Effect of p-chlorophenylalanine on rat reproduction under different conditions of lighting (author's transl)]

Reproduction in female rats kept on artificial cycles of light/darkness, continuous lighting and continuous darkness, has been studied. Three weekly doses of p-chlorophenylalanine (p-CPA), 100 mg/kg, were given to half of the rats in each group during the two preconditioning months before copulation. An evaluation has been made of the insemination, fecundation, number of embryos, ovarian cycle and level of 5-HT in the hypothalamus. The administration of p-CPA had an inhibitory effect on the reproductive behavior, especially pronounced in rats kept under continuous lighting and under continuous darkness. The difference in 5-TH levels were greater among the groups kept on cycles of light/darkness without treatment and with p-CPA (0.05 greater than P greater than 0.01). The importance of 5-HT in the mechanisms of reproductive behavior is emphasized.     

Observations on the effects of nicotinic acid,cyclospasmol and ronicol on the electrocortical activity and automatic movement of the rat

A report account of the effects of cerebral circulatory drugs viz., nicotinic acid, Cyclospasmol, Ronicol on electrocortical activity and automatic movement behaviour of rats, has been presented. Observations ware made of the tats kept in a sound proof, well aerated (ventilated) dimly lighted chamber with one way glass. Electrocortical activity was recorded from the unanaesthetised, unrestrained rats chronically implanted with electrodes. Results obtained showed that the administration of nicotinic acid resulted in sleep-like condition lasting for about one and a half hours, with concomittant changes in electrical activity and behaviour. Cyclospasmol and Ronicol did not produce any change in the electrical activity and behaviour of the animals. Cyclospasmol, however, prevented the effects of nicotinic acid. Ronicol appeared to be somewhat less effective in this respect. Autocorrelation and Fowler analysis of electrocortical activity were also performed. Actions of the drugs used have been discussed and explained with respect to their known effects on cerebral blood flow.     

Importance of the water regimen for animal growth in increased motor activity

Growth rate of male rats exposed to intensive physical exercise and the impact of exercise on the muscle system have been studied. To increase the locomotor activity the animals were kept in higher, as compared to the control, cages with the feeding rack attached to the ceiling. A tendency to an increase in body weight and specifically in gastrocnemius was noted. A reduction in water consumption was shown to slow the growth rate of rats in increased locomotor activity, while in low physical activity water shortage exerted but a negligible effect on the animal growth.     

Morphologic changes in the pineal gland of rats exposed to continuous darkness

We examined the pineal structure of rats exposed to constant darkness (DD) at light microscopic level. Two groups of rats were exposed to 12:12 light/dark cycle (LD) or DD from their prenatal ontogenesis and then for 3 months after birth. The gland structure of DD rats was observed to have an active appearance. Some of the observed pinealocytes with light nuclei from DD rats were determined to contain double nucleoli. Nuclear area and perimeter of both dark and light types were greater in rats kept in DD than in LD. Rats exposed to DD had more cells with light nuclei and lesser cells with dark ones than rats kept in LD. No significant differences in nuclear characteristics of intermediate type were found between rats kept in LD and those kept in DD. The activity of mammalian pineal can be altered by light conditions to which the animal is exposed.     

Effect of Silver Ions on Copper Metabolism during Mammalian Ontogenesis

Copper metabolism was studied in laboratory rats that received silver ions with food (Ag diet) from birth for 5, 20, 40, and 180 days. Parameters of the copper status in the blood serum were determined, and data on the distribution of silver ions in the body were obtained. A comparative histological analysis of brain, liver, kidney, and spleen sections of adult rats kept on the Ag diet for 30 or 180 days was performed. Copper and silver content, expression levels of the genes of copper transport proteins, and the activity of copper enzymes were determined in the cells of the liver, the central organ responsible for copper metabolism in mammals. In adult rats kept on the Ag diet for 30 days, copper status parameters dropped to near-zero values. In contrast, these parameters were decreased only twofold in rats that had been kept on the Ag diet for 6 months from birth. At the same time, the expression of genes involved in copper homeostatis was downregulated. The expression of genes that encode copper enzymes was unchanged. The activity of ceruloplasmin, the main copper-containing protein of the blood, was decreased, while the activity of SOD1, a cellular copper enzyme, was unchanged. The pathways by which silver can interfere with copper metabolism and the mechanisms that compensate these effects are discussed. The data obtained may help assess the potential consequences of growing environmental exposure to silver due to increasing use of silver nanoparticles in different areas of human activity.     

