Eicosapentaenoic acid inhibits the growth of liver preneoplastic lesions and alters membrane phospholipid composition and peroxisomal beta-oxidation.
The purpose of this study was to determine whether individual administration of highly purified eicosapentaenoic acid (EPA), one of the main components of the n-3 polyunsaturated fatty acid family, would alter the growth of focal lesions during hepatocarcinogenesis. The protocol used to induce chemical carcinogenesis in liver was the Solt-Farber model (diethylnitrosamine as initiator and 2-acetylaminofluorene and carbon tetrachloride associated with partial hepatectomy as promoters). Proliferative lesions were quantified with the histochemical marker gamma-glutamyltranspeptidase at partial hepatectomy and at sacrifice. The number and size of the gamma-glutamyltranspeptidase-positive foci observed were significantly lower in rats supplemented with EPA. Fatty acid treatment increased EPA and docosapentaenoic acid content in membrane total phospholipids, in phosphatidylethanolamine, and in phosphatidylcholine. The content of arachidonic acid decreased significantly only in total phospholipids and in phosphatidylethanolamine. Fatty acid content of phosphatidylinositol was not modified. Moreover, we observed an increase in the activity of palmitoyl-CoA oxidase, the limiting enzyme of peroxisomal beta-oxidation, the preferential metabolic pathway of n-3 polyunsaturated fatty acid. Conversely, unmodified levels of alpha-tocopherol and unchanged production of lipid peroxidation products (malondialdehyde) were observed. These results suggest that the EPA inhibitory effect on preneoplastic foci development may be related to alteration of fatty acid composition in phospholipid classes and to enhancement of peroxisomal beta-oxidation and H2O2 production.
Calviello
G
G
Institute of General Pathology, Catholic University, Rome, Italy.
Palozza
P
P
Franceschelli
P
P
Frattucci
A
A
Piccioni
E
E
Tessitore
L
L
Bartoli
G M
GM
D000818:Animals; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000187:drug effects* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011230:Precancerous Conditions / Q000188:drug therapy*; D051381:Rats; D011916:Rats, Inbred F344
D008563:Membrane Lipids; D010743:Phospholipids; D008315:Malondialdehyde; D015118:Eicosapentaenoic Acid