title: Inhibition by acetylsalicylic acid, a cyclo-oxygenase inhibitor, and p-bromophenacylbromide, a phospholipase A2 inhibitor, of both cirrhosis and enzyme-altered nodules caused by a choline-deficient, L-amino acid-defined diet in rats.
abstract: Effects of inhibitors of arachidonic acid (AA) metabolism on the development of fatty liver, cirrhosis, glutathione-S-transferase placental form (GST-P)-positive nodules and the generation of 8-hydroxydeoxyguanosine (8-OHdG) and thiobarbituric acid-reactive substances (TBARS), caused by a choline-deficient, L-amino acid-defined (CDAA) diet, were examined in male Fischer 344 rats by feeding CDAA diets supplemented with the inhibitors for 12 and 30 weeks. Acetylsalicylic acid (ASA) (at doses of 0.1 and 0.2%) and p-bromophenacylbromide (BPB) (0.1 and 0.2%) were used as inhibitors of, respectively, cyclo-oxygenase and phospholipase A2, and quercetin (QU) (0.75 and 1.5%) and nordihydroguaiaretic acid (NDGA) (0.1 and 0.2%) as inhibitors of lipoxygenase. None of the inhibitors affected the development of fatty liver caused by the CDAA diet. ASA at a doe of 0.2% almost completely prevented the appearance of cirrhosis, GST-P-positive nodules, 8-OHdG and TBARS in seven out of 11 (63.7%) rats. BPB at a dose of 0.2% also exerted inhibitory effects on all of these lesions but to a lesser extent than ASA. QU and NDGA exerted inhibitory effects limited to the GST-P-positive nodule case. The results indicate that a perturbed AA metabolism, particularly of the cyclo-oxygenase pathway, derived secondarily from depletion of labile methyl groups or phosphatidylcholine, might play key roles in the cirrhosis, hepatocarcinogenesis and oxidative stress caused by a CDAA diet. The results also indicated a possible involvement of the lipoxygenase pathway in hepatocarcinogenic processes.
authors.affiliation: Department of Oncological Pathology, Cancer Center, Nara Medical University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Endoh
authors.forename: Q
authors.initials: Q
authors.lastname: Tang
authors.forename: A
authors.initials: A
authors.lastname: Denda
authors.forename: O
authors.initials: O
authors.lastname: Noguchi
authors.forename: E
authors.initials: E
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: K
authors.initials: K
authors.lastname: Horiguchi
authors.forename: H
authors.initials: H
authors.lastname: Ogasawara
authors.forename: T
authors.initials: T
authors.lastname: Tsujiuchi
authors.forename: D
authors.initials: D
authors.lastname: Nakae
authors.forename: M
authors.initials: M
authors.lastname: Sugimura
authors.forename: Y
authors.initials: Y
authors.lastname: Konishi
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002794:Choline / Q000008:administration & dosage; D002796:Choline Deficiency; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005234:Fatty Liver / Q000209:etiology / Q000517:prevention & control; D005982:Glutathione Transferase / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000517:prevention & control*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D009637:Masoprocol / Q000494:pharmacology*; D008715:Methionine / Q000008:administration & dosage; D018384:Oxidative Stress; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011230:Precancerous Conditions / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D000098:Acetophenones; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; C013190:phenacyl bromide; D009637:Masoprocol; D011794:Quercetin; D008715:Methionine; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; D010741:Phospholipases A; D054467:Phospholipases A2; D002794:Choline; D001241:Aspirin