Dietary protein level alters gentamicin-induced nephrotoxicity in rats.

Aminoglycosides (AG) such as gentamicin are antimicrobial drugs widely used in the hospital setting due to their efficacy in the treatment of severe gram-negative bacterial infections. However, all AG have the potential to cause nephrotoxicity. Two studies have been conducted (1) to assess the protein level of a diet that would give the best renal outcome with gentamicin administration, and (2) to get a better idea about the rhythms of food ingestion associated with the different protein levels. Adult female Sprague-Dawley rats fully adapted to a standard chow diet, the standard chow with 20% or 55% added casein were chronically treated for 10 days with a nephrotoxic dose of gentamicin sulfate (40 mg/kg/day, i.p.) or a saline solution. Food ingestion patterns of rats were recorded every hour using a Diet Scan system and gentamicin nephrotoxicity indices were measured. The second study used rats that were fed the same diets and given a sham injection. Corticosterone was assayed to quantify the stress of the animals. Results showed that chronic gentamicin treatment leads to a decrease in food intake and flattening of the rhythms of food ingestion. Also, chow feeding and the 20% casein diet were found to be more protective against gentamicin-induced nephrotoxicity than the 55% casein diet. Therefore, while a protein-rich diet can be protective against gentamicin-induced nephrotoxicity, the present study demonstrates that a diet too high in protein might rather be harmful to the kidneys.

Is melatonin the hormonal missing link between magnetic field effects and human diseases?

The disruption of melatonin secretion has been largely studied since it could provide the missing link between the exposure to 50/60-Hz electric and magnetic fields (EMF) and the occurrence of possible health effects as the "melatonin hypothesis". We analysed the current experimental data from animal (rodents) where contradictory results have been observed, and from human studies conducted with volunteers or with workers in various conditions of exposure, biological endpoints and metrics. In humans, even in long lasting exposures, the overall results of these studies do not support the "melatonin hypothesis". It is unlikely that malignancies or mood disorders reported by people exposed to 50/60-Hz EMF could be related to the disruption of the melatonin levels.

Evaluation of the nocturnal levels of urinary biogenic amines in men exposed overnight to 50-Hz magnetic field.

The aim of this study was to determine whether exposure to magnetic fields might affect human health and to look for possible effects of acute exposure (9 hours) to 50-Hz magnetic fields (10 microT) on the urinary concentration of biogenic amines. Thirty-two young men (20-30 years old) were divided into two groups (sham-exposed and exposed group) of 12 to 16 subjects each. All subjects participated in two 24-hour experiments to evaluate the effects of both continuous and intermittent exposure to magnetic fields. The subjects were exposed to the magnetic field from 2300 to 0800, while lying down. Total urine (from 2300 to 0800) was collected at 0800. The results (expressed as a ratio of biogenic amine excretion to creatinine excretion (nmol/mmol)) did not differ significantly between sham-exposed and exposed men for any of the parameters measured: adrenaline, noradrenaline, dopamine, dihydroxyphenylalanine, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid. These results suggest that nocturnal exposure to either continuous or intermittent 50-Hz magnetic fields of 10 microT does not affect, at least under our experimental conditions, the nocturnal excretion of biogenic amines in healthy young men.

Effect of melatonin on total food intake and macronutrient choice in rats.

Melatonin, a hormone secreted in a rhythmic manner over 24 h mainly by the pineal gland, is used to alleviate the symptoms of jetlag and treat sleeping problems. The objective of the present study was to examine the effects of a 7-h phase-shift from the natural peak of melatonin secretion on total food intake and macronutrient selection. Forty-eight adult Wistar rats of both sexes were divided in three dietary groups, each group offered a simultaneous and different choice of a carbohydrate- and a protein-rich diet. Macronutrient intakes following intraperitoneal administration of four doses of melatonin (3000, 6000, 10000 and 15000 pg/ml blood) at dark onset were examined. Melatonin increased short- (4 h postinjection) and long-term (12 h postinjection) nocturnal total food intake in both male and female rats, mainly with the two highest doses. This effect of melatonin was mainly due to a short-term increase of intake across all carbohydrate-rich diet preparations (dextrin/cornstarch, cornstarch, and sucrose/cornstarch) and across genders. This consistent effect of melatonin on the intake of carbohydrate-rich diets with contrasting sensory attributes rules out the possibility that melatonin acts on sensorymotor pathways, thus suggesting that melatonin's effect on food intake is controlled by the carbohydrate content of the diet. In contrast, melatonin could be affecting some sensory or motor processes peculiar to the ingestion of protein since it increased protein-rich diet intake inconsistently across the various preparations (casein, soy isolate, and egg protein) as well as genders. This evidence supports the view that melatonin acts as a time indicator, reinforcing the animals with a "night cue", and favors predominant carbohydrate intake normally occurring at the beginning of the activity period.

