Search PubMed⌕ Search

Biomedical subjects

R J Reiter

Publications and source records attributed to R J Reiter.

At least 163 records · Page 9Linked to original sources
PubMed1996

Sexual differences in 5'-deiodinase activity in the Harderian gland of Syrian hamsters and the effect of pinealectomy: regulation by androgens.

Sexual differences on thyroxin 5'-deiodinase (5'-D) in the Harderian gland of Syrian hamsters were investigated. We compared the 24-h profile of 5'-D activity in male and female hamsters, observing a clear rhythm in males but not in females. Female values were always significantly higher than male ones. After pinealectomy day/night variations in male 5'-D activity at the time points studied were abolished, results that are in correlation with serum thyroid hormones. We also studied the regulation by androgen of the enzyme activity. Basal 5'-D activity increased in castrated males and levels fell when animals were implanted with testosterone or its product 5 alpha-dihydrotestosterone (DHT). Female 5'-D activity was also inhibited by androgens. As only the addition of DHT in the presence of epitestosterone, an inhibitor of the conversion of testosterone on DHT, in castrated males was able to decrease 5'-D activity to the control animal levels, we suggest a probable direct effect of DHT by itself.

Androgens↗
PubMed1996

Melatonin affords protection against kainate-induced in vitro lipid peroxidation in brain.

Melatonin protection against in vitro kainic acid-induced oxidative damage in rat brain is shown. Brain disrupted cell homogenates were incubated with different concentrations of kainate and with or without different concentrations of melatonin. The concentration of malonaldehyde and 4-hydroxyalkenals was measured as an index of lipid peroxidation. When administered together with kainate, melatonin produced a concentration-dependent decrease in kainate-induced lipid peroxidation ranging from 20% to 100%. Moreover, when added to the reaction mixture alone, melatonin decreased the basal level of lipid peroxidation compared to controls.

Animals↗
PubMed1996

Mg(2+)-dependent and Ca2+, Mg(2+)-dependent ATPase activities in the harderian gland of rodents: age and sex influences.

Three experiments employing male and female Syrian hamsters (aged 1, 2, and 8-10 months), male Sprague-Dawley rats (aged 1, 2, and 10 months) and male C57B1 mice (aged 2, 7, 13, and 29 months) examined the effects of age and sex on Mg(2+)-dependent and Ca2+, Mg(2+)-dependent ATPase activity in the Harderian gland. Significant differences due to age and sex were observed in the hamsters and rats but not with age in mice. Generally, male hamsters had significantly higher Mg(2+)-dependent and Ca2+, Mg(2+)-dependent (exception at one timepoint) ATPase activity than did females. Age-matched male and female rats had similar values of Mg(2+)-dependent ATPase activity, but males had significantly higher Ca2+, Mg(2+)-dependent ATPase activity than females at 2 months of age.

Aging↗
PubMed1996

Paraquat toxicity and oxidative damage. Reduction by melatonin.

The ability of melatonin to protect against paraquat-induced oxidative damage in rat lung, liver, and serum was examined. Changes in the levels of malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HDA) and reduced and oxidized glutathione concentrations were measured. Paraquat (50 mg/kg) was injected i.p. into either Sprague-Dawley or Wistar rats with or without the co-administration of 5 mg/kg melatonin. Paraquat alone increased MDA + 4-HDA levels in serum and lungs of both rat strains, with these increases being abolished by melatonin co-treatment. Paraquat also decreased reduced glutathione levels and increased oxidized glutathione concentrations in lung and liver; these changes were negated by melatonin. The effect of melatonin on paraquat-induced mortality was also studied. Paraquat at a dose of 79 mg/kg was lethal for 50% of animals within 24 hr; when administered together with melatonin, the LD50 for paraquat increased to 251 mg/kg.

Animals↗
PubMed1996

Effect of melatonin on mitotic and proliferation indices, and sister chromatid exchange in human blood lymphocytes.

Cells from human peripheral blood were cultured in vitro in the presence of 0.05 to 1.00 mM melatonin, 10(-7) M mitomycin C (positive control) and 0.5% ethanol (solvent control) for 72 h at 37 +/- 1 degree C. Lymphocytes were examined for mitotic and proliferation indices, and for the incidence of sister chromatid exchange. The results indicate that the lymphocytes which were cultured in the presence of > or = 0.20 mM concentrations of melatonin exhibited a significant and concentration-dependent decrease in mitotic index and alteration in proliferation kinetics. This was demonstrated by an increase in the frequency of lymphocytes in their first division, with a concomitant decrease in the second and third or later division cells. The incidence of sister chromatid exchange was similar in the lymphocytes exposed to 0.05 to 1.00 mM melatonin and untreated controls. Exposure of the cells to ethanol, the solvent used, did not alter either the mitotic or proliferation indices, or the frequency of sister chromatid exchange. The lymphocytes treated with mitomycin C showed the expected decrease in mitotic and proliferation indices, and an increased incidence of sister chromatid exchange. These observations indicate that melatonin, when continuously present in the cultures for 72 h at the concentrations tested, while not genotoxic as indicated by the sister chromatid exchange assay, inhibits the proliferation of mitogen stimulated (and proliferating) human blood lymphocytes at supraphysiological concentrations.

