The treatment involved administration of the substances tested from day 0, i.e. the day of immunization, to the experimental day 28. The following parameters were monitored: change of the hind paw volume (HPV) on day 14, 21 and 28, luminol-enhanced chemiluminescence (CL) of the joint and myeloperoxidase (MPO) activity in hind paw joint homogenates (day 28).

RESULTS: Arthritic animals treated with PIN showed a decrease in HPV, significantly on days 14 and 28. PIN decreased CL of the joint as well as MPO activity of the joint homogenate, in comparison with untreated animals. PTE had no effect on HPV and MPO activity in hind paw joint homogenates and exerted only a partial effect on luminol-enhanced CL.

CONCLUSIONS: On the basis of our results we conclude that the effect of PTE on CL was only partial. PIN, on the other hand, had a beneficial anti-inflammatory and antioxidant effect on oxidative stress induced biochemical changes occurring in AA, as determined by all three functional parameters....

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Evaluation Studies 2010; 31(Suppl 2): 62-68 PubMed PMID: 21187825 Citation  Keywords:  Animals, Antidotes:pharmacology, Antioxidants:pharmacology, Glutathione Reductase:metabolism, Liver:drug effects, Male, Models, Animal, Oxidative Stress:drug effects, Oximes:pharmacology, Pyridinium Compounds:pharmacology, Radiation, Ionizing, Rats, Rats,.   

OBJECTIVES: HI-6 is an antidotum suitable for treatment of intoxication by nerve agents. The recent investigation appointed its modulation of inflammatory response as well as vegetative nervous system activity. However, the present experiments were carried out in order to assess the antioxidant effect of HI-6 in irradiated animals.

METHODS: male Wistar rats were irradiated by ionizing radiation (7.5 Gy, LD50/30). Animals were divided into four groups: i.e. controls (A), irradiated (B), treated with HI-6 (C), and both irradiated and treated with HI-6 (D). Ferric reducing antioxidant power (FRAP), thiobarbituric acid reactive substances (TBARS) and glutathione reductase activity were assayed in liver, spleen, plasma, and whole blood. Clinical biochemistry markers were determined in plasma samples.

RESULTS: We found significantly increased FRAP levels in liver, while its levels decreased in the spleen of B group animals. Ionising radiation (B group) also significantly elevated TBARS values in spleen. HI-6 reversed FRAP and TBARS values to control levels. Glutathione reductase activity was significantly elevated in spleen and liver of animals exposed to HI-6 (C and D groups). Clinical biochemistry markers were shifted only slightly. The in vitro test confirmed the inhibitory effect of HI-6 towards acetylcholinesterase.

CONCLUSIONS: In conclusion, HI-6 is potent in suppressing oxidative stress and might be a promising drug in the field of radiation protection....

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Journal Article 2010; 31(Suppl 2): 84-90 PubMed PMID: 21187824 Citation  Keywords:  Antioxidants:pharmacology, Apoptosis:drug effects, Caspase 3:metabolism, Cell Survival:drug effects, Computer Simulation, Dose-Response Relationship, Drug, Humans, In Vitro Techniques, Male, Neutrophils:cytology, Phosphorylation:drug effects, Protein Kina.   

OBJECTIVE: Pterostilbene, a naturally occurring phenolic derivative, exhibits various pharmacological effects, e.g. anti-cancerous, antioxidant, anti-inflammatory and anti-diabetic. Based on our previous study, we assessed the cellular and molecular effects of pterostilbene on human neutrophils and in cell free systems. Experimental and theoretical molecular descriptors of stilbene derivatives were also determined.

METHODS: We assessed the antioxidant properties of pterostilbene using cell free system and computational methods. The effect of pterostilbene on protein kinase C activation/phosphorylation was detected by special anti-phospho protein kinase C antibodies. Membrane associated changes determining the life span of neutrophils and human recombinant caspase-3 assay were examined.

RESULTS: Pterostilbene possessed comparable antioxidant properties as resveratrol in cell free system. Computational methods were used to establish the molecular characteristics of stilbene derivatives. The values of electronic parameters suggest a slight enhancement of electron donor properties of pterostilbene compared to resveratrol. Phosphorylation and thus activation of protein kinase C alpha/beta II in activated neutrophils was not decreased by pterostilbene. Pterostilbene in concentrations of 10-100 μM was found to inhibit the activity of human caspase-3 purified enzyme and did not influence cell viability significantly.

CONCLUSION: Pterostilbene, an analog of resveratrol, was identified as a good natural antioxidant compound. However, reducing the oxidative burst of human neutrophils during their activation in vitro with pterostilbene does not include protein kinase C phosphorylation pathway. Pterostilbene showed dose dependent activation/inhibition of caspase-3 enzyme activity....

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Journal Article 2010; 31(3): 313-318 PubMed PMID: 20588243 Citation  Keywords:  Animals, Antioxidants:pharmacology, Blood Glucose:drug effects, Body Weight:drug effects, Carbolines:pharmacology, Diabetes Mellitus, Experimental:drug therapy, Glycosylation End Products, Advanced:metabolism, Kidney:drug effects, Male, Oxidative Stress:d.   

OBJECTIVES: Recent basic research and clinical data have provided new insights into the role of glycoxidative and nitrosative stresses (both oxidative stress) in diabetic complications, such as diabetic nephropathy, suggesting a different and innovative approach to antioxidant therapy. In streptozotocin-induced diabetic rat kidney, the present study investigated the effects of the synthetic pyridoindole antioxidant stobadine (STB) on renal total antioxidant potential (AOP) and protein oxidation parameters such as protein carbonyl content (PCC), advanced oxidation protein products (AOPPs) and nitrotyrosine (NT), a marker specific for protein modification by peroxynitrite.

MATERIALS AND METHODS: Wistar Albino rats were divided into two groups: normal and streptozotocin-induced diabetic rats. Each group of the animals was further divided into two groups: untreated and treated with stobadine (24.7 mg/kg) during 16 weeks daily by oral gavage.

RESULTS: The renal tissue AOP and the levels of AOPPs, PCC and NT were increased in diabetic rats compared with the untreated control animals. Furthermore, stobadine treatment significantly decreased protein carbonylation and AOPPs but not NT.

CONCLUSIONS: These findings indicate that STB is an antioxidant factor which can improve glycoxidative stress markers in kidney, while it has no effect on protein nitrosylation....

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