An overview of rodent toxicities: liver and kidney effects of fumonisins and Fusarium moniliforme.

Fumonisins are produced by Fusarium moniliforme F. verticillioides) and other Fusarium that grow on corn worldwide. They cause fatal toxicoses of horses and swine. Their effects in humans are unclear, but epidemiologic evidence suggests that consumption of fumonisin-contaminated corn contributes to human esophageal cancer in southern Africa and China. Much has been learned from rodent studies about fumonisin B1(FB1), the most common homologue. FB1 is poorly absorbed and rapidly eliminated in feces. Minor amounts are retained in liver and kidneys. Unlike other mycotoxins, fumonisins cause the same liver cancer promotion and subchronic (studies (3/4) 90 days) liver and kidney effects as (italic)F. moniliforme. FB 1 induces apoptosis of hepatocytes and of proximal tubule epithelial cells. More advanced lesions in both organs are characterized by simultaneous cell loss (apoptosis and necrosis) and proliferation (mitosis). Microscopic and other findings suggest that an imbalance between cell loss and replacement develops, a condition favorable for carcinogenesis. On the molecular level, fumonisins inhibit ceramide synthase, and disrupt sphingolipid metabolism and, theoretically, sphingolipid-mediated regulatory processes that influence apoptosis and mitosis. Liver sphingolipid effects and toxicity are correlated, and ceramide synthase inhibition occurs in liver and kidney at doses below their respective no-observed-effect levels. FB1 does not cross the placenta and is not teratogenic in vivoin rats, mice, or rabbits, but is embryotoxic at high, maternally toxic doses. These data have contributed to preliminary risk evaluation and to protocol development for carcinogenicity and chronic toxicity studies of FB1 in rats and mice.

Fusaric acid and modification of the subchronic toxicity to rats of fumonisins in F. moniliforme culture material.

Fumonisins and fusaric acid (FA) are mycotoxins produced by Fusarium moniliforme and other Fusarium which grow on corn. Fumonisins cause animal toxicities associated with F. moniliforme and, like F. monliforme, they are suspected human oesophageal carcinogens. Toxic synergism was obtained by simultaneous administration of FA and fumonisin B1 to chicks in ovo. To determine the effect of FA on in vivo toxicity of F. moniliforme culture material (CM), male rats (12 groups, n = 5/ group) were fed diets containing 0.025, 0.10 or 2.5% CM (providing dietary levels of 3.4, 18.4 or 437 ppm fumonisins, respectively) to which, at each CM level, 0, 20, 100 or 400 ppm FA were added. Additionally, an FA control group was fed 400 ppm FA only and an untreated control group was given neither FA nor culture material. Apoptosis and other effects consistent with those caused by fumonisins were present in the kidneys of animals fed 0.025% or more CM and in the livers of animals fed 2.5% CM. FA was without effect. No differences between the untreated and FA control groups were noted and no differences among the four groups (0-400 ppm FA) fed 0.025% CM, the four groups fed 0.10% CM or the four groups fed 2.5% CM were apparent. Thus, FA exerted no synergistic, additive or antagonistic effects on the subchronic in vivo toxicity of fumonisin-producing F. moniliforme.

Evaluation of sorghum ergot toxicity in broilers.

Three experiments evaluated the performance of broilers fed sorghum ergot consisting of sphacelia/sclerotia of Claviceps africana present in tailings removed by conditioning of seed from grain sorghum hybrid seed production fields near Uvalde (Experiments 1 and 2) and Dumas (Experiment 3), Texas. Percentage sphacelia/sclerotia and total alkaloid content, respectively, in sorghum ergot tailings were 8% and 11.3 ppm for Uvalde and 75% and 235 ppm for Dumas. Sorghum ergot and control sorghum diets were based on the NRC (1994) requirements for starting broilers. In Experiment 1, neither growth nor feed efficiency were significantly reduced in male broilers fed sorghum ergot from hatch to 3 wk of age, but liver weights were significantly greater than those in the control. In Experiment 2, straight-run broilers were raised to 6 wk of age in floor pens using a three-phase feeding program. Sorghum ergot significantly reduced gain in 4-wk-old broilers and cumulative body weight at 5 wk. Feed conversion was significantly reduced during all three phases of feeding. In Experiment 3, control sorghum and the 75% ergot tailings were added to corn-soy basal diets at rates of 2.5, 5, and 10% by weight and fed to male broilers from hatch to 3 wk of age. Sorghum ergot did not significantly reduce growth, but, during Weeks 2 and 3, feed-to-gain ratios were higher. Neither type nor concentration of sorghum ergot significantly affected relative liver weights. We did not observe significant mortality or obvious symptoms of ergot toxicity, such as necrotic lesions of the feet or vesicular dermatitis of the comb, in any of the three experiments.

