Porter J K, Wray E M, Rimando A M, Stancel P C, Bacon C W, Voss K A
Toxicology and Mycotoxin Research Unit, R. B. Russell Agriculture Research Center, Athens, Georgia 30605-2720, USA.
J Toxicol Environ Health. 1996 Oct 11;49(2):161-75. doi: 10.1080/009841096160907.
Fusaric acid is produced by several species of Fusarium and is found in corn, corn-based foods and feeds, wheat, barley, and other cereal grains. Given parenterally to rats, the mycotoxin affects neurochemical parameters in the pineal gland associated with growth and maturation. Since little information exists concerning the dietary effects of fusaric acid, the mycotoxin was mixed with feed at 10, 75, and 200 ppm and fed ad libitum to pregnant rats (F0 dams) from d 11-12 of gestation, through parturition and weaning (F1 generation). On d 4 postpartum, F1 pups were culled to 9-10 pups/litter; the stomach colostrum was collected from the culls and analyzed for fusaric acid. The mycotoxin in the colostrum (ng fusaric acid/100 mg colostrum) was directly related to the amount consumed by the nursing dams (i.e., 200 ppm pups, 3547 ng; 75 ppm pups, 1449 ng; 10 ppm pups, 80 ng; controls pups, 18 ng). All other animals survived, and appeared normal, healthy, and in good pelage. F0 dam feed consumption and dam and pup weights were not statistically different, but there was an inverse relation between pup average weight gain and amount of fusaric acid in the diets (i.e., weight gains: control pup > 10 ppm pup > 75 ppm pups > 200 ppm pups). At weaning, the F1 pups were randomly assigned to two groups per treatment: one group (F1A) for reproduction and fusaric acid effects on the F2 generation, and another group (F1B) for neurochemical comparisons. The F1A rats were maintained on their respective diets to age 13-14 wk; animals were bred (i.e., control males x control females, 10 ppm x 10 ppm, etc.) and the F1A dams and F2 pups were monitored as already described. Weight gains and fusaric acid in stomach colostrum from the F2-culls were analogous to the F1 generation. On d 5-6 and 7-8 postpartum, using litter weight gains as an indication of milk production in the F1A dams (controls vs. 200 ppm), the controls gained 32.5% (p < .01) and 13.3% (p < .02), respectively, more than 200 ppm F2 pups. At weaning, no differences were observed in neurochemicals in the pineal gland for the F1 generation. However, in the F2 200 ppm male and female weanlings, fusaric acid decreased pineal serotonin (males, p < or = .001; females, p < or = .15) and tyrosine (males, p < or = .04; females, p < or = .07). The results indicate fusaric acid in diets at < or = 0.3 ppm (i.e., background control diet) lactationally passes from nursing dams to the neonate; in weanlings, at 200 ppm, fusaric acid decreases pineal serotonin and tyrosine. The data also suggest limited neonate weight gains may be related to either decreased milk production in dams or mycotoxin effects on the neonate. This is the first report of fusaric acid's lactational passage from the feed of nursing dams to neonates and the oral suppression of pineal serotonin and tyrosine in offspring.
镰刀菌酸由多种镰刀菌产生,存在于玉米、玉米类食品和饲料、小麦、大麦及其他谷物中。给大鼠注射该霉菌毒素后,其会影响松果体中与生长和成熟相关的神经化学参数。由于关于镰刀菌酸饮食影响的信息较少,于是将该霉菌毒素以10、75和200 ppm的浓度混入饲料中,从妊娠第11 - 12天起随意喂食怀孕大鼠(F0代母鼠),直至分娩和断奶(F1代)。产后第4天,将F1代幼崽每窝挑选至9 - 10只;从挑选出的幼崽中收集胃初乳并分析其中的镰刀菌酸。初乳中的霉菌毒素(纳克镰刀菌酸/100毫克初乳)与哺乳母鼠的摄入量直接相关(即200 ppm组幼崽,3547纳克;75 ppm组幼崽,1449纳克;10 ppm组幼崽,80纳克;对照组幼崽,18纳克)。所有其他动物均存活,且外观正常、健康,被毛良好。F0代母鼠的饲料消耗量以及母鼠和幼崽的体重无统计学差异,但幼崽平均体重增加量与饲料中镰刀菌酸含量呈负相关(即体重增加量:对照组幼崽>10 ppm组幼崽>75 ppm组幼崽>200 ppm组幼崽)。断奶时,将F1代幼崽按每种处理随机分为两组:一组(F1A)用于繁殖及研究镰刀菌酸对F2代的影响,另一组(F1B)用于神经化学比较。F1A组大鼠维持各自的饮食至13 - 14周龄;进行繁殖(即对照组雄鼠×对照组雌鼠、10 ppm组雄鼠×10 ppm组雌鼠等),并如前所述监测F1A代母鼠和F2代幼崽。F2代挑选出的幼崽胃初乳中的体重增加量和镰刀菌酸与F1代相似。产后第5 - 6天和7 - 8天,以窝仔体重增加量作为F1A代母鼠(对照组与200 ppm组)产奶量的指标,对照组分别比200 ppm组F2代幼崽多增重32.5%(p<0.01)和13.3%(p<0.02)。断奶时,F1代松果体中的神经化学物质未观察到差异。然而,在F2代200 ppm组的雄性和雌性断奶幼崽中,镰刀菌酸降低了松果体中的血清素(雄性,p≤0.001;雌性,p≤0.15)和酪氨酸(雄性,p≤0.04;雌性, p≤0.07)。结果表明,饮食中≤0.3 ppm(即背景对照饮食)的镰刀菌酸在哺乳期从哺乳母鼠传递给新生儿;在断奶幼崽中,200 ppm的镰刀菌酸会降低松果体中的血清素和酪氨酸。数据还表明,新生儿体重增加受限可能与母鼠产奶量减少或霉菌毒素对新生儿的影响有关。这是关于镰刀菌酸从哺乳母鼠饲料经乳汁传递给新生儿以及对后代松果体血清素和酪氨酸产生口服抑制作用的首次报道。