Michal Karasek

Effect of melatonin on the oxidative stress in erythrocytes of healthy young and elderly subjects

Abstract:  The disturbances in pro‐ and antioxidant balance may play an important role in the pathomechanism of aging. The pineal hormone melatonin, which exerts effective antioxidative properties, is suggested to be involved in the aging process. The aim of this study was to compare the oxidative stress in erythrocytes of healthy young adults and elderly people, and to determine the influence of melatonin supplementation on measured parameters in both examined groups. The malondialdehyde (MDA) and reduced glutathione levels as well as Cu‐Zn superoxide dismutase (SOD‐1), catalase, glutathione peroxidase (GSH‐Px), glutathione S‐transferase (GST) and glutathione reductase (GR) activities in erythrocytes and morning serum melatonin concentration in 14 healthy young adults and 14 healthy elderly people at baseline and after the 30th day of melatonin (5 mg daily) supplementation were determined. A significant age effect on increasing the MDA level and decreasing SOD‐1, GSH‐Px and GR activities as well as melatonin concentration was observed. Melatonin supplementation resulted in a significant increase in melatonin concentration, SOD‐1 and GR activities and a decrease in the MDA level in both examined groups. These data indicate an age‐related augmentation of oxidative stress in erythrocytes and the improvement of erythrocytic antioxidative defense by melatonin administration. These results might suggest melatonin supplementation to prevent age‐related diseases and to prolong the lifespan and improve the quality of life of elderly people.

Circadian Variations in Plasma Melatonin, FSH, LH, and Prolactin and Testosterone Levels in Infertile Men

Circadian patterns of plasma melatonin, FSH, LH, prolactin, and testosterone were studied in 10 healthy men, 20 men with oligozoospermia, and 8 men with azoosper‐mia. Circadian rhythms were found in concentrations of melatonin and prolactin, with higher values at night in comparison with daytime levels. In patients with oligozoospermia and azoospermia an elevation in melatonin levels was observed, and an increase in melatonin concentrations occurred before onset of darkness (i. e., at 2000 h). Levels of FSH, LH, and prolactin were elevated in infertile patients. The possibilities that an increase in melatonin concentrations is either the primary feature that leads to the regression of the seminiferous epithelium or is secondary and depends on elevated gonadotropins and/or prolactin levels are discussed.

Day-night differences in the number of pineal “synaptic” ribbons in two diurnal rodents, the chipmunk (Tamias striatus) and the ground squirrel (Spermophilus richardsonii)

SummaryDaytime numbers of pineal “synaptic” ribbons higher than reported in the pineal gland of any other mammalian species were observed in two diurnal rodents, the eastern chipmunk and Richardsons ground squirrel. The number of “synaptic” ribbons was lower during the daytime and higher at night in both of these species.

Influence of melatonin and serotonin on the number of rat pineal “synaptic” ribbons and spherules in vitro

SummaryPrevious studies have shown that the “synaptic” ribbons (SR) and spherules (SS) of the mammalian pineal gland may respond differently under physiological and various experimental conditions. The aim of the present study was to gain insight into the mechanisms that may be responsible for the numerical changes of these organelles during a 24-h cycle. As the possibility exists that the structures are influenced by substances synthesized within the pinealocyte, rat pineal glands were cultured with and without added melatonin or serotonin, using an experimental protocol such that the addition of melatonin and serotonin mimicks the circadian changes of the respective substances within the pineal. The tissue was processed for electron microscopy and the numbers of SR and SS were counted in a unit area of pineal tissue. The results obtained indicate that melatonin added to the incubation medium increases the number of SR in the first half of the night; serotonin decreases SR numbers in the morning. SS numbers, by contrast, decrease following melatonin administration in the afternoon, and increase in the morning following serotonin administration. It thus appears that the numbers of SR and SS are influenced by melatonin and serotonin and that the two structures are regulated by differential, but nevertheless biochemically closely related mechanisms.

