Submitted to: Journal of Pharmacology and Experimental Therapeutics Toxicology Section
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/15/1997
Publication Date: N/A
Citation: N/A Interpretive Summary: In much of the corn grown throughout the world, there is found a toxic chemical produced by a common mold that grows within the plant from the time it is a seed. These toxic chemicals are called fumonisins. At the moment we know very little about these toxic chemicals, however, occasionally the amount of the toxic fumonisin in the corn can become quite high and cause the death of farm animals. But what is happening when animals consume small amounts of the fumonisins? We now know that the fumonisin interrupt a pathway of fat metabolism and cause certain very unusual fats to accumulate while some of these unusual fats become depleted. One of the functions of the fats that are changed is to control how cells respond to infections and tissue damage. Thus it is suspected that the changes in these fats inside cells might change the way the body protects itself from disease. In this study we found that the fumonisins did indeed cause changes in certain factors that are very important to the way animals respond to infection, stress, and disease. This work is significant because we need to be able to predict how much fumonisin a farm animal can eat before its ability to repair injury or fight off infection is impaired.
Technical Abstract: Fumonisin B1 is a toxic product of Fusarium moniliforme that 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 s.c. with 0-6.75 mg/kg/d 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 i.p. 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) but not of Interleukin-1-alpha. No effect was seen on interferon gamma production when splenocytes were incubated with concanavalin A. Elevated leukocyte and reticulocyte counts were reversed by pretreatment with anti-TNF antibody after a single dose of fumonisin B1 (25 mg/kg); supporting the hypothesis that the fumonisin B1 toxicity involves TNF. Cultures of J774A.1 cells, when treated with fumonisin B1 produced TNF in vitro. Results indicate that fumonisin B1 toxicity may involve secretion of TNF by TNF producing cells without altering other cytokines. The influence on TNF production may be a contributing factor to fumonisin B1-induced apoptosis and other observed toxic effects in animals.