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1.
Proc Soc Exp Biol Med ; 208(1): 98-102, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7892304

ABSTRACT

The idea that alcoholic beverages might contain biologically active phytoestrogenic congeners stemmed from findings of overt feminization observed in alcoholic men with alcohol-induced cirrhosis. Specifically, in addition to being hypogonadal, these chronically alcohol-abusing men with cirrhosis frequently manifest gynecomastia, palmar erythema, spider angiomata, and a female escutcheon. These physical signs of exposure to active estrogen occur in the presence of normal or only minimally elevated levels of endogenous steroid estrogens. Because levels of circulating steroid hormones failed to provide a satisfactory explanation for the feminization observed, alternate explanations were considered. If the estrogenization observed was not entirely a function of tissue expose to steroid estrogens produced endogenously, then perhaps tissues were being exposed to exogenous estrogenic substances from dietary sources. Given the degree of alcohol abuse in the population in which hypotheses for feminization were being formed, alcoholic beverages became a prime candidate as a dietary source of exogenous estrogenic substances.


Subject(s)
Alcoholic Beverages , Estrogens, Non-Steroidal/pharmacology , Isoflavones , Alcoholic Beverages/analysis , Animals , Estrogens, Non-Steroidal/chemistry , Humans , Phytoestrogens , Plant Preparations
2.
Am J Physiol ; 266(5 Pt 1): G799-806, 1994 May.
Article in English | MEDLINE | ID: mdl-8203526

ABSTRACT

Oxygen free radical (OFR) formation and lipid peroxidation (LP) were measured in freshly isolated perfused rat hepatocytes during 2-h reoxygenation after 2.5 h of anoxia. Superoxide anions and hydrogen peroxide (H2O2) were detected by enhanced chemiluminescence. LP and cell damage were assessed by measuring malondialdehyde (MDA) and lactic dehydrogenase (LDH) release, respectively. During anoxia, the chemiluminescence decreased to background levels and MDA remained constant, whereas LDH release increased progressively to 168 +/- 22 mU/min in 2.5 h. During reoxygenation after a 2.5-h period of anoxia, superoxide formation increased rapidly to 125 +/- 16 nA and then it declined progressively toward the control level. At the same time, H2O2 production exhibited a biphasic pattern with an initial peak reaching 78 +/- 16 nA at 15.5 +/- 1 min, followed by a slower increase to 92 +/- 14 nA during the 2nd h. LDH release increased from 168 +/- 22 to 286 +/- 32 mU/min in the first 30 min of reoxygenation and then declined toward the control rate during the 2nd h. MDA release increased continuously from 1.16 +/- 0.18 to 7.75 +/- 0.74 pmol/min. OFR generation occurred 15-30 min before the peak rise in LDH. Moreover, after shorter periods of anoxia (1-2 h), hepatocytes produced measurable amount of OFR but without a significant increase in LDH release. These results demonstrate that 1) isolated liver parenchymal cells generate measurable amounts of superoxide anions and of H2O2 during reoxygenation after 1-2.5 h of anoxia, 2) lipid peroxidation follows the formation of OFR, and 3) reoxygenation injury is correlated to OFR generation but not to lipid peroxidation.


Subject(s)
Hydrogen Peroxide/toxicity , Lipid Peroxidation , Liver/cytology , Liver/metabolism , Superoxides/toxicity , Acridines , Allopurinol/pharmacology , Animals , Antimycin A/pharmacology , Cell Hypoxia , Cells, Cultured , Deferoxamine/pharmacology , Free Radicals/metabolism , Horseradish Peroxidase , Kinetics , L-Lactate Dehydrogenase/analysis , Lipid Peroxidation/drug effects , Liver/drug effects , Luminescent Measurements , Luminol , Male , Malondialdehyde/analysis , Rats , Rats, Sprague-Dawley , Regression Analysis , Time Factors , Vitamin E/pharmacology
3.
Alcohol Clin Exp Res ; 17(6): 1207-9, 1993 Dec.
Article in English | MEDLINE | ID: mdl-8116832

