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De novo synthesis of sphingolipid and metabolism. Fumonisin B1 (FB1) inhibits ceramide synthase and results in the accumulation of sphinganine and sphingosine. Blockade of ceramide synthase by FB1 results in the decrease of the level of ceramide.
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Fumonisin B1 (FB1) structurally resembles sphingolipids and interferes with their metabolism leading to sphingolipid dysregulation. We questioned if FB1 could exacerbate liver or kidney toxicities in glutathione peroxidase 1 (Gpx1) and catalase (Cat) knockout mice. While higher serum levels of thiobarbituric acid reactive substances (TBARS) and sph...
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... were present. When we see the pathway of de novo synthesis of sphingolipid and its metabolism, we can understand why the level of Sa (So) was elevated but the level of Cer was decreased after FB1 treatment in mice. FB1 inhibits ceramide synthase and results in the accumulation of Sa and So. Blockade of ceramide synthase by FB1 resulted in (Fig. 6). FB1 toxicity in mice was accompanied by marked elevation of Sa levels in liver and kidney tissues. While in Gpx1/Cat KO mice with their wild type counter parts, we found So and Sa concentrations were less in tissue homogenates obtained from Gpx1/Cat KO mice than wild type mice. We speculated that this could be due to the accumulation ...
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... Fumonisin B1 disrupts the de novo synthesis of sphingolipids due to inhibition of the crucial ceramide synthase enzyme, resulting mainly in a build-up of Sa, causing a timedependent increase in the Sa/So ratio [43,44]. This correlates to the findings in this study, where the increase of the ratio in the placebo group was attributed to an increase in Sa. ...
Fumonisins, a group of highly prevalent and toxic mycotoxins, are suspected to be causal agents of several diseases in animals and humans. In the animal feed industry, fumonisin esterase is used as feed additive to prevent mycotoxicosis caused by fumonisins. In humans, a popular dosage form for dietary supplements, with high patient acceptance for oral intake, is capsule ingestion. Thus, fumonisin esterase provided in a capsule could be an effective strategy against fumonisin intoxication in humans. To determine the efficacy of fumonisin esterase through capsule ingestion, two modes of application were compared using piglets in a small-scale preliminary study. The enzyme was administered intraorally (in-feed analogue) or intragastrically (capsule analogue), in combination with fumonisin B1 (FB1). Biomarkers for FB1 exposure; namely FB1, hydrolysed FB1 (HFB1) and partially hydrolysed forms (pHFB1a and pHFB1b), were measured both in serum and faeces using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and toxicokinetic parameters were calculated. Additionally, the serum sphinganine/sphingosine (Sa/So) ratio, a biomarker of effect, was determined using LC-MS/MS. A significantly higher Sa/So ratio was shown in the placebo group compared to both esterase treatments, demonstrating the efficacy of the esterase. Moreover, a significant decrease in serum FB1 area under the concentration-time curve (AUC) and an increase of faecal HFB1 AUC were observed after intraoral esterase administration. However, these effects were not observed with statistical significance after intragastric esterase administration with the current sample size.
... Fumonisin B1 disrupts the de novo synthesis of sphingolipids due to inhibition of the crucial ceramide synthase enzyme, resulting mainly in a build-up of Sa, causing a timedependent increase in the Sa/So ratio [70,279]. This correlates to the findings in this study, ...
In sub-Sahara Afrika blijft besmetting van gewassen met mycotoxigene schimmels een groot probleem. Hun secondaire metabolieten, mycotoxinen, kunnen ernstige gezondheidsproblemen veroorzaken na opname door zowel dier als mens. In Afrika doet het grootste deel van de bevolking aan zelfvoorzienende landbouw. Hierdoor ontlopen hun geteelde producten iedere vorm van controle, en is er een reële kans op mycotoxinebesmetting, wat voedselveiligheid en -zekerheid in gevaar brengt. Vooral de mycotoxinen aflatoxine B1 (AFB1) en fumonisine B1 (FB1), die regelmatig maïs en pindanoten en hun afgeleide producten besmetten, baren grote zorgen. Bovendien is maïs een basisvoedsel in vele Afrikaanse landen, waardoor het risico van en de blootstelling aan deze specifieke mycotoxinen verhoogd is.
