Effects of melatonin on DNA damage induced by cyclophosphamide in rats

The antioxidant and free radical scavenger properties of melatonin have been well described in the literature. In this study, our objective was to determine the protective effect of the pineal gland hormone against the DNA damage induced by cyclophosphamide (CP), an anti-tumor agent that is widely applied in clinical practice. DNA damage was induced in rats by a single intraperitoneal injection of CP (20 or 50 mg/kg). Animals received melatonin during the dark period for 15 days (1 mg/kg in the drinking water). Rat bone marrow cells were used for the determination of chromosomal aberrations and of formamidopyrimidine DNA glycosylase enzyme (Fpg)-sensitive sites by the comet technique and of Xpf mRNA expression by qRT-PCR. The number (mean ± SE) of chromosomal aberrations in pinealectomized (PINX) animals treated with melatonin and CP (2.50 ± 0.50/100 cells) was lower than that obtained for PINX animals injected with CP (12 ± 1.8/100 cells), thus showing a reduction of 85.8% in the number of chromosomal aberrations. This melatonin-mediated protection was also observed when oxidative lesions were analyzed by the Fpg-sensitive assay, both 24 and 48 h after CP administration. The expression of Xpf mRNA, which is involved in the DNA nucleotide excision repair machinery, was up-regulated by melatonin. The results indicate that melatonin is able to protect bone marrow cells by completely blocking CP-induced chromosome aberrations. Therefore, melatonin administration could be an alternative and effective treatment during chemotherapy.

The brain decade in debate: IV. Chronobiology

The present article is the adapted version of an electronic symposium organized by the Brazilian Society of Neuroscience and Behavior (SBNeC) which took place on June 14, 2000. The text is divided into three sections: I. The main issues, II. Chronodrugs, and III. Methods. The first section is dedicated to the perspectives of chronobiology for the next decade, with opinions about the trends of future research being emitted and discussed. The second section deals mostly with drugs acting or potentially acting on the organism's timing systems. In the third section there are considerations about relevant methodological issues concerning data analysis

Perfil hormonal da progesterona em ovelhas (Ovis aries) no início da gestaçäo, no pré-parto e início da lactaçäo / Evaluation of progesterone hormone profile on ewes at early pregnancy, preterm and early lactation

Foram utilizadas 15 ovelhas prenhes e em lactaçäo com o objetivo de se determinarem os padröes fisiológicos da progesterona, e de se verificar a presença ou näo de ritmo circadiano. Observou-se aumento crescente dos níveis de progesterona durante a gestaçäo, com diminuiçäo abrupta aos dois dias pré-parto. A análise de autocorrelaçäo revelou que esse hormônio apresentou no período de pré-parto ritmo circadiano muito mais evidente que no início da gestaçäo e lactaçäo

The regulation of insulin action in isolated adipocytes. Role of the periodicity of food intake, time of day and melatonin

Isolated adipocytes from rats submitted to four weeks of ad libitum feeding (AL) or meal feeding (MF, 2 h/22 h, feeding/fasting, meal time: 8:00-10:00 a.m.) schedules or pre-incubated with or without melatonin (0, 1 nM, 10 nM, 100 nM) for 5 h were submitted to insulin-stimulated [3H]-2-deoxyglucose (0.1 mM, 0.12 microCi) uptake rate measurements and insulin binding assays. Insulin sensitivity was defined as the hormone concentration capable of producing the half-maximal transport rate. Insulin sensitivity varied depending on the previous conditions of the adipocytes. In MF animals, adipose cells were more sensitive (EC50 = 0.175 ng/ml) just at the moment of the expected meal. In AL rats, sensitivity was lower (EC50 = 0.678 ng/ml) at 8:00 a.m. and increased (EC50 = 0.398 ng/ml) at 4:00 p.m. These data clearly implicate the expectation of food and period of the day with the regulation of insulin action. All these modifications in sensitivity occurred without any change in insulin receptor number or affinity. Melatonin, a secretory product of the pineal gland, induced an increase in cell sensitivity to insulin in adipocytes incubated with the highest hormone concentration (100 nM). We conclude that factors related to feeding training and circadian rhythmicity modulate cell sensitivity to insulin.

Remarkable similarities between the temporal organization of neocortical electrographic sleep patterns of rats and humans

Electrocorticographic activity was automatically recorded in albino rats for 72 consecutive h and analyzed by procedures suitable to detect 24-h rhythms. Beta (alert wakefulness), theta (somnolence), delta (slow wave sleep) and sigma 1 (superficial synchronized sleep) activities showed a robust circadian rhythmic distribution. The acrophases (maxima of the adjusted cosine curve) occurred at 23:39, 07:59, 08:37 and 13:25 h, respectively. EMG atonia and extreme hypotonia (less than 10% of mean EMG level) episodes showed a 24-h rhythm peaking at 14:18 h. The temporal sequence within the circadian rest period, i.e., somnolence, slow, wave sleep, superficial synchronized sleep and paradoxical sleep, is very similar to that known to occur during the nocturnal sleep of humans

Lack of similarity between the effect of lesions of the suprachcasmatic nucleus and subparaventricular hypothalamic zone on behavioral circadian rhythms

Rats were submitted to eletrolytic lesion of either the suprachiasmatic nucleus (SCN) or the subparaventricular hypothalamic zone (SPVH) and the effects on circadian behavioral rhythms were compared. While the SCN lesion abolished the circadian rythmicity of all behavioral patterns, the SPVH lesion only abolished that of the eating and drinking behavior and reduced the amplitude of a behavioral item usually associated with REM sleep