Effects of ethanol treatment and castration on liver alcohol dehydrogenase activity

Gillion, Rachel B.; Crow, Kathryn E.; Batt, Richard D.; Hardman, Michael J.

doi:10.1016/0741-8329(85)90012-6

Cited by 6 publications

(3 citation statements)

References 10 publications

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“…Of interest is the unusual case of the Selective Serotonin Reuptake Inhibitors (SSRI). In preclinical research, these drugs showed efficacy in almost all experimental animal models used to investigate their effect on alcohol drinking, including genetically selected alcohol preferring rats (Ciccocioppo et al 1997; Maurel et al 1999; Murphy et al 1985; Rezvani et al 2000). In addition, reinstatement studies (ie., resumption of extinguished drug-paired lever responding following extinction or after an imposed period of abstinence) demonstrated that fluoxetine reduces also stress-induced relapse in rodents (Le et al 1998).…”

Section: Genetically Selected Alcohol Preferring Rats: Predictive Valmentioning

confidence: 99%

“…These findings support the translational value of pharmacological findings in alcohol preferring rats. However, as described in previous paragraphs, there are other examples (i.e., the case of 5-HT2 receptor antagonists or the case of SSRIs) in which preclinical data in genetically selected alcohol preferring rat lines was unable to clearly predict actual clinical outcomes (Ciccocioppo et al 1997; Ciccocioppo et al 1995; Johnson et al 1996; Maurel et al 1999; Murphy et al 1985; Overstreet et al 1997; Rezvani et al 2000; Roberts et al 1998). …”

Section: Conclusion and Remarksmentioning

confidence: 99%

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Genetically Selected Alcohol Preferring Rats to Model Human Alcoholism

Ciccocioppo

2012

Behavioral Neurobiology of Alcohol Addiction

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Animal models have been successfully developed to mimic and study alcoholism. These models have the unique feature of allowing the researcher to control for the genetic characteristics of the animal, alcohol exposure and environment. Moreover, these animal models allow pharmacological, neurochemical and behavioural manipulations otherwise impossible. Unquestionably, one of the major contributions to the understanding of the neurobiological basis of alcoholism comes from data that have been obtained from the study of genetically selected alcohol-preferring rat lines and from the consequences that alcohol drinking and environmental manipulations (/i.e., protracted alcohol drinking, intoxication, exposure to stress etc) have on them. In fact, if on the one hand genetic factors may account for about 50–60% of the risk of developing alcohol dependence, on the other hand protracted alcohol exposure is a necessary precondition to actually develop the disease, while environmental vulnerability factors may be crucial for disease progression. The present article will offer an overview of the different genetically selected alcohol preferring rat lines developed and used to study alcoholism. The predictive, face and construct validity of these animal models and the translational significance of findings achieved through their use will be critically discussed.

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Section: Genetically Selected Alcohol Preferring Rats: Predictive Valmentioning

confidence: 99%

Section: Conclusion and Remarksmentioning

confidence: 99%

Genetically Selected Alcohol Preferring Rats to Model Human Alcoholism

Ciccocioppo

2012

Behavioral Neurobiology of Alcohol Addiction

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“…The value of the Flux Control Coefficient is not a constant and it will vary if the activities of some of the enzymes in a pathway change. For example, rats with high liver alcohol dehydrogenase activity would be expected to show low values of Cj, We have previously observed a variation in liver alcohol dehydrogenase activity of almost 2-fold between different groups of rats of the same strain as those used in this study (]Braggins & Crow, 1981;Gillion et al, 1985).…”

Section: Hepatocytes From Starved Ratsmentioning

confidence: 79%

The importance of alcohol dehydrogenase in regulation of ethanol metabolism in rat liver cells

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Kitson

Hardman

1991

Biochemical Journal

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We used titration with the inhibitors tetramethylene sulphoxide and isobutyramide to assess quantitatively the importance of alcohol dehydrogenase in regulation of ethanol oxidation in rat hepatocytes. In hepatocytes isolated from starved rats the apparent Flux Control Coefficient (calculated assuming a single-substrate irreversible reaction with non-competitive inhibition) of alcohol dehydrogenase is 0.3-0.5. Adjustment of this coefficient to allow for alcohol dehydrogenase being a two-substrate reversible enzyme increases the value by 1.3-1.4-fold. The final value of the Flux Control Coefficient of 0.5-0.7 indicates that alcohol dehydrogenase is a major rate-determining enzyme, but that other factors also have a regulatory role. In hepatocytes from fed rats the Flux Control Coefficient for alcohol dehydrogenase decreases with increasing acetaldehyde concentration. This suggests that, as acetaldehyde concentrations rise, control of the pathway shifts from alcohol dehydrogenase to other enzymes, particularly aldehyde dehydrogenase. There is not a single rate-determining step for the ethanol metabolism pathway and control is shared among several steps.

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Organic Solvents

Leira¹,

Fonnum²,

Syversen³

2009

General, Applied and Systems Toxicology

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This chapter describes the exposure, absorption, metabolism and toxic effects, particularly effects to the nervous system, of organic solvents. Since both occupational and domestic exposure is usually to mixtures of individual solvents rather than to single compounds, the metabolic interaction of solvents is addressed, as well as toxic effects of mixtures. Organic solvents have many clinical effects in common, but some solvents have individual effects, for example, the polyneuropathy induced by n ‐hexane, leukaemia induced by benzene and ventricular fibrillation induced by chlorinated solvents. Such effects, as well as particular metabolic profiles are described in individual sections on aliphatic solvents (chlorinated and nonchlorinated), alicyclic and aromatic solvents, alcohols and glycol ethers. Future challenges include exposure assessment, particularly with regard to occupational exposure. Furthermore, the mechanisms underlying the effects of organic solvents on the central nervous system are still not clear. Further work is also needed regarding carcinogenic properties, the role of genetic polymorphisms and possible immunotoxicological effects.

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Effects of ethanol treatment and castration on liver alcohol dehydrogenase activity

Cited by 6 publications

References 10 publications

Genetically Selected Alcohol Preferring Rats to Model Human Alcoholism

Genetically Selected Alcohol Preferring Rats to Model Human Alcoholism

The importance of alcohol dehydrogenase in regulation of ethanol metabolism in rat liver cells

Organic Solvents

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