title: Chronic ethanol consumption induces histopathological changes and increases nitric oxide generation in the rat liver.
abstract: In the present work we evaluated the effect of ethanol consumption in histopathological liver changes and several biochemical biomarkers employed in the detection of hepatic dysfunction. Male Wistar rats were treated with ethanol 20% (vol/vol) for 6 weeks. Histopathological investigation of livers from ethanol-treated animals revealed steatosis. Indices of hepatic function (transaminases) and mitochondrial respiration were not altered in ethanol-treated rats. Chronic ethanol consumption did not alter malondialdehyde (MDA) levels in the liver. Ethanol consumption induced a significant increase on hepatic nitrite and nitrate levels. Treatment with ethanol increased both mRNA expression and immunostaining of iNOS, but not eNOS. Finally, ethanol consumption did not alter hepatic levels of metalloproteinase (MMP)-2 and MMP-9. We conclude that alterations on biochemical biomarkers (nitrite and nitrate levels) and histopathology occurred in ethanol-treated rats, supporting the practice of including both types of evaluation in toxicity studies to detect potential ethanol-related hepatic effects. In our model of ethanol consumption, histopathological liver changes were accompanied by elevation in nitrite and nitrate levels indicating increased nitric oxide (NO) generation. Since iNOS-derived NO contributes to hepatic injury, the increased levels of NO described in our study might contribute to a progressive hepatic damage. Therefore, increases in NO generation may be an early indicator of ethanol-induced liver damage.
authors.affiliation: Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Brazil. crtirapelli@eerp.usp.br
authors.forename: Luis F
authors.initials: LF
authors.lastname: Tirapelli
authors.forename: Marcelo E
authors.initials: ME
authors.lastname: Batalhão
authors.forename: Ana L
authors.initials: AL
authors.lastname: Jacob-Ferreira
authors.forename: Daniela P
authors.initials: DP
authors.lastname: Tirapelli
authors.forename: Evelin C
authors.initials: EC
authors.lastname: Carnio
authors.forename: José E
authors.initials: JE
authors.lastname: Tanus-Santos
authors.forename: Regina H
authors.initials: RH
authors.lastname: Queiroz
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Uyemura
authors.forename: Cláudia M
authors.initials: CM
authors.lastname: Padovan
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Tirapelli
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D000431:Ethanol / Q000008:administration & dosage*; D005234:Fatty Liver / Q000139:chemically induced* / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D045726:Metalloproteases / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism / Q000473:pathology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D000431:Ethanol; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D045726:Metalloproteases