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Fenofibrate - A lipid-lowering drug - Reduces voluntary alcohol drinking in rats

dc.contributor.authorKarahanian E.
dc.contributor.authorQuintanilla M.E.
dc.contributor.authorFernandez K.
dc.contributor.authorIsrael Y.
dc.date.accessioned2020-09-02T22:21:04Z
dc.date.available2020-09-02T22:21:04Z
dc.date.issued2014
dc.identifier10.1016/j.alcohol.2014.08.004
dc.identifier.citation48, 7, 665-670
dc.identifier.issn07418329
dc.identifier.urihttps://hdl.handle.net/20.500.12728/4994
dc.descriptionThe administration of disulfiram raises blood acetaldehyde levels when ethanol is ingested, leading to an aversion to alcohol. This study was aimed at assessing the effect of fenofibrate on voluntary ethanol ingestion in rats. Fenofibrate reduces blood triglyceride levels by increasing fatty acid oxidation by liver peroxisomes, along with an increase in the activity of catalase, which can oxidize ethanol to acetaldehyde. UChB drinker rats were allowed to consume alcohol 10% v/v freely for 60 days, until consumption stabilized at around 7g ethanol/kg/24h. About 1-1.2g ethanol/kg of this intake is consumed in the first 2h of darkness of the circadian cycle. Fenofibrate subsequently administered (50mg/kg/day by mouth [p.o.]) for 14 days led to a 60-70% (p<0.001) reduction of 24-h ethanol consumption. When ethanol intake was determined within the first 2h of darkness, the reduction was 85-90% (p<0.001). We determined whether animals chronically allowed access to ethanol and subsequently treated with fenofibrate, would a) increase liver catalase activity, and b) increase blood acetaldehyde levels after a 24-h ethanol deprivation and the subsequent administration of 1g ethanol/kg. The oral administration of 1g ethanol/kg produced a rapid increase in blood (arterial) acetaldehyde in fenofibrate-treated animals versus controls also administered 1g/kg ethanol (70μM vs. 7μM; p<0.001). Liver catalase activity following fenofibrate treatment was increased 3-fold (p<0.01). Other hepatic enzymes responsible for the metabolism of ethanol (alcohol dehydrogenase and aldehyde dehydrogenase) remained unchanged. No liver damage was induced, as measured by serum glutamic-pyruvic transaminase (GPT) activity. The effect of fenofibrate in reducing alcohol intake was fully reversible. Overall, in rats allowed chronic ethanol intake, by mouth (p.o.), fenofibrate administration increased liver catalase activity and reduced voluntary ethanol intake. The administration of 1g ethanol/kg (p.o.) to these animals increased blood acetaldehyde levels in fenofibrate-treated animals, suggesting the possible basis for the reduction in ethanol intake. © 2014 Elsevier Inc.
dc.language.isoen
dc.publisherElsevier Inc.
dc.subjectAlcoholism
dc.subjectCatalase
dc.subjectFenofibrate
dc.subjectFibrates
dc.subjectPeroxisome proliferator-activated receptor
dc.subjectTreatment
dc.subjectacetaldehyde
dc.subjectalanine aminotransferase
dc.subjectalcohol dehydrogenase
dc.subjectaldehyde dehydrogenase
dc.subjectcatalase
dc.subjectfenofibrate
dc.subjecttriacylglycerol
dc.subjectacetaldehyde
dc.subjectalanine aminotransferase
dc.subjectalcohol
dc.subjectantilipemic agent
dc.subjectcatalase
dc.subjectfenofibrate
dc.subjectalanine aminotransferase blood level
dc.subjectalcohol consumption
dc.subjectalcohol metabolism
dc.subjectanimal experiment
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectcontrolled study
dc.subjectdrinking behavior
dc.subjectdrug mechanism
dc.subjectenzyme activity
dc.subjectfatty acid oxidation
dc.subjectmale
dc.subjectnonhuman
dc.subjectrat
dc.subjecttriacylglycerol blood level
dc.subjectanimal
dc.subjectblood
dc.subjectdrug effects
dc.subjectdrug therapy
dc.subjectenzymology
dc.subjectliver
dc.subjectmetabolism
dc.subjectWistar rat
dc.subjectRattus
dc.subjectAcetaldehyde
dc.subjectAlanine Transaminase
dc.subjectAlcohol Drinking
dc.subjectAnimals
dc.subjectCatalase
dc.subjectEthanol
dc.subjectFenofibrate
dc.subjectHypolipidemic Agents
dc.subjectLiver
dc.subjectMale
dc.subjectRats
dc.subjectRats, Wistar
dc.titleFenofibrate - A lipid-lowering drug - Reduces voluntary alcohol drinking in rats
dc.typeArticle


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