The influence of functional alteration on monoamine oxidase and catechol-O-methyl transferase in the visual pathway of rats

—Rats were reared in complete darkness or under chronic stimulation with flashing light from birth to the age of 7 weeks. Light deprivation caused a significant increase in monoamine oxidase activity (measured with [¹⁴C]serotonin) of about 30 per cent in the structures of the visual pathway. Chronic stimulation with flashing light had no influence on the activity of monoamine oxidase in either visual or non-visual structures. The activity of catechol-O-methyl transferase in the brain areas of light-deprived rats was reduced, in light-stimulated rats it was slightly increased. In mother rats kept together with their litters in either complete darkness or flashing light for 5 weeks no change in monoamine oxidase activity was observed. The activity of catechol-O-methyl transferase in mother rats kept in darkness was significantly decreased in all brain regions studied; in light-stimulated animals the enzyme activity was not affected.     

Development of the duodenal glands in rats on a high cellulose diet

Wistar weaned rats were kept on cellulose-rich diet for 3 months. They revealed the duodenal gland area of increased length, as compared to the control group kept on standard pellets. Glandular-duodenal index, that is a relative indication of gland development, also rose. Cellulose-fed rats showed a lower pH of the stomach contents. The correlation between pH and gland development has been established. Possible reasons for a more intensive gland enlargement in herbivorous animals are being discussed.     

Activity of cAMP-dependent protein kinases and cAMP-binding proteins from rat renal cytosol upon dehydration

The activity of cAMP-dependent protein kinases, cAMP binding and the spectrum of cAMP-binding proteins in renal papillary cytosol of intact rats and of rats kept on a water-deprived diet for 24 hours were investigated. It was found that the stimulation of protein kinases by 10(-6) M cAMP in the experimental group was significantly higher than in the control one. On DEAE-cellulose chromatography, the position of peaks of the specific cAMP binding corresponded to those of the regulatory cAMP-dependent protein kinases type I and II. Under these conditions, more than 80% of the binding activity in intact animals was localized in peak II, whereas in rats kept on a water-deprived diet over 60% of the binding activity was localized in peak I. The total binding activity of cytosol in experimental animals remained unchanged is compared to intact rats. It is suggested that in renal papilla dehydration is accompanied by the induction of synthesis of regulatory subunits of cAMP-dependent protein kinase type I.     

Effect of melatonin on oxidative status of rat brain, liver and kidney tissues under constant light exposure

An enormous amount of data has been published in recent years demonstrating melatonin's defensive role against toxic free radicals. In the present study, we examined the role of melatonin as an antioxidant against the effect of continuous light exposure. Rats were divided into three groups. Control rats (group A) were kept under natural conditions whereas other group of rats (group B and C) were exposed to constant light for inhibition of melatonin secretion by the pineal gland. Group C rats also received melatonin via s.c. injection (1 mg x kg(- 1) body weight x day(- 1)). At the end of experiment, all animals were sacrificied by decapitation, serum and tissue samples were removed for determination of malondialdehyde (MDA), a product of lipid peroxidation, conjugated dienes levels and glutathione peroxidase (GSH-Px) activity levels. It was found that lipid peroxidation was increased in the rats which were exposed to constant light. Melatonin injection caused a decrease in lipid peroxidation, especially in the brain. In addition, melatonin application resulted in increased GSH-Px activity, which has an antioxidant effect. Thus, melatonin is not only a direct scavenger of toxic radicals, but also stimulates the antioxidative enzyme GSH-Px activity to detoxify hydroxyl radical produced by constant light exposure.     

