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Article: Bleomycin toxicity. Alterations in oxidative metabolism in lung and liver microsomal fractions

TitleBleomycin toxicity. Alterations in oxidative metabolism in lung and liver microsomal fractions
Authors
Issue Date1980
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharm
Citation
Biochemical Pharmacology, 1980, v. 29 n. 24, p. 3239-3244 How to Cite?
AbstractSeparate groups of male rats received low doses (5 units) or high doses (15 units) of bleomycin i.p. twice weekly for 1.5, 3 or 6 weeks. The susceptibility of tissue lipid to peroxidation and the activities of mixed function oxidations were examined in microsomal fractions prepared from lung and liver. ADP-Fe (III)-initiated lipid peroxidation was stimulated in lung microsomal fractions only in animals treated with high-dose bleomycin for 1.5 weeks, whereas a 2- to 4-fold enhancement was observed in liver preparations from all bleomycin-treated animals. Microsomal ADP-Fe (III)-initiated lipid peroxidation was inhibited, however, by the in vitro addition of bleomycin in both lung and liver preparations, but this inhibition was an artifact resulting from the chelation of Fe (III) by bleomycin. Soybean lipoxygenase I-initiated microsomal lipid peroxidation, which does not require added iron, was unaffected by bleomycin in lung preparations but was inhibited in liver. Following in vivo treatment, lung microsomal hydrogen peroxide generation was inhibited by 1.5 weeks of high-dose bleomycin treatments, whereas benzphetamine N-demethylation was unchanged. These cytochrome P-450-dependent reactions were both suppressed, however, in liver microsomal fractions. In vitro, both reactions were also inhibited by bleomycin in liver but not in lung microsomal fractions. The lack of effect of in vitro bleomycin treatments on superoxide generation in lung or liver preparations suggests that the NADPH cytochrome P-450 reductase component of the mixed function oxidase system was not affected. Minimal alterations in lipid peroxidizability and mixed function oxidase activities in lung microsomal fractions of bleomycin-treated animals suggest that the insensitivity could be due to: (1) the site of toxicity not being at the level of the endoplasmic reticulum; or (2) the target of bleomycin toxicity being limited to a small population of pulmonary cell types. Even though the liver is not susceptible to bleomycin toxicity, the hepatic microsomal mixed function oxidase system is highly sensitive to this chemical.
Persistent Identifierhttp://hdl.handle.net/10722/170611
ISSN
2015 Impact Factor: 5.091
2015 SCImago Journal Rankings: 2.263

 

DC FieldValueLanguage
dc.contributor.authorTom, WMen_US
dc.contributor.authorMontgomery, MRen_US
dc.date.accessioned2012-10-30T06:10:08Z-
dc.date.available2012-10-30T06:10:08Z-
dc.date.issued1980en_US
dc.identifier.citationBiochemical Pharmacology, 1980, v. 29 n. 24, p. 3239-3244en_US
dc.identifier.issn0006-2952en_US
dc.identifier.urihttp://hdl.handle.net/10722/170611-
dc.description.abstractSeparate groups of male rats received low doses (5 units) or high doses (15 units) of bleomycin i.p. twice weekly for 1.5, 3 or 6 weeks. The susceptibility of tissue lipid to peroxidation and the activities of mixed function oxidations were examined in microsomal fractions prepared from lung and liver. ADP-Fe (III)-initiated lipid peroxidation was stimulated in lung microsomal fractions only in animals treated with high-dose bleomycin for 1.5 weeks, whereas a 2- to 4-fold enhancement was observed in liver preparations from all bleomycin-treated animals. Microsomal ADP-Fe (III)-initiated lipid peroxidation was inhibited, however, by the in vitro addition of bleomycin in both lung and liver preparations, but this inhibition was an artifact resulting from the chelation of Fe (III) by bleomycin. Soybean lipoxygenase I-initiated microsomal lipid peroxidation, which does not require added iron, was unaffected by bleomycin in lung preparations but was inhibited in liver. Following in vivo treatment, lung microsomal hydrogen peroxide generation was inhibited by 1.5 weeks of high-dose bleomycin treatments, whereas benzphetamine N-demethylation was unchanged. These cytochrome P-450-dependent reactions were both suppressed, however, in liver microsomal fractions. In vitro, both reactions were also inhibited by bleomycin in liver but not in lung microsomal fractions. The lack of effect of in vitro bleomycin treatments on superoxide generation in lung or liver preparations suggests that the NADPH cytochrome P-450 reductase component of the mixed function oxidase system was not affected. Minimal alterations in lipid peroxidizability and mixed function oxidase activities in lung microsomal fractions of bleomycin-treated animals suggest that the insensitivity could be due to: (1) the site of toxicity not being at the level of the endoplasmic reticulum; or (2) the target of bleomycin toxicity being limited to a small population of pulmonary cell types. Even though the liver is not susceptible to bleomycin toxicity, the hepatic microsomal mixed function oxidase system is highly sensitive to this chemical.en_US
dc.languageengen_US
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharmen_US
dc.relation.ispartofBiochemical Pharmacologyen_US
dc.subject.meshAdenosine Diphosphate - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBleomycin - Toxicityen_US
dc.subject.meshIron - Pharmacologyen_US
dc.subject.meshLipid Peroxides - Biosynthesisen_US
dc.subject.meshLung - Drug Effects - Metabolismen_US
dc.subject.meshMaleen_US
dc.subject.meshMicrosomes - Drug Effectsen_US
dc.subject.meshMicrosomes, Liver - Drug Effects - Metabolismen_US
dc.subject.meshMixed Function Oxygenases - Antagonists & Inhibitorsen_US
dc.subject.meshRatsen_US
dc.titleBleomycin toxicity. Alterations in oxidative metabolism in lung and liver microsomal fractionsen_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.doi10.1016/0006-2952(80)90297-Xen_US
dc.identifier.pmid6163432-
dc.identifier.scopuseid_2-s2.0-0019160376en_US
dc.identifier.volume29en_US
dc.identifier.issue24en_US
dc.identifier.spage3239en_US
dc.identifier.epage3244en_US
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridTom, WM=7003709519en_US
dc.identifier.scopusauthoridMontgomery, MR=24441141600en_US

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