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  • 1
    Electronic Resource
    Electronic Resource
    Scavenging effect of melatonin on hydroxyl radicals generated by alloxan (2000)
    Copenhagen : Munksgaard International Publishers
    Journal of pineal research 29 (2000), S. 0 
    Details
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Alloxan can act as a generator of reactive oxygen species (ROS) as long as sufficient suitable reducing agents (e.g. reduced glutathione) and oxygen are available. Using electron spin resonance-spectroscopy and the oxygen-centered spin trap DEPMPO, we demonstrate that hydroxyl radicals (OHzrad;) are formed in vitro by alloxan in the presence of glutathione (GSH) and chelated divalent iron. Furthermore, peroxidation of polyunsaturated fatty acids from phosphatidylcholine-containing liposomes with concomitant formation of malondialdehyde (MDA) was used as a further indicator for a preceding OHzrad; formation. Melatonin, the main secretory product of the pineal gland, is an effective scavenger of OHzrad;. The 50%-inhibitor concentration (IC50-value) for melatonin to scavenge OHzrad; generated from the alloxan/GSH-reaction in the presence of ferrous ions was 23 μmol/L. In contrast to the ability to effectively scavenge OHzrad;, the potential of melatonin to prevent lipid peroxidation is considerably less pronounced.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0633.2002.290402.x
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  • 2
    Electronic Resource
    Electronic Resource
    Circannual Oscillations of Thyroxine and Cholesterol Levels After Pinealectomy and Ganglionectomy Related to the Weight Changes of the Pineal, Pituitary, and Thyroid Glands (1988)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of pineal research 5 (1988), S. 0 
    Details
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Circannual rhythms of thyroxine (T4) and cholesterol blood levels, as well as of pineal, pituitary and thyroid weights were compared in intact, pinealectomized (Px), and ganglionectomized (Gx) rats. Special emphasis was put on the similarities and differences between the effect of Px and of Gx exerted on the neuroendocrine regulation of thyroid function.Animals were kept under changing lighting schedules simulating the natural seasonal conditions (December, L:D 8:16; June, L:D 16:8; March and September, L:D 12:12). Animals were killed 90 d after surgical interventions in the above-mentioned 4 months. In each season, animals were killed at four time points of the daily rhythm, and the means of the four data of a single day were used for further analysis evaluating Circannual changes.All the investigated five parameters showed a monophasic Circannual rhythm. The lowest T4 blood level was measured in summer; in contrast, cholesterol level and organ weights had a maximum in the same season of the year.The annual mean value of T4 level was diminished, while cholesterol level and pituitary and thyroid weights were increased in Px and Gx animals. Pineal weight showed a decrease in the Gx animals. Both Px and Gx failed to influence the Circannual rhythms of the measured parameters. However, a significant T4-decreasing effect of Px and Gx was observed in the second half of the year, whereas a cholesterol-level-increasing effect, as well as thyroid hypertrophy, was registered in the first half of the year. These results suggest a prothyroid function of the pineal gland.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-079X.1988.tb00781.x
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  • 3
    Electronic Resource
    Electronic Resource
    Transformation of barbituric acid into alloxan by hydroxyl radicals: interaction with melatonin and with other hydroxyl radical scavengers (2002)
    Oxford, UK : Munksgaard International Publishers
    Journal of pineal research 33 (2002), S. 0 
    Details
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Barbituric acid (2,4,6-pyrimidinetrione) can be transformed by a non-enzymatic hydroxylation into alloxan (2,4,5,6-pyrimidinetetrone). This transformation can be used as a reaction indicating the formation of hydroxyl radicals (·OH). This conversion was detected using HPLC. Formation of ·OH was demonstrated by electron spin resonance (ESR) spectroscopy combined with spin-trapping techniques. It was shown that ·OH generated via the Fenton reaction abstracts first a hydrogen atom from barbituric acid (BA) and forms intermediately a paramagnetic derivative of BA. After a second attack by another ·OH, the BA radical is transformed into dialuric acid (DA), which autoxidizes via the alloxan radical (·ALX) to ALX. Superoxide radicals (·O2−) are formed during autoxidation of DA and ·ALX. They are able to regenerate ferrous ions. As a result, traces of iron salts are capable of catalyzing the conversion of large amounts of BA into ALX. Several scavengers of ·OH were tested with regard to their efficiency in preventing the transformation of BA into ALX. Of all the scavengers analyzed, melatonin was shown to be one of the most potent compounds.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-079X.2002.02936.x
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  • 4
    Electronic Resource
    Electronic Resource
    Circannual Serum Creatine Kinase Patterns After Ganglionectomy and Pinealectomy of the Wistar Rat (1989)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of pineal research 6 (1989), S. 0 
