Fumonisin B1 - WikiHQ

Fumonisin B1 is the most prevalent member of a family of toxins, known as fumonisins, produced by multiple species of Fusarium molds, such as Fusarium verticillioides, which occur mainly in maize (corn), wheat and other cereals. Fumonisin B1 contamination of maize has been reported worldwide at mg/kg levels. Human exposure occurs at levels of micrograms to milligrams per day and is greatest in regions where maize products are the dietary staple.

Fumonisin B1 is hepatotoxic and nephrotoxic in all animal species tested. The earliest histological change to appear in either the liver or kidney of fumonisin-treated animals is increased apoptosis followed by regenerative cell proliferation. While the acute toxicity of fumonisin is low, it is the known cause of two diseases which occur in domestic animals with rapid onset: equine leukoencephalomalacia and porcine pulmonary oedema syndrome. Both of these diseases involve disturbed sphingolipid metabolism and cardiovascular dysfunction.

History

[[Image:Corn mold.jpg|right|thumb|Figure 1: Fusarium ear rot, caused by the fungi Fusarium verticillioides and F. proliferatum, may typically be a more common ear rot of corn.

Source: UIUC available at: http://www.extension.umn.edu/cropenews/2007/07MNCN42.html

]]

In 1970, an outbreak of leukoencephalomalacia in horses in South Africa was associated with the contamination of corn with the fungus Fusarium verticillioides. It is one of the most prevalent seed-borne fungi associated with corn. Another study was done on the possible role of fungal toxins in the etiology of human esophageal cancer in a region in South Africa. The diet of the people living in this area was homegrown corn and F. verticillioides was the most prevalent fungus in the corn consumed by the people with high incidence of esophageal cancer. The structures were elucidated in collaboration with the Council for Scientific and Industrial Research. Several isomers of fumonisin B1 have been detected in solid rice culture. Now more than 100 different fumonisins are known, the most important ones being fumonisin B1, B2 and B3.

Toxicokinetics

Regarding toxicokinetics there is no human data available, but research on animals has been done.

Absorption

FB1 is taken orally via food. Overall, FB1 is poorly absorbed, less than 6%.

Absorption of orally administered fumonisin B1 (10 mg/kg body weight) to rats is low (3.5% of dose) but rapid (Tmax = 1.02 h).

FB1 does not significantly permeate through the human skin and hence has no significant systemic health risk after dermal exposure.

Distribution

After absorption, some appears to be retained in liver and kidneys. For rats that were fed diets containing fumonisins for several weeks, the concentrations of the fumonisins in the kidneys were approximately 10-fold higher than in the liver.

Plasma distribution of the absorbed dose conformed to a two-compartment open model and the tissue (liver, kidney) concentration time results were consistent with a one-compartment open model.]]

Figure 2 shows the sphingolipid metabolism (schematic) and the inhibition caused by fumonisins. Fumonisin B1 inhibits the enzyme ceramide synthase (sphingosine N-acyltransferase), which acylates sphingoid bases. This blocks the formation of ceramide via two pathways. It inhibits de formation via de novo sphinganine and fatty acyl-CoA and via sphingosine produced by the breakdown of ceramide by ceramidase.

The inhibition results in increased concentrations of sphinganine, sphingosine and their 1-phosphate metabolites and in decreased concentrations of complex sphingolipids.

The accumulation of sphinganine and sphingosine is a primary cause of the toxicity of fumonisin B1 Sphinganine and sphingosine are cytotoxic, and have growth inhibitory effects. Also, these sphingoid bases induce apoptosis. Increased apoptosis seems to play an important role in the toxic effects including tumor induction.

Also, the decreased concentrations of complex sphingolipids appear to play a role in the abnormal behavior and altered morphology of the affected cells.

Until now, nothing about the kinetics and metabolism of fumonisin B1 in humans have been reported. On other animals much research has been done, but it might not be comparable to humans. In mice the elimination of FB1 is very rapid, but in humans it could be much slower considering their body weight. Epidemiological studies and clinical trials have pointed out folate deficiency as a major risk factor for neural tube defects. FB1 disrupts sphingolipid metabolism and therefore this could affect folate uptake and cause neural tube defects. Regions in China and South Africa with high corn consumption also have a high prevalence of neural tube defects.

Esophageal cancer

It is thought that there is a relationship between the occurrence of F. verticillioides and human esophageal cancer. A low socioeconomic status and a less varied diet, that mainly consists of corn and wheat, is associated with the appearance of esophageal cancer. On top of this it seems that people with a high corn intake are at higher risk to develop esophageal cancer than people with low corn intake. This is observed by people in regions in Italy, Iran, Kenia, Zimbabwe, United States and Brazil with high incidence of esophageal cancer.

Another study on the relationship between sphingolipid levels and cancer incidence did not show any significant relationship between serum sphingolipids and risk of esophageal cancer. This is quite remarkable, because elevated levels of sphingolipids sphinganine and sphingosine are believed to be biomarkers for exposure of FB1. In pigs and rats there is a wide distribution of FB1 and small amounts have been found to accumulate only in liver and kidneys. In vervet monkeys, some FB1 is partially hydrolyzed in the gut.

Porcine pulmonary edema

Porcine pulmonary edema due to FB1 is intensively studied after the first report in 1981 of swine with pulmonary edema after exposure to corn contaminated with F. verticillioides. Alteration in sphingolipid biosynthesis are reported, especially in lung, heart, kidney and liver tissue. Lethal pulmonary edema was developed within 4–7 days after exposure to feed with concentrations of FB1 >16 mg/kg body weight (>92 parts per million). Doses of 10 parts per million caused a milder form of pulmonary edema.

Toxicity in laboratory animals

Effects of feeding rats with FB1 for up to 90 days were usually nephrotoxicity. Between different strains of rats, sensitivity to FB1 varied. In the kidneys the main effect was apoptosis. Also tubular atrophy and regeneration as well as decreased kidney weight was reported.

References

External links

International Agency for Research on Cancer (IARC) - review on Fumonisin B11
Fumonisin Toxicosis, Merck Veterinary Manual