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Journal Article 2010; 31(4): 517-523 PubMed PMID: 20802456 Citation  Keywords:  Analysis of Variance, Animals, Ferrous Compounds:pharmacology, Growth Hormone:pharmacology, Insulin-Like Growth Factor I:pharmacology, Lipid Peroxidation:drug effects, Liver:drug effects, Malondialdehyde:metabolism, Rats, Swine, Thyroid Gland:drug effects.   

OBJECTIVES: Growth hormone (GH) and its tissue mediator, insulin-like growth factor-I (IGF-I), are involved in oxidative processes, lipid peroxidation (LPO) included. Bivalent iron (Fe2+) is frequently used to experimentally induce oxidative damage to macromolecules (Fe2++H2O2+H+→Fe3++•OH+H2O). The aim of the study was to evaluate the effect of GH and/or IGF-I on the iron-induced LPO in the rat liver and porcine thyroid homogenates.

METHODS: Rat liver and porcine thyroid homogenates were incubated in presence of GH (100; 10; 1.0; 0.1; 0.01; 0.001; 0.0001 µg/ml) or IGF-I (1000; 100; 10; 1.0; 0.1; 0.01; 0.001; 0.0001 µg/ml) or GH (100 µg/ml)+IGF-I, or FeSO4+H2O2 plus GH and/or IGF-I. The level of LPO was expressed as concentrations of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA) per mg of protein.

RESULTS: GH and/or IGF-I did not change the basal level of oxidative damage to lipids. In the rat liver homogenates, GH did not affect the iron-induced LPO, whereas IGF-I--in the lowest two concentrations--enhanced the process. In porcine thyroid homogenates, GH--in its two lowest concentrations--prevented, whereas in other concentrations, it enhanced the iron-induced LPO. IGF-I, in all used concentrations, enhanced the iron-induced LPO.

CONCLUSION: GH and/or IGF-I may reveal prooxidative effects. This fact does not support their application in the treatment of disorders associated with increased oxidative damage....

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Journal Article 2010; 31(4): 489-496 PubMed PMID: 20802448 Citation  Keywords:  Analysis of Variance, Animals, Brain:drug effects, Kidney:drug effects, Lipid Peroxidation:drug effects, Lipopolysaccharides:pharmacology, Liver:drug effects, Male, Malondialdehyde:metabolism, Melatonin:pharmacology, Rats, Rats, Wistar, Serotonin:analogs .   

OBJECTIVE: Bacterial lipopolysaccharide (LPS) causes lipid peroxidation (LPO). We have found that LPS induces LPO in vitro, in tissue homogenates in a concentration-dependent manner, the concentration of 400 µg/ml demonstrating the most efficient lipid damaging effect . Both melatonin and its precursor, N-acetylserotonin, must possess antioxidant activities, both in vivo or in vitro, however, following some claims, N-acetylserotonin is a more effective extra- and intracellular antioxidant than melatonin. The aim of our study was to compare the effects of melatonin and N-acetylserotonin on the LPS-induced LPO in vitro.

METHODS: Malondialdehyde (MDA) plus 4-hydroxyalkenal (4-HDA) concentrations were measured as the indices of induced membrane peroxidative damage in brain, liver and kidney homogenates. Both melatonin and N-acetylserotonin were used at increasing concentrations, starting from 0.01-5 mM, together with LPS at one concentration level of 400 µg/ml.

RESULTS: In all the examined tissues, LPS stimulated LPO, while both melatonin and N-acetylserotonin decreased LPS-stimulated LPO. Furthermore, the capacity of N-acetylserotonin reducing LPO was higher than that of melatonin.

CONCLUSIONS: The results of the reported study clearly indicate that N-acetylserotonin is a much stronger antioxidant in vitro than melatonin in terms of reducing oxidative damage to lipid membranes. However, it remains still unclear how the features relate to in vivo circumstances....

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Journal Article 2010; 31(4): 477-482 PubMed PMID: 20802439 Citation  Keywords:  Analysis of Variance, Animals, Axons:pathology, Blood-Brain Barrier:pathology, Brain Edema:chemically induced, Dentate Gyrus:pathology, Female, Male, Mannitol, Myelin Sheath:pathology, Rats, Rats, Wistar, Time Factors,.   

OBJECTIVES: Clinically very serious condition of ischaemia and brain injury which are often associated with brain oedema is frequently accompanied by the impairment of the structural integrity of axons. We wondered whether the brain oedema (without ischemia brain injury) can induce structural axonal impairment.