Adult↗
PubMed1996

Lipopolysaccharide-induced DNA damage is greatly reduced in rats treated with the pineal hormone melatonin.

The ability of melatonin to influence lipopolysaccharide (LPS)-induced genotoxicity was tested using micronuclei as an index in both bone marrow and peripheral blood cells of rats. LPS was given as a single dose of 10 mg/kg. Melatonin (5 mg/kg) was injected prior to LPS administration and thereafter at 6 h intervals to the conclusion of the study (72 h). The number of micronucleated polychromatic erythrocytes increased significantly after LPS administration both in cells from peripheral blood and bone marrow. Melatonin administration to LPS-treated rats highly significantly reduced micronuclei formation in both peripheral blood and bone marrow cells beginning at 24 h after LPS administration and continuing to the end of the study. In blood the increase in micronuclei formation was time-dependent in LPS-treated rats with peak values being reached at 36-48 h. The ability of melatonin to reduce LPS-related genotoxicity is likely related to its antioxidant activity.

Animals↗
PubMed1996

Iron decreases the nuclear but not the cytosolic content of the neurohormone melatonin in several tissues in chicks.

This paper describes the influence of iron on both nuclear and cytosolic melatonin contents in several tissues of chicks. The neurohormone melatonin was estimated by means of radioimmunoassay. Iron, administered as FeCl3, decreased the nuclear melatonin level in a variety of tissues, including brain, heart, lung, kidney, and erythrocytes (nucleated cells in chicks) but was not seen in either the liver or gut. All variations related with iron were seen in the nuclear fraction, while only in the pineal gland did the melatonin content of the cytosol change as a result of iron treatment. We also observed a day-night rhythm in the nuclear melatonin: high nuclear levels of melatonin at night and low levels during the light period. This is the first report of nuclear localization of melatonin in any avian cell.

Animals↗
PubMed1996

Effect of melatonin on NF-kappa-B DNA-binding activity in the rat spleen.

It was recently demonstrated that the pineal neurohormone melatonin is a hydroxyl radical scavenger and antioxidant, and that it plays an important role in the immune system. In studies reported herein, we have investigated the relationship of the melatonin level and the NF-kB DNA binding activity in the spleen of Sprague. Dawley rats. These in vivo results indicate that NF-kB DNA binding activity in the spleen is lower at night, when endogenous melatonin levels are elevated, than during the day, when endogenous melatonin levels are lower. Furthermore, exogenously administered melatonin (10 mg/kg) was shown to cause a significant decrease in NF-kB DNA binding activity in the spleen at 60 min after intraperitoneal injection (as compared with vehicle-treated rats). These new findings suggest that the normal night time rise which can be expected for melatonin may be associated with increased NF-kB DNA binding activity in the spleen. The melatonin, therefore, could potentially act to modulate spleen function and/or the immune system by regulating the NF-kB DNA binding activity in the spleen.

Animals↗
PubMed1996

Nocturnal decreases in nitric oxide and cyclic GMP contents in the chick brain and their prevention by light.

The diurnal variations in the contents of nitric oxide (NO) and cyclic GMP were studied in the chick brain. NO and cyclic GMP contents in the chick brain were lower at night than during the day and were inversely correlated with high night-time tissue melatonin levels. Furthermore, when animals were kept in light at night, tissue melatonin levels remained at low diurnal values, whereas NO and cyclic GMP contents remained high. Since we have previously shown that physiological concentrations of melatonin inhibit nitric oxide synthase (NOS) activity in different brain areas, the nocturnal decrease in brain NO and cyclic GMP contents may be, in part, a consequence of the nocturnal inhibitory effect of melatonin on NOS activity.

Animals↗
PubMed1996

Evaluation of the antioxidant activity of melatonin in vitro.

Melatonin is being increasingly promoted as a treatment for "jet lag" and insomnia and has been suggested to act as an antioxidant in vivo. The antioxidant and potential pro-oxidant activities of melatonin were investigated in vitro. Melatonin was able to scavenge hypochlorous acid (HOCl) at a rate sufficient to protect catalase against inactivation by this molecule. Melatonin could also prevent the oxidation of 5-thio-2-nitrobenzoic acid by HOCl. Melatonin decreased the peroxidation of ox-brain phospholipids with a calculated IC50 of (210 +/- 2.3) microM. In contrast, serotonin which also scavenged HOCl, was much more effective in decreasing phospholipid peroxidation (IC50 15 +/- 5 microM). Both compounds reacted with trichloromethylperoxyl radical (CCl3O2) with rate constants of (2.7 +/- 0.2) x 10(8) and (1.2 +/- 0.1) x 10(8)M-1 s- respectively. Melatonin did not scavenge superoxide radical and weakly protected DNA against damage by the ferric bleomycin system. By contrast serotonin was weakly pro-oxidant in the ferric-bleomycin system and strongly pro-oxidant in the Fe(3+)-EDTA/H2O-deoxyribose system. Solubility restrictions precluded examination of melatonin in this system. Our data show that melatonin exerts only limited direct antioxidant activities.