    Details
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previous investigations have shown that an inverse correlation exists between serum thyroxine levels (T4) and serum creatine kinase activity (CK) both in hypothyroid and hyperthyroid states. In the present study, serum T4 levels and total serum CK activity were analysed after thyroidectomy (TX), ganglionectomy (extirpation of the superior cervical sympathetic ganglion) (GX), or pinealectomy (PX) four times a year (March, June, September, and December). Blood samples were taken four times daily (at midlight, middark, and at 1 hour after the onset of the light and dark periods). Animals were kept under an artificial light schedule that simulated natural light-dark periods. The annual main values of serum T4 levels were significantly decreased after the operations, whereas serum CK activities were increased. Our circannual investigations demonstrated an inverse correlation between serum T4 levels and total serum CK activity (under hypothyroid circumstances). In addition, the circannual pattern of the serum CK activity demonstrated maxima under short-day (winter) conditions and minima under long-day (summer) conditions. GX and PX provoke an unimportant shift (a little longer than 2 months) in maxima and minima of the annual rhythm. Circannual curves exhibited differences in the degree of the increase of serum CK activity of GX and PX groups. These results indirectly confirm the assumption that experimental sympathetic denervation or removal of the pineal gland will induce a hypothyroid state over the long term.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-079X.1989.tb00434.x
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  • 5
    Electronic Resource
    Electronic Resource
    Alloxan acts as a prooxidant only under reducing conditions: influence of melatonin (1999)
    Springer
    Cellular and molecular life sciences 55 (1999), S. 487-493 
    Details
    ISSN: 1420-9071
    Keywords: Key words. Alloxan; free radicals; oxidative stress; diabetes; melatonin; antioxidant; prooxidant; lucigenin; NBT.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Depending on the availability of suitable reducing agents, alloxan can be either a prooxidant or an antioxidant. Alloxan and its reduced derivative, dialuric acid, act as a redox couple, driven by reduced glutathione (GSH) or L-cysteine, generating in vitro in the presence of oxygen, both superoxide radical and hydrogen peroxide. The production of superoxide radicals was shown by the appearance of lucigenin chemiluminescence (CL) as well as by the generation of formazan from nitroblue tetrazolium (NBT). The lucigenin CL as well as the NBT reduction was inhibited by superoxide dismutase and partially by catalase. Melatonin inhibited alloxan-mediated CL. In contrast, in the absence of reducing agents, alloxan is a scavenger of superoxide radicals formed by other reactions. Because of the high content of reducing compounds in the cell (e.g. glutathione), it is suggested that alloxan acts in vivo mainly as a generator of reactive oxygen species.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000180050305
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  • 6
    Electronic Resource
    Electronic Resource
    Evidence for a circadian rhythm of insulin release from perifused rat pancreatic islets (1998)
    Springer
    Diabetologia 41 (1998), S. 1085-1092 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Pancreatic islets ; circadian rhythm ; insulin ; melatonin ; in vitro.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study aims to analyse a circadian rhythm of insulin secretion from isolated rat pancreatic islets in vitro and its potential modulation by melatonin, the concentrations of which change in vivo inversely to that of insulin. The circadian rhythm was evaluated in a perifusion system, adapted to the specific conditions of pancreatic islets. To determine rhythmicity of insulin secretion, 30-min fractions were collected continuously for investigative periods of 44 to 112 h. Insulin secretion in 10 experiments was analysed by using the MacAnova-program for period length (τ), the χ2-periodogram for test of significance (p 〈 0.001), and additionally the empirical cosine adaptation for amplitude and goodness-of-fit. Thereby a circadian pattern was observed with periods (τ) between 21.8 and 26.2 h. The period duration (mean ± SEM) was 23.59 ± 0.503 h, the overall mean insulin release 1038 ± 13 pmol/l and the mean amplitude 88 ± 17 pmol/l. Adding melatonin (10 nmol/l, t = 2 h) as a hormonal Zeitgeber during analysis of circadian insulin secretion phase-response studies show phase-shifts with approximately 9 h phase advance. Thereafter the circadian period was maintained, while the amplitude was enhanced. From this it is concluded that an endogenous circadian oscillator is located within the pancreatic islets of the rat that regulates circadian insulin secretion of the insulin-producing beta cells. The pacemaker is remarkably stable, because its periodicity is not affected by factors altering insulin secretion. In agreement with inhibitory influences of melatonin (range 0.5 nmol/l to 5 μmol/l) on the insulin response in vitro, the phase-responses support the contention that pancreatic beta cells may be targets for melatonin action. [Diabetologia (1998) 42: 1085–1092]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051034