ABSTRACT

Phytoestrogenic substances have previously been isolated and identified in two alcoholic beverages: bourbon and beer. To delineate the relative potencies of the estrogenic substances of plant origin thus far identified in these commonly consumed alcoholic beverages, we evaluated the ability of biochanin A, beta-sitosterol, genistein, and daidzein to bind to cytosolic estrogen receptor binding sites. The in vitro studies demonstrated that each of the contained substances was capable of effectively competing for cytosolic estrogen receptor binding sites of rat liver and uterus. Further, the two phytoestrogenic constituents of bourbon, beta-sitosterol and biochanin A, were less potent than those present in beer. Given the high concentration of beta-sitosterol in bourbon, we chose to evaluate the estrogenicity of beta-sitosterol in vivo using ovariectomized rats. beta-sitosterol was administered either daily or intermittently at 3 doses, based on amounts previously determined to be present in bourbon. The in vivo studies demonstrated that beta-sitosterol is capable of producing a weak estrogenic effect only at the lowest dose (6.2 micrograms/dl) administered intermittently. These responses suggest that beta-sitosterol may be weakly estrogenic at low doses, but is unable to maintain such an effect at higher doses.


Subject(s)
Alcoholic Beverages/analysis , Beer/analysis , Estrogens, Non-Steroidal , Estrogens/pharmacokinetics , Genistein , Receptors, Estrogen/metabolism , Animals , Cytosol/metabolism , Dose-Response Relationship, Drug , Estrogens/isolation & purification , Female , Isoflavones/isolation & purification , Isoflavones/pharmacokinetics , Liver/metabolism , Male , Phytoestrogens , Plant Preparations , Rats , Rats, Wistar , Sitosterols/isolation & purification , Sitosterols/pharmacokinetics , Uterus/metabolism
4.
Alcohol Clin Exp Res ; 17(2): 355-8, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8488979

ABSTRACT

Substantial interest exists as to whether or not differential effects in liver injury based on the pattern of alcohol intake exist; and further, if they do, are they simply a function of the total dose over time. A rat model in which ethanol (ETOH) at doses of 12%, 24%, or 36% of total calories was isocalorically administered for 4 months either daily or intermittently (4 days of ETOH, 3 days of control diet, repeatedly) was used to assess this question. There were significant differences in the two feeding pattern groups between 36% ETOH rats for the liver weight corrected for body weight, the fat infiltration score, the total amount of ETOH consumed/mg body weight, the proportion of animals with a fat infiltration score > 2, and albumin levels. There was a significant difference between 12% ETOH rats for the liver weight corrected for body weight. Of particular relevance is the comparison to be made between Daily 12% ETOH and Binge 24% ETOH animals, because these two groups consumed an identical total amount of ETOH/mg body weight (Daily: 445 +/- 5 vs. Binge: 468 +/- 15) and thus these animals are comparable in terms of ETOH dose over time but different in terms of the pattern of ETOH exposure. There were no differences in the liver/body ratio (Daily: 235 +/- 6 vs. Binge: 232 +/- 4), fat infiltration score (Daily: 2.5 +/- 4 vs. Binge: 2.4 +/- 0.3), the proportion of animals with a fat infiltration score > 2 (Daily: 5/10 vs. Binge: 4/8), or albumin levels (Daily: 3.0 +/- 0.1 vs. Binge: 3.1 +/- 0.1.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Alcohol Drinking/adverse effects , Estrogens/physiology , Liver Diseases, Alcoholic/pathology , Age Factors , Alcohol Drinking/pathology , Animals , Dose-Response Relationship, Drug , Female , Liver/pathology , Ovariectomy , Rats , Rats, Wistar
5.
Alcohol Clin Exp Res ; 16(5): 843-5, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1443418

ABSTRACT

Two estrogenic substances of plant origin have been identified in beer using gas chromatography/mass spectrometry. These phytoestrogens, daidzein and genistein, have previously been shown to be biologically active in animals. Confirming the presence of biologically active phytoestrogens in beer and their possible presence in other beverages, suggests that there may be clinically significant effects related to sustained exposure to phytoestrogens contained in alcoholic beverages.