Antagonist activities of mecamylamine and nicotine show reciprocal dependence on beta subunit sequence in the second transmembrane domain.

We show that a portion of the TM2 domain regulates the sensitivity of beta subunit-containing rat neuronal nicotinic AChR to the ganglionic blocker mecamylamine, such that the substitution of 4 amino acids of the muscle beta subunit sequence into the neuronal beta4 sequence decreases the potency of mecamylamine by a factor of 200 and eliminates any long-term effects of this drug on receptor function. The same exchange of sequence that decreases inhibition by mecamylamine produces a comparable potentiation of long-term inhibition by nicotine. Inhibition by mecamylamine is voltage-dependent, suggesting a direct interaction of mecamylamine with sequence elements within the membrane field. We have previously shown that sensitivity to TMP (tetramethylpiperidine) inhibitors is controlled by the same sequence elements that determine mecamylamine sensitivity. However, inhibition by bis-TMP compounds is independent of voltage. Our experiments did not show any influence of voltage on the inhibition of chimeric receptors by nicotine, suggesting that the inhibitory effects of nicotine are mediated by binding to a site outside the membrane's electric field. An analysis of point mutations indicates that the residues at the 6' position within the beta subunit TM2 domain may be important for determining the effects of both mecamylamine and nicotine in a reciprocal manner. Single mutations at the 10' position are not sufficient to produce effects, but 6' 10' double mutants show more effect than do the 6' single mutants.

Effects of Fusarium mycotoxins on levels of serotonin, melatonin, and 5-hydroxytryptophan in pineal cell cultures.

Analysis of melatonin (MEL) in pineal cell cultures by enzyme linked immunosorbent assay showed its concentration was increased by fusaric acid (FA), a mycotoxin produced by Fusarium species and associated with toxic duck and ostrich feeds. Subsequent cell culture studies demonstrated the precursors of MEL, 5-hydroxytryptophan (5HTP) and serotonin (5HT), were also affected by FA as well as other Fusarium mycotoxins. Herein we describe a technique for the analysis of 5HTP and 5HT in pineal cell cultures using HPLC with electrochemical detection (EC), and report on the effects of FA alone and in combination with fumonisin B1 (FB1) and deoxynivalenol (DON) on the levels of these MEL precursors.

Fusaric acid increases melatonin levels in the weanling rat and in pineal cell cultures.

Fusaric acid (FA) is produced by several Fusarium species that commonly infect cereal grains and other agricultural commodities. FA in the feed of nursing dams is lactationally transferred to the suckling offspring and alters serotonin (5-hydroxytryptamine, 5HT) in the pineal gland of the neonate rat. 5HT is involved in melatonin (MEL) production by the pineal gland. MEL is a hormone important in reproduction and seasonality in animals. Therefore, the effects of FA on MEL in the serum and pineal gland of male and female 21-d-old weanling rats from dams on an FA diet were studied. MEL was measured by enzyme-linked immunosorbent assay (ELISA), which was standardized for directly measuring MEL in rat serum and pineal homogenates. At 200 ppm in the diet of nursing dams, FA increased serum MEL in both sexes. Results obtained from ELISA were supported by high-performance liquid chromatography (HPLC) analysis with fluorescence detection. MEL analysis of the pineal gland homogenates by ELISA and HPLC supported observations in the serum. Analogously, in pineal cell monolayer cultures, FA at 1 microM and 100 microM concentrations increased MEL in a dose-dependent manner as compared to the control cells. This is the first report that FA increases MEL in vivo and in vitro and suggests that FA contamination of diets may affect mechanisms involving MEL synthesis.

Production of fusaric acid by Fusarium species.

Fusaric acid is a mycotoxin with low to moderate toxicity, which is of concern since it might be synergistic with other cooccurring mycotoxins. Fusaric acid is widespread on corn and corn-based food and feeds and is frequently found in grain, where Fusarium spp. are also isolated. We surveyed 78 strains of Fusarium moniliforme, F. crookwellense, F. subglutinans, F. sambucinum, F. napiforme, F. heterosporum, F. oxysporum, F. solani, and F. proliferatum for their ability to produce fusaric acid. Strains in Fusarium section Liseola also were assigned to mating population of the Gibberella fujikuroi species complex. The fungi could be divided into three classes, low (< 100 micrograms/g), moderate (100 to 500 micrograms/g), and high (> 500 micrograms/g), based on the amounts of this mycotoxin produced in culture on autoclaved corn. Strains of mating populations C from rice consistently produced moderate to high concentrations of fusaric acid. Two isolates, one each from mating populations C and D, produced fusaric acid in excess of 1,000 micrograms/g of corn. No isolates of any of the Fusarium species examined were negative for the production of fusaric acid on autoclaved corn.