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  • 7
    Electronic Resource
    Electronic Resource
    Dynamic insulin secretion from perifused rat pancreatic islets (1998)
    Springer
    Cellular and molecular life sciences 54 (1998), S. 733-743 
    Details
    ISSN: 1420-9071
    Keywords: Key words. Pancreatic islets; insulin; perifusion; secretion kinetics.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Insulin secretion from isolated pancreatic islets of 8- to 12-day-old rats was investigated in a dynamic in vitro (perifusion) system. The aims of the study were (i) to describe a carefully controlled in vitro method to study the mechanism of insulin secretion and to analyse the effects and dynamic interactions of bioactive compounds on isolated rat pancreatic islets, (ii) to validate the method by comparing fundamental data on the functions of the islets obtained with this method to those collected with other techniques; and (iii) to find novel features of the control of insulin secretion. The method was carefully designed to maintain the functional capacity of the explanted cells. A functional standardization system was elaborated consisting of (i) analysis of the changes in the basal hormone secretion of the cells; (ii) evaluating responses to a standard, specific stimuli (50 mM glucose for 3 min); (iii) determining the alteration of the momentary size of the hormone pool with responses to KCl; and (iv) direct determination of the total intracellular hormone content from the extract of the column. The technique provides accurate quantitative data on the dynamic responses to biologically active compounds that act directly on the pancreatic islets. The islets maintained their full responsiveness for up to 7 days, and responses as close as in 1-min intervals could be distinguished. A linear dose-response relationship was found on the glucose-induced insulin release in case of 3-min stimulation with 4 and 500 mM of glucose (lin-log graph). Utilizing this method, we showed that no desensitization to glucose-induced insulin release can be observed if the responsiveness of the cells is properly maintained and the parameters of the stimulation are carefully designed. Exposure of the explanted islets to 10 μM acetylcholine or 30 mM arginine (Arg) induced a transitory elevation of insulin release similar in shape to that experienced after glucose stimulation. Norepinephrine (NE), dopamine (DA) and somatostatin (SS) did not induce any detectable alteration on the basal insulin secretion of the islets. However, 100 nM SS given together with 50 mM glucose, 30 mM Arg or 10 μM acetylcholine significantly reduced the insulin-releasing effect of these substances (by 75.5, 71.5 and 72.5%, respectively). At the same time, SS did not alter the insulin response of the islets to 100 mM elevation of K+ concentration. SS also inhibited glucose-induced insulin release in a dose-dependent way (ED50 = 22 nM). A similar dose-dependent inhibitory effect on glucose-induced insulin release was found with NE (ED50 = 89 nM) and DA (ED50 = 2.2 μM). γ-Aminobutyric acid (GABA) did not influence insulin release under similar circumstances.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000180050201
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  • 8
    Electronic Resource
    Electronic Resource
    ‘Classical’ and ‘new’ diabetogens—comparison of their effects on isolated rat pancreatic islets in vitro (2000)
    Springer
    Cellular and molecular life sciences 57 (2000), S. 158-164 
    Details
    ISSN: 1420-9071
    Keywords: Key words. Alloxan; streptozotocin; xanthine oxidase/hypoxanthine; SNAP; reactive oxygen species.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. This study compares functional and morphological alterations caused by application of alloxan, streptozotocin, xanthine oxidase/hypoxanthine (generation of reactive oxygen species), or S-nitroso-N-acetyl-D,L-penicillamine (SNAP, liberation of nitric oxide) to isolated rat pancreatic islets in vitro. In perifusion experiments, membrane leakage—detected by non-stimulated insulin release—was found after application of all drugs, but showed a substance-specific time pattern. Twenty-four hours after application of the classical diabetogens (alloxan or streptozotocin), potassium chloride- and glucose-stimulated insulin secretion were markedly reduced, while a persistent reduction was observed neither after exposure to xanthine oxidase/hypoxanthine, nor to SNAP. Morphological analysis of the islets revealed that nearly all β-cells were destroyed following alloxan or streptozotocin treatment, while the majority of β-cells were configured regularly after application of xanthine oxidase/hypoxanthine or SNAP. Necrotic cells found after xanthine oxidase/hypoxanthine usually differed in morphology from those observed after application of the classical diabetogens. While the former cells were characterised by swollen nuclei, the latter had shrunken nuclei with irregular condensed chromatin. Apoptosis was found only following nitric oxide exposure. Due to these differences, it seems unlikely that alloxan, streptozotocin, xanthine oxidase/hypoxanthine, and nitric oxide have a common major feature in their toxic action.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000180050505
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