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C J Eriksson

Publications and source records attributed to C J Eriksson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Consequence of long-term exposure to corticosterone or dexamethasone on ethanol consumption in the adrenalectomized rat, and the effect of type I and type II corticosteroid receptor antagonists.

The daily fluid intake of male Wistar rats with simultaneous access to 6% ethanol and water was determined during a baseline period (1 week), following adrenalectomy (1 week) and for 3 weeks following SC implantation of hormone pellets containing corticosterone (CORT) or dexamethasone (DEX). Ethanol consumption dropped during the first week of adrenalectomy (ADX) but increased again in the absence of hormone replacement to reach preoperative levels during the ensuing weeks. The CORT treatment, which produced plasma hormone levels similar to the 24-h mean concentration of adrenally intact rats, not only reversed the effect of ADX on alcohol consumption but also enhanced it to levels above those observed in intact rats. Water intake was not affected by the CORT treatment. DEX implants stimulated water intake, but did not enhance the drinking of ethanol. SC injections of RU 28318 (type I corticosterone receptor antagonist; 10 mg/kg) or mifepristone (RU 38486; type II receptor antagonist; 25 mg/kg) at the beginning and halfway through three daily, 6-h tests failed to affect ethanol drinking in adrenally intact rats or in ADX rats bearing CORT implants. Similarly, there was no effect of giving the two antagonists in combination. These results suggest that exogenous CORT can induce excessive alcohol intake in genetically unselected rats and that this facilitatory effect may be mediated by non-genomic cellular mechanisms.

Adrenalectomy↗
PubMed1994

Hepatic aldehyde and alcohol dehydrogenases in alcohol-preferring and alcohol-avoiding rat lines.

The alcohol-avoiding ANA (Alko, Non-Alcohol) and alcohol-preferring AA (Alko, Alcohol) rat lines are known to differ in their acetaldehyde metabolism and were originally found to differ in hepatic alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities in the 1970s. At the beginning of the 1980s, these rat lines were revitalized and some previously found line differences were lost. Thus, the purpose of this study was to determine whether these enzymatic line differences still exist and, if so, to study them further at the isoenzyme level. ADH and ALDH activities were measured from liver homogenates and different subcellular fractions of the rats. The ANA rats were found to have lower hepatic ALDH and higher ADH activities than AA rats, in accordance with the previous study. The line difference in ALDH activity was observed in all fractions, but was more apparent with millimolar than micromolar substrate concentrations and generally more pronounced in females than in males. The line difference in the microsomal ALDH activity was found to be quantitative, and it seemed to concern both microsomal ALDH isoenzymes. A qualitative line difference concerning mitochondrial high Km ALDH isoenzyme was found, and three different cytosolic ALDH isoenzyme patterns were observed, the frequencies of which were found to be different in the two lines. In conclusion, the results of the present study support the assumption that line differences in hepatic ADH and ALDH activities may be relevant to the acetaldehyde accumulation and the particularly low ethanol consumption of the ANA rats.

Alcohol Dehydrogenase↗
PubMed1993

Mitochondrial aldehyde dehydrogenase (ALDH2) polymorphism in AA and ANA rats: lack of genotype and phenotype line differences.

Polymorphism of the gene coding for mitochondrial ALDH2 in humans is known to be associated with differences in alcohol drinking behavior. Recently, two different alleles of the ALDH2 gene, ALDH2R and ALDH2Q, have been found in rats also and a possible relationship between the frequencies of the two alleles and drinking behavior has been proposed. In this study, we examined whether this polymorphism of ALDH2 was the underlying cause for the previously reported acetaldehyde accumulation in the alcohol-avoiding ANA rat line and, thus, could be one of the factors explaining the differences in alcohol drinking behavior between the ANA and the alcohol-preferring AA rat lines. The experimental animals were genotyped and their mitochondrial ALDH activities and blood acetaldehyde concentrations after ethanol injection were measured. The two lines did not differ in their frequencies of ALDH2R and ALDH2Q alleles. Thus, the polymorphism in the ALDH2 gene does not explain the acetaldehyde accumulation in ANA rats and it does not seem to be associated with differences in the alcohol drinking behavior in these rat lines.

Acetaldehyde↗
PubMed1993

Detection of a CA repeat polymorphism in the rat class I alcohol dehydrogenase gene.