Effect of rearing conditions on nucleic acid synthesis in the brain of rats of different genotypes

The incorporation of [3H]thymidine into DNA and of [14C]uridine into RNA has been investigated in different areas of brain and in liver of inbred August rats, non-inbred Wistar rats and hybrids between male wild-type and female Wistar rats which were kept either under normal conditions or under intensive sensory stimulation at different age. DNA metabolism has been found to display tissue, regional, age-dependent and interlinear differences. Sensory stimulation influences considerably the synthesis of nucleic acids which is maximal at early ontogenesis stages and in the brain of hybrid animals.     

Sex differences of plasma cholinesterase in the rat.

Plasma cholinesterase activity of adult female HAN-Wistar rats was found to be 5.5-fold higher than that of adult male rats kept under constant specified pathogen-free (SPF) conditions up to their 870th day of life.     

The State of the Adenyl Nucleotide System in the Liver of Rats with Toxic Hepatitis under Conditions of Protein Deficiency

Adenyl nucleotide levels and activity of AMP catabolism enzymes in the cytosolic liver fraction of rats with acetaminophen-induced hepatitis have been studied under different dietary protein regimens. It was found that in animals with toxic hepatitis maintained on a diet rich in protein the ATP and ADP levels decreased, while AMP levels were similar to those in control animals. At the same time, in the cytosolic liver fraction of rats with acetaminophen-induced hepatitis kept under conditions of protein deficiency, ATP and AMP pools were depleted. Changes in the adenyl nucleotides content were accompanied by altered activity of AMP catabolism enzymes, such as 5′-nucleotidase and AMP deaminase. It was found that in rats with toxic hepatitis that were fed a complete diet, AMP deaminase activity increased in comparison to the control level along with 5′-nucleotidase stimulation. At the same time, in protein-restricted rats with toxic liver damage, AMP deaminase activity decreased, while 5′-nucleotidase activity was elevated in comparison to control values. These results indicate depletion of energy sources in the liver cells of rats with acetaminophen-induced hepatitis that were fed a low-protein diet. The observed changes in the activity of AMP catabolism enzymes may be considered as one of the mechanisms that regulate the cellular energy function.     

Effect of prolonged ethanol ingestion on hepatic lipogenesis and related enzyme activities

1. Hepatic lipogenesis in vivo and the activities of enzymes associated with fatty acid synthesis in the liver were studied in rats fed for 21 days on liquid diets containing ethanol. 2. The ethanol-fed rats developed a moderate hepatic triacylglycerol accumulation during this period. When carbohydrate was replaced by ethanol in the diet, the rate of fatty acid synthesis was slower in the ethanol-fed rats on low-, medium- and high-fat diets than in the appropriate controls. However, when the fat/carbohydrate ratio was kept the same in the ethanol-fed and control rats, ethanol had no influence on the rate of fatty acid synthesis. 3. Glucose 6-phosphate dehydrogenase activity was lower in the ethanol-fed group. ;Malic' enzyme activity did not change during the ethanol treatment when the fat/carbohydrate ratio was kept unchanged. 4. The ATP citrate lyase activity was lower in the ethanol-fed rats on all diets, whereas acetyl-CoA synthetase activity was independent of the composition of the control diet, but was lower in the ethanol-fed rats, in which the concentration of the active form of pyruvate dehydrogenase was also lower. 5. It is concluded that hepatic fatty acid synthesis does not play any major role in ethanol-induced triacylglycerol accumulation. Careful design of the diets is necessary to reveal the specific effects of ethanol on the enzymes associated with lipogenesis.     

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.     