Antiproliferative Effects of Melatonin and CGP 52608

The antiproliferative effects of melatonin and CGP 52608, an exogenous ligand for RZR/ROR receptors, are compared in the present paper. Both compounds exerted similar inhibitory effects on the proliferation of neoplastic cells in mouse colonic adenocarcinoma, DU 145 human prostate cancer, MCF-7 human breast carcinoma, and rat diethylstilbestrol-induced prolactinoma. Although it has been suggested that melatonin may influence the proliferation of tumor cells via RZR/ROR receptors, it cannot be excluded that the antiproliferative effects of melatonin and CGP 52608 are unrelated and mediated by different intracellular mechanisms.

Melatonin inhibits prostaglandin E release from the medial basal hypothalamus of pinealectomized rats.

The effects of pinealectomy and of melatonin administration on prostaglandin E synthesis in the medial basal hypothalamus were studied in male rats. Melatonin treatment significantly decreased prostaglandin E release from the medial basal hypothalamus in pinealectomized rats. The results of the present study suggest that melatonin modulates hypothalamo‐hypophyseal function, at least in part, via inhibition of hypothalamic prostaglandin synthesis.

Ultrastructure of pinealocytes of the kangaroo rat (Dipodomys ordi)

SummaryThe ultrastructure of the pinealocytes of the wild-captured ord kangaroo rat (Dipodomys ordi) was examined. A homogeneous population of pinealocytes was present in the pineal gland of the kangaroo rat. The Golgi apparatus, granular endoplasmic reticulum, mitochondria, lysosomes, dense-core vesicles, vacuoles containing a flocculent material and lipid droplets were consistent components of the pinealocyte cytoplasm, whereas infrequently-observed organelles included centrioles, multivesicular bodies, subsurface cisternae, “synaptic” ribbons and cilia. The number of dense-core vesicles was relatively high and dense-core vesicles and vacuoles containing a flocculent material were present in the same cell.Although it has been recently suggested that two different secretory processes, i.e., neurosecretory-like (Golgi apparatus — dense-core vesicles) and ependymal-like (granular endoplasmic reticulum — vacuoles containing a flocculent material) may be involved in different regulatory mechanisms in the pinealocytes, the definitive answer to this is still far from clear. Therefore, the pineal gland of the kangaroo rat appears to be a good model for the study of the potential relationship between these two secretory processes, especially in respect to seasonal changes.

A reciprocal relationship between the adenohypophysis and the pineal gland

Data are presented which indicate an influence of the pineal gland on the adenohypophysis and the effects of some adenohypophyseal hormones on the pineal gland, suggesting the existence of a reciprocal relationship between these two glands.

Effects of long and short photoperiod on the ultrastructure of pinealocytes of the cotton rat (Sigmodon hispidus).

The ultrastructure of the pinealocytes of wild‐captured cotton rats (Sigmodon hispidus) housed in either long or short photoperiod was examined. Quantitative comparison of selected pinealocyte organelles revealed larger relative volumes of mitochondria, granular endoplasmic reticulum and ribosomes, Golgi apparatus, and inclusion bodies, as well as a higher number of dense‐core vesicles in the animals kept in short photoperiod (LD 8:16) as compared to those in animals kept in long photoperiod (LD 16:8). These observations suggest that restricting the amount of light to which animals are exposed activates pinealocytes of the cotton rat.

Effects of experimentally induced chronic hyperprolactinemia on the ultrastructure of pinealocytes in male rats.

The influence on the ultrastructure of pinealocytes of long‐term hyperprolactinemia caused by ectopic pituitary transplants and of suppression of prolactin release by bromocriptine was examined morphometrically in male rats. Hyperprolactinemia resulted in an increase in the relative volumes of granular endoplasmic reticulum, vacuoles containing a flocculent material, mitochondria, and lipid droplets. Treatment of grafted rats with bromocriptine reversed the effects of hyperprolactinemia. However, bromocriptine had no apparent influence on the pinealocytes of intact rats. The effects of hyperprolactinemia on the ependymallike secretory process in the pinealocyte were especially pronounced.