Differences in the amount of alcohol dehydrogenase (ADH) expressed in liver could play a role in altering ethanol metabolic rates and thus influence alcohol consumption. There is an alternating purine-pyrimidine repeat length polymorphism in the first intron of mouse Adh-1. Mouse strains that lack 101 basepairs of this 288 basepairs alternating sequence express only half as much ADH mRNA and have lower ADH-A2 activity, suggesting that this alternating sequence might modify transcription of the gene. The rat class I ADH gene also has a CA repeat in the first intron. A polymerase chain reaction (PCR) method was used to amplify the CA repeat region in different rat lines to determine whether this CA repeat is polymorphic in the rat and if so, if different length repeats correlate with the drinking behavior of rats selectively bred for high [preferring (P); high alcohol drinking (HAD); Alko, Alcohol (AA) lines] and low [non-preferring (NP); low alcohol drinking (LAD); Alko, Non-Alcohol (ANA) rat lines] alcohol drinking. A CA repeat polymorphism was detected in rat class I ADH of these different rat lines, but there was no difference in the length of the repeat between the high and low drinking rats in each line. Liver ADH activity was also not significantly different between two rat lines that have different CA repeat lengths. Thus, there is CA repeat length polymorphism in the first intron of rat class I ADH, which may be useful in genomic mapping, but it is not associated with differences in ADH activity or drinking behavior in these rat lines.

Alcohol Dehydrogenase↗
PubMed1993

Occurrence of blood acetaldehyde in women during ethanol intoxication: preliminary findings.

The question of gender differences regarding blood acetaldehyde levels during ethanol intoxication has not been clarified because of the difficulties in the determination of acetaldehyde levels. Although the blood acetaldehyde levels in men during normal ethanol oxidation are reported to be undetectable, no valid data on female blood acetaldehyde levels have yet been reported. Thus, in the present investigation, 13 young healthy nonalcoholic women, almost all of which took oral contraceptives regularly, were challenged with different doses of ethanol (0.34, 0.68, and 1.02 g/kg) during three different sessions. Venous blood acetaldehyde and ethanol levels were then determined by headspace gas chromatography involving appropriate correction for artefactual acetaldehyde formation during blood treatment and analytical procedures. Corrected blood acetaldehyde levels (mean 2 microM, range 0-6 microM) were observed, predominantly at lower ethanol concentrations. Elevated acetaldehyde levels in women may explain why ethanol is less frequently abused and causes tissue damage more rapidly in women than men.

Acetaldehyde↗
PubMed1993

Human blood acetaldehyde (update 1992).

Previously, it has been concluded that no detectable, adequately determined, acetaldehyde is to be found in the venous blood of normal Caucasian subjects during acute ethanol intake (Eriksson, 1983). Nevertheless, since then a number of reports on human blood acetaldehyde concentrations have been published. Most, if not all, of these levels can, however, be explained as being the result of artefactual sources. Thus, the early conclusion still holds, according to which the concentration of "free" and/or "loosely bound" acetaldehyde is below detection (< 0.5 microM), during normal conditions, i.e., with no deficiency in, or inhibition of, aldehyde dehydrogenase activity. Even if "free" and/or "loosely bound" acetaldehyde cannot be detected, the question of "more firmly bound" acetaldehyde has still remained open, and a number of papers have been published during the last few years on this aspect. Unfortunately, these investigations also have been seriously hampered by artefactual acetaldehyde formations during different hemolysation, hydrolysation, heating and/or other analytical procedures. The appropriate determination of bound acetaldehyde should in the future be better controlled for artefactual formations, even at very low ethanol concentrations (< 0.1 mM). Even if most of the artefactual formation is ethanol-derived, other sources for formation should also be considered. With a view to the present criteria, there is yet no valid demonstration of released acetaldehyde in human venous blood before, during, or after, normal ethanol intoxication.

Acetaldehyde↗
PubMed1993

Problems involved in the determination of endogenous acetaldehyde in human blood.

Little is known about the possible existence of endogenous acetaldehyde in human blood. This has partly been due to analytical difficulties preventing accurate determination of blood acetaldehyde levels with and without the presence of ethanol. In the present study the possible existence of endogenous acetaldehyde in human blood was investigated with headspace gas chromatography using three different procedures for the treatment of samples: (1) no treatment of whole blood, cells, or plasma (direct headspace method), (2) hemolysation, and (3) perchloric acid (PCA) precipitation, prior to the headspace determinations. In in vitro experiments, with the direct headspace and the hemolysation methods, higher acetaldehyde peaks were obtained depending on the headspace incubation time, temperature and ethanol concentration. Both methods displayed about the same values of acetaldehyde in blood cells, ranging between 0 and 40 microM, at incubation times between 15 and 180 min, an incubation temperature of 65 degrees C, and ethanol concentrations less than 5 microM. Less acetaldehyde formation (0-15 microM) was obtained with PCA precipitates of whole blood and cell components. Very low acetaldehyde levels (0-1 microM) were obtained in the supernatants without precipitates from either whole blood or cells after headspace equilibration. Substantially less acetaldehyde was formed in plasma preparations than with whole blood and cell fractions. In human experiments, the disturbance of endogenous or exogenous ethanol was minimized by separating and washing the blood cells followed by PCA treatment. No differences in acetaldehyde concentrations were observed in blood samples taken before, during, or after ethanol intoxication (1.5 g/kg dose) of four healthy non-alcoholic volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1993