Lactational passage of fusaric acid from the feed of nursing dams to the neonate rat and effects on pineal neurochemistry in the F1 and F2 generations at weaning.

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.

Analysis of endophyte toxins: fescue and other grasses toxic to livestock.

Research on livestock toxicoses caused by Acremonium (endophyte)-infected grasses strongly implicate the ergopeptine alkaloids with A. coenophialum-infected fescue and paxilline and the lolitrem alkaloids with A. lolii-infected perennial ryegrass as the causative agents. Isolation, identification, and detection of these toxins involves extraction with appropriate solvents, clean-up procedures, and chromatographic methods with known standards. Thin-layer, high-performance liquid and gas chromatography along with ultraviolet and mass spectrometric (i.e., electron impact, chemical ionization, tandem mass) characterizations have been reported. These methods have varying degrees of success depending on the matrix from which the alkaloids have been extracted. Ergovaline is the primary ergopeptine alkaloid isolated from cultures of A. coenophialum and also from infected fescue grass and seeds toxic to livestock. Other compounds isolated from the endophyte-infected fescue include: lysergic acid amide (ergine), the clavine class of ergot alkaloids (chanoclavine I, agroclavine, elymoclavine, penniclavine), the pyrrolizidine alkaloids (N-formylloline, N-acetylloline, N-methyloline, N-acetylnorloline), and the unique pyrrolopyrazine alkaloid peramine. The loline alkaloids and peramine have been more associated with the insect-deterrent properties of the endophyte-infected fescue than with livestock toxicoses. Also, both peramine and the ergopeptine alkaloids (ergovaline, ergotamine) have been isolated from A. lolii-infected perennial ryegrass. More recently, paxilline and lolitrem B have been detected in laboratory cultures of A. coenophialum isolated from tall fescue. The ergot alkaloids in endophyte-infected perennial ryegrass may be more related to decreased animal productivity (weight gains, reproduction problems), whereas the lolitrems cause the staggers syndrome. The detection, isolation, identification, and analyses of these compounds from Acremonium-infected grasses is presented.

Fusaric acid in Fusarium moniliforme cultures, corn, and feeds toxic to livestock and the neurochemical effects in the brain and pineal gland of rats.

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.

Toxic interaction of fumonisin B1 and fusaric acid measured by injection into fertile chicken egg.

Toxic interactions of fusaric acid and fumonisin B1, two mycotoxins produced by Fusarium moniliforme, were studied in the chicken embryo. The yolk sacs of fertile White Leghorn eggs were injected before incubation with separate and combined solutions of either fusaric acid and or fumonisin B1. The toxins were administered in either a sterile 10 mM buffered phosphate solution, pH 6.90, which produced a final pH of 6.6 +/- 0.2, or sterile distilled water. Toxicity was based on absence of egg pip at the end of the 21-day incubation period. Toxins administered in the phosphate buffer solution were more toxic than those administered in distilled water. When both toxins were combined in equal concentrations and injected into eggs, increased toxicity resulted. Fusaric acid was shown to be a mild toxin to the eggs and when a relatively nontoxic concentration of it was combined with graded doses of fumonisin B1, a synergistic toxic response was obtained. Fusaric acid is only moderately toxic to the chicken egg, however its co-occurrence with other fusaria toxins found on corn and other cereals might present possible antagonisms or synergisms. The results of this egg model suggest that fusaric acid might play a role in enhanced and unpredicted toxicity in mammalian systems if it is consumed with other mycotoxins.

Fumonisin- and AAL-Toxin-Induced Disruption of Sphingolipid Metabolism with Accumulation of Free Sphingoid Bases.

Fumonisins (FB) and AAL-toxin are sphingoid-like compounds produced by several species of fungi associated with plant diseases. In animal cells, both fumonisins produced by Fusarium moniliforme and AAL-toxin produced by Alternaria alternata f. sp. lycopersici inhibit ceramide synthesis, an early biochemical event in the animal diseases associated with consumption of F. moniliforme-contaminated corn. In duckweed (Lemna pausicostata Heglem. 6746), tomato plants (Lycopersicon esculentum Mill), and tobacco callus (Nicotiana tabacum cv Wisconsin), pure FB1 or AAL-toxin caused a marked elevation of phytosphingosine and sphinganine, sphingoid bases normally present in low concentrations. The relative increases were quite different in the three plant systems. Nonetheless, disruption of sphingolipid metabolism was clearly a common feature in plants exposed to FB1 or AAL-toxin. Resistant varieties of tomato (Asc/Asc) were much less sensitive to toxin-induced increases in free sphinganine. Because free sphingoid bases are precursors to plant "ceramides," their accumulation suggests that the primary biochemical lesion is inhibition of de novo ceramide synthesis and reacylation of free sphingoid bases. Thus, in plants the disease symptoms associated with A. alternata and F. moniliforme infection may be due to disruption of sphingolipid metabolism.