METHODS: Brain oedema was induced by osmotic blood-brain barrier opening with 20% mannitol applied selectively into the internal carotid. Axonal changes were recognized as signs of myelin disintegration (oedematous vesicles, varicosity, myelin fragmentation) at histological sections stained with Black Gold in hippocampal areas CA1 and CA3 and in the dentate gyrus and cerebral cortex at time intervals of one hour, one day, three days and one week after the oedema induction.

RESULTS: Impairment of the structural integrity was identified in myelin sheets in all areas studied in all experimental groups. Whereas in the control group axon were of the uniform diameter, in the experimental groups various forms of myelin disintegration were observed. The progression of myelin damage depended on the time elapsed after the oedema induction.

CONCLUSION: Opening the blood-brain barrier with an osmotic insult induces brain oedema which represents a factor triggering axonal impairment accompanied with myelin changes. The development of axonal changes initiated by brain oedema only (without ischemia brain injury) is a novel observation....

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Journal Article 2010; 31(4): 530-537 PubMed PMID: 20802438 Citation  Keywords:  Animals, Axons:pathology, Microscopy, Electron, Nerve Regeneration:physiology, Optic Nerve:pathology, Optic Nerve Injuries:pathology, Rats,.   

OBJECTIVE: The present work was aimed at studying the ultra structural changes of the proximal (retinal) stump of the intracranially transected optic nerve of the rat for any possible regenerative ability.

METHODS: Specimens were collected one (1 wpo) and four weeks(4 wpo) after the transection and the cross sections of the stumps were studied by electron microscopy by dividing them into three zones, (1) the central zone, (2) the intermediate zone, and (3) the peripheral zone.

RESULTS: The present results showed evident morphological changes in these zones both in the 1 wpo and 4 wpo groups. The signs of degeneration were more marked in the central zone than in the peripheral zone and they were more prominent in the 1 wpo group than in the 4 wpo group. The most prominent sign of the degeneration was loss or lack of the healthy myelinated axons. The main evidence of the regenerative ability was the reappearance of the apparently healthy myelinated axonal profiles, with a parallel decrease of the non myelinated ones. This regenerative feature was more prominent peripherally and might be an indication that ischemia was the cause of optic nerve degeneration.

CONCLUSIONS: The present work revealed a clear morphological evidence of the regenerative capability of the intracranially transected optic nerve though it is considered as a part of the CNS....

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Comparative Study 2009; 30(1): 139-143 PubMed PMID: 19300396 Citation  Keywords:  Animals, Binding, Competitive, Carps:metabolism, Female, Gonadotropin-Releasing Hormone:metabolism, Humans, Mammals:metabolism, Pituitary Gland:metabolism, Protein Binding, Radioactive Tracers, Rats, Receptors, LHRH:metabolism, Salmon:metabolism,.   

OBJECTIVES: Receptor binding of GnRH is connected with the stimulation of pituitary gonadotropic cells leading to both the release and biosynthesis of gonadotropins. The binding is connected with the conformational changes in the receptor which induce the specific intracellular signalisation. The study of fish GnRHs and their receptors may give us new knowledge of the complex interplay of different mechanisms involved in neuroendocrine regulation of reproduction.

METHODS: Receptor binding of both mGnRH and sGnRH were compared by the study utilizing the displacement method with mGnRH or sGnRH as radioactive tracers. Incubation was performed at 2 degrees C to avoid ligand degradation.

RESULTS: The comparative binding of mGnRH and sGnRH with GnRH receptors from the female rat pituitary and female carp pituitary was studied. At the 50% of displacement, the binding of sGnRH to the rat pituitary receptor was very small and in comparison to the binding of mGnRH (100%) was in the range 2-15%. However, the binding of mGnRH to carp pituitary receptors is small in comparison with the binding of sGnRH (100%) and was in the range 5-20%.

CONCLUSION: The results demonstrated the differences in binding of different GnRHs to the receptor in rats and carp. This suggests that the structures of GnRH and its receptor undergo co-evolution in different classes of animals....

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Comparative Study 2009; 30(1): 25-31 PubMed PMID: 19300387 Citation  Keywords:  Animals, Anti-Anxiety Agents:pharmacology, Anxiety:drug therapy, Behavior, Animal:drug effects, Diazepam:pharmacology, Exploratory Behavior:drug effects, Male, Motor Activity:drug effects, Neuropsychological Tests, Rats, Rats, Wistar,.   

OBJECTIVES: Anxiety is an emotional state experienced by people, and is not readily modeled in animals. In order to extend till now ethologically derived paradigms used in the evaluation of anxiety and fear in rodents, a modified open-field was designed.