[Alcohol consumption and brain adenylate cyclase system in rats: brain adenylate cyclase activity in alcohol-preferring AA and alcohol-avoiding ANA rats].

Brain adenylate cyclase (AC) activity in the alcohol-preferring AA (Alko Alcohol) and alcohol-avoiding ANA (Alko, Non-Alcohol) rats was examined. Both basal and Gpp(NH) p-stimulated AC activities were higher in the cerebral cortex of the ANA rats than in the AA rats. Isoproterenol-stimulated AC activity tended to increase in the cerebral cortex of the ANA rats compared to the AA rats. Basal AC activity in the striatum of the AA rats was higher than that in the ANA rats, however, striatal Gpp(NH)p-stimulated AC activity was not different between the two rats lines. In the mesolimbic and cerebellum, there was no difference in AC activity between the rat lines. These results suggest that the noradrenergic function in the cerebral cortex has an important role in the regulation of alcohol intake.

Adenylyl Cyclases↗
PubMed1990

Ethanol-induced inhibition of testosterone biosynthesis in rat Leydig cells: central role of mitochondrial NADH redox state.

The mechanisms by which ethanol (EtOH) inhibits the human chorionic gonadotropin (hCG)-stimulated testosterone synthesis was studied in isolated rat Leydig cells in vitro. EtOH inhibited steroidogenesis, but this inhibition was reversed by L-glutamate (Glu) and an uncoupler of the oxidative phosphorylation, 2,4-dinitrophenol (DNP). The mechanism of EtOH-induced inhibition was studied by measuring steroidogenic precursors and comparing them with the cytosolic and mitochondrial NADH redox states during uncoupling or in the presence of Glu. DNP had a dual effect. Low concentrations abolished the EtOH-induced inhibition of progesterone to testosterone formation suggesting that the inhibitory step was at or before progesterone formation. A large concentration led to an overall decrease in steroidogenesis indicating toxic effects on steroidogenesis. The mitochondrial NADH/NAD+ ratio, measured as the 3-hydroxybutyrate/acetoacetate ratio, decreased simultaneously when steroidogenesis was stimulated, either during uncoupling or in the presence of Glu, whereas cytosolic NADH/NAD+ ratio, measured as lactate/pyruvate ratio showed no response. These results demonstrate that the rise in the mitochondrial NADH/NAD+ ratio rather than in the cytosolic one is connected with the inhibition of testosterone synthesis by EtOH in isolated Leydig cells. The EtOH-induced high mitochondrial NADH/NAD+ ratio may deplete mitochondrial oxalacetate concentrations. This can decrease the activity of several transport shuttles and interrupt the flow of mitochondrial citrate into the smooth endoplasmic reticulum, which then reflects to decreased rate of steroidogenesis in the presence of ethanol.

Animals↗
PubMed1990

Ethanol-induced inhibition of testosterone biosynthesis in rat Leydig cells: role of L-glutamate and pyruvate.

The mechanisms by which ethanol (EtOH) inhibits testicular testosterone biosynthesis were studied with isolated rat Leydig cells in vitro comparing the effects of EtOH in six different culture media. The actual sites of inhibition by EtOH, identified by measuring the steroidogenic precursors, varied depending on the medium used. In Krebs-Ringer bicarbonate buffer, EtOH inhibited both the conversion of pregnenolone to progesterone and androstenedione to testosterone. In the pyruvate (Pyr) supplemented Dulbecco's Modified Eagle medium, the decreased progesterone concentrations in the presence of EtOH were reflected to all successive steroids 17-OH-progesterone, androstenedione and testosterone. The presence of L-glutamate (Glu) in the medium elevated testosterone production, but EtOH still inhibited the conversion of pregnenolone to progesterone, and also the androstenedione/testosterone ratio was elevated because of the decreased testosterone concentrations. In the presence of both Glu and Pyr in the medium the EtOH-induced decreases in the steroid concentrations were fully recovered in isolated Leydig cells. These results demonstrate that both Pyr and Glu supplementations are essential for the maintenance of maximal rate of testosterone synthesis in vitro in the presence of EtOH.

