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.
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Authors | T Endoh, Q Tang, A Denda, O Noguchi, E Kobayashi, K Tamura, K Horiguchi, H Ogasawara, T Tsujiuchi, D Nakae, M Sugimura, Y Konishi |
Journal | Carcinogenesis
(Carcinogenesis)
Vol. 17
Issue 3
Pg. 467-75
(Mar 1996)
ISSN: 0143-3334 [Print] England |
PMID | 8631132
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Acetophenones
- Cyclooxygenase Inhibitors
- Lipoxygenase Inhibitors
- phenacyl bromide
- Masoprocol
- Quercetin
- Methionine
- gamma-Glutamyltransferase
- Glutathione Transferase
- Phospholipases A
- Phospholipases A2
- Choline
- Aspirin
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Topics |
- Acetophenones
(pharmacology)
- Animals
- Aspirin
(pharmacology)
- Choline
(administration & dosage)
- Choline Deficiency
- Cyclooxygenase Inhibitors
(pharmacology)
- Fatty Liver
(etiology, prevention & control)
- Glutathione Transferase
(metabolism)
- Lipoxygenase Inhibitors
(pharmacology)
- Liver
(drug effects, enzymology, pathology)
- Liver Cirrhosis, Experimental
(etiology, prevention & control)
- Liver Neoplasms, Experimental
(enzymology, etiology, prevention & control)
- Male
- Masoprocol
(pharmacology)
- Methionine
(administration & dosage)
- Oxidative Stress
- Phospholipases A
(antagonists & inhibitors)
- Phospholipases A2
- Precancerous Conditions
(enzymology, etiology, prevention & control)
- Quercetin
(pharmacology)
- Rats
- Rats, Inbred F344
- Time Factors
- gamma-Glutamyltransferase
(metabolism)
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