The induction of low nocturnal secretion of melatonin caused by reverse feeding rhythms depends on availability of macronutrient diets.

The present study investigated the effect of single chow diet and two-way dietary choice between a protein-rich and a carbohydrate-rich diet ingested during free access or daytime access (08.00-16.00 h) on the rhythms of ingestion and on nocturnal levels of serum melatonin and pineal N-acetyltransferase activity in rats. Animals with free access to the single or the choice diets displayed a circadian rhythmicity of total food intake with peaks at the beginning, the middle and the end of the dark phase. Rats fed the dietary choice displayed a preference for carbohydrate at the beginning, and a preference for protein at the middle and the end of the dark phase. Under daytime feeding access, both dietary conditions resulted in only one peak of total intake at the beginning of the access period. Rats fed the choice diets on the daytime feeding schedule initially preferred carbohydrate to protein but this preference disappeared subsequently. Nocturnal peaks of serum melatonin and pineal NAT activity were lower with daytime access to dietary choice compared to ad libitum access. The results suggest that in a two-way selection of macronutrients, feeding cycle can directly act on the rhythms expressed within the pineal gland.

Food access schedule and diet composition alter rhythmicity of serum melatonin and pineal NAT activity.

This study investigated the effect of dietary composition and food access schedule on the rhythmicity of serum melatonin and pineal N-acetyltransferase (NAT) activity. Wistar rats maintained on a 12:12 h light-dark cycle were assigned to two dietary groups: a group fed rat chow and a group fed a choice between a protein-rich and a carbohydrate-rich diet. Each dietary group was further divided based on feeding schedule, with food available between 0800 and 1600 h or ad lib access to food. Regardless of dietary condition, total food and carbohydrate intake of rats having free access to food was higher than under the restricted food access schedule. Protein intake of rats fed the dietary choice was lower with the restricted access than in the free access. In rats fed the dietary choice, melatonin levels and NAT activity were significantly decreased with restricted access compared to free access. Such results were not found in rats offered restricted chow. This study suggests that the rhythms of melatonin secretion and NAT activity can be altered by dietary composition.

Assessment of the effects of nocturnal exposure to 50-Hz magnetic fields on the human circadian system. A comprehensive study of biochemical variables.

The proposed laboratory investigation was designed to evaluate the effects of acute exposure to both continuous and intermittent magnetic fields (MFs) (50 Hz-10 microT) on the circadian rhythm of clinical chemistry variables in humans: electrolytes (magnesium, calcium, phosphorus, sodium, potassium, and chloride), enzymes (amylase, lipase, aldolase, gamma glutamyl-transferase [GGT], lactate dehydrogenase [LDH], aspartate aminotransferase [ASAT], and alkaline phosphatase [ALP]), lipids (cholesterol, high-density lipoprotein [HDL], apolipoprotein A1 [ApoA1], and ApoB), proteins (total proteins and albumin), nitrogen substances (uric acid, urea, and creatinine), iron, glycemia, and transferrin. Young volunteers (32 subjects; 16 exposed and 16 sham exposed) were selected according to the screening criteria. Each subject participated in two sessions held within a 4-week period. In the first session, one group of volunteers (16 subjects) was exposed to a continuous MF and then, in the second session, to an intermittent MF. The second group (16 subjects) served as a control for both sessions. At each session, blood samples were collected at 3 h intervals from 11:00 to 20:00 and hourly from 22:00 to 08:00. The results indicate that both continuous and intermittent 50-Hz linearly polarized MFs of 10 microT intensity have no effects on the circadian rhythms or on the levels of the variables studied here.

Age-related differences in serum melatonin and pineal NAT activity and in the response of rat pineal to a 50-Hz magnetic field.

In a previous study we have shown that exposure to a 50-Hz sinusoidal magnetic field decreased serum melatonin concentration and pineal enzyme activities in young rats (9 weeks). In the present study we looked for the effect of a magnetic field of 100 microT on serum melatonin and pineal NAT activity in aged rats and compared them to young rats. We hypothesized that aging may change sensitivity of rats to a magnetic field. Two groups of Wistar male rats [aged rats (23 months) and young rats (9 weeks)] were exposed to 50-Hz magnetic fields of 100 microT for one week (18h/day). The animals were kept under a standard 12:12 light: dark cycle with a temperature of 25 degrees C and a relative humidity of 45 to 50%. Control (sham-exposed) animals were kept in a similar environment but without exposure to a magnetic field. The animals were sacrificed under red dim light. Serum melatonin concentration and pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) activities were studied. Our results showed that sinusoidal magnetic fields altered the production of melatonin (28% decrease; P <0.05) through an inhibition of pineal NAT activity (52% decrease; P <0.05) in the young rats whereas no effect was observed in aged ones. On the other hand, when comparing data from control animals between young and aged rats, we observed that serum melatonin level and NAT activity, but not HIOMT activity, decreased in aged rats (decrease by about 38% and 36% respectively). Our data strongly suggest that old rats are insensitive to the magnetic field.