Subject(s)
Beer/analysis , Estrogens/isolation & purification , Estrogens, Non-Steroidal/isolation & purification , Gas Chromatography-Mass Spectrometry , Humans , Isoflavones/isolation & purification , Phytoestrogens , Plant Preparations
6.
Alcohol Clin Exp Res ; 15(2): 205-6, 1991 Mar.
Article in English | MEDLINE | ID: mdl-2058796

ABSTRACT

Four phytoestrogens have previously been isolated and identified in alcoholic beverages. Before studies to evaluate the degree of estrogenicity of these substances can be performed, it is necessary to determine appropriate doses to be administered to experimental animals. Because beta-sitosterol is the most plentiful, being present in bourbon at microgram/dl quantities, we have chosen to begin our quantitation work with this compound. The variability of the amount of beta-sitosterol contained in various brands of bourbon and in different lots of the same brand of bourbon have been assessed using combined gas chromatography/mass spectrometry (GC/MS) for quantitation following a simplified procedure to extract compounds of interest from bourbon.


Subject(s)
Alcoholic Beverages/analysis , Sitosterols/analysis , Gas Chromatography-Mass Spectrometry , Humans
7.
Free Radic Biol Med ; 7(5): 569-77, 1989.
Article in English | MEDLINE | ID: mdl-2693225

ABSTRACT

That alcohol abuse may lead to testicular lipid peroxidation is suggested by the fact that ethanol is a known testicular toxin and its chronic use leads to both endocrine and reproductive failure. Because testicular membranes are rich in polyenoic fatty acids that are prone to undergo peroxidative decomposition, it is reasonable to consider that lipid peroxidation may contribute to the membrane injury and gonadal dysfunction that occurs as a result of alcohol abuse and/or chronic use. The present report reviews the studies supporting the concept that testicular lipid peroxidation is a metabolic consequence of chronic alcohol administration to animals and that its presence correlates with the gonadal injury present in animals ingesting ethanol for prolonged periods. Consistent with such a mechanism for putative alcohol-associated testicular toxicity are the observed reductions in the testicular content of polyenoic fatty acids and glutathione (GSH) content of the testes of alcohol-fed animals as compared to isocalorically fed controls. The later finding demonstrates that ethanol modifies the precarious antioxidant balance of testicular tissue such that enhanced peroxidation can occur. It is well known that peroxidation injury can be attenuated when it occurs in association with dietary vitamin A supplementation. Thus, it is of interest to note that vitamin A, acting as an antioxidant, stabilizes testicular membranes by reducing lipid peroxidation and prevents the alcohol-induced atrophy that occurs in animals not receiving vitamin-A-enriched diets. Taken together, these observations suggest that the enhanced peroxidation of testicular lipids that occurs following ethanol exposure may be an important factor in the pathogenesis of alcohol-associated gonadal injury.


Subject(s)
Ethanol/toxicity , Lipid Peroxidation/drug effects , Testis/drug effects , Animals , Free Radicals , Humans , Male , Rats , Testis/injuries , Testis/metabolism , Vitamin A/pharmacology
8.
Alcohol Clin Exp Res ; 11(4): 399-406, 1987 Aug.
Article in English | MEDLINE | ID: mdl-3307512

ABSTRACT

The nonethanol congeners of bourbon have been found to possess estrogenic activity when tested using an in vivo oophorectomized rat bioassay, as well as an in vivo estrogen receptor assay system. The phytoestrogen, biochanin A, as well as the plant sterol, beta-sitosterol, were identified in the bourbon preparation using gas chromatography/mass spectrometry. These findings, using three methodological approaches, demonstrate that bourbon contains at least one biologically active phytoestrogen and suggest that the effects of alcoholic beverage use or abuse, particularly as they relate to endocrine systems, should not be viewed as resulting solely from exposure to ethanol.


