Oxidatively damaged DNA and inflammation in the liver of dyslipidemic ApoE-/- mice exposed to diesel exhaust particles.

2.50
Hdl Handle:
http://hdl.handle.net/10146/33859
Title:
Oxidatively damaged DNA and inflammation in the liver of dyslipidemic ApoE-/- mice exposed to diesel exhaust particles.
Authors:
Folkmann, Janne Kjaersgaard; Risom, Lotte; Hansen, Christian Stevns; Loft, Steffen; Moller, Peter
Abstract:
Epidemiological studies have shown that exposure to air pollution particles is associated with cardiovascular diseases, whereas the role in the initiation of atherosclerosis is unresolved. Atherosclerosis is considered to be an inflammatory disease that also involves oxidative stress. Here we investigated effects of oxidative stress elicited by diesel exhaust particles (DEP) in the aorta, liver, and lung of dyslipidemic ApoE(-/-) mice at the age when visual plaques appear in the aorta (11-13 weeks). DEP was administrated by intraperitoneal injection (0, 50, 500 and 5,000 microg DEP/kg bodyweight) in order to omit vascular effects secondary to pulmonary inflammation. The mice were killed either 6 or 24h after the administration. Inflammation was measured as the expression of inducible nitric oxide synthase (iNOS) and serum nitric oxide and DNA damage was measured by the comet assay. The expression of iNOS mRNA was increased in the liver 6h after the administration. The level of oxidized purine bases, determined as formamidopyrimidine DNA glycosylase sites was increased by 67% (95% CI: 11-124%) in the liver after 24h in the mice administrated with only 50 microg/kg bodyweight. However, there was no indication of systemic inflammation determined as the serum concentration of nitric oxide and iNOS expression, and DNA damage was not increased in the aorta. These observations indicate that intraperitoneal DEP injection does not induce inflammation or oxidatively damaged DNA in the lung and aorta, whereas a direct effect in terms of inflammation and oxidized DNA was observed in the liver of dyslipidemic ApoE(-/-) mice.
Citation:
Toxicology 2007, 237 (1-3):134-144
Journal:
Toxicology
Issue Date:
31-Jul-2007
URI:
http://hdl.handle.net/10146/33859
DOI:
10.1016/j.tox.2007.05.009
PubMed ID:
17602821
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCN-4NS2GNG-2&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=57c998f28c592ff59f7a2bee5340b2b4
Type:
Article
Language:
en
ISSN:
0300-483X
Sponsors:
The work was partly supported by Environmental Cancer Risk, Nutrition and Individual Susceptibility (ECNIS), a network of excellence operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety” (Contract No. 513943) and the Danish Research Councils.
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorFolkmann, Janne Kjaersgaard-
dc.contributor.authorRisom, Lotte-
dc.contributor.authorHansen, Christian Stevns-
dc.contributor.authorLoft, Steffen-
dc.contributor.authorMoller, Peter-
dc.date.accessioned2008-08-01T11:33:23Z-
dc.date.available2008-08-01T11:33:23Z-
dc.date.issued2007-07-31-
dc.identifier.citationToxicology 2007, 237 (1-3):134-144en
dc.identifier.issn0300-483X-
dc.identifier.pmid17602821-
dc.identifier.doi10.1016/j.tox.2007.05.009-
dc.identifier.urihttp://hdl.handle.net/10146/33859-
dc.description.abstractEpidemiological studies have shown that exposure to air pollution particles is associated with cardiovascular diseases, whereas the role in the initiation of atherosclerosis is unresolved. Atherosclerosis is considered to be an inflammatory disease that also involves oxidative stress. Here we investigated effects of oxidative stress elicited by diesel exhaust particles (DEP) in the aorta, liver, and lung of dyslipidemic ApoE(-/-) mice at the age when visual plaques appear in the aorta (11-13 weeks). DEP was administrated by intraperitoneal injection (0, 50, 500 and 5,000 microg DEP/kg bodyweight) in order to omit vascular effects secondary to pulmonary inflammation. The mice were killed either 6 or 24h after the administration. Inflammation was measured as the expression of inducible nitric oxide synthase (iNOS) and serum nitric oxide and DNA damage was measured by the comet assay. The expression of iNOS mRNA was increased in the liver 6h after the administration. The level of oxidized purine bases, determined as formamidopyrimidine DNA glycosylase sites was increased by 67% (95% CI: 11-124%) in the liver after 24h in the mice administrated with only 50 microg/kg bodyweight. However, there was no indication of systemic inflammation determined as the serum concentration of nitric oxide and iNOS expression, and DNA damage was not increased in the aorta. These observations indicate that intraperitoneal DEP injection does not induce inflammation or oxidatively damaged DNA in the lung and aorta, whereas a direct effect in terms of inflammation and oxidized DNA was observed in the liver of dyslipidemic ApoE(-/-) mice.en
dc.description.sponsorshipThe work was partly supported by Environmental Cancer Risk, Nutrition and Individual Susceptibility (ECNIS), a network of excellence operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety” (Contract No. 513943) and the Danish Research Councils.en
dc.language.isoenen
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCN-4NS2GNG-2&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=57c998f28c592ff59f7a2bee5340b2b4en
dc.subjectatherosclerosisen
dc.subjectComet assayen
dc.subjectDiesel exhaust particlesen
dc.subjectinflammationen
dc.subjectoxidative DNA damageen
dc.subject.meshAnimals-
dc.subject.meshAorta-
dc.subject.meshApolipoproteins E-
dc.subject.meshAtherosclerosis-
dc.subject.meshComet Assay-
dc.subject.meshDNA Damage-
dc.subject.meshDyslipidemias-
dc.subject.meshFemale-
dc.subject.meshHepatitis, Toxic-
dc.subject.meshLiver-
dc.subject.meshLung-
dc.subject.meshMice-
dc.subject.meshMice, Knockout-
dc.subject.meshNitric Oxide-
dc.subject.meshNitric Oxide Synthase Type II-
dc.subject.meshOxidative Stress-
dc.subject.meshParticulate Matter-
dc.subject.meshVehicle Emissions-
dc.titleOxidatively damaged DNA and inflammation in the liver of dyslipidemic ApoE-/- mice exposed to diesel exhaust particles.en
dc.typeArticleen
dc.identifier.journalToxicologyen

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