Biomedical subjects

C Guerri

Publications and source records attributed to C Guerri.

At least 73 records · Page 4Linked to original sources

PubMed1987

The role of maternal alcohol damage on ethanol teratogenicity in the rat.

To study the severity and degree of in utero alcohol effects in relation to the rate of maternal alcohol damage, multiparous 1-year alcohol-fed rats were used, with an appropriate pair-fed control group. During pregnancy, alcoholic dams showed relatively high acetaldehyde levels (41 +/- 19 mumol/l) and blood alcohol levels of 22.8 +/- 14 mmol/l. They also showed marked histological alterations in liver as well as high serum aspartate-aminotransferase, alanine-aminotransferase, alkaline phosphatase, glutamate dehydrogenase, and gamma-glutamyltransferase activities. The increase in serum enzyme levels did not correlate with an increase in hepatic enzyme levels since only glutamate dehydrogenase was enhanced in liver after 1 year of alcohol intake. In addition, except for an increase in low Km aldehyde dehydrogenase activity, there were no changes in liver alcohol metabolizing enzymes in chronic alcohol vs. pair-fed females. Alcoholic rats showed a high incidence of damage in their progeny (resorptions, immature fetuses, decrease in fetal weight, etc.), and rats with the highest serum levels of the above enzymes (especially glutamate dehydrogenase and gamma-glutamyl transferase) had severely affected progeny. Rats with minimal histological liver damage, in contrast, did not show resorptions. Thus, the results presented suggest that the stage of maternal alcohol illness, as indicated mainly by the extent of liver damage, plays an important role in the frequency and severity of in utero alcohol effects in the rat.

Alcoholism↗

PubMed1987

A biochemical and stereological study of neonatal rat hepatocyte subpopulations. Effect of pre- and postnatal exposure to ethanol.

Hepatocytes from 12-day-old rats, pre- and post-natally exposed to alcohol, together with those from pair-fed controls, were isolated and subfractionated in six cell subpopulations on Percoll density gradients. These cells were characterized using a combination of biochemical and stereological methods. The low density cells (F2) mainly showed biochemical and stereological features of perivenous hepatocytes, whereas the heavier cells (F6) were primarily periportal hepatocytes. The alcohol-metabolizing enzymes, alcohol dehydrogenase and aldehyde dehydrogenase (high and low Km) showed more activity in the F2 fraction. Alcohol-altered mitochondria and Golgi apparatus occurred mainly in F2 cells, whereas the endoplasmic reticulum and lysosomes appeared to be more altered in the F6 hepatocytes. Alcohol also induced the appearance of some small hepatocytes, with a well-developed rough endoplasmic reticulum and an increased number of mitochondria. Biochemical data indicated that glutamate dehydrogenase and alanine aminotransferase were more affected in F2 cells from alcohol-treated rats, and that the activity of the ethanol-metabolizing enzymes was alos reduced in these hepatocytes. Our results indicate that alcohol exposure during zonal development in the liver could have a selective effect on specific cell components depending on the acinar zone, and that the perivenous hepatocytes appear to be more damaged under these conditions.

Alanine Transaminase↗

PubMed1987

Chronic ethanol consumption affects filipin-cholesterol complexes and intramembranous particles of synaptosomes of rat brain cortex.

To assess the effect of ethanol on the planar distribution of cholesterol as well as on the surface architecture of presynaptic terminals of rats, synaptosomes isolated from cerebral cortex of rats chronically exposed to alcohol were incubated with filipin, a cytochemical marker for beta-hydroxycholesterol, and analyzed using both conventional (qualitative and quantitative) and freeze-fracture electron microscopy. Synaptosomes incubated in the absence of filipin were used as cytochemical controls. Biochemical determination indicates a 12% increase of cholesterol in synaptosomal membranes from alcohol treated rats. This increase was confirmed by a significant increment in the number of filipin-cholesterol complexes. Synaptosomes of treated rats showed a reduction in the total number of synaptic vesicles (SV) as well as a decrease in the density and total number of intramembranous particles (IMP) per synaptosome. In control rats, most synaptosomal IMP were distributed in clusters whereas in those of rats exposed to alcohol they were distributed at random. These changes in distribution of IMP were also observed in presynaptic terminals analyzed "in situ." These findings indicate that ethanol acts on the presynaptic terminals. The variations in cholesterol content as well as in the density and distribution of IMP appear to be related to alcohol-induced changes in the physicochemical properties of components of the synaptosomal membrane.

