Tumor necrosis factor-alpha as a contributor in fumonisin B1 toxicity.
Fumonisin B1 is a toxic product of Fusarium moniliforme, which inhibits ceramide synthase, leading to accumulation of free sphingoid bases. Despite its known biochemical action, the mechanism of toxicity is not fully understood. Male BALB/c mice were injected subcutaneously with 0 to 6.75 mg/kg/day of fumonisin B1 for 5 days. One day after the last treatment, spleens were collected, and peritoneal macrophages were obtained from separate groups after an intraperitoneal injection of thioglycolate broth. Peripheral leukocyte counts were increased and kidney weights were decreased by fumonisin B1 treatment. Presence of apoptotic cells in the liver and kidney of treated mice was confirmed by enzymatic immunoassay. Macrophages cultured with lipopolysaccharide indicated an increased secretion of tumor necrosis factor-alpha (TNF-alpha) but not of interleukin-1alpha. No effect was seen on interferon-gamma production when splenocytes were incubated with concanavalin A. Elevation of leukocyte and reticulocyte counts was abrogated by pretreatment with anti-TNF-alpha antibody before a single dose of fumonisin B1 (25 mg/kg), supporting the hypothesis that the fumonisin B1 toxicity involves TNF-alpha. Cultures of J774A.1 cells, when treated with fumonisin B1, produced TNF-alpha in vitro. Results indicate that fumonisin B1 toxicity may involve secretion of TNF-alpha by TNF-alpha-producing cells without altering interleukin-1alpha or interferon-gamma. The influence on TNF-alpha-production may be a contributing factor to fumonisin B1-induced apoptosis and other observed toxic effects in animals.
Dugyala
R R
RR
Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, Georgia 30602-7389, USA.
Sharma
R P
RP
Tsunoda
M
M
Riley
R T
RT
D000818:Animals; D017209:Apoptosis; D002264:Carboxylic Acids / Q000633:toxicity*; D037341:Fumonisins; D007371:Interferon-gamma / Q000187:drug effects / Q000502:physiology; D007375:Interleukin-1 / Q000502:physiology; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D007958:Leukocyte Count / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D013723:Teratogens / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000276:immunology / Q000502:physiology
D002264:Carboxylic Acids; D037341:Fumonisins; D007375:Interleukin-1; D013723:Teratogens; D014409:Tumor Necrosis Factor-alpha; C056933:fumonisin B1; D007371:Interferon-gamma