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Article: Biochemical and morphological assessments of bleomycin pulmonary toxicity in rats

TitleBiochemical and morphological assessments of bleomycin pulmonary toxicity in rats
Authors
Issue Date1980
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/taap
Citation
Toxicology And Applied Pharmacology, 1980, v. 53 n. 1, p. 64-74 How to Cite?
AbstractLow doses (5 units) or high doses (15 units) of bleomycin were administered ip twice weekly to separate groups of male rats. A progressive dose-dependent reduction in body weight gain with a concomitant increase in wet lung weight to body weight ratio was observed over 6 weeks of treatments. Light microscopic confirmation of perivascular edema suggested that the increase in wet lung weight resulted from fluid accumulation. Although histological evidence of mild fibrosis was also present following low-dose treatment, only a slight increase in collagen content was observed biochemically. In vivo elevation of prolyl hydroxylase activity was observed in lungs of animals treated with low-dose bleomycin for 6 weeks. High-dose bleomycin regimen did not accelerate fibrosis, but rather inhibited the prolyl hydroxylase activity. In vitro, this enzyme activity was also stimulated at 1-10 μM concentration, but was inhibited at 0.1 mM. Lung angiotensin-converting enzyme activity was examined as an indication of damage to endothelial cells. This activity was unchanged after low-dose bleomycin treatments until 6 weeks, at which time a 59% decrease in activity was observed. High-dose bleomycin treatment produced a biphasic response in angiotensin-converting enzyme activity, with an initial 32% stimulation after 1.5 weeks of treatment followed by a 41% inhibition after 3 weeks. Kinetic analysis of the in vitro interaction of purified porcine plasma angiotensin-converting enzyme with bleomycin indicated that bleomycin acts as a competitive inhibitor with a K(i) of 3.7 μM. Stimulation of angiotensin-converting enzyme activity following acute high-dose bleomycin administration could be due to the initial endothelial cell repair, while the inhibition at later stages may indicate extensive destruction of endothelial surface upon repeated bleomycin administration. Direct inhibition of the enzyme by the chelating effect of bleomycin may also be a possibility.
Persistent Identifierhttp://hdl.handle.net/10722/170598
ISSN
2015 Impact Factor: 3.847
2015 SCImago Journal Rankings: 1.593
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTom, WMen_US
dc.contributor.authorMontgomery, MRen_US
dc.date.accessioned2012-10-30T06:10:05Z-
dc.date.available2012-10-30T06:10:05Z-
dc.date.issued1980en_US
dc.identifier.citationToxicology And Applied Pharmacology, 1980, v. 53 n. 1, p. 64-74en_US
dc.identifier.issn0041-008Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/170598-
dc.description.abstractLow doses (5 units) or high doses (15 units) of bleomycin were administered ip twice weekly to separate groups of male rats. A progressive dose-dependent reduction in body weight gain with a concomitant increase in wet lung weight to body weight ratio was observed over 6 weeks of treatments. Light microscopic confirmation of perivascular edema suggested that the increase in wet lung weight resulted from fluid accumulation. Although histological evidence of mild fibrosis was also present following low-dose treatment, only a slight increase in collagen content was observed biochemically. In vivo elevation of prolyl hydroxylase activity was observed in lungs of animals treated with low-dose bleomycin for 6 weeks. High-dose bleomycin regimen did not accelerate fibrosis, but rather inhibited the prolyl hydroxylase activity. In vitro, this enzyme activity was also stimulated at 1-10 μM concentration, but was inhibited at 0.1 mM. Lung angiotensin-converting enzyme activity was examined as an indication of damage to endothelial cells. This activity was unchanged after low-dose bleomycin treatments until 6 weeks, at which time a 59% decrease in activity was observed. High-dose bleomycin treatment produced a biphasic response in angiotensin-converting enzyme activity, with an initial 32% stimulation after 1.5 weeks of treatment followed by a 41% inhibition after 3 weeks. Kinetic analysis of the in vitro interaction of purified porcine plasma angiotensin-converting enzyme with bleomycin indicated that bleomycin acts as a competitive inhibitor with a K(i) of 3.7 μM. Stimulation of angiotensin-converting enzyme activity following acute high-dose bleomycin administration could be due to the initial endothelial cell repair, while the inhibition at later stages may indicate extensive destruction of endothelial surface upon repeated bleomycin administration. Direct inhibition of the enzyme by the chelating effect of bleomycin may also be a possibility.en_US
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/taapen_US
dc.relation.ispartofToxicology and Applied Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBleomycin - Toxicityen_US
dc.subject.meshBody Weight - Drug Effectsen_US
dc.subject.meshHydroxyproline - Metabolismen_US
dc.subject.meshLung Diseases - Chemically Induced - Metabolism - Pathologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMicrosomes - Metabolismen_US
dc.subject.meshOrgan Size - Drug Effectsen_US
dc.subject.meshProcollagen - Metabolismen_US
dc.subject.meshProcollagen-Proline Dioxygenase - Metabolismen_US
dc.subject.meshRatsen_US
dc.titleBiochemical and morphological assessments of bleomycin pulmonary toxicity in ratsen_US
dc.typeArticleen_US
dc.identifier.emailTom, WM:wmtoma@hkucc.hku.hken_US
dc.identifier.authorityTom, WM=rp00237en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/0041-008X(80)90382-8-
dc.identifier.pmid6155717-
dc.identifier.scopuseid_2-s2.0-0018843939en_US
dc.identifier.volume53en_US
dc.identifier.issue1en_US
dc.identifier.spage64en_US
dc.identifier.epage74en_US
dc.identifier.isiWOS:A1980JM76400010-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridTom, WM=7003709519en_US
dc.identifier.scopusauthoridMontgomery, MR=24441141600en_US

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