Alcoholism↗

PubMed1987

Prenatal exposure to alcohol alters the Golgi apparatus of newborn rat hepatocytes: a cytochemical study.

The effect of prenatal exposure to ethanol on the Golgi apparatus of newborn rat hepatocytes has been studied cytochemically using several trans-Golgi markers (thiamine pyrophosphatase, uridine diphosphatase, inosine diphosphatase, acid phosphatase, and 5'-nucleotidase) as well as a cis-side marker (osmium impregnation). The amount of cerium phosphate formed in the cytochemical reactions was roughly quantitated by stereologic methods. The Golgi apparatus of about 40% of the hepatocytes appeared disorganized after alcohol treatment, and in the other 60%, the electron density of reaction product deposits for all phosphatases investigated was decreased. 5'-Nucleotidase was completely absent in cisternae of Golgi apparatus of treated cells. In control cells impregnated with osmium tetroxide, reduced osmium compounds were observed in most Golgi cisternae and in nearby vesicles. In contrast, only small vesicles appeared positive in treated hepatocytes. These results suggest that prenatal alcohol exposure alters some Golgi functions. Thus, the decrease in nucleoside diphosphatase and 5'-nucleotidase cytochemical activities after ethanol exposure strongly suggests that this treatment could affect glycosylation in the Golgi apparatus of newborn rat hepatocytes.

5'-Nucleotidase↗

PubMed1987

Synaptic membrane alterations in rats exposed to alcohol.

Synaptic membranes were isolated from 2 and 4-month-old rats, pair-fed controls (PF), prenatally (PAE) or pre + postnatally (PPAE) exposed to alcohol, and the activities of some membrane-bound enzymes were measured. We found a 22-36% reduction in the levels of the (Na + K)ATPase, Ca++ATPase, acetylcholinesterase and 5'-nucleotidase from PAE rats. This reduction was greater in PPAE animals. The transition temperature in Arrhenius plots of the synaptosomal (Na + K)ATPase activity from PPAE rats was lower than in control rat membranes, indicating an alteration of lipid-protein interactions. No change in transition temperature was noted in PAE animals. Also, there was a decreased cholesterol content in PPAE synaptic membranes, vs. controls, while there was no change in PAE membranes. Kinetic parameters of the synaptosomal (Na + K)ATPase from PPAE rats, revealed a decrease in the Km and Vmax for potassium. These findings indicate that prenatal alcohol exposure probably delays synaptic development, whereas continued alcohol exposure during lactation may, in addition, alter the physicochemical structure of synaptic membranes.

5'-Nucleotidase↗

PubMed1987

Effect of pre- and postnatal exposure to alcohol on perivenous and periportal neonatal rat hepatocytes.

Hepatocytes from 12-day-old rats, pre and postnatally exposed to alcohol and pair-fed controls, were isolated and subfractionated in six cell subpopulations on Percoll density gradients. These cells were characterized using biochemical, stereological and cytofluorometric methods. Our results show that the low density cells (F2) are mainly perivenous cells, whereas the heavier cells (F6) were primarily periportal cells. These results were confirmed by alanine aminotransferase (ALAT), and glutamate dehydrogenase (GDH) activity levels and by stereological parameters. Alcohol seems to especially affect perivenous hepatocytes, with the damaged hepatocytes appearing in the perivenous and midzonal hepatocyte populations.

Alanine Transaminase↗

PubMed1987

Prenatal exposure to ethanol alters lateral plasma membranes and gap junctions of newborn rat hepatocytes as revealed by freeze-fracture.

The effects of prenatal exposure to ethanol on the lateral (contiguous) plasma membrane of newborn rat hepatocytes was investigated using qualitative and quantitative freeze-fracture. The number of free intramembranous particles decreased by 11% and 17% in P- and E-faces, respectively. Alcohol also induced the appearance of particle-free areas within the gap junctions, in addition to a three-fold increase in the mean area and an increment in the percent of plasma membrane occupied by these elements. However, no differences in either the size of gap junction particles or in the mean interparticle distance were found between control and alcohol-treated animals. On the other hand, prenatal exposure to ethanol did not alter the structure of tight junctions.

Animals↗

PubMed1986

Alcohol and acetaldehyde in rat's milk following ethanol administration.

Alcohol and acetaldehyde were measured in milk and peripheral blood in chronic alcoholic rats, at 5 and 15 days of lactation. Ethanol in blood increased throughout lactation and the levels of acetaldehyde were much higher than in nonlactating alcoholic rats. The concentration of acetaldehyde in milk was always ca. 50% of that in blood, whereas that of ethanol varied within the range of 44-80% of the blood levels. Blood alcohol levels in the corresponding sucking pups were much lower than in maternal blood and increased throughout lactation. The time course of ethanol and acetaldehyde concentration in blood and milk were determined in normal lactating rats after cyanamide (40 mg/kg) and ethanol administration (2 or 4 g/kg). Milk alcohol reached higher concentrations than in blood within the first hour of ethanol administration, decreasing and remaining constant thereafter at ca. 65% of those in blood. Acetaldehyde levels in milk were always 35-45% lower than in blood. No alcohol dehydrogenase activity was found in homogenates of mammary tissue; however there was some aldehyde dehydrogenase activity. A significant decrease in mammary tissue aldehyde dehydrogenase was found in chronic alcoholic rats. The role of this enzyme is discussed.

Acetaldehyde↗

PubMed1986

Neuronal membrane enzymes in rat lines selected for differential motor impairment by ethanol.

Neuronal membrane enzyme activities were determined in naive and ethanol-treated (30 min after 2 g/kg) male and female rats of lines developed for more (ANT) and less (AT) ethanol-induced motor impairment. Ethanol did not affect acetylcholinesterase, (Na+K)-ATPase or 5'-nucleotidase activities, but adenylate cyclase activities were lowered in both cerebellum and cerebrum. Cerebral acetylcholinesterase activities were higher in ANT than AT rats. No consistent line difference was observed regarding (Na+K)-ATPase activities. Slightly higher cerebellar 5'-nucleotidase activities were found in the ANT line. Cerebellar adenylate cyclase levels were substantially higher in the AT line. No line differences were displayed in the activation of adenylate cyclase activity by dopamine or norepinephrine. It is concluded that ethanol in vivo may inhibit neuronal adenylate cyclase activity and that cerebellar phosphorylation may be a regulator of motor impairment. Cholinergic mechanisms may also be connected to the ethanol-induced motor impairment.

5'-Nucleotidase↗

PubMed1986

Chronic ethanol intake in lactating rats: milk analysis.

Milk was analyzed at 5 and 15 days of lactation in rats fed an ethanol liquid diet or appropriate control diet. Alcoholic rats showed blood ethanol levels as high as 43 mM at the end of lactation. Milk from ethanol-fed rats showed an increase in pH, protein and lipids and a decrease in lactose, compared with controls. Chronic ethanol consumption seems to reduce the yield of milk. The nutritional status of sucklings from alcoholic mothers seems to be related more to the quantity of milk than to its quality.

Alcoholism↗

PubMed1986

Effect of prenatal alcohol exposure on sexual maturation of female rat offspring.

To assess sexual maturation of female offspring from alcoholic rats, vaginal opening, body weight, prolactin (PRL), luteinizing hormone (LH) and growth hormone (GH) were followed during development. The vaginal opening in the female offspring from alcohol-fed dams was delayed compared with the offspring from both pair-fed and normally fed dams. There was an increase in plasma PRL levels together with a decrease in levels of plasma LH at the time of the opening of the vagina in rats prenatally exposed to alcohol (PEA) with respect to both control groups. The increase in PRL was the only hormonal alteration which persisted into adulthood (120 days). In general, there were no changes in levels of plasma GH between experimental and control groups. These data indicate that PEA results in a modification in secretions of PRL and LH as well as in a delay in the opening of the vagina.

Animals↗

PubMed1986

The effects of chronic alcohol consumption on pregnant rats and their offspring.

The effect of chronic ethanol intake during gestation was studied in rats fed a liquid diet in which ethanol provided 36% of the total calories. The animals were chronically alcoholised before mating, and the body weight gain and nutritional status during pregnancy were noted. Blood ethanol levels were measured during pregnancy and parturition. Specifically, we have shown that chronic ethanol intake during pregnancy lengthens the gestation period, decreases foetal viability, increases the placental weight and diminishes foetus, liver and brain weights, as well as the protein and DNA content of foetal brain. The reduced body weight of rats prenatally exposed to alcohol continued for the first two months of the postnatal period and was most apparent during lactation.

Alcoholism↗

PubMed1985

Qualitative and quantitative ultrastructural alterations in hepatocytes of rats prenatally exposed to ethanol with special reference to mitochondria, golgi apparatus and peroxisomes.

To assess the effect of ethanol on the liver of the offspring of alcohol-fed rats, the hepatocytes of newborn rats whose mothers were fed: a) a liquid diet containing alcohol, b) the same diet isocalorically balanced, or c) a chow diet, were analyzed using both quantitative and qualitative electron microscopy as well as cytophotometric and biochemical methods. Hepatocytes of chow-fed and pair-fed controls showed differences in the amounts of glycogen and lipids as well as in several stereologically measured variables including mitochondria, Golgi apparatus and smooth endoplasmic reticulum. These differences are probably due to the composition of the diet. Rats prenatally exposed to alcohol showed increases in the hepatocyte and mitochondria volumes and in the number of peroxisomes. Moreover, the Golgi apparatus of these cells appeared disorganized and composed exclusively of small size vesicles, suggesting an impairment of their function.

Animals↗

PubMed1985

Alterations in the cytochemical activity of several phosphatases in hepatocytes from rats exposed prenatally to ethanol.

The activities of acid phosphatase, alkaline phosphatase, glucose-6-phosphatase, uridine diphosphatase, inosine diphosphatase, thiamine pyrophosphatase and 5'-nucleotidase have been investigated cytochemically in hepatocytes of the offspring of alcohol-fed rats, using cerium ions as a capturing agent and qualitative and quantitative electron microscopy. All these enzyme activities were decreased in the experimental animals compared with controls not exposed to ethanol. The pattern of deposition of the product of glucose-6-phosphatase activity in the cisternae of the endoplasmic reticulum was also different in the two groups. The phosphatases analyzed are functional markers of different cell components, and the results suggest that prenatal exposure of rats to ethanol causes functional alterations in the endoplasmic reticulum, Golgi apparatus, lysosomes and plasma membrane of hepatocytes.

Animals↗

PubMed1985

Chronic ethanol intake modifies estrous cyclicity and alters prolactin and LH levels.

The effect on the estrous cycle, as well as prolactin, luteinizing hormone (LH) and alcohol levels, were studied in female rats during chronic alcohol intake. Rats were fed the following diets for 5 weeks: a liquid ethanol diet (5% ethanol, w/v), an isocaloric liquid diet (pair-fed) or laboratory rat-chow and water ad lib. Ethanol-fed rats showed an irregular estrous cycle with a significant decrease in the frequency of the estrus + proestrus phases, and an increase in the duration of the diestrus + metaestrus phases, when compared with both the pair-fed and rat-chow groups. In these alcoholic rats, the estrous cycle phase was correlated with blood alcohol levels, which were found to be lower in the estrus + proestrus than in the other phases of the cycle. At the same time plasma prolactin levels were higher and plasma LH levels lower in the alcoholic rats than in either control group. These data indicate that chronic ethanol consumption prolongs the diestrus phase together with altered plasma prolactin and LH levels in female rats.

Alcoholism↗

PubMed1985

The effects of alcohol exposure in utero on acetylcholinesterase, Na/K-ATPase and Ca-ATPase activities in six regions of rat brain.

The neural membrane-bound enzymes, acetylcholinesterase, Na/K-ATPase and Ca-ATPase were examined in six brain areas in perinatal rats at 5, 15 and 25 days of age following alcohol exposure in utero. Female Wistar rats were mated with adult male Wistar rats and maintained on either a liquid diet containing ethanol (5% w/v) or on a control liquid diet for various periods during gestation and the perinatal period. These periods were: before and during gestation only (until birth of the offspring); before and during gestation and following birth; during only a period of gestation and continuing postnatally. Enzyme activity was determined by spectrophotometric methods in the following areas of the brain in each offspring: telencephalon, cerebellum, hippocampus, septal area, preoptic area, and medial basal hypothalamic area. Analysis of the data indicates that alcohol exposure in utero will heterogeneously decrease enzyme activity among the six brain areas when compared to enzyme activity in the same brain areas in animals which were not exposed to alcohol in utero. The activity of the three enzymes were most significantly reduced on day 5 of age, compared to levels in the control animals. Enzyme activity in each brain area was generally most significantly affected in animals exposed to alcohol both pre- and postnatally. The results indicate that fetal alcohol exposure reduces neuronal enzyme activity relative to the period of ethanol exposure in utero; the longer the period of time that alcohol was consumed by the mothers pre- and postnatally, the greater the effect of alcohol on the enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗

PubMed1984

Effects of ammonia on synaptosomal membranes.

Acute and sustained hyperammonemia in mice resulted in a decrease of the transition temperature of Arrhenium plots of synaptosomal (Na+-K+)ATPase. The activation energies in both phases of the plots were increased. "In vitro" addition of ammonia produced similar changes. This seems to indicate that ammonia alters the physical properties of synaptosomal membranes. The "in vitro" interaction of ammonia and ethanol at the membrane level was also investigated. Both agents together produced a further shift in the transition temperature and affected the activation energies. The relevance of these findings regarding the mechanism of ammonia toxicity and the protective effect of ethanol thereon is discussed.

Acetates↗

PubMed1984

Growth, enzymes and hormonal changes in offspring of alcohol-fed rats.

Consumption of ethanol by rats during pregnancy reduces the body and brain weight of their fetuses and pups. The reduction is greater if the offspring are kept with their alcohol-fed mothers rather than with control surrogate mothers during lactation. The activity of several enzymes of the neuronal cell membranes (Na+, K+-ATPase, Ca2+-ATPase, acetylcholinesterase, 5'-nucleotidase) is also reduced. This decrease in enzyme activity may be related to the decrease in neuronal development and could produce profound alterations in brain function. Altered hypothalamic-hypophysial function may be partly responsible for developmental anomalies found in the fetal alcohol syndrome. The levels of plasma luteinizing hormone are lower in pups exposed prenatally to ethanol, and prolactin levels are much higher. Concentrations of ethanol were essentially the same in maternal blood and in the fetus. Acetaldehyde levels in the placenta, amniotic fluid and the remaining fetal tissue at days 15 and 19 of gestation were about 40-50% of those in maternal blood. Acetaldehyde may be important in the pathogenesis of the fetal alcohol syndrome.

Acetaldehyde↗