The Role of Wheel Running in the Coupling of Two Simultaneous Circadian Rhythms of Motor Activity in the Rat

Motor activity is among the non-photic stimuli that act on the internal clock. We have tested the role of motor activity in the circadian pattern of rats under conditions near the lower limits of entrainment, that induce circadian rhythm dissociation. Three groups of 8 rats each were used: a) rats kept individually in 25×25×15 cm cages, b) rats in 50×25×15 cm cages, and c) rats in 50×25×15 cm cages with access to a running wheel. All the rats were kept under light-dark cycles of 22 hours (T22, 11L:11D) for 50 days, after which they were transferred to constant darkness. All the rats without a running wheel showed a motor activity pattern with two statistically significant circadian rhythms in the periodogram of Sokolove and Bushell: one circadian component entrained by the LD cycle, and another free-running. The rats with access to a running wheel showed several patterns: 5 rats showed only one rhythm entrained to the LD cycle, 2 rats showed circadian rhythm dissociation, and 1 showed only a free running rhythm. We believe that the simultaneous manifestation of two circadian components reflects the functional dissociation of the oscillators population that constitutes the circadian pacemaker, of the rat. Physical exercise acts on the pacemaker reinforcing the strongest group of oscillators, which, depending on the structure of the circadian system of the rat, is usually the one entrained to the LD cycle. This study supports the hypothesis that motor activity couples the oscillators that form the circadian system of the rat.     

The Role of Wheel Running in the Coupling of Two Simultaneous Circadian Rhythms of Motor Activity in the Rat

Motor activity is among the non-photic stimuli that act on the internal clock. We have tested the role of motor activity in the circadian pattern of rats under conditions near the lower limits of entrainment, that induce circadian rhythm dissociation. Three groups of 8 rats each were used: a) rats kept individually in 25×25×15 cm cages, b) rats in 50×25×15 cm cages, and c) rats in 50×25×15 cm cages with access to a running wheel. All the rats were kept under light-dark cycles of 22 hours (T22, 11L:11D) for 50 days, after which they were transferred to constant darkness. All the rats without a running wheel showed a motor activity pattern with two statistically significant circadian rhythms in the periodogram of Sokolove and Bushell: one circadian component entrained by the LD cycle, and another free-running. The rats with access to a running wheel showed several patterns: 5 rats showed only one rhythm entrained to the LD cycle, 2 rats showed circadian rhythm dissociation, and 1 showed only a free running rhythm. We believe that the simultaneous manifestation of two circadian components reflects the functional dissociation of the oscillators population that constitutes the circadian pacemaker, of the rat. Physical exercise acts on the pacemaker reinforcing the strongest group of oscillators, which, depending on the structure of the circadian system of the rat, is usually the one entrained to the LD cycle. This study supports the hypothesis that motor activity couples the oscillators that form the circadian system of the rat.     

New derivatives of argininosuccinic acid in the urine of a patient with argininosuccinicaciduria

1. The relationships between nutritional state, lipoprotein lipase activity in epididymal fat-pads, and the concentrations of glucose, insulin and unesterified fatty acids in the plasma were studied in rats that had been adapted for 3 weeks to one of two controlled feeding schedules. In one of these, rats had access to food for 14h during each 24h period, and in the other, they had access to food for 14h during each 48h period. Groups of animals were killed at different times during the 14h when they had access to food and during the following period when they were deprived of food. 2. Low lipoprotein lipase activity, low concentrations of plasma glucose and insulin and high concentrations of plasma unesterified fatty acids were found in rats deprived of food for 34h. Feeding resulted in increases in lipoprotein lipase activity and in the concentrations of glucose and insulin in the plasma. Enzyme activity continued to increase during the first 6-9h of the feeding period. 3. After adapted rats had been deprived of food for 12-16h there was a marked and unexpected increase in lipoprotein lipase activity; this occurred even when the rats were kept in an isolated environment. 4. The findings suggest that factors other than the absolute concentrations of insulin and glucose in the blood can exert a considerable influence on lipoprotein lipase activity in the epididymal fat-pad of a rat.     