... Anyway, the molecular mechanisms behind fumonisin toxicity in liver and kidney are supposed to be linked with early events of oxidative stress [33], but the role of them in the male reproductive organs is less studied. As well, a direct link between fumonisins and the glutathione redox system is not fully elucidated; in glutathione peroxidase-1/catalase knocked out (KO) mice FB1 toxicity was not influenced by the existence or lack of the induced mutation (KO), referring to a likewise indirect relationship between FB1 and oxidative stress [34]. If fumonisin is really not a direct induction factor of the slight oxidative stress detected, then there shall be a plausible alternative process responsible for the dose dependent increase in the tissue GSH level and the associated reaction of GSHPx. ...
... We assume that quickly proliferating cells (like hepatic and germinal cells) of rabbits may be prone for FBs induced oxidative stress at a subclinical intoxication level, without markedly compromised function. A more general view might be the supposal of slight cellular apoptosis and necrosis, which has only been shown in the renal and hepatic cases [34], but this has not been proven or tested in this study. Ultimately, it shall be added that FBs acted like a slight prooxidants in the rabbit testis, augmenting non-enzymatic and enzymatic adaptation (GSH and GSHPx), leading to the lowered concentration of conjugated fatty acid derivatives (dienes and trienes), as early phase lipid peroxidation indicators. ...
A 65-day study was undertaken to test the effects of two doses (10 and 20 mg/kg) of dietary fumonisin Bs (FB) on the rabbit male reproduction system. Body and testicular weight was not affected by the intoxication, neither the fatty acid composition of the testicular total phospholipids; the testis histological analysis failed to reveal any toxic effect. The FBs increased the testicular concentration and activity of reduced glutathione and glutathione peroxidase and decreased initial phase lipid peroxidation (conjugated dienes and trienes) in a dose dependent manner. Sperm morphology and chromatin condensation were monitored on Feulgen-stained smears. No significant differences were observed between the treatment groups and between sampling time points. The live cell ratio in the sperm (as assessed with flow cytometry) was not different among groups at any of the five sampling timepoints and was also identical within groups. Similarly, the spermatozoa membrane lipid profile was also identical in all three groups after the total intoxication period. In summary, it was demonstrated that FBs in an unrealistic and unjustified high dose still do not exert any drastic harmful effect on the leporine, male reproduction system, meanwhile slightly augmenting testicular antioxidant response.
Fumonisin B1 (FB1) contaminates various crops, causing huge losses to agriculture and livestock worldwide. This review summarizes the occurrence regularity, toxicity, toxic mechanisms and management strategies of FB1. Specifically, FB1 contamination is particularly serious in developing countries, humid and hot regions. FB1 exposure can produce different toxic effects on the nervous system, respiratory system, digestive system and reproductive system. Furthermore, FB1 can also cause systemic immunotoxicity. The mechanism of toxic effects of FB1 is to interfere with the normal pathway of sphingolipid de novo biosynthesis by acting as a competitive inhibitor of ceramide synthase. Meanwhile, the toxic products of sphingolipid metabolic disorders can cause oxidative stress and apoptosis. FB1 also often causes feed contamination by mixing with other mycotoxins, and then exerts combined toxicity. For detection, lateral flow dipstick technology and enzyme linked immunosorbent assay are widely used in the detection of FB1 in commercial feeds, while mainstream detection methods such as high performance liquid chromatography and liquid chromatography-mass spectrometry are widely used in the laboratory theoretical study of FB1. For purification means of FB1, some natural plant extracts (such as Zingiber officinale and Litsea Cubeba essential oil) and their active compounds have been proved to inhibit the toxic effects of FB1 and protect livestock due to their antifungal and antioxidant effects. Natural plant extract has the advantages of high efficiency, low cost and no contamination residue. This review can provide information for comprehensive understanding of FB1, and provide reference for formulating reasonable treatment and management strategies in livestock production.
