Demonstration of in-situ apoptosis in mouse liver and kidney after short-term repeated exposure to fumonisin B1.
Fumonisin B1, a mycotoxin produced by Fusarium moniliforme, inhibits the activity of ceramide synthetase, the key enzyme in sphingolipid biosynthesis, leading to accumulation ofsphinganine and sphingosine. Ceramide and other sphingolipid pathways have been implicated in signal-induced apoptosis in cells. Groups of male BALB/c mice received subcutaneous injections (0, 0.25, 0.75, 2.25 or 6.25 mg/kg) of fumonisin B1 daily for 5 days and the liver and kidneys were sampled 1 day after the last injection. A decrease in kidney weight was observed after fumonisin treatment. A "blind" random evaluation of stained sections revealed dose-dependent fumonisin B1-associated hepatic and renal lesions in all groups. Terminal uridine triphosphate (UTP) nick-end labelling (TUNEL) in liver and kidney sections confirmed the presence of dose-related apoptotic cells at all treatment levels. Thus fumonisin B1 produced apoptosis after a brief exposure to relatively low doses. The toxicity of fumonisin B1 was greater than that previously found in studies on oral toxicity.
Sharma
R P
RP
Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens 30602, USA.
Dugyala
R R
RR
Voss
K A
KA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002264:Carboxylic Acids / Q000008:administration & dosage*; D002452:Cell Count / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D037341:Fumonisins; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009183:Mycotoxins / Q000008:administration & dosage*
D002264:Carboxylic Acids; D037341:Fumonisins; D009183:Mycotoxins; C056933:fumonisin B1