METHODS: Spontaneous behavior of male rats was investigated in the elevated arena; the bottom was divided by inter-space of different width (2, 4, 6, 8 and 10 cm) into two identical parts. Anxiolytic effects of diazepam (DZP) at doses 0.5, 1.0, 2.5 and 5.0 mg/kg were investigated in the newly designed device and compared with the effects of similar doses in a large circular open-field arena.

RESULTS: In Experiment 1 the progressive extension of the inter-space prolonged the first passing, decreased the total number of passing, and increased the inter-space sniffing in intact animals. In Experiment 2 DZP at doses 1.0, 2.5 and 5.0 mg/kg significantly enhanced the readiness to cross, the frequency of passing the inter-space and decreased inter-space sniffing as compared to controls. In Experiment 3 we found that DZP at doses 0.1 and 0.3 mg/kg increased behavioral activity both along the perimeter and in the center of the arena, thus indicating lower level of anxiety.

CONCLUSION: The presented modified open-field test is a useful paradigm to investigate risk assessment behavior in rats, and may provide a sensitive novel model of anxiety and fear level....

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Journal Article 2009; 30(5): 582-591 PubMed PMID: 20035269 Citation  Keywords:  Anemia:drug therapy, Animals, Antineoplastic Agents, Alkylating:toxicity, Bone Marrow:drug effects, Cyclophosphamide:toxicity, Humans, Leukopenia:drug therapy, Melatonin:pharmacology, Random Allocation, Rats, Rats, Wistar,.   

BACKGROUND: In the course of the last few years, various studies have researched the relations linking melatonin (MLT) with hematopoiesis and the immune-hematopoietic system. Nevertheless, to date there are numerous issues still opened and many questions are yet unanswered. Much emphasis has been recently placed on the reducing role of MLT, which has been demonstrated by many studies to mitigate the genotoxic damage inflicted by various alkylating agents. Although in vitro MLT has shown to be effective in limiting the cytological alterations provoked by chemotherapeutic drugs, some clinical studies seem to point to a somewhat lower effectiveness in countering chemotherapy-induced leukopenia and anemia.

OBJECTIVE: The aim of this study was to evaluate the activity exerted by pharmacological doses of MLT in limiting leukopenia, anemia and other hemocytometric modifications in animals facing acute toxicity caused by the treatment with cyclophosphamide (CP). Moreover, we have compared the activity of MLT with well-known alpha-tocopherol/ascorbic acid antioxidant system.

RESULTS: Our results indicate that overall MLT exerts a remarkable countering activity towards leukopenia and anemia in the early phase of administration of CP.

CONCLUSIONS: Our findings suggest possible active involvement of MLT in hematopoiesis and erythrocyte- and leukocyte turnover. This paper summarizes the essential aspects of the available literature, researching the possible relations between MLT and immune-hematopoietic system....

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Journal Article 2009; 30(5): 592-598 PubMed PMID: 20035268 Citation  Keywords:  Animals, Antidepressive Agents:metabolism, Cell Line, Tumor, GTP-Binding Protein alpha Subunits:metabolism, Male, Rats, Rats, Wistar,.   

OBJECTIVES: Neurochemical studies on the etiopathogenesis of depression are also focusing on the transduction system beyond receptors. Trimeric G-proteins play a crucial role in the transmembrane signalling, signal amplification and intracellular processing. Abnormalities of G-protein levels are observed in subjects with depression, G-protein modulation is considered to play a role in the antidepressant mode of action.

METHODS: We studied acute or chronic administration of antidepressants from different pharmacological groups. We used immunochemical estimation (ELISA) of the main types of G-protein alpha subunits from isolated membranes of C6 glioma cells and rat brain tissue.

RESULTS: Significant elevation of G alpha q/11 subunits after chronic administration of sertraline and significant reduction of G alpha s subunit levels following both acute and chronic administrations of sertraline were found. In contrast, no significant effects on G alpha subunit levels following acute desipramine and moclobemide administration were observed in vitro. Chronic moclobemide effect in vivo is causing significant elevation of Galpha s and Galpha i1,2 subunit levels.

CONCLUSIONS: Results show involvement of antidepressant drugs in the C6 glioma signal transduction cascades modulation in dependence on the antidepressant class. Significant influence in the cAMP system modulation is observed after administration both SSRI and MAOA inhibitors. Astrocytoma cells - C6 glioma cells also can offer a model system of the glia where modulation of cell signalization cascades can influence cell functioning and production of neurotrophic factor molecules relevant to the antidepressant treatment and depression etiopathogenesis....

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