[Melatonin and aging]. / Mélatonine et vieillissement.

Melatonin is a hormone secreted mainly by the pineal gland but also by the retina. It is synthesized from tryptophan and its characteristic circadian rhythm is ruled by light through the control of two limiting enzymic activities N-acetyl-transferase and hydroxyindole-O-methyl-transferase. In man--as in all studied species--its maximum plasma concentration is at night. Therefore it is considered as a signal transducing information on solar light within the organism thus providing the temporal framework upon which metabolic pathways are organized. Since its circulating levels decrease with ageing the question arises as to the origin and/or the consequences of this decrease, as well as the possible beneficial effects which could result from its administration in ageing humans.

Endocrine functions in young men exposed for one night to a 50-Hz magnetic field. A circadian study of pituitary, thyroid and adrenocortical hormones.

In recent years, some epidemiologic studies have suggested that extremely low frequency magnetic and electric fields might affect human health, and, in particular, that the incidence of certain types of cancer, depression, and miscarriage might increase among individuals living or working in environments exposed to such fields. Work in our laboratory studies whether and how changes in the electromagnetic environment might affect human health. The study presented here was designed to look for possible effects of acute exposure to 50-Hz linearly polarized magnetic fields (10 microT) on the hormones of the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes. Thirty-two young men (20-30 years old) were divided into two groups (sham-exposed or control group, and exposed group) of 16 subjects each. All subjects participated in two 24-hour experiments to evaluate the effects of both continuous and intermittent (one hour "off" and one hour "on" with the field switched "on" and "off" every 15 seconds) exposure to linearly polarized magnetic fields. The subjects were exposed to the magnetic field (generated by three Helmholtz coils per bed) from 2300 to 0800 while recumbent. Blood samples were collected during each session at 3 hour intervals from 1100 to 2000 and hourly from 2200 to 0800. Total urine was collected every 3 hours from 0800 to 2300 and then again at 0800. No significant differences were observed between sham-exposed and exposed men for any of the parameters measured: thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, triiodothyronine, thyroxine, free triiodothyronine, free thyroxine, thyroxine-binding globulin, cortisol, 17-hydroxycorticosteroids (17-OH-CS) and TBK. These results suggest that acute exposure to either continuous or intermittent 50-Hz linearly polarized magnetic fields of 10 microT does not affect, at least under our experimental conditions, these endocrine functions or their circadian rhythmicity in healthy young men.

Acute exposure to 50 Hz magnetic field does not affect hematologic or immunologic functions in healthy young men: a circadian study.

Some epidemiological studies report a relationship between magnetic field exposure and such human diseases as leukemia and immune system disturbances. The few published studies on animals do not demonstrate field exposure-related alterations in hematologic and immune systems. The data presented here are part of a broader study designed to investigate the possible effects of acute exposure to a 50 Hz linearly polarized magnetic field (10 microT) on hematologic and immunologic functions. Thirty-two young men (20-30 years old) were divided into two groups (control group i.e., sham-exposed. 16 subjects; exposed group, 16 subjects). All subjects participated in two 24 h experiments to evaluate the effects of both continuous and intermittent (1 h "off" and 1 h with the field switched "on" and "off" every 15 s) exposure to linearly polarized magnetic fields. The subjects were exposed to the magnetic field (generated by three Helmholtz coils per bed) from 23:00 to 08:00 while lying down. Blood samples were collected during each session at 3 h intervals from 11:00 to 20:00 and hourly from 22:00 to 08:00. No significant differences were observed between sham-exposed (control) and exposed men for hemoglobin concentration, hematocrit, red blood cells, platelets, total leukocytes, monocytes, lymphocytes, eosinophils, or neutrophils. Immunologic variables [CD3, CD4, CD8, natural killer (NK) cells and B cells] were unaltered. To our knowledge, this study is the first to document the effects of a 50 Hz magnetic field on the circadian rhythm of human hematologic and immune functions, and it suggests that acute exposure to either a continuous or an intermittent 50 Hz linearly polarized magnetic field of 10 microT, at least under the conditions of our experiment, does not affect either these function or their circadian rhythms in healthy young men.