Androstenedione↗
PubMed1990

Role of ethanol metabolism in the inhibition of testosterone biosynthesis in rats in vivo: importance of gonadotropin stimulation.

The mechanisms by which ethanol (EtOH, 1.5 g/kg) inhibits testicular testosterone synthesis were studied in nonstimulated and human chorionic gonadotropin (hCG, 50 IU/kg)-treated male rats. To dissociate the effects caused by ethanol metabolism, the alcohol dehydrogenase inhibitor 4-methylpyrazole (4MP, 10 mg/kg) was given to half of the rats 30 min before EtOH. The 4MP had little or no effect in the nonstimulated rats on the EtOH-induced decreases in the concentrations of serum testosterone and of the intratesticular steroids of the testosterone biosynthetic pathway measured, but reduced the EtOH-induced elevation in the intratesticular pregnenolone-to-progesterone ratio. In contrast, 4MP pretreatment markedly reversed the EtOH-induced decrease in serum and intratesticular testosterone and increase in intratesticular pregnenolone concentrations in the hCG-stimulated rats. Simultaneously, the EtOH-induced elevations in the intratesticular pregnenolone/progesterone and androstenedione/testosterone ratios were abolished. In the EtOH-treated rats whose EtOH metabolism was blocked by 4MP pretreatment, the intratesticular testosterone concentrations were negatively correlated with the elevated serum corticosterone levels. It is concluded that: (1) EtOH metabolism is involved in the inhibition of testicular steroidogenesis in vivo. This effect is pronounced during gonadotropin-stimulated conditions. Thus, previously reported "discrepancies" between the in vivo and in vitro results are clarified; (2) corticosterone seems also to be involved in the EtOH-induced inhibition of steroidogenesis. This effect is also pronounced during gonadotropin-stimulated conditions; and (3) without external gonadotropin stimulation other inhibitory mechanisms, such as decreased stimulation by luteinizing hormone, are prevalent.

Alcohol Dehydrogenase↗
PubMed1990

Hemoglobin-acetaldehyde adducts in human volunteers following acute ethanol ingestion.

Rabbit antibodies against albumin-acetaldehyde adduct were used in an enzyme-linked immunosorbent assay to detect acetaldehyde-hemoglobin condensates from the blood of 12 volunteers following ingestion of 1.3 to 2.9 g of ethanol per kg body weight during 8 hr. Blood samples were drawn before drinking and between 2 to 46 hr after starting the drinking session. While there were no significant increases in blood acetaldehyde levels in these samples, acetaldehyde-hemoglobin adducts were significantly increased in the samples drawn after ethanol had been eliminated from the body. Administration of ethanol (0.1 g/kg) to an Oriental flusher resulted in an increase both in blood acetaldehyde and the hemoglobin-acetaldehyde adduct levels. These results suggest that acetaldehyde-hemoglobin condensates are formed in vivo following acute ethanol ingestion. Such condensates may be of value to mark alcohol consumption.

Acetaldehyde↗
PubMed1990

Ethanol-induced inhibition of testosterone biosynthesis in rat Leydig cells: role of mitochondrial substrate shuttles and citrate.

The mechanisms by which ethanol inhibits testicular testosterone synthesis in rats were studied in vitro using isolated rat Leydig cells. The ethanol-induced inhibition was reversed by 4-methylpyrazole, an alcohol dehydrogenase inhibitor, suggesting that ethanol metabolism was responsible for this inhibition. L-glutamate and pyruvate, when added to the Krebs-Ringer incubation medium, reversed the inhibition by ethanol. The membrane glutamate receptor agonists kainic acid and quisqualic acid had no effects, indicating metabolic mechanisms for the L-glutamate action. This was verified also by observations that the metabolic transaminase inhibitors aminooxyacetate and cycloserine inhibited testosterone synthesis. In the amino acid supplemented Krebs-Ringer, pyruvate could not fully prevent inhibition by ethanol alone, but addition of L-glutamate to this medium abolished ethanol-induced inhibition. Experiments performed using a new inhibitor of testosterone biosynthesis in intact Leydig cells, triethylcitrate, indicated that active citrate metabolism, and/or efflux from mitochondria, was essential for the steroidogenic pathway from pregnenolone to testosterone in the smooth endoplasmic reticulum. The early steps of hCG stimulation before pregnenolone formation were most sensitive to its effect. Our results indicate that the inhibition of steroidogenesis by ethanol results from decreased availability of the metabolites involved in the substrate shuttles maintaining the NAD(P)H redox states between the mitochondrial and the smooth endoplasmic reticulum compartments, and that the inhibition can be overcome by a proper selection of exogenous sources for these metabolites.

