摘要:

Abstract:This survey summarizes the findings, accumulated within the last 2 years, concerning melatonin's role in defending against toxic free radicals. Free radicals are chemical constituents that have an unpaired electron in their outer or‐bital and, because of this feature, are highly reactive. Inspired oxygen, which sustains life, also is harmful because up to 5% of the oxygen (O2) taken in is converted to oxygen‐free radicals. The addition of a single electron to O2produces the superoxide anion radical (O2); C2: is catalytic‐reduced by superoxide dismutase, to hydrogen peroxide (H2O2). Although H2O2is not itself a free radical, it can be toxic at high concentrations and, more importantly, it can be reduced to the hydroxyl radical (OH). The OH is the most toxic of the oxygen‐based radicals and it wreaks havoc within cells, particularly with macromolecules. In recent in vitro studies, melatonin was shown to be a very efficient neutralizer of the OH; indeed, in the system used to test its free radical scavenging ability it was found to be significantly more effective than the well known antioxidant, glutathione (GSH), in doing so. Likewise, melatonin has been shown to stimulate glutathione peroxidase (GSH‐Px) activity in neural tissue; GSH‐PX metabolizes reduced glutathione to its oxidized form and in doing so it converts H2O2to H2O, thereby reducing generation of the OH by eliminating its precursor. More recent studies have shown that melatonin is also a more efficient scavenger of the peroxyl radical than is vitamin E. The peroxyl radical is generated during lipid peroxidation and propagates the chain reaction that leads to massive lipid destruction in cell membranes. In vivo studies have demonstrated that melatonin is remarkably potent in protecting against free radical damage induced by a variety of means. Thus, DNA damage resulting from either the exposure of animals to the chemical carcinogen safrole or to ionizing radiation is markedly reduced when melatonin is co‐administered. Likewise, the induction of cataracts, generally accepted as being a consequence of free radical attack on lenticular macromolecules, in newborn rats injected with a GSH‐depleting drug are prevented when the animals are given daily melatonin injections. Also, paraquat‐induced lipid peroxidation in the lungs of rats is overcome when they also receive melatonin during the exposure period. Paraquat is a highly toxic herbicide that inflicts at least part of its damage by generating free radicals. Finally, bacterial endotoxin (lipopolysaccharide or LPS)‐induced free radical damage to a variety of organs is highly significantly reduced when melatonin is also administered; LPS, like paraquat, produces at least part of its damage to cells by inducing the formation of free radicals. Physiological melatonin concentrations have also been shown to inhibit the nitric oxide (NO)‐generting enzyme, nitric oxide synthase. The reduction of NO‐ production would contribute to melatonin's antioxidant action since NO‐ can generate the peroxynitrite anion, which can degrade into the OH. Thus, melatonin seems to have multiple ways either to reduce free radical generation or, once produced, to neutralize them. Melatonin accomplishes these actions without membrane receptors, indicating that the indole has important metabolic functions in every cell in the organism, not only those that obviously contain membrane re

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00133.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Pineal tissue calcifications (male, ages 14, 47, 62, 82), which were metallographically embedded and polished at controlled levels and studied by transmission electron microscopy and microanalytic spectroscopy, showed age‐related differences. Results show that concentrically arranged crescent‐shaped lamellae increase in number and decrease in width with age. Calcium (Ca) and phosphorus (P) per point measurements in dark and light lamellae at various distances from the core show Ca/P molar ratios between 1.49–1.62 in the 82‐year‐old specimen as compared to 1.26 to 1.41 in the younger specimens. The 62‐year‐old specimens show a decrease in P and an increase in Ca from periphery to center. These data and other descriptive details suggest that the sum of these changes represent remodelling of the mineralogical structure within the same calcification throughout

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00134.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The effects of a 1‐hr light pulse on the timing of the circadian rhythm in the blood plasma concentration of melatonin were documented in Soay rams. Groups of 5 to 6 animals were transferred from short days (LD 8: 16) to constant dim red light (DD) for 6 days, and were exposed to a 1‐hr light pulse at one of 16 different times throughout 24 hr on day 3. Blood samples were collected hourly for 30 hr before (day 2–3) and after the light pulse (day 5–6), and the plasma concentrations of melatonin were measured by radioimmunoassay. The animals were allocated to experimental groups based on the circadian time (CT) when the light pulse was given using two hourly blocks through the circadian day; the onset of enhanced melatonin secretion (melatonin peak) was designated as CT 12. Under DD there was a clearly defined plasma melatonin rhythm in all animals. The mean duration of the melatonin peak was 13.24 ± 0.16 hr (n = 91) and the mean period between the onset of successive melatonin peaks was 23.55 ± 0.10 hr (n = 21). The effect of the 1‐hr light pulse on the time of onset of the melatonin peak varied significantly with the circadian time when the light pulse was given (ANOVA,P= 0.031). Light‐induced significant (pre‐ vs post‐pulse onset, Students t‐test,P<0.05) phase delays in the onset of the melatonin peak in the early subjective day at CT 2.5 hrs (mean ø: ‐1.9 hr), and in the early subjective night at CT 12.5 and 14.5 (mean ø: ‐2.0 hrs), but not at other times. The light pulse never induced significant phase advances. The effects of the light pulse on the offset of plasma melatonin peak did not vary significantly with the time of the light pulse (ANOVA,P= 0.780), although significant differences in the pre‐ and post‐pulse offset occurred at CT 14.5 and 18.5 (mean ø: ‐1.5 hr). The differential changes in the onset and the offset of the melatonin peak resulted in changes in the duration of the peak (maximum difference between means: 3.8 hr). The results indicate that entrainment occurs under natural 24 hr LD cycles when light impinges on the early subjective night and induces a net phase delay, thus extending the period of the melatonin rhythm to 24 hr. This causes a close phase relationship between the end of the light period and the onset of the melatonin peak as occurs in sheep under natural cycles. The results are also consistent with a multiple oscillator governing melatonin secretion, and that differential entrainment of the component oscillators by light affects th

