The role of aldehyde oxidase in ethanol-induced hepatic lipid peroxidation in the rat
Hepatic lipid peroxidation has been implicated in the pathogenesis of alcohol-induced liver injury, but the mechanism(s) by which ethanol metabolism or resultant free radicals initiate lipid peroxidation is not fully defined. The role of the molybdenum-containing enzymes aldehyde oxidase and xanthin...
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| Veröffentlicht in: | Biochemical journal 1990-06, Vol.268 (3), p.579-583 |
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| creator | Shaw, S Jayatilleke, E |
| description | Hepatic lipid peroxidation has been implicated in the pathogenesis of alcohol-induced liver injury, but the mechanism(s) by which ethanol metabolism or resultant free radicals initiate lipid peroxidation is not fully defined. The role of the molybdenum-containing enzymes aldehyde oxidase and xanthine oxidase in the generation of such free radicals was investigated by measuring alkane production (lipoperoxidation products) in isolated rat hepatocytes during ethanol metabolism. Inhibition of aldehyde oxidase and xanthine oxidase (by feeding tungstate at 100 mg/day per kg) decreased alkane production (80-95%), whereas allopurinol (20 mg/kg by mouth), a marked inhibitor of xanthine oxidase, inhibited alkane production by only 35-50%. Addition of acetaldehyde (0-100 microM) (in the presence of 50 microM-4-methylpyrazole) increased alkane production in a dose-dependent manner (Km of aldehyde oxidase for acetaldehyde 1 mM); menadione, an inhibitor of aldehyde oxidase, virtually inhibited alkane production. Desferrioxamine (5-10 microM) completely abolished alkane production induced by both ethanol and acetaldehyde, indicating the importance of catalytic iron. Thus free radicals generated during the metabolism of acetaldehyde by aldehyde oxidase may be a fundamental mechanism in the initiation of alcohol-induced liver injury. |
| doi_str_mv | 10.1042/bj2680579 |
| format | Article |
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The role of the molybdenum-containing enzymes aldehyde oxidase and xanthine oxidase in the generation of such free radicals was investigated by measuring alkane production (lipoperoxidation products) in isolated rat hepatocytes during ethanol metabolism. Inhibition of aldehyde oxidase and xanthine oxidase (by feeding tungstate at 100 mg/day per kg) decreased alkane production (80-95%), whereas allopurinol (20 mg/kg by mouth), a marked inhibitor of xanthine oxidase, inhibited alkane production by only 35-50%. Addition of acetaldehyde (0-100 microM) (in the presence of 50 microM-4-methylpyrazole) increased alkane production in a dose-dependent manner (Km of aldehyde oxidase for acetaldehyde 1 mM); menadione, an inhibitor of aldehyde oxidase, virtually inhibited alkane production. Desferrioxamine (5-10 microM) completely abolished alkane production induced by both ethanol and acetaldehyde, indicating the importance of catalytic iron. Thus free radicals generated during the metabolism of acetaldehyde by aldehyde oxidase may be a fundamental mechanism in the initiation of alcohol-induced liver injury.</description><identifier>ISSN: 0264-6021</identifier><identifier>EISSN: 1470-8728</identifier><identifier>DOI: 10.1042/bj2680579</identifier><identifier>PMID: 2363695</identifier><language>eng</language><publisher>England</publisher><subject>Aldehyde Oxidase ; Aldehyde Oxidoreductases - antagonists & inhibitors ; Aldehyde Oxidoreductases - metabolism ; Allopurinol - pharmacology ; Animals ; Deferoxamine - pharmacology ; ethanol ; Ethanol - pharmacology ; Ethanol - toxicity ; Hepatitis, Alcoholic - enzymology ; Hepatitis, Alcoholic - metabolism ; lipid peroxidation ; Lipid Peroxidation - drug effects ; Liver - drug effects ; Liver - enzymology ; Liver - metabolism ; Male ; Rats ; Rats, Inbred Strains ; Tungsten - pharmacology ; Vitamin K - pharmacology ; Xanthine Oxidase - antagonists & inhibitors ; Xanthine Oxidase - metabolism</subject><ispartof>Biochemical journal, 1990-06, Vol.268 (3), p.579-583</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-9b1c37d74c8b34ea77ada995145d198fe820b21af19d93e077655f392cf67543</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1131477/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1131477/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2363695$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shaw, S</creatorcontrib><creatorcontrib>Jayatilleke, E</creatorcontrib><title>The role of aldehyde oxidase in ethanol-induced hepatic lipid peroxidation in the rat</title><title>Biochemical journal</title><addtitle>Biochem J</addtitle><description>Hepatic lipid peroxidation has been implicated in the pathogenesis of alcohol-induced liver injury, but the mechanism(s) by which ethanol metabolism or resultant free radicals initiate lipid peroxidation is not fully defined. The role of the molybdenum-containing enzymes aldehyde oxidase and xanthine oxidase in the generation of such free radicals was investigated by measuring alkane production (lipoperoxidation products) in isolated rat hepatocytes during ethanol metabolism. Inhibition of aldehyde oxidase and xanthine oxidase (by feeding tungstate at 100 mg/day per kg) decreased alkane production (80-95%), whereas allopurinol (20 mg/kg by mouth), a marked inhibitor of xanthine oxidase, inhibited alkane production by only 35-50%. Addition of acetaldehyde (0-100 microM) (in the presence of 50 microM-4-methylpyrazole) increased alkane production in a dose-dependent manner (Km of aldehyde oxidase for acetaldehyde 1 mM); menadione, an inhibitor of aldehyde oxidase, virtually inhibited alkane production. Desferrioxamine (5-10 microM) completely abolished alkane production induced by both ethanol and acetaldehyde, indicating the importance of catalytic iron. Thus free radicals generated during the metabolism of acetaldehyde by aldehyde oxidase may be a fundamental mechanism in the initiation of alcohol-induced liver injury.</description><subject>Aldehyde Oxidase</subject><subject>Aldehyde Oxidoreductases - antagonists & inhibitors</subject><subject>Aldehyde Oxidoreductases - metabolism</subject><subject>Allopurinol - pharmacology</subject><subject>Animals</subject><subject>Deferoxamine - pharmacology</subject><subject>ethanol</subject><subject>Ethanol - pharmacology</subject><subject>Ethanol - toxicity</subject><subject>Hepatitis, Alcoholic - enzymology</subject><subject>Hepatitis, Alcoholic - metabolism</subject><subject>lipid peroxidation</subject><subject>Lipid Peroxidation - drug effects</subject><subject>Liver - drug effects</subject><subject>Liver - enzymology</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Tungsten - pharmacology</subject><subject>Vitamin K - pharmacology</subject><subject>Xanthine Oxidase - antagonists & inhibitors</subject><subject>Xanthine Oxidase - metabolism</subject><issn>0264-6021</issn><issn>1470-8728</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1Lw0AQhhdRaq0e_AFCToKH6H5msxdBil9Q8FLPy2Z3Yrak2ZhNxP57U1uKnmZgHp4Z5kXokuBbgjm9K1Y0y7GQ6ghNCZc4zSXNj9EU04ynGabkFJ3FuMKYcMzxBE0oy1imxBS9LytIulBDEsrE1A6qjRv7b-9MhMQ3CfSVaUKd-sYNFlxSQWt6b5Pat94lLXS_bO9Ds6X7rc305-ikNHWEi32doeXT43L-ki7enl_nD4vU8kz2qSqIZdJJbvOCcTBSGmeUEoQLR1ReQk5xQYkpiXKKAZYyE6Jkitoyk4KzGbrfaduhWIOz0PSdqXXb-bXpNjoYr_9PGl_pj_ClCWHjm-QouN4LuvA5QOz12kcLdW0aCEPURCgsOMEjeLMDbRdi7KA8LCFYbyPQhwhG9urvVQdy_3P2A15igjI</recordid><startdate>19900615</startdate><enddate>19900615</enddate><creator>Shaw, S</creator><creator>Jayatilleke, E</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>M81</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>19900615</creationdate><title>The role of aldehyde oxidase in ethanol-induced hepatic lipid peroxidation in the rat</title><author>Shaw, S ; Jayatilleke, E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-9b1c37d74c8b34ea77ada995145d198fe820b21af19d93e077655f392cf67543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>Aldehyde Oxidase</topic><topic>Aldehyde Oxidoreductases - antagonists & inhibitors</topic><topic>Aldehyde Oxidoreductases - metabolism</topic><topic>Allopurinol - pharmacology</topic><topic>Animals</topic><topic>Deferoxamine - pharmacology</topic><topic>ethanol</topic><topic>Ethanol - pharmacology</topic><topic>Ethanol - toxicity</topic><topic>Hepatitis, Alcoholic - enzymology</topic><topic>Hepatitis, Alcoholic - metabolism</topic><topic>lipid peroxidation</topic><topic>Lipid Peroxidation - drug effects</topic><topic>Liver - drug effects</topic><topic>Liver - enzymology</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Tungsten - pharmacology</topic><topic>Vitamin K - pharmacology</topic><topic>Xanthine Oxidase - antagonists & inhibitors</topic><topic>Xanthine Oxidase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shaw, S</creatorcontrib><creatorcontrib>Jayatilleke, E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 3</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biochemical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shaw, S</au><au>Jayatilleke, E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of aldehyde oxidase in ethanol-induced hepatic lipid peroxidation in the rat</atitle><jtitle>Biochemical journal</jtitle><addtitle>Biochem J</addtitle><date>1990-06-15</date><risdate>1990</risdate><volume>268</volume><issue>3</issue><spage>579</spage><epage>583</epage><pages>579-583</pages><issn>0264-6021</issn><eissn>1470-8728</eissn><abstract>Hepatic lipid peroxidation has been implicated in the pathogenesis of alcohol-induced liver injury, but the mechanism(s) by which ethanol metabolism or resultant free radicals initiate lipid peroxidation is not fully defined. The role of the molybdenum-containing enzymes aldehyde oxidase and xanthine oxidase in the generation of such free radicals was investigated by measuring alkane production (lipoperoxidation products) in isolated rat hepatocytes during ethanol metabolism. Inhibition of aldehyde oxidase and xanthine oxidase (by feeding tungstate at 100 mg/day per kg) decreased alkane production (80-95%), whereas allopurinol (20 mg/kg by mouth), a marked inhibitor of xanthine oxidase, inhibited alkane production by only 35-50%. Addition of acetaldehyde (0-100 microM) (in the presence of 50 microM-4-methylpyrazole) increased alkane production in a dose-dependent manner (Km of aldehyde oxidase for acetaldehyde 1 mM); menadione, an inhibitor of aldehyde oxidase, virtually inhibited alkane production. Desferrioxamine (5-10 microM) completely abolished alkane production induced by both ethanol and acetaldehyde, indicating the importance of catalytic iron. Thus free radicals generated during the metabolism of acetaldehyde by aldehyde oxidase may be a fundamental mechanism in the initiation of alcohol-induced liver injury.</abstract><cop>England</cop><pmid>2363695</pmid><doi>10.1042/bj2680579</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Biochemical journal, 1990-06, Vol.268 (3), p.579-583 |
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| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Aldehyde Oxidase Aldehyde Oxidoreductases - antagonists & inhibitors Aldehyde Oxidoreductases - metabolism Allopurinol - pharmacology Animals Deferoxamine - pharmacology ethanol Ethanol - pharmacology Ethanol - toxicity Hepatitis, Alcoholic - enzymology Hepatitis, Alcoholic - metabolism lipid peroxidation Lipid Peroxidation - drug effects Liver - drug effects Liver - enzymology Liver - metabolism Male Rats Rats, Inbred Strains Tungsten - pharmacology Vitamin K - pharmacology Xanthine Oxidase - antagonists & inhibitors Xanthine Oxidase - metabolism |
| title | The role of aldehyde oxidase in ethanol-induced hepatic lipid peroxidation in the rat |
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