Magnetic fields and pineal function in humans: evaluation of nocturnal acute exposure to extremely low frequency magnetic fields on serum melatonin and urinary 6-sulfatoxymelatonin circadian rhythms.

Exposure to a 50/60-Hz electromagnetic field can decrease the nocturnal production of melatonin in rodents. Melatonin is considered to be a marker of circadian rhythms, and abnormalities in its secretion are associated with clinical disorders, including fatigue, sleep disruption, mood swings, impaired performance, and depression, which are consequences of desynchronisation. Interestingly, some epidemiological studies have been reported finding most of these clinical disorders in individuals living or working in an environment exposed to electromagnetic fields. This experiment was designed to look for the possible effects of acute exposure (9 hours) to 50-Hz linearly polarized magnetic fields (10 mu T) on the pineal function. Thirty-two young men (20-30 years old) were divided into two groups (control group, i.e., sham-exposed: 16 subjects; exposed group: 16 subjects). All subjects participated in two 24-hour experiments to evaluate the effects of both continuous and intermittent exposure to linearly polarized magnetic fields. They were synchronized with a diurnal activity from 08:00 to 23:00 and nocturnal rest. The experiment lasted two months (mid-February to mid-April). The subjects were exposed to the magnetic fields (generated by three Helmholtz coils per bed) from 23:00 to 08:00, while lying down. Blood samples were collected during each session at 3-hour intervals from 11:00 to 20:00 and hourly from 22:00 to 08:00. Total urine was collected every 3 hours from 08:00 to 23:00 and once during the night, from 23:00 to 08:00. The levels of serum melatonin and its metabolite in urine (6-sulfatoxymelatonin) in exposed men did not differ significantly from those in control (sham-exposed) subjects. This study shows that nocturnal acute exposure to either continuous or intermittent 50-Hz linearly polarized magnetic fields of 10 mu T does not affect melatonin secretion in humans.

[Melatonin and biological rhythms: various aspects in human physiopathology]. / Mélatonine et rythmes biologiques: quelques aspects en physiopathologie humaine.

Melatonin (N-Acetyl-5-methoxytryptamine) is a hormone secreted mainly by the pineal gland or epiphyse and in smaller amounts by the retina. It is biosynthesized from tryptophan, the two critical enzymatic steps depend upon N-Acetyl-transferase (NAT) and 5-hydroxyindole-O-methyltransferase (5-HIOMT). The circadian rhythm of melatonin is the same in man and all the laboratory animals studied until now with noctural plasma concentrations 3-10 times greater than during daytime. The secretion and release of melatonin depend upon a large number of exogenous and endogenous factors as e.g. sex, age, pubertal stage, menstrual cycle, drugs, season... Light is the major regulating factor which acts through the retino-hypothalamic tract. Melatonin is considered as a transducer of the light signal forwarding to the organism the information about day length (relative length of day and night). It is a time-clue provider used by the organism to adapt itself to its environment.

Sinusoidal 50-Hz magnetic fields depress rat pineal NAT activity and serum melatonin. Role of duration and intensity of exposure.

The purpose of this study was to determine whether the exposure to a 50-Hz sinusoidal magnetic field could influence serum melatonin concentration and pineal enzymes activities in rats. The effects of both duration and intensity of exposure were also looked at. Two groups of Wistar male rats were exposed to 50-Hz magnetic fields of either 1, 10 or 100 microT. The first group was exposed for 12 hours and the second for 30 days (18 hours per day). During this time the animals were kept under a standard 12:12 light: dark cycle with a temperature of 25 degrees C and a relative humidity of 45 to 50%. Control (Sham-exposed) animals were kept in a similar environment but without exposure to a magnetic field. The animals were sacrificed under red dim light. Serum melatonin concentration and pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) activities were studied. Long-term exposure to a magnetic field (10 and 100 microT) significantly depressed the nocturne peak of serum melatonin concentration and pineal NAT activity whereas no effect was observed on HIOMT activity. Short-term exposure depressed both pineal NAT activity and nocturnal serum melatonin concentration but only with the highest intensity used (100 microT). Our results suggest that sinusoidal magnetic fields alter the production of melatonin through an inhibition of pineal NAT activity. Both duration and intensity of exposure play an important role in this effect. This work shows that, 1) sinusoidal magnetic field depresses NAT activity as static magnetic field does whereas HIOMT activity remains unaltered whatever the type of experiment and the intensity used, 2) the effect observed is related to both the duration of exposure and the intensity of magnetic fields, 3) the sensitivity threshold to magnetic fields vary with the duration of exposure which strongly suggests a cumulative effect of sinusoidal magnetic fields on pineal function.