Effect of fumonisin B1 on the levels and fatty acid composition of selected lipids in rat liver in vivo.
The modulating role of fumonisin B1 (FB1) on lipid biosynthesis was evaluated in a short-term (21 day) experiment using male Fischer rats fed high dietary levels (50, 100 and 250 mg FB1/kg) and in a long-term (2 yr) experiment using male BD IX rats fed low dietary levels (1, 10 and 25 mg FB1/kg) of FB1. The total serum and liver cholesterol was significantly (P < 0.01) increased in the rats fed 250 mg FB1/kg diet for 21 days, while the liver phospholipids, sphingomyelin and phosphatidylethanolamine (PE) were significantly decreased (P < 0.01) and increased (P < 0.05), respectively. In the long-term study, only PE was significantly (P < 0.05) increased in all the FB1-treated animals. Fatty acid (FA) analysis of PE indicated that C18:2n-6 was significantly increased (P < 0.05 to P < 0.01) in the FB1-treated rats of the short-term study, while it was markedly (not significantly) increased in phosphatidylcholine (PC). The same pattern was observed in the PC and PE fractions of the liver of the FB1-treated rats from the long-term studies, but the changes were not significant due to the small number (three rats per group) of rats analysed. The levels of C22:5n-6 and C22:6n-3 were also markedly decreased and increased respectively in the 10 and 25 mg FB1/kg-treated groups. When the FAs were determined in the total lipids in a larger number of rats (four to six animals per group) the level of C18:2n-6 was significantly increased in the 10 (P < 0.01) and 25 (P < 0.05) mg FB1/kg-treated groups. Similar effects were noticed in plasma PC with respect to the C18:5n-6 and C22:55n-6 in both the long- and short-term treated groups, except that C20:4n-6 was also lower in both cases. The total n-6 FAs and polyunsaturated FAs were significantly (P < 0.01) and markedly reduced in PC and PE, respectively, of the rats fed the 250 mg FB1/kg diet. In the long-term experiment the n-6/n-3 ratio was significantly (P < 0.01) decreased in PE and markedly lowered in PC due to a significant (P < 0.05) increase in the n-3 FAs of both phospholipid fractions. The sphinganine/sphingosine ratio was significantly (P < 0.05) altered in the liver of the rats fed the 100 and 250 mg FB1/kg diets for 21 days, while in the long-term study no significant changes were noticed in either the liver or sera. The present data indicate that FB1 affects lipid biosynthesis in rat liver and plasma differently, depending on the dietary level and duration of treatment. Alterations to the n-3 and n-6 FA biosynthetic pathways, detected in rats fed relatively low dietary levels of FB1, are likely to be important mediators for FB1-induced effects on hepatocyte cell proliferation.
Gelderblom
W C
WC
Programme on Mycotoxins and Experimental Carcinogenesis, Medical Research Council, Tygerberg, South Africa.
Smuts
C M
CM
Abel
S
S
Snyman
S D
SD
Van der Westhuizen
L
L
Huber
W W
WW
Swanevelder
S
S
D000818:Animals; D002264:Carboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D002274:Carcinogens, Environmental / Q000008:administration & dosage / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism*; D037341:Fumonisins; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010743:Phospholipids / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015430:Weight Gain / Q000187:drug effects
D002264:Carboxylic Acids; D002274:Carcinogens, Environmental; D005227:Fatty Acids; D037341:Fumonisins; D010743:Phospholipids; C056933:fumonisin B1; D002784:Cholesterol