van der Westhuizen L, Shephard G S, van Schalkwyk D J
Programme on Mycotoxins and Experimental Carcinogenesis, Medical Research Council, PO Box 19070, 7505, Tygerberg, South Africa.
Toxicon. 2001 Jul;39(7):969-72. doi: 10.1016/s0041-0101(00)00235-x.
Fumonisins occur widely around the world in maize products intended for human and animal consumption posing a health hazard. Direct measurement of fumonisins in physiological fluids as a biomarker of exposure is not practicable, however fumonisins disrupt sphingoid metabolism by inhibition of sphinganine N-acyltransferase. In this study the disruption in sphinganine (Sa) and sphingosine (So) levels in plasma and urine was measured in vervet monkeys (Cercopithecus aethiops) dosed with repeated gavages of 1mg fumonisin B1 (FB1)/kg body weight three times/week continuously over a 51-day period. The plasma Sa/So ratio reached a maximum (mean of 4.3) after 30 days in the dosed monkeys with a three-fold increase above the ratio of the control monkeys and then declined slowly to double the value in controls after 51 days. The lack of a clear elevation in urinary Sa/So ratios after 51 days of multiple exposure in the dosed monkeys indicates that the plasma ratio is more sensitive than urinary changes in monkeys. This is confirmed by the plasma levels of liver function enzymes of which aspartate transaminase, glutamyl-transferase and lactate dehydrogenase were increased in the dosed monkeys, while the plasma indicators of renal function were not increased above the levels in the control monkeys. Thus repeated low doses of FB1 can cause sustained disruption of sphingoid metabolism.
伏马毒素在世界各地广泛存在于供人类和动物食用的玉米制品中，对健康构成危害。直接测量生理体液中的伏马毒素作为接触生物标志物并不可行，然而伏马毒素通过抑制鞘氨醇N-酰基转移酶破坏鞘脂类代谢。在本研究中，对绿猴（长尾黑颚猴）连续51天每周三次重复灌胃1mg伏马毒素B1（FB1）/kg体重，测量其血浆和尿液中鞘氨醇（Sa）和鞘氨醇（So）水平的变化。给药猴子在30天后血浆Sa/So比值达到最高（平均为4.3），比对照猴子的比值增加了三倍，然后在51天后缓慢下降至对照猴子的两倍。给药猴子多次接触51天后尿Sa/So比值没有明显升高，表明血浆比值比猴子尿液变化更敏感。这通过血浆肝功能酶水平得到证实，给药猴子中天门冬氨酸转氨酶、谷氨酰转移酶和乳酸脱氢酶升高，而血浆肾功能指标未高于对照猴子的水平。因此，重复低剂量的FB1可导致鞘脂类代谢持续紊乱。
