| Prevention by inhibitors of arachidonic acid cascade of liver carcinogenesis, cirrhosis and oxidative DNA damage caused by a choline-deficient, L-amino acid-defined diet in rats. | |
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MedLine Citation:
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PMID: 9675312 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Effects of inhibitors of arachidonic acid (AA) cascade on the development of fatty liver, cirrhosis, glutathione S-transferase placental form (GST-P)-positive preneoplastic nodules, neoplastic nodules and generation of 8-hydroxydeoxyguanosine (8-OHdG), caused by a choline-deficient, L-amino acid-defined (CDAA) diet, were examined in Fischer 344 male rats by feeding CDAA diet supplemented with the inhibitors for 12 and 30 weeks. None of the inhibitors affected fatty liver. Among cyclooxygenase (COX) inhibitors, an irreversibly acting acetylsalicylic acid and a long-acting piroxicam, and to a much lesser extent the short-acting ibuprofen but not indomethacin, inhibited the development of cirrhosis, GST-P-positive and neoplastic nodules and generation of 8-OHdG. A phospholipase A2 inhibitor p-bromophenacylbromide (BPB) also exerted similar but lesser extent of inhibitory effects. Lipoxygenase inhibitors quercetin and nordihydroguiaretic acid inhibited GST-P-positive nodules but not cirrhosis or 8-OHdG. Present results suggest that perturbed AA cascade, particularly augmented COX pathway, might play key roles in the causation of liver lesions in the CDAA diet model. |
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Authors:
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A Denda; T Endoh; Q Tang; T Tsujiuchi; D Nakae; Y Konishi |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Mutation research Volume: 402 ISSN: 0027-5107 ISO Abbreviation: Mutat. Res. Publication Date: 1998 Jun |
Date Detail:
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Created Date: 1998-09-01 Completed Date: 1998-09-01 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0400763 Medline TA: Mutat Res Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 279-88 Citation Subset: IM |
Copyright Information:
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Copyright 1998 Elsevier Science B.V. All rights reserved. |
Affiliation:
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Department of Oncological Pathology, Cancer Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids
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administration & dosage Animals Arachidonic Acid / antagonists & inhibitors* Body Weight Choline Deficiency / complications* Cyclooxygenase Inhibitors / pharmacology DNA Damage* Deoxyguanosine / analogs & derivatives, metabolism Feeding Behavior Glutathione Transferase / metabolism Lipoxygenase Inhibitors / pharmacology Liver Cirrhosis, Experimental / pathology, prevention & control* Liver Neoplasms, Experimental / enzymology, pathology, prevention & control* Male Oxidative Stress* Phospholipases A / antagonists & inhibitors Phospholipases A2 Rats Rats, Inbred F344 |
| Chemical | |
Reg. No./Substance:
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0/8-hydroxy-2'-deoxyguanosine; 0/Amino Acids; 0/Cyclooxygenase Inhibitors; 0/Lipoxygenase Inhibitors; 506-32-1/Arachidonic Acid; 961-07-9/Deoxyguanosine; EC 2.5.1.18/Glutathione Transferase; EC 3.1.1.-/Phospholipases A; EC 3.1.1.4/Phospholipases A2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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