The effect of repeated gavage doses of fumonisin B1 on the sphinganine and sphingosine levels in vervet monkeys.
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.
Programme on Mycotoxins and Experimental Carcinogenesis, Medical Research Council, PO Box 19070, 7505, Tygerberg, South Africa. liana.van.der.westhuizen@mrc.ac.za
L
L
van der Westhuizen
G S
GS
Shephard
D J
DJ
van Schalkwyk
D000818:Animals; D002264:Carboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000097:blood; D005260:Female; D037341:Fumonisins; D007441:Intubation, Gastrointestinal; D007677:Kidney Function Tests; D008111:Liver Function Tests; D009183:Mycotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism*
D002264:Carboxylic Acids; D037341:Fumonisins; D009183:Mycotoxins; C056933:fumonisin B1; D002784:Cholesterol; D013110:Sphingosine; C005682:safingol