Melatonin and pineal neurochemicals in steers grazed on endophyte-infected tall fescue: effects of metoclopramide.

Plasma and pineal melatonin (MEL) and selected pineal neurochemicals (5-hydroxytryptophan, serotonin, N-acetylserotonin, dopamine, norepinephrine) associated with MEL synthesis were determined in steers grazing Acremonium coenophialum (endophyte)-infected 'Kentucky-31' tall fescue paddocks. Paddock treatments included low (LE, 33%) or high (HE, 74%) endophyte at either low (134 kg.ha-1 x yr-1, LN) or high (335 kg.ha-1 x yr-1, HN) nitrogen fertilization. Twelve pairs of yearling Angus steers were randomly assigned to three replications of the paddock treatments (LEHN, HEHN, LELN, and HELN). One steer in each of the 12 paddocks received per os either a dopamine antagonist, metoclopramide (MC; 15 mg/kg), or sucrose (S; 15 mg/kg) three times weekly for 10 wk. Blood was collected via jugular cannulas during the day and night for plasma MEL analysis and pineal glands were collected at termination. Day and night plasma MEL in the S/HEHN steers was reduced by 31.7 and 35.4% (P < .05), respectively, compared with that in S/LEHN steers. Mean night plasma MEL in the S/HELN steers was reduced by 26.7% (P < .05) compared with that in S/LELN steers. Metoclopramide reduced mean day and night plasma MEL by 22.9 and 38.3% (P < .05), respectively, in the LEHN steers and increased night MEL in the HELN animals by 35.1% (P < .05). During the day and night, there was a MC x pasture treatment interaction (P < .05). No differences were observed in either pineal MEL or the pineal neurochemicals. Acremonium coenophialum-infected fescue reduced plasma concentrations of MEL in steers, whereas treatment with MC altered plasma MEL biphasically.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurotransmitters in rats fed fumonisin B1.

Fumonisin B1, a toxin produced by Fusarium moniliforme, has been associated with a neurotoxic syndrome in horses known as equine leukoencephlomalacia. Previous investigations showed that F. moniliforme cultured on corn and incorporated into rat chow increased brain 5-hydroxyindoleacetic acid (5HIAA) and 5HIAA: serotonin (5HT) ratios in these animals. Therefore, this study was undertaken to determine whether fumonisin B1 would produce related neurochemical effects in the brain and pineal gland of male and female rats. Rats were fed fumonisin B1 at 15, 50, and 150 ppm for 4 weeks. No differences occurred in brain concentrations of norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine, homovanillic acid, 5HT, 5HIAA, and the 5HIAA to 5HT ratios in either male or female rats, nor where there differences between the sexes. When compared across sexes, the norepinephrine to dopamine ratios were decreased (P < 0.05) in the 150-ppm-treated animals. This may suggest a fumonisin B1-induced imbalance in brain norepinephrine and/or dopamine. No differences were observed in pineal norepinephrine, 5HT, 5HIAA, and the 5HIAA to 5HT ratios. Since fumonisin B1 failed to duplicate the effects of the F. moniliforme-induced imbalances in 5HT and 5HIAA metabolism in the brains of rats, other mycotoxins from F. moniliforme may be responsible for these effects.

[Ergot alkaloids and alkaloids from other endophytes, responsible for causing toxic syndrome in cattle after eating contaminated grass]. / Alakloidy sporyn'i i drugikh éndofitov, vyzyvaiushchie toksichnyi sindrom u skota pri pitanii zarazhennymi travami.

Different signs of ergotism in livestock associated with animals consuming feed grains and pasture grasses infected by Clavicipitaceae (e.g. Balansia spp. and Acremonium spp.) have been considered. Endophyte-infected tall fescue causes the damage to livestock, and its toxicity and ryegrass in livestock are associated with ergopeptide alkaloid ergovaline and indole-isoprenoid lolitrems produced by A. coenophialum and A. lolii. The role of another compound attendant to endophyte-infected fescue such as peramine and loline alkaloid is discussed. Concentration of alkaloids depends upon the season and the period of growing plant-host. The advantages and the problems of endophyte-grass mutualistic symbiosis in pasture conditions are considered. The perspective of genetic manipulation of grass and fungus to produce endophyte-infected grasses with stress and insect deterences without affecting ruminant health.

Effects of fescue toxicosis on reproduction in livestock.

Fescue toxicosis in livestock is due to ingestion of endophyte (Acremonium coenophialum) -infected tall fescue. Understanding mechanisms responsible for decreased calving and growth rates, delayed onset of puberty, and impaired function of corpora lutea in heifers at puberty consuming endophyte-infected fescue