Alcoholism↗
PubMed1989

Ethanol-induced inhibition of testosterone biosynthesis in rat Leydig cells: role of culture medium composition.

The biochemical mechanisms responsible for the ethanol-induced inhibition of testicular testosterone synthesis were studied in isolated rat Leydig cells in vitro. This inhibition was removed when HAM-F12 nutrient mixture was added to the DME culture medium. The components of HAM-F12, i.e. vitamins, amino acids and other supplements, were tested individually and the amino acids L-glutamate (Glu) and L-aspartate (Asp) were found to potentiate strongly the hCG stimulated testosterone synthesis. None of the other components of HAM-F12 had any effect upon testosterone synthesis or its ethanol-induced inhibition. Moreover, Glu, but not Asp, effectively reversed the acute inhibition of steroidogenesis by ethanol. These results demonstrate the importance of the composition of the culture media and provide the first piece of evidence that the metabolic stress in rat Leydig cells in vitro induced by the metabolism of ethanol can be overcome by proper culture medium supplementation.

Amino Acids↗
PubMed1989

Effects of chronic and acute ethanol treatment during prenatal and early postnatal ages on testosterone levels and sexual behaviors in rats.

This study was prompted by previous findings that prenatal ethanol exposure may interfere with the differentiation of the sexual behavior in rats. Ethanol (6 g/kg) administered daily from day 15 postconception, resulted in elevated testosterone (T) levels on Day 18 in male and female fetuses. No alterations of sexual behavior in the ethanol-treated male offspring were seen under these conditions. However, in ethanol-treated female offspring the onset of regular estrous cycling was significantly delayed. Acute treatment with doses of ethanol, 2, 4 or 6 g/kg, was ineffective in influencing plasma T levels of the fetuses. Acute treatment with 3 g/kg ethanol did not prevent the rise of T levels normally occurring immediately after birth. In adulthood, but not at prepubertal age (Day 30), treatment of male rats with 2 g/kg ethanol caused a depression of plasma T levels. Possible mechanisms affected by ethanol exposure and influencing on the fetal development were discussed.

Age Factors↗
PubMed1989

Methionine lowers circulating levels of acetaldehyde after ethanol ingestion.

Methionine, administered to ethanol treated mice and rats, significantly reduced circulating acetaldehyde levels without altering circulating levels of ethanol. Hepatic levels of acetaldehyde were also lowered by methionine. Methionine was effective when given prior to or after the administration of ethanol, but the time course of the action of methionine suggested the necessity for metabolic transformation of this amino acid in order for the acetaldehyde-lowering effect to be evidenced. Studies with humans, given methionine doses of approximately one-tenth of those used with mice, indicated that methionine can also lower acetaldehyde in humans ingesting ethanol. Given the toxic characteristics of acetaldehyde, methionine may prove effective in reducing the damaging effects of ethanol ingestion.

Acetaldehyde↗
PubMed1989

Methanol as a marker of alcohol abuse.

Serum methanol levels were studied in 16 skid-row alcoholics, 16 alcoholics entering a detoxification unit, 193 drunken drivers, and 50 social drinkers, all of whom had a blood-ethanol concentration exceeding 5 mmol/liter at the time of sampling. Highest mean serum methanol level was found in alcoholics entering detoxification (636 +/- 68 mumol/liter, p less than 0.001 as compared to social drinkers), followed by skid-row alcoholics (567 +/- 105 mumol/liter, p less than 0.001), drunken drivers (231 +/- 11 mumol/liter, p less than 0.001) and social drinkers (127 +/- 10 mumol/liter). During 2 days heavy drinking mean serum methanol concentration in 10 nonalcoholic volunteers increased from 177 +/- 15 mumol/liter 1 h after the beginning of drinking to 322 +/- 29 mumol/liter 42 h after the beginning of drinking (p less than 0.001). In 70 of the drunken drivers urinary methanol concentration was determined as well and a fairly good correlation (r = +0.56, p less than 0.001) between serum and urinary methanol levels were found. Our results suggest that methanol determined either from serum or urine can be used as a biological marker of alcohol abuse.

Adult↗