The effects of D-fenfluramine on the development of aflatoxin-B1 induced GGT+ hepatic foci in F344 rats.
The role of total caloric intake and attained body weight in the carcinogenic process in rodents is controversial. In the present study we examined the development of hepatic pre-neoplastic foci in rats treated with aflatoxin-B1 (AFB) and given the drug D-fenfluramine (FEN). Ingestion of this drug leads to a reduction in body weight by increasing the thermogenic response to a meal and by transiently reducing food intake. Young male rats were dosed with AFB or vehicle alone and were then assigned to receive control diet (NO FEN) or control diet + FEN (FEN; 0.15 g/kg diet) for 12-14 weeks. Body weight gain and food intake were reduced among animals given FEN; brown adipose tissue weight (% body weight) was elevated in these groups. Indices of protein status, and concentrations of T3, T4 and insulin did not differ among the groups. All animals given FEN developed GGT+ hepatic foci. The number and volume fraction of foci were significantly larger in FEN relative to NO FEN animals. The mean diameter of foci was slightly enhanced among FEN animals. These results suggest that FEN promotes the development of AFB-induced hepatocellular foci, despite reduced food intake and lower body weight. Since FEN is widely used as a weight loss aid, these findings deserve further study.
Bell
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Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853.
Levitsky
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Campbell
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D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D016604:Aflatoxin B1; D000818:Animals; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D004032:Diet; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005277:Fenfluramine / Q000008:administration & dosage / Q000494:pharmacology*; D007473:Ion Channels; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D000071256:Uncoupling Protein 1; D005723:gamma-Glutamyltransferase
D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D000071256:Uncoupling Protein 1; D005277:Fenfluramine; D016604:Aflatoxin B1; D005723:gamma-Glutamyltransferase