Subject(s)
Alcoholic Beverages/analysis , Estrogens, Non-Steroidal/analysis , Flavonoids/analysis , Genistein , Isoflavones/analysis , Sitosterols/analysis , Animals , Body Weight/drug effects , Estrogens, Non-Steroidal/pharmacology , Fallopian Tubes/drug effects , Female , Gas Chromatography-Mass Spectrometry , Isoflavones/pharmacology , Organ Size/drug effects , Rats , Receptors, Estrogen/drug effects , Sitosterols/pharmacology , Uterus/drug effects
9.
Alcohol Alcohol ; 22(3): 241-9, 1987.
Article in English | MEDLINE | ID: mdl-3619999

ABSTRACT

The interaction of ethanol (ETOH) with testicular subcellular membranes contributes, at least in part, to alcohol-induced gonadal dysfunction. Vitamin A reaches the testes via the circulation as the retinyl ester and is converted to the free alcohol (retinol) and then to the aldehyde (retinal); retinal is the form of the vitamin which is essential for normal spermato-genesis. Because retinol can function as a free radical scavenger, testicular mitochondria were evaluated for evidence of a protective role provided by supplemental dietary vitamin A on ETOH-induced alterations in testicular structure and function in rats. Lipid peroxidation was evaluated by measurement of malonaldehyde formation and glutathione content of the testes. Compared to isocalorically matched dextrimaltose-fed controls (ISO) receiving a modified vitamin A containing diet, rats fed the corresponding ETOH diet for 50 days had a reduced testes/body ratio (ETOH: 0.0114 +/- 0.0004 vs ISO: 0.0128 +/- 0.0004). Mitochondrial enriched extracts obtained from the testes of these ETOH-fed rats showed significant increases in malonaldehyde formation; moreover, glutathione levels were reduced in the testes of the alcohol-fed animals when compared to their isocaloric controls. In contrast, no evidence for testicular atrophy was present in ETOH-fed rats receiving a standard vitamin A enriched diet; moreover, such ETOH-fed rats had a reduced rate of malonaldehyde formation as compared to their respective controls. Similarly, glutathione levels were not depleted in the testes of the ETOH-fed rats receiving the vitamin A enriched diet. Taken together, these data suggest that lipid peroxidation is a consequence of ethanol metabolism which can be attenuated, at least in part, by vitamin A.


Subject(s)
Ethanol/pharmacology , Lipid Peroxides/metabolism , Membrane Lipids/metabolism , Testis/drug effects , Vitamin A/pharmacology , Animals , Atrophy , Diet , Ethanol/metabolism , Glutathione/metabolism , Male , Malondialdehyde/metabolism , Rats , Rats, Inbred Strains , Testis/metabolism , Testis/pathology , Vitamin A/administration & dosage
10.
Alcohol Alcohol Suppl ; 1: 545-9, 1987.
Article in English | MEDLINE | ID: mdl-3426731

ABSTRACT

The feminization seen in alcoholic male cirrhotics, in whom circulating levels of estrone and estradiol are normal or only moderately elevated, is not fully understood. Conceptualization of the puzzle has heretofore focused on the ethanol component of alcoholic beverages. In addition to ethanol, however, alcoholic beverages contain a myriad of substances which are collectively termed congeners. To examine the possibility that the congeners of alcoholic beverages include substances which are capable of producing an estrogenic effect, the congeners of bourbon were prepared and administered to ovariectomized rats. Exposure to bourbon congeners produced a dose response in both the mass of the uterus plus fallopian tubes and in plasma levels of luteinizing hormone. These findings provide evidence that the congeners of at least one alcoholic beverage are capable of eliciting responses which are consistent with a hypothesis that alcoholic beverages contain estrogenically active substances.


