Analytical method for the determination of sphinganine and sphingosine in serum as a potential biomarker for fumonisin exposure

Castegnaro, M.; Garren, Liliane; Galendo, D.; Gelderblom, Wentzel C. A.; Chelule, Paul Kiprono; Dutton, Michael F.; Wild, C.

doi:10.1016/s0378-4347(98)00446-0

Cited by 48 publications

(29 citation statements)

References 23 publications

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“…Entretanto, um problema encontrado é o nível extremamente baixo das bases esfingóides na urina de seres humanos do sexo masculino, tornando-se necessário a utilização de grandes volumes de urina (CASTEGNARO et al, 1998; VAN DER WESTHUIZEN et al, 1999).…”

Section: Relação Sa:sounclassified

Fumonisinas: efeitos toxicológicos, mecanismo de ação e biomarcadores para avaliação da exposição

et al. 2004

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ResumoFumonisinas são toxinas produzidas por Fusarium verticillioides Sacc. Niremberg (F. moniliforme Sheldon), patógeno primário de milho, que está implicado em inúmeras doenças animais, com ênfase em leucoencefalomalácia em eqüinos, edema pulmonar em suínos e carcinomas hepáticos e renais em ratos e camundongos. Em seres humanos, os estudos epidemiológicos têm associado o consumo de milho altamente contaminado com fumonisinas ao câncer esofágico em populações da China e África do Sul. Além disso, a contaminação de milho por Fusarium spp. causa perdas econômicas consideráveis em todo o mundo. Estruturalmente, a fumonisina B 1 (FB 1 ) assemelha-se às bases esfingóides, sendo a toxicidade e carcinogenicidade associada à capacidade de inibir a ceramida sintetase, uma enzima chave na via de biossíntese dos esfingolipídeos, causando acúmulo de esfinganina e depleção de esfingolipídeos complexos importantes nas funções celulares. Devido à ocorrência global, as fumonisinas têm sido alvo de intensas investigações na tentativa de desenvolver biomarcadores capazes de avaliar a exposição à FB 1 e, estabelecer os níveis de contaminação que não causem danos à saúde humana e animal. Esta revisão apresenta os principais aspectos referentes à toxicidade de fumonisinas em animais e sistemas in vitro, aliado ao mecanismo de ação bioquímica e aos biomarcadores visando avaliação da exposição. Palavras-chave: Fumonisinas, esfingolipídios, Fusarium verticillioides, biomarcadores, milho. AbstractFumonisins, mycotoxins produced by Fusarium verticillioides Sacc. Niremberg (F. moniliforme Sheldon), the prevalent seed borne fungus of corn (Zea mays), have been associated with several animal diseases, such as equine leukoencephalomalacia, porcine pulmonary edema and hepatic and renal carcinomas in rats and mice. Epidemiological studies have linked consumption of fumonisin-contaminated corn with esophageal cancer in human populations in China and South Africa. In addition, fungal growth and further corn contamination by fumonisins cause great economic losses throughout the world. The

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Section: Relação Sa:sounclassified

Fumonisinas: efeitos toxicológicos, mecanismo de ação e biomarcadores para avaliação da exposição

et al. 2004

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“…Notably, based on the above-mentioned inhibition of sphingolipid biosynthesis, an alteration in the ratio of sphinganine/sphingosine can be detected in tissues, blood, and urine following fumonisin exposure (18,19). In animal studies, this ratio has been shown to closely reflect the dose of fumonisin administered (12,18). However, in studies in human populations, the altered ratio appears to have limited sensitivity to detect environmental levels of exposure (19,20).…”

Section: Introductionmentioning

confidence: 99%

Association between Tortilla Consumption and Human Urinary Fumonisin B1 Levels in a Mexican Population