Animals↗
PubMed1996

Tissue changes in glutathione metabolism and lipid peroxidation induced by swimming are partially prevented by melatonin.

The present study used male Sprague-Dawley rats to investigate changes in glutathione [reduced (GSH) and oxidized GSH (GSSG)]. lipid peroxidation (as indicated by tissue levels of malonaldehyde and 4-hydroxyalkenals), and the activity of the antioxidant enzyme glutathione peroxidase after a bout of swimming (30 min.) with or without melatonin (N-acetyl-5-methoxytryptamine) treatment. In muscle, the concentration of GSH and the GSH/GSSG ratio were decreased following 30 min. of swimming: these changes are indicative of enhanced oxidative stress. Pretreatment with melatonin prevented these effects. In liver, swimming increased significantly both GSH and GSSG, and decreased the GSH/GSSG ratio. When animals were treated with melatonin, concentrations of GSH and GSSG were also increased after swimming: however, the reduction in the GSH/GSSG ratio was prevented by melatonin. Brain GSH/GSSG ratio was not affected by exercise or by melatonin. Swimming enhanced the levels of lipid peroxidation products is muscle: this was prevented in animals treated with melatonin. Glutathione peroxidase activity was significantly elevated after swimming in both liver and brain with the change not being influenced by concurrent melatonin treatment. It is concluded that swimming imposes an oxidative stress on liver and skeletal muscle and the results show that melatonin confers partial protection against oxidative toxicity, especially in muscle.

Animals↗
PubMed1996

Twenty-four hour urinary excretion of 6-hydroxymelatonin sulfate in Down syndrome subjects.

Because of the overexpression of the enzyme superoxide dismutase, individuals with Down syndrome (DS) are believed to suffer from increased oxidative stress as a result of the excessive production of oxygen-based free radicals; their exposure to higher than normal free radical production may account in part for signs of premature aging, early onset of cataracts, and of Alzheimer's disease. Free radicals are normally neutralized by free radical scavengers and other antioxidants. The pineal hormone melatonin is a potent scavenger of both the hydroxyl and peroxyl radicals, both of which are highly toxic, and a stimulator of the antioxidative enzyme glutathione peroxidase. Considering this, we deemed it important to define the day/night rhythm and levels of melatonin production in DS subjects. To do this, we assessed the urinary excretion of the chief melatonin metabolite, 6-hydroxymelatonin sulfate, throughout a 24 hr period in DS subjects; comparisons were made with the metabolite levels in the urine of non-Down siblings and parents of the DS subjects. All 8 non-Down subjects exhibited what was classified as normal urinary excretion of 6-hydroxymelatonin sulfate with the usual low daytime and high night-time levels of the melatonin metabolite. Of 12 DS subjects studied, 10 exhibited the normal day/night rhythm in urinary 6-hydroxymelatonin sulfate levels; 2 subjects were devoid of a rhythm. However, when all the data from each group were averaged, there were no noticeable differences in the absolute levels or 24 hr variations in urinary 6-hydroxymelatonin sulfate excretion between DS and non-Down subjects.

Adolescent↗
PubMed1996

Melatonin reduces nitric oxide synthase activity in rat hypothalamus.

In this report, rat hypothalamic nitric oxide synthase (NOS) activity is shown to be partially inhibited by physiological concentrations of the pineal hormone melatonin. In vitro studies demonstrate that 1 nM melatonin, which approximates the physiological concentration of the hormone at night, significantly inhibited NOS activity. In vivo studies show that administering melatonin or collecting the hypothalamus from animals at night, when endogenous melatonin levels are elevated, results in a significant decrease of NOS activity. Results also show that calmodulin may be involved in this process since its presence in the incubation medium prevents the inhibitory effect of melatonin on NOS activity.

Animals↗
PubMed1995

Lipopolysaccharide-induced hepatotoxicity is inhibited by the antioxidant melatonin.

Oxidative damage to the liver of lipopolysaccharide-treated rats was evaluated using four parameters: level of lipid peroxidation, changes in total GSH and GSSG concentrations and hepatic morphology. Bacterial lipopolysaccharide (10 mg/kg b.w.) was injected i.p. either at 6, 16 or 24 h before animals were killed. Lipopolysaccharide increased lipid peroxidation most dramatically when it is injected 6 h before killing. Hepatic total GSH increased after lipopolysaccharide in a time-dependent manner. The highest level of GSSG and largest GSSG/total GSH ratio were also observed in the group of animals injected with lipopolysaccharide 6 h before tissue collection. In a second study, lipopolysaccharide was injected 6 h before the animals were killed, with or without 1 mg/kg b.w. melatonin. Melatonin totally abolished lipopolysaccharide-induced increase in lipid peroxidation, exaggerated the rise in total GSH and reversed the increase in GSSG concentration. The liver showed obvious histological degenerative changes after lipopolysaccharide, effects that were counteracted by melatonin administration. The protection conferred by melatonin is presumably due to its antioxidant activity.

Animals↗