Effect of short light-dark cycles on young and adult TGR(mREN2)27 rats

Animals placed under short light-dark (LD) cycles show a dissociation of their circadian rhythms. However, this effect has only been studied in Wistar rats and with the motor activity (MA) rhythm. Thus, in the present experiment, we studied in TGR(mREN2)27 (TGR) rats, a strain of hypertensive rats, the effect of a short LD cycle on the circadian rhythms of MA, heart rate (HR), and blood pressure (BP). Our aim was [1] to investigate whether the exposure of TGR rats to a short LD cycle induced a dissociation of their circadian rhythms, [2] to study the effect of short LD cycles on the development of the circadian rhythms of TGR rats, and [3] to compare the effect of short LD cycles on young and adult TGR rats. One group of TGR rats was maintained under LD cycles of 22h periods (group G22). The progress in time of their rhythms was compared to that of TGR rats of the same age that had been kept under LD cycles of 24h periods (group G24). For the third point, the rhythms of a group of 5-week-old TGR rats kept under LD 22h cycles (young rats) were compared to those of a group of 11-week-old TGR rats (adult rats). Results showed that there is a dissociation of the circadian rhythms of all the variables monitored in TGR rats maintained under LD 22h cycles, independent of age. We have also found that group G22 showed a higher increase in BP with age and a higher mortality due to malignant hypertension compared to group G24. Finally, it seems that it is harder for young rats to entrain to short LD cycles than for adult rats, and young rats have a higher mortality due to malignant hypertension than adult rats. In conclusion, we demonstrated that short LD cycles produce a dissociation in the HR, BP, and MA circadian rhythms. The results of this experiment, compared to those previously obtained in Wistar rats, suggest that the light perception, the responses of the circadian system to light, or both are altered in the TGR rats. (Chronobiology International, 18(4), 641-656, 2001)     

The effect of supplying rats with vitamin K and administration of pelentane on Na,K- and spectrin-dependent ATPase in erythrocyte ghosts]

It was found that the activity of spectrin-dependent ATPase of erythrocyte ghosts isolated from rats with alimentary deficiency of vitamin K was significantly increased as compared with control animals, whereas in rats kept on a vicasol-rich diet this parameter was unchanged. In vitamin K-deficient rats the amount of proteins loosely bound to erythrocyte membranes was significantly reduced. At the same time, the activity of the integral enzyme (Na, K-ATPase) did not depend on the vitamin K provision despite the fact that in vitamin K-deficient animals kept on a vicasol-rich diet the enzyme affinity for ouabain was strongly decreased as compared with control. It was suggested that this effect might be due to the changes in the lipid and protein environment of the membrane-bound enzyme. Administration of the antivitamin K, pelentane, did not induce any conspicuous changes in the enzyme activities. It was concluded that antivitamin K does not induce any modification of the properties of erythrocyte-linked enzymes observed under conditions of vitamin K deficiency.     

Effect of housing rats within a pyramid on stress parameters

The Giza pyramids of Egypt have been the subject of much research. Pyramid models with the same base to height ratio as of the Great Pyramid of Giza, when aligned on a true north-south axis, are believed to generate, transform and transmit energy. Research done with such pyramid models has shown that they induced greater relaxation in human subjects, promoted better wound healing in rats and afforded protection against stress-induced neurodegnerative changes in mice. The present study was done to assess the effects of housing Wistar rats within the pyramid on the status of oxidative damage and antioxidant defense in their erythrocytes and cortisol levels in their plasma. Rats were housed in cages under standard laboratory conditions. Cages were left in the open (normal control), under a wooden pyramid model (experimental rats) or in a cubical box of comparable dimensions (6 hr/day for 14 days). Erythrocyte malondialdehyde and plasma cortisol levels were significantly decreased in rats kept within the pyramid as compared to the normal control and those within the square box. Erythrocyte reduced glutathione levels, erythrocyte glutathione peroxidase and superoxide dismutase activities were significantly increased in the rats kept in the pyramid as compared to the other two groups. There was no significant difference in any of the parameters between the normal control and rats kept in the square box. The results showed that exposure of adult female Wistar rats to pyramid environment reduces stress oxidative stress and increases antioxidant defense in them.