Interaction between aflatoxin B1 and oxytetracycline in isolated rat hepatocytes.
Isolated rat hepatocytes were used as an in vitro model to investigate a possible interaction between oxytetracycline (OXT) and aflatoxin B1 (AFB1). LDH leakage, RNA and protein synthesis and glycogen accumulation were measured in the presence of both drugs, either separately or in combination. The evolution of LDH leakage during the incubation was identical in untreated and treated cells. AFB1 inhibited RNA and protein synthesis at a concentration of 10(-7) M and 10(-6) M, respectively, and higher, whereas OXT did not influence RNA synthesis but inhibited protein synthesis at the highest tested concentration, 10(-3) M. As far as glycogen is concerned, rats were injected with glucagon before sacrifice in order to obtain a constant synthesis rate in isolated hepatocytes. AFB1 inhibited the accumulation of glycogen from 10(-6) M upward. This effect was never observed before 90 min of incubation. OXT had no effect on glycogen synthesis. In the presence of both drugs, no interaction was demonstrated as far as RNA and protein synthesis were concerned, but OXT opposed the inhibition induced by AFB1 on glycogen accumulation. If the "in vivo" protection, provided by OXT against AFB1-induced toxicity, is due to a direct interference in the toxic mechanisms of the mycotoxin, these results show that OXT does not influence the AFB1-inhibition of RNA and protein synthesis. The latter are early and sensitive parameters inhibited by AFB1. On the contrary, taking into consideration the results on glycogen accumulation, it seems more interesting to investigate further this metabolism.
Blaude
M N
MN
Unit of Biochemical Toxicology and Cancerology, School of Pharmacy, Université Catholique de Louvain, Brussels, Belgium.
Goethals
F M
FM
Ansay
M A
MA
Roberfroid
M B
MB
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D004347:Drug Interactions; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D010118:Oxytetracycline / Q000008:administration & dosage / Q000494:pharmacology*; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D000348:Aflatoxins; D008112:Liver Glycogen; D012313:RNA; D016604:Aflatoxin B1; D010118:Oxytetracycline