Subject(s)
Alcoholic Beverages , Estrogens, Non-Steroidal , Estrogens , Isoflavones , Alcoholic Beverages/adverse effects , Animals , Dose-Response Relationship, Drug , Estradiol/blood , Female , Luteinizing Hormone/blood , Organ Size/drug effects , Ovariectomy , Phytoestrogens , Plant Preparations , Rats , Uterus/drug effects
11.
Alcohol Alcohol Suppl ; 1: 551-5, 1987.
Article in English | MEDLINE | ID: mdl-3426733

ABSTRACT

There is considerable evidence that several plant metabolites have estrogenic properties. Given that many alcoholic beverages are made from plants which have been shown to possess estrogenic activity, we considered the possibility that alcoholic beverages may contain estrogenically active substances. To evaluate this hypothesis we first extracted and then used gas chromatography/mass spectrometry to identify two phytoestrogens, biochanin A and beta-sitosterol in the bourbon extracts. Based on these findings we suggest that the feminization observed in chronic male alcoholics with liver disease may reflect, at least in part, the presence of biologically active phytoestrogens in the alcoholic beverages they consume.


Subject(s)
Alcoholic Beverages/analysis , Estrogens, Non-Steroidal , Estrogens/isolation & purification , Genistein , Chemical Phenomena , Chemistry , Gas Chromatography-Mass Spectrometry , Isoflavones/isolation & purification , Phytoestrogens , Plant Preparations , Sitosterols/isolation & purification
12.
Biomed Mass Spectrom ; 9(7): 278-85, 1982 Jul.
Article in English | MEDLINE | ID: mdl-7126761

ABSTRACT

Radiogas chromatography, used in conjunction with mass spectrometry, has been used to analyze the sterol content of cultured chick muscle cells. Seven sterols, plus lanosterol, were detected. These sterols conformed to a linear biosynthetic pathway linking lanosterol and cholesterol. The reaction sequence is: C-14 demethylation, C-4 demethylation, delta 8 leads to delta 5 double bond rearrangement, delta 24 double bond reduction. When chick cells were treated with increasing concentrations of 20,25-diazacholesterol, components of this pathway and aberrant products accumulated. These accumulations suggest that diazacholesterol affects reductases, double bond isomerases and the C-14 demethylation enzymes of sterol biosynthesis.


Subject(s)
Azacosterol/pharmacology , Cholesterol/analogs & derivatives , Cholesterol/biosynthesis , Muscles/drug effects , Animals , Cells, Cultured , Chick Embryo , Desmosterol/biosynthesis , Gas Chromatography-Mass Spectrometry/methods , Lanosterol/metabolism , Muscles/metabolism , Squalene/metabolism
14.
Biomed Mass Spectrom ; 7(6): 259-64, 1980 Jun.
Article in English | MEDLINE | ID: mdl-7426690

ABSTRACT

The value of selected ion monitoring in analyzing biological radio isotope incorporation experiments by radiogas chromatography mass spectrometry is illustrated with reference to the biosynthesis of the mycotoxin mycophenolic acid and the mode of action of the anticholesterolemic drug 20,25-diazacholesterol. It is shown that the increased sensitivity and specificity of the selected ion monitoring mode detector permits straightforward detection and identification of the relatively small cellular pools associated with metabolic intermediates. The computer program RADSIM is described. Problems that still exist in using radiogas gas chromatography mass spectrometry technology to analyse isotope incorporation experiments are discussed.


Subject(s)
Gas Chromatography-Mass Spectrometry/methods , Acetates/metabolism , Animals , Anticholesteremic Agents/pharmacology , Chick Embryo , Muscles/metabolism , Mycophenolic Acid/biosynthesis , Penicillium/metabolism , Steroids/biosynthesis
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