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00135.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Melatonin, the chief hormone of the pineal gland in vertebrates, is widely distributed in the animal kingdom. Among many functions, melatonin synchronizes circadian and circannual rhythms, stimulates immune function, may increase life span, inhibits growth of cancer cells in vitro and cancer progression and promotion in vivo, and was recently shown to be a potent hydroxyl radical scavenger and antioxidant. Hydroxyl radicals are highly toxic by‐products of oxygen metabolism that damage cellular DNA and other macromolecules. Herein we report that melatonin, in varying concentrations, is also found in a variety of plants. Melatonin concentrations, measured in nine different plants by radioimmunoassay, ranged from 0 to 862 pg melatonin/mg protein. The presence of melatonin was verified by gas chromatography/mass spectrometry. Our findings suggest that the consumption of plant materials that contain high levels of melatonin could alter blood melatonin levels of the indole as well as provide protection of macromolecules against oxidative damag

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00136.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:In the present study, we investigated the population of pinealocytes in the pineal gland of aging rats. Dark and light pinealocytes were analyzed as to their calcium content. Calcium localization was realized in dark and light cells by means of cytochemistry and X‐ray microanalysis. Calcium was mainly localized in dark pinealocytes characterized by many ultrastructural signs of degeneration. The number of pinealocytes per square surface of aged rats (28 months) was com‐pared to young ones (3–4 months). While there is a significant increase in the number of dark pinealocytes there is a decrease in the total number of pinealo‐cytes in aged rats. This age‐related loss of pinealocytes may explain the age‐related functional decline of the pineal gland activity (e.g., the decrease of the nocturnal melatonin

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00137.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The study was performed to investigate the physiological relationship between the pineal hormone melatonin and pituitary functions in normal men. Se‐ries of blood samples were obtained at 10‐min intervals for 24‐hr periods from 10 male volunteers (age 19–25 years). Samplings were repeated after 2 weeks and 3 months. Serum levels of melatonin, follicle‐stimulating hormone (FSH), luteiniz‐ing hormone (LH), prolactin (PRL), and testosterone (T) were estimated by immu‐noassay methods (LH, PRL, every sample; melatonin, every 30 min; T, every 4 hrs; FSH once for each session). Diurnal characteristics of PRL and melatonin profiles were estimated by complex cosinor analysis, while short‐term pulsatility of LH and PRL secretion was analyzed by the PULSAR algorithm. Data were cor‐related by linear regression analysis. The combined information of all three sam‐pling sessions revealed significant negative correlations between the following parameters (N = 10): Amplitude (Ampl) melatonin and Ampl PRL: r = ‐0.727,P<0.02; Ampl melatonin and maximal (Max) PRL values: r = ‐0.73,P<0.02; Max melatonin and Max PRL: r = ‐0.725,P<0.02; area under the curve (AUC) melatonin and Ampl PRL: r = ‐0.637,P<0.05; AUC melatonin and Max PRL: r = ‐0.640;P<0.05; duration (Dur) of melatonin synthesis and Ampl PRL: r = ‐0.685,P<0.03; Dur melatonin and Max PRL: r = ‐0.676,P<0.04; Dur mela‐tonin and FSH levels: r = ‐0.663,P<0. 04; AUC melatonin and LH mean con‐centration: r = ‐0.732,P<0. 02; Max melatonin and LH mean concentration: r = ‐0.657,P<0.04. These correlations varied considerably between the three ses‐sions, mainly due to intra‐individual variabilities of secretory patterns of PRL and LH, while the melatonin profiles were comparably stable. The results indicate that melatonin production and pituitary functions may be related in normal men. Be‐cause of the substantial intra‐ and inter‐individual variations in hormone secretory patterns, large numbers of volunteers and/or repeated measurements are essential for studies addres

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00138.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Understanding 6‐hydroxymelatonin (6HM) sulfation is deemed impor‐tant to explaining normal and oncostatic actions of the pineal gland. Here we identify the enzymatic basis for this sulfation in rats. First, a quantitative assay was designed for measuring hepatic 6HM sulfotransferase (6HMST) activity. The as‐say was then used to identify a male dominant sexual dimorphism wherein liver from males contains double the 6HMST per g or per 100 g body weight seen in fe‐males. Examination of other rat tissues showed that most in vivo 6HM sulfation was likely to occur in liver. In addition, DEAE‐Sephadex chromatography of liver cytosol indicated that 80–90% of the 6HMST activity in both sexes was due to an enzyme we named 6HMST II. A minor 6HM sulfotransferase (6HMST I) eluted from the columns prior to the main enzyme. 6HMST II, purified additionally, was shown to convert 6HM to a product that appeared to be 6HM sulfate (6‐sulfa‐toxymelatonin). The enzyme was inhibited by Na+, K+, Zn2+, and Cd2+. Its pH op‐timum was 7.80 ± 0.30. Comparisons are made between 6HMST II, dopamine sulfotransferase II, and aryl s

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00139.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY