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C J Eriksson

Publications and source records attributed to C J Eriksson.

At least 55 records · Page 3Linked to original sources
PubMed1989

Penetration of ethanol into the male reproductive tract.

We studied the pharmacokinetics of ethanol in the rat rete testis fluid, interstitial fluid, seminiferous tubules, epididymal fluid, and whole testis after 0.75 g/kg and 1.5 g/kg intraperitoneal injections. Ethanol concentration in these tissues was compared to that in capillary and arterial blood. The data was characterized by fitting to a mathematical model. The highest ethanol concentrations in orbital capillary blood were measured 10 min after the injections. Ethanol content in testis homogenate and interstitial fluid did not generally differ from that of orbital blood. However, in rete testis fluid the highest ethanol values were measured at 60 min by the 1.5 g/kg dose and at 30 min by 0.75 g/kg. Ethanol values before this differed from those of capillary blood and interstitial fluid (p less than 0.05-0.001). In seminiferous tubules, the highest ethanol concentration was reached at 20 min, and ethanol content was in general lower than in orbital blood (p less than 0.001-0.01). Ethanol levels in epididymal fluid were comparable to capillary blood. The transportability factor from the model for rete testis was low, which indicates a barrier of penetration of ethanol from blood. In addition, water contents of testicular compartments were calculated. The area under the curve values of rete testis and seminiferous tubules were approximately 10 and 30%, respectively, smaller than that of interstitial fluid, for example. Therefore, the germ cells are somewhat better protected from ethanol than the interstitial cells.

Animals↗
PubMed1987

Inhibition of testosterone biosynthesis by ethanol: multiple sites and mechanisms in dispersed Leydig cells.

Isolated rat Leydig cells were incubated for 2 h in sealed polycarbonate tubes under O2/CO2 atmosphere with 10 mIU/ml human chorionic gonadotropin. 20 mmol/l ethanol reduced the concentration of testosterone (16%, P less than 0.025); raised the concentrations of pregnenolone (60%, P less than 0.001), androstenedione (86%, P less than 0.001) and dehydroepiandrosterone (81%, P less than 0.001); but did not change concentrations of progesterone and 17 alpha-hydroxyprogesterone in the incubation medium. Ethanol also raised the lactate/pyruvate ratio in the Leydig cell suspension. 4-Methylpyrazole (0.5 mmol/l) abolished the ethanol-induced changes. The present results suggest that ethanol inhibits testosterone synthesis in isolated rat Leydig cells at the pregnenolone-to-testosterone pathway by inhibiting 3 beta-hydroxy-5-ene-steroid dehydrogenase/5-ene-4-ene-isomerase catalyzed reactions and the conversion of androstenedione to testosterone. These inhibitions are caused by consequences of ethanol metabolism. A likely mechanism for the former inhibition is that the increase in the NADH/NAD+ ratio in Leydig cells leads to inhibition of reactions catalyzed by 3 beta-hydroxy-5-ene-steroid dehydrogenase/5-ene-4-ene isomerase, but the inhibition mechanism operating at the androstenedione-to-testosterone step remains to be characterized.

3-Hydroxysteroid Dehydrogenases↗
PubMed1987

International Commission for Protection against Environmental Mutagens and Carcinogens. ICPEMC Working Paper No. 15/3. Human acetaldehyde levels: aspects of current interest.

The determination of acetaldehyde levels in blood and other tissues is a difficult task, and depends on the method used. Different methods and their pros and cons are discussed in detail. Quantitative results are shown for endogenous acetaldehyde levels and for acetaldehyde levels during alcohol intoxication. One article pertains to acetaldehyde bound to blood and tissue proteins.

Acetaldehyde↗
PubMed1987

Plasma testosterone in rats exposed to ethanol during vitamin E deficiency.

The effects of short and long-term ethanol administration on plasma testosterone level were studied in rats with vitamin E deficiency. The animals underwent a vitamin E depletion period of 5 weeks followed by an acute dose of ethanol (1 g/kg body wt i.p.). Two hours after the ethanol dose, the plasma testosterone level had decreased both in a control group (-32%, nonsignificant) and in the vitamin E deficient group (-45%, P less than 0.05) as compared with saline-treated rats. The rats which had received an ethanol dose were then exposed to ethanol in the drinking water (10% w/v) for two weeks, after which the acute ethanol dose was repeated. One hour after this second acute dose of ethanol, the plasma testosterone showed a decrease of 24% (nonsignificant) in the control group and 50% (P less than 0.05) in the vitamin E deficient group compared with saline-treated rats. Two hours after the second acute dose of ethanol, the plasma testosterone level was significantly (P less than 0.05) down both in the control group and in the vitamin E deficient group (-41 and -54%, respectively). Thus, vitamin E deficiency strengthened the effect of acute ethanol treatment on plasma testosterone in rats. Long-term exposure to ethanol appeared to sensitize rats to acute doses of ethanol, as judged by the fall in plasma testosterone levels. The present results are in agreement with previous findings in vitro thus supporting the notion that free radicals arising during ethanol oxidation have an inhibitory effect on testosterone synthesis.

Animals↗
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

5-Hydroxyindoleacetic acid and 5-hydroxytryptophol levels in rat brain: effects of ethanol, pyrazole, cyanamide and disulfiram treatment.

The two serotonin metabolites 5-hydroxyindoleacetic acid (5HIAA) and 5-hydroxytryptophol (5HTOL) were measured in two regions of rat brain (pons medulla and diencephalon) using a gas chromatographic-mass spectrometric (GC-MS) method. Acute ethanol intoxication effected an elevation of 5-hydroxytryptophol levels, while 1 week of treatment with ethanol appeared to have no effect on either metabolite when measured 24 h after the last dose. Disulfiram and cyanamide treatment produced an approximately 2-fold increase in 5-hydroxytryptophol and a slight reduction in 5-hydroxyindole-acetic acid. Pyrazole treatment produced an increase in both metabolites. This effect was, however, counteracted by the simultaneous administration of ethanol.

Animals↗
PubMed1985

Endogenous acetaldehyde in rats. Effects of exogenous ethanol, pyrazole, cyanamide and disulfiram.

Male Long-Evans rats consumed the alcohol and aldehyde dehydrogenase inhibitors pyrazole, cyanamide or disulfiram, for 6 days. No endogenous blood acetaldehyde could be detected in controls and pyrazole treated rats, endogenous blood concentrations up to 2-5 nmoles/ml were, however, measured in the cyanamide and disulfiram-treated animals. Other rats received daily ethanol gastric intubations in addition to the consumption of the inhibitors. Little or no acetaldehyde was detected in the controls and pyrazole treated animals during acute ethanol intoxication or on the subsequent days. High blood levels (200-500 nmoles/ml) were observed in the rats consuming cyanamide and disulfiram, and concentrations up to 10-12 nmoles/ml were still found on the following day after all the ethanol had been eliminated. This acetaldehyde and the endogenous acetaldehyde could only be observed with the hemolyzation method in which blood hemolyzates were directly heated prior to headspace GC analysis; none was detected if blood proteins were first precipitated and removed with perchloric acid. It is suggested that aldehyde dehydrogenase inhibitors elevate endogenous concentrations of bound acetaldehyde and that exogenous ethanol increases this form of acetaldehyde.

Acetaldehyde↗
PubMed1984

Blood and liver acetaldehyde concentrations during ethanol oxidation in C57 and DBA mice.

Hepatic and blood acetaldehyde concentrations during ethanol oxidation were determined in C57 and DBA mice. Liver acetaldehyde was determined with the perchloric acid-thiourea method (no artefactual acetaldehyde formation). Levels ranging from 5 to 118 nmole/g were observed. At ethanol concentrations below 50-60 mumole/g, liver acetaldehyde concentrations were higher in DBA compared with C57 mice. A positive correlation was found between the ethanol and acetaldehyde concentration, when ethanol concentration was below 25 (DBA) or 70 mumole/g (C57). At higher ethanol concentrations the correlations tended to become negative. Artefactual acetaldehyde formation during the analytical procedures was obtained with the use of hemolysis, with or without thiourea, and semicarbazide methods for blood acetaldehyde determination. The magnitude of the artefactually formed acetaldehyde was of such order that no conclusions regarding the existence of true in vivo blood acetaldehyde concentrations could be drawn. Earlier reported mice blood acetaldehyde concentrations are suggested to be re-evaluated.

Acetaldehyde↗
PubMed1984

Inhibition of testosterone biosynthesis by ethanol: relation to the pregnenolone-to-testosterone pathway.

The concentrations of metabolites in the pregnenolone in equilibrium testosterone pathway were determined in freeze-stopped testes in control rats and during ethanol intoxication (2 h after injection of 1.5 g ethanol/kg body wt). Ethanol lowered the mean testicular concentrations of testosterone (by 63-74%), androstenedione (49-81%), 17-hydroxyprogesterone (60-76%), progesterone (29-67%) and pregnenolone (12-25%). 4-Methylpyrazole had no effect on the ethanol-induced changes. The present results reveal no inhibition at the 17-hydroxyprogesterone----androstenedione----testosterone steps, but do not exclude inhibition before the step yielding pregnenolone and at the pregnenolone----progesterone----17-hydroxyprogesterone steps.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Roles of chlorpropamide, alcohol and acetaldehyde in determining the chlorpropamide-alcohol flush.

The value and reproducibility of the chlorpropamide-alcohol flush (CPAF) have been questioned, and objective measures of the test are required. Recording of facial skin temperature, measurement of chlorpropamide, ethanol and acetaldehyde concentrations have been proposed for this purpose. The present study was designed to evaluate the relative contributions of these variables in determining CPAF. Twenty-one Type 2 (non-insulin-dependent) diabetic patients (11 CPAF-positive and 10 CPAF-negative according to previous tests with standard amounts of alcohol and chlorpropamide) were investigated in a random fashion with either chlorpropamide or placebo given on three subsequent evenings before a two-step alcohol challenge with increasing body-weight-matched amounts of alcohol. Higher rises in facial skin temperature and heart rate, higher flush-score and higher acetaldehyde levels resulted from chlorpropamide therapy than followed placebo. After smaller alcohol challenges (with chlorpropamide pretreatment) there were positive intercorrelations between flush-score, rise in facial skin temperature, and plasma concentrations of chlorpropamide and blood acetaldehyde. The increased alcohol dose abolished most of these correlations and a minimum temperature rise of 1.8 degrees C appeared in all but two subjects regardless of previous CPAF classification. During the current experimental conditions, the previously-classified CPAF-positive and CPAF-negative patients did not differ with respect to flush-score, rise in skin temperature, heart rate, blood acetaldehyde or ethanol concentrations, whereas they differed with respect to chlorpropamide concentrations. The present results support the view that CPAF is associated with elevated blood acetaldehyde levels due to inhibition of aldehyde dehydrogenase by chlorpropamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1984

Chlorpropamide-alcohol flush: significance of body weight, sex and serum chlorpropamide level.

Chlorpropamide-alcohol flush (CPAF) tests were carried out in 15 male and 15 female Type 2 diabetics. Twelve subjects were CPAF-positive and 18 were -negative. The two groups did not differ in age or duration of diabetes, but the CPAF-positive subjects weighed less (mean difference 13 kg) and had higher plasma chlorpropamide levels. There was a negative correlation between plasma chlorpropamide and body weight, and a positive correlation between plasma chlorpropamide and the increase in facial skin temperature. Females had higher plasma chlorpropamide, a greater skin temperature increase and lower body weight than males; there were 11 females and only 1 male amongst the 12 CPAF-positive subjects. The findings confirm that plasma chlorpropamide is a major determinant of the CPAF reaction and also show that body weight strongly influences the chlorpropamide level and, consequently, the outcome of the CPAF test. The sex difference in body weight probably accounts for most, if not all, of the sex difference in the incidence of the CPAF.

Body Weight↗
PubMed1983

Inhibition of testosterone biosynthesis by ethanol. Relation to hepatic and testicular acetaldehyde, ketone bodies and cytosolic redox state in rats.

In experiments in which liver and testis freeze-stops were performed on pentobarbital-anaesthetized rats, ethanol (1.5 g/kg body wt.) reduced plasma testosterone concentration from 13.1 to 3.2 nmol/litre. 4-Methylpyrazole abolished the ethanol-induced hepatic and testicular increase in the lactate/pyruvate ratio, and the testicular acetaldehyde level, but did not diminish the reduction in plasma testosterone concentration. In testes, but not in liver, ethanol decreased the 3-hydroxybutyrate/acetoacetate ratio, and 4-methylpyrazole did not prevent this effect. In experiments in which freeze-stop was performed after cervical dislocation, ethanol decreased the testis testosterone concentration from 590 to 220 pmol per g wet wt. The effects of ethanol and 4-methylpyrazole on testis acetaldehyde, lactate/pyruvate and 3-hydroxybutyrate/acetoacetate ratios were the same as found during anaesthesia. The NAD+-dependent ethanol oxidation capacity in testis ranged from 0.1 to 0.2 mumol/min per g wet wt. and seemed to be inhibited by 4-methylpyrazole both in vivo and in vitro. In additional experiments, ethanol doses between 0.3 and 0.9 g/kg body wt. did not alter the plasma testosterone concentration in rats treated, or not treated, with cyanamide, which induced elevated acetaldehyde levels in blood and testes. The results suggest that ethanol-induced inhibition of testosterone biosynthesis was not caused by extratesticular redox increases, or by extra- or intra-testicular acetaldehyde per se. The inhibition is accompanied by changes in testicular ketone-body metabolism.

Acetaldehyde↗
PubMed1983

Human blood acetaldehyde concentration during ethanol oxidation (update 1982).

A wide variety of levels of human blood acetaldehyde have been reported in the past. During the last few years, however, it has become increasingly evident that most, if not all, of the previously observed acetaldehyde concentrations during normal (i.e., no deficiency in, or inhibition of, aldehyde dehydrogenase activity) ethanol oxidation merely reflected artefactual acetaldehyde formed during the analytical procedures. The artefactual acetaldehyde formation, which occurs mainly during blood protein precipitation, is effectively minimized by the recently improved PCA method in which blood is immediately mixed with a perchloric acid-saline solution, and by the semicarbazide method in which blood is treated with a fresh isotonic semicarbazide solution before removal of the plasma. Nevertheless, a procedure involving control blood with ethanol added should be employed to control for any artefactual acetaldehyde still produced. Based on the improved analytical procedures, no detectable acetaldehyde was found in the venous blood of Caucasian subjects after acute ethanol intake.

Acetaldehyde↗
PubMed1983

Tetrahydro-beta-carbolines: effect on alcohol intake in rats.

Some beta-carbolines, such as tetrahydro-beta-carboline (THBC) and 6-methoxy-THBC, occur normally in mammalian tissues, and 1-methyl-THBC has been found in human blood after alcohol intake. Continuous intraventricular (ICV) infusion of THBC and 1-methyl-THBC for 14 days was shown to increase voluntary alcohol intake in rats during the second week of infusion. In this study the experimental arrangement was slightly modified. Alcohol was offered for 7 days before the start of the 14 days of ICV infusion with Alzet minipumps and alcohol concentration (3-30% v/v) was increased every second day. The rats consumed less alcohol in the second day with the same concentration. Also, the dose of 47 nmoles/hr of 1-Me-THBC increased the voluntary alcohol intake over the controls, but only during the last 7 days. The same dose of 6-MeO-THBC, a serotonergic beta-carboline, was ineffective. Neither drug changed the total fluid intake. This study suggests that the increased voluntary alcohol intake by THBC's is not due to their serotonergic effect. A hypothesis concerning a possible involvement of opiate receptors is presented.

Alcohol Drinking↗
PubMed1983

Alcohol and the heart. Intense hemodynamic changes associated with alcohol flush in orientals.

To evaluate the hemodynamic changes related to alcohol flush, the effects of ethanol intake (0.5 g/kg) were studied by echocardiography and systolic time intervals in 10 Finnish and 9 Japanese healthy volunteers. In 5 Japanese subjects, post-drink facial flush was associated with elevated blood acetaldehyde (peak levels 20-83 mumol/l) and marked cardiocirculatory stimulation. Heart rate was increased directly post ingestion by 65% (p less than 0.01), stroke index by 23% (p less than 0.05), and cardiac index by 106% (p less than 0.05). Diastolic blood pressure was simultaneously decreased by 23% (p less than 0.05), peripheral vascular resistance by 54% (p less than 0.01), and circumferential wall stress by 22% (p less than 0.05); ejection fraction was raised by 26% (p less than 0.01). The other Japanese and the Finnish subjects had no detectable acetaldehyde in blood after ethanol ingestion. The average hemodynamic alterations in them were similar in direction to the changes presented above, but quantitatively 6-10 times smaller (p less than 0.005 for each of these variables). Thus, in Orientals with genetically defective acetaldehyde oxidation, ingestion of even small amounts of alcohol evokes intense enhancement of left ventricular function, probably because of acetaldehyde-induced catecholamine release and peripheral vasodilation.

Acetaldehyde↗
PubMed1982

Alcohol drinking in the rat: increases following intracerebroventricular treatment with tetrahydro-beta-carbolines.

Voluntary alcohol intake has been reported to increase in rats after the repeated intracerebroventricular (ICV) administration of 1,2,3,4-tetrahydro-beta-carboline (THBC) and some tetrahydroisoquinolines, although negative results have also been reported. THBC is a normal constituent in human plasma and platelets; 1-methyl-1,2,3,4-tetrahydro-beta-carboline (1-Me-THBC), however, occurs in the blood after a person drinks alcohol. We have evaluated the effects of two doses of THBC and 1-Me-THBC on voluntary alcohol consumption in rats. ICV infusions were given with Alzet minipumps for 14 days rather than giving repeated ICV injections. Stability of the drugs in the pump was verified using mass spectrometry. On each day the rats chose between water, alcohol (increasing concentrations from 3 to 30%) and an empty bottle. Alcohol intake increased by about 100% (p less than 0.05) during the last six days when 47 nmoles/hr of either THBC or 1-Me-THBC was infused. At the end of the experiment elevated blood concentrations of alcohol (0.02-0.78(0)/00) were found in rats belonging to the THBC or 1-Me-THBC groups and drinking 30% alcohol. The infusion of 0.47 nmoles/hr of either drug did not increase alcohol intake as compared to control.

Alcohol Drinking↗