In vivo formation of N-acyl-fumonisin B1
详细信息 查看全文
- 作者：Henning Harrer ; Hans Ulrich Humpf ; Kenneth A. Voss
- 关键词：Fumonisin ; Metabolism ; Mycotoxin ; Biodistribution ; N ; acyl ; fumonisins
- 刊名：Mycotoxin Research
- 出版年：2015
- 出版时间：February 2015
- 年：2015
- 卷：31
- 期：1
- 页码：33-40
- 全文大小：551 KB
- 参考文献：1. Bulder AS, Arcella D, Bolger M, Carrington C, Kpodo K, Resnik S, Riley RT, Wolterink G, Wu F (2012) Fumonisins (addendum), in: safety evaluation of certain food additives and contaminants. WHO Food Additives Series 65, World Health Organization. Geneva 65:325-94
2. Burns TD, Snook ME, Riley RT, Voss KA (2008) Fumonisin concentrations and in vivo toxicity of nixtamalized Fusarium verticillioides culture material: evidence for fumonisin-matrix interactions. Food Chem Toxicol 46:2841-848 CrossRef
3. Collins TFX, Sprando RL, Black TN, Olejnik N, Eppley RM, Shackelford ME, Howard PC, Rorie JI, Bryant M, Ruggles DI (2006) Effects of aminopentol on in utero development in rats. Food Chem Toxicol 44:161-69 CrossRef
4. Dragan YP, Bidlack WR, Cohen SM, Goldsworthy TL, Hard GC, Howard PC, Riley RT, Voss KV (2001) Implications of apoptosis for toxicity, carcinogenicity, and risk assessment: fumonisin B1 as an example. Toxicol Sci 61:6-7 CrossRef
5. Gelderblom WC, Jaskiewicz K, Marasas WF, Thiel PG, Horak RM, Vleggaar R, Kriek NP (1988) Fumonisins—novel mycotoxins with cancer-promoting activity produced by Fusarium moniliforme. Appl Environ Microbiol 54:1806-811
6. Gelderblom WCA, Cawood ME, Snyman SD, Vleggaar R, Marasas WFO (1993) Structure-activity relationships of fumonisins in short-term carcinogenesis and cytotoxicity assays. Food Chem Toxicol 31:407-14 CrossRef
7. Gelineau-van Waes J, Starr L, Maddox J, Aleman F, Voss KA, Wilberding J, Riley RT (2005) Maternal fumonisin exposure and risk for neural tube defects: mechanisms in an in vivo mouse model. Birth Defects Res A Clin Mol Teratol 73:487-97 CrossRef
8. Gelineau-van Waes J, Voss KA, Stevens VL, Speer MC, Riley RT (2009) Maternal fumonisin exposure as a risk factor for neural tube defects. Adv Food Nutr Res 56:145-81 CrossRef
9. Gelineau-van Waes J, Rainey MA, Maddox JR, Voss KA, Sachs AJ, Gardner NM, Wilberding JD, Riley RT (2012) Increased sphingoid base-1-phosphates and failure of neural tube closure after exposure to fumonisin or FTY720. Birth Defects Res A Clin Mol Teratol 94:790-03 CrossRef
10. Harrer H, Laviad EL, Humpf HU, Futerman AH (2013) Identification of N-acyl-fumonisin B1 as new cytotoxic metabolites of fumonisin mycotoxins. Mol Nutr Food Res 57:516-22 CrossRef
11. Harrison LR, Colvin BM, Greene JT, Newman LE, Cole JR Jr (1990) Pulmonary edema and hydrothorax in swine produced by fumonisin B1, a toxic metabolite of Fusarium moniliforme. J Vet Diagn Invest 2:217-21 CrossRef
12. Howard PC, Eppley RM, Stack ME, Warbritton A, Voss KA, Lorentzen RJ, Kovach RM, Bucci TJ (2001) Fumonisin b1 carcinogenicity in a two-year feeding study using F344 rats and B6C3F1 mice. Environ Health Perspect 109(Suppl 2):277-82
13. Howard PC, Couch LH, Patton RE, Eppley RM, Doerge DR, Churchwell MI, Marques MM, Okerberg CV (2002) Comparison of the toxicity of several fumonisin derivatives in a 28-day feeding study with female B6C3F(1) mice. Toxicol Appl Pharmacol 185:153-65 CrossRef
14. Hübner F, Harrer H, Fraske A, Kneifel S, Humpf HU (2012) Large scale purification of B-type fumonisins using centrifugal partition chromatography (CPC). Mycotoxin Res 28:37-3 CrossRef
15. Humpf HU, Schmelz EM, Meredith FI, Vesper H, Vales TR, Wang E, Menaldino DS, Liotta DC, Merrill AH Jr (1998) Acylation of naturally occurring and synthetic 1-deoxysphinganines by ceramide synthase. Formation of N-palmitoyl-aminopentol produces a toxic metabolite of hydrolyzed fumonisin, AP1, and a new category of ceramide synthase inhibitor. J Biol Chem 273:19060-9064
文摘
Fumonisins are fungal toxins found in corn and in corn-based foods. Fumonisin B1 (FB1) is the most common and is toxic to animals, causes cancer in rodents, and is a suspected risk factor for cancer and birth defects in humans. The hydrolyzed form of FB1 (HFB1) also occurs in foods and is metabolized by rats to compounds collectively known as N-acyl-HFB1 (also known as N-acyl-AP1). N-acyl-HFB1 is structurally similar to ceramides, metabolites which have important structural and signaling functions in cells. FB1 is N-acylated in vitro to ceramide-like metabolites which, like FB1, are cytotoxic. However, metabolism of FB1 and inhibition of ceramide synthase by its metabolites in vivo has not been demonstrated. Male rats were dosed ip with 0.5, 1, or 2?mg/kg body weight FB1 on five consecutive days and the liver and kidney thereafter processed for chemical analysis. N-acyl derivatives of fumonisin B1 were identified for the first time in these principal target organs of FB1 in rats, at levels up to 0.4?nmol/g tissue using mass spectrometry. The N-acyl chain length of the metabolites varied in a tissue-dependent manner with C16 derivatives predominating in the kidney and C24 derivatives being prevalent in the liver. The toxicological significance of N-acyl-fumonisins is not known and warrants investigation.