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Article: Increased severity of alcoholic liver injury in female rats: Role of oxidative stress, endotoxin, and chemokines

TitleIncreased severity of alcoholic liver injury in female rats: Role of oxidative stress, endotoxin, and chemokines
Authors
Issue Date2001
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpgi.physiology.org/
Citation
American Journal Of Physiology - Gastrointestinal And Liver Physiology, 2001, v. 281 n. 6 44-6, p. G1348-G1356 How to Cite?
AbstractAlcoholic liver injury is more severe and rapidly developing in women than men. To evaluate the reason(s) for these gender-related differences, we determined whether pathogenic mechanisms important in alcoholic liver injury in male rats were further upregulated in female rats. Male and age-matched female rats (7/group) were fed ethanol and a diet containing fish oil for 4 wk by intragastric infusion. Dextrose isocalorically replaced ethanol in control rats. We analyzed liver histopathology, lipid peroxidation, cytochrome P-450 (CYP)2E1 activity, nonheme iron, endotoxin, nuclear factor-KB (NF-KB) activation, and mRNA levels of cyclooxygenase-1 (COX-1) and COX-2, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2). Alcohol-induced liver injury was more severe in female vs. male rats. Female rats had higher endotoxin, lipid peroxidation, and nonheme iron levels and increased NF-KB activation and upregulation of the chemokines MCP-1 and MIP-2. CYP2E1 activity and TNF-α and COX-2 levels were similar in male and female rats. Remarkably, female rats fed fish oil and dextrose also showed necrosis and inflammation. Our findings in ethanol-fed rats suggest that increased endotoxemia and lipid peroxidation in females stimulate NF-KB activation and chemokine production, enhancing liver injury. TNF-α and COX-2 upregulation are probably important in causing liver injury but do not explain gender-related differences.
Persistent Identifierhttp://hdl.handle.net/10722/67809
ISSN
2015 Impact Factor: 3.297
2015 SCImago Journal Rankings: 1.936
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorNanji, AAen_HK
dc.contributor.authorJokelainen, Ken_HK
dc.contributor.authorFotouhinia, Men_HK
dc.contributor.authorRahemtulla, Aen_HK
dc.contributor.authorThomas, Pen_HK
dc.contributor.authorTipoe, GLen_HK
dc.contributor.authorGrace, LSUen_HK
dc.contributor.authorDannenberg, AJen_HK
dc.date.accessioned2010-09-06T05:58:27Z-
dc.date.available2010-09-06T05:58:27Z-
dc.date.issued2001en_HK
dc.identifier.citationAmerican Journal Of Physiology - Gastrointestinal And Liver Physiology, 2001, v. 281 n. 6 44-6, p. G1348-G1356en_HK
dc.identifier.issn0193-1857en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67809-
dc.description.abstractAlcoholic liver injury is more severe and rapidly developing in women than men. To evaluate the reason(s) for these gender-related differences, we determined whether pathogenic mechanisms important in alcoholic liver injury in male rats were further upregulated in female rats. Male and age-matched female rats (7/group) were fed ethanol and a diet containing fish oil for 4 wk by intragastric infusion. Dextrose isocalorically replaced ethanol in control rats. We analyzed liver histopathology, lipid peroxidation, cytochrome P-450 (CYP)2E1 activity, nonheme iron, endotoxin, nuclear factor-KB (NF-KB) activation, and mRNA levels of cyclooxygenase-1 (COX-1) and COX-2, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2). Alcohol-induced liver injury was more severe in female vs. male rats. Female rats had higher endotoxin, lipid peroxidation, and nonheme iron levels and increased NF-KB activation and upregulation of the chemokines MCP-1 and MIP-2. CYP2E1 activity and TNF-α and COX-2 levels were similar in male and female rats. Remarkably, female rats fed fish oil and dextrose also showed necrosis and inflammation. Our findings in ethanol-fed rats suggest that increased endotoxemia and lipid peroxidation in females stimulate NF-KB activation and chemokine production, enhancing liver injury. TNF-α and COX-2 upregulation are probably important in causing liver injury but do not explain gender-related differences.en_HK
dc.languageengen_HK
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpgi.physiology.org/en_HK
dc.relation.ispartofAmerican Journal of Physiology - Gastrointestinal and Liver Physiologyen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshChemokine CCL2 - geneticsen_HK
dc.subject.meshChemokine CXCL2en_HK
dc.subject.meshChemokines - genetics - physiologyen_HK
dc.subject.meshCyclooxygenase 1en_HK
dc.subject.meshCyclooxygenase 2en_HK
dc.subject.meshCytochrome P-450 CYP2E1 - metabolismen_HK
dc.subject.meshDietary Fats, Unsaturated - administration & dosageen_HK
dc.subject.meshEndotoxemia - physiopathologyen_HK
dc.subject.meshEndotoxins - physiologyen_HK
dc.subject.meshEthanol - administration & dosageen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshFish Oils - administration & dosageen_HK
dc.subject.meshIron - metabolismen_HK
dc.subject.meshIsoenzymes - geneticsen_HK
dc.subject.meshLipid Peroxidationen_HK
dc.subject.meshLiver - chemistry - metabolism - pathologyen_HK
dc.subject.meshLiver Diseases, Alcoholic - pathology - physiopathologyen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMembrane Proteinsen_HK
dc.subject.meshNF-kappa B - metabolismen_HK
dc.subject.meshOxidative Stressen_HK
dc.subject.meshProstaglandin-Endoperoxide Synthases - geneticsen_HK
dc.subject.meshRNA, Messenger - analysisen_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Wistaren_HK
dc.subject.meshSex Characteristicsen_HK
dc.subject.meshTumor Necrosis Factor-alpha - geneticsen_HK
dc.subject.meshWeight Gainen_HK
dc.titleIncreased severity of alcoholic liver injury in female rats: Role of oxidative stress, endotoxin, and chemokinesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0193-1857&volume=281&issue=6&spage=1348&epage=1356&date=2001&atitle=Increased+severity+of+alcoholic+liver+injury+in+female+rats:+role+of+oxidative+stress,+endotoxin,+and+chemokinesen_HK
dc.identifier.emailTipoe, GL:tgeorge@hkucc.hku.hken_HK
dc.identifier.authorityTipoe, GL=rp00371en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.pmid11705739-
dc.identifier.scopuseid_2-s2.0-0035665313en_HK
dc.identifier.hkuros67756en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035665313&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume281en_HK
dc.identifier.issue6 44-6en_HK
dc.identifier.spageG1348en_HK
dc.identifier.epageG1356en_HK
dc.identifier.isiWOS:000172095000004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridNanji, AA=35885060300en_HK
dc.identifier.scopusauthoridJokelainen, K=6603792075en_HK
dc.identifier.scopusauthoridFotouhinia, M=14067501000en_HK
dc.identifier.scopusauthoridRahemtulla, A=7003799325en_HK
dc.identifier.scopusauthoridThomas, P=16074032300en_HK
dc.identifier.scopusauthoridTipoe, GL=7003550610en_HK
dc.identifier.scopusauthoridGrace, LSU=19034263700en_HK
dc.identifier.scopusauthoridDannenberg, AJ=7102256248en_HK

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