Gong

Torres‐Sánchez

López‐Carrillo

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Fumonisins are mycotoxins produced by Fusarium spp. and commonly contaminate maize and maize products worldwide. Fumonisins are rodent carcinogens and have been associated with human esophageal cancer. However, the lack of a valid exposure biomarker has hindered both the assessment of human exposure and the evaluation of disease risk. A sensitive liquid chromatography-mass spectrometry method to measure urinary fumonisin B1 (FB1) following extraction on Oasis MAX cartridges was established and applied to urine samples from women in a cohort recruited in Morelos County, Mexico. Urinary FB1 was compared with dietary information on tortilla consumption. FB1 recovery in spiked samples averaged 94% as judged by deuterium-labeled FB1 internal standard. Urinary FB1 was determined in 75 samples from women selected based on low, medium, or high consumption of maizebased tortillas. The geometric mean (95% confidence interval) of urinary FB1 was 35.0 (18.8-65.2), 63.1 (36.8-108.2), and 147.4 (87.6-248.0) pg/mL and the frequency of samples above the detection limit (set at 20 pg FB1/mL urine) was 45%, 80%, and 96% for the low, medium, and high groups, respectively. Women with high intake had a 3-fold higher average FB1 levels compared with the ''low intake'' group (F = 7.3; P = 0.0015). Urinary FB1 was correlated with maize intake (P trend = 0.001); the correlation remained significant after adjusting for age, education, and place of residence. This study suggests that measurement of urinary FB1 is sufficiently sensitive for fumonisin exposure assessment in human populations and could be a valuable tool in investigating the associated health effects of exposure. (Cancer Epidemiol Biomarkers Prev 2008;17(3):688 -94)

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“…Based on our data, the ability of Sph to inhibit potently and directly thrombin generation extends to reaction mixtures containing purified clotting factors (see below). The strong inhib- (25,26) and because Sph that is locally generated could achieve much higher levels, we speculate that Sph anticoagulant activity could potentially be physiologic.…”

Section: Effect Of Sph and Related Compounds On Plasma Clottingmentioning

confidence: 95%

Sphingolipids as Bioactive Regulators of Thrombin Generation

Deguchi

Yegneswaran

Griffin

2004

Journal of Biological Chemistry

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Sphingolipids contribute to modulation of two opposing cell processes, cell growth and apoptotic cell death; ceramide and sphingosine promote the latter and sphingosine-1-phosphate triggers the former. Thrombin, a pro-inflammatory protease that is regulated by the blood coagulation cascade, exerts similar effects depending on cell type. Here we report a new mechanism for cross-talk between sphingolipid metabolism and thrombin generation. Sphingosine and sphinganine, but not ceramide or sphingosine-1-phosphate, down-regulated thrombin generation on platelet surfaces (IC 50 ‫؍‬ 2.4 and 1.4 M for sphingosine and sphinganine, respectively) as well as in whole plasma clotting assays. Thrombin generation was also inhibited by glucosylsphingosine, lysosphingomyelin, phytosphingosine, and primary alkylamines with >10 carbons. Acylation of the amino group ablated anticoagulant activities. Factor Va was required for the anticoagulant property of sphingosine because prothrombin activation was inhibited by sphingosine, sphinganine, and stearylamine in the presence but not in the absence of factor Va. Sphingosine did not inhibit thrombin generation when Gla-domainless factor Xa was used in prothrombinase assays, whereas sphingosine inhibited activation of Gla-domainless prothrombin by factor Xa/factor Va in the absence of phospholipids (IC 50 ‫؍‬ 0.49 M). Fluorescence spectroscopy studies showed that sphingosine binds to fluoresceinlabeled factor Xa and that this interaction required the Gla domain. These results imply that sphingosine disrupts interactions between factor Va and the Gla domain of factor Xa in the prothrombinase complex. Thus, certain sphingolipids may be bioactive lipid mediators of thrombin generation such that certain sphingolipid metabolites may modulate proteases that affect cell growth and death, blood coagulation, and inflammation.

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Analytical method for the determination of sphinganine and sphingosine in serum as a potential biomarker for fumonisin exposure

Cited by 48 publications

References 23 publications

Fumonisinas: efeitos toxicológicos, mecanismo de ação e biomarcadores para avaliação da exposição

Fumonisinas: efeitos toxicológicos, mecanismo de ação e biomarcadores para avaliação da exposição

Association between Tortilla Consumption and Human Urinary Fumonisin B1 Levels in a Mexican Population

Sphingolipids as Bioactive Regulators of Thrombin Generation

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