Porter J K, Bacon C W, Wray E M, Hagler W M
Toxicology and Mycotoxin Research Unit, USDA/ARS, Richard B. Russell Agricultural Research Center, Athens, GA 30605-5677, USA.
Nat Toxins. 1995;3(2):91-100. doi: 10.1002/nt.2620030206.
Fusaric acid is produced by several species of Fusarium, which commonly infect corn and other agricultural commodities. Since this mycotoxin may augment the effects of other Fusarium toxins, a gas chromatography/mass spectrometry method of analysis in feeds was developed. Fusaric acid was analyzed as the trimethylsilyl-ester from F. moniliforme-cultures, -contaminated corn screenings, and feeds toxic to livestock. The mycotoxin was found in all samples and ranged from 0.43 to 12.39 micrograms/g sample. Also, fusaric acid was tested for its neurochemical effects in the brain and pineal gland of rats. Animals were dosed intraperitoneally (100 mg/kg body weight) 30 min prior to the onset of the dark phase (lights out) and the effects were studied at 1.5, 3.5, and 5.5 h after treatment. Brain serotonin (5HT), 5-hydroxyindoleacetic acid (5HIAA), tyrosine (TYRO), and dopamine (DA) were increased (P < 0.05) by fusaric acid, and norepinephrine (NEpi) was decreased (P < 0.05). Analogously, DA in the pineal gland increased and NEpi decreased (P < 0.05). Pineal N-acetylserotonin (NAc5HT) was increased (P < 0.05), whereas pineal 5HT and its two major metabolites 5HIAA and 5-hydroxytryptophol (5HTOL) decreased (P < 0.05). Elevated brain TYRO and brain and pineal DA, with decreased NEpi, may be consistent with fusaric acid's partial inhibitory effect on tyrosine-hydroxylase and its inhibitory effect on dopamine-beta-hydroxylase, respectively. Elevated pineal Nac5HT is consistent with decreased pineal 5HT and the increased pineal DA, and support the dopaminergic stimulatory activity of the enzyme responsible for the conversion of 5HT to NAc5HT. This is the first report of fusaric acid's in vivo effect on pineal DA, NEpi, 5HT, and NAc5HT in rats, and a relation for the effects on TYRO, 5HT, and 5HIAA in brain tissue. The results indicate fusaric acid alters brain and pineal neurotransmitters and may contribute to the toxic effects of Fusarium-contaminated feeds.
镰刀菌酸由多种镰刀菌产生，这些镰刀菌通常会感染玉米和其他农产品。由于这种霉菌毒素可能会增强其他镰刀菌毒素的作用，因此开发了一种用于分析饲料的气相色谱/质谱分析法。镰刀菌酸被分析为来自串珠镰刀菌培养物、受污染的玉米筛屑以及对家畜有毒的饲料中的三甲基硅烷基酯。在所有样品中均发现了这种霉菌毒素，含量范围为每克样品0.43至12.39微克。此外，还测试了镰刀菌酸对大鼠大脑和松果体的神经化学作用。在黑暗期（熄灯）开始前30分钟，给动物腹腔注射（100毫克/千克体重），并在处理后1.5、3.5和5.5小时研究其作用。镰刀菌酸使大脑中的血清素（5HT）、5-羟基吲哚乙酸（5HIAA）、酪氨酸（TYRO）和多巴胺（DA）增加（P<0.05），去甲肾上腺素（NEpi）减少（P<0.05）。类似地，松果体中的DA增加，NEpi减少（P<0.05）。松果体N-乙酰血清素（NAc5HT）增加（P<0.05），而松果体中的5HT及其两种主要代谢产物5HIAA和5-羟基色醇（5HTOL）减少（P<0.05）。大脑中TYRO以及大脑和松果体中DA的升高，同时NEpi降低，可能分别与镰刀菌酸对酪氨酸羟化酶的部分抑制作用及其对多巴胺-β-羟化酶的抑制作用一致。松果体中Nac5HT升高与松果体中5HT降低和松果体中DA增加一致，并支持负责将5HT转化为NAc5HT的酶的多巴胺能刺激活性。这是关于镰刀菌酸对大鼠松果体DA、NEpi、5HT和NAc5HT的体内作用以及对脑组织中TYRO、5HT和5HIAA作用关系的首次报道。结果表明，镰刀菌酸会改变大脑和松果体中的神经递质，并可能导致受镰刀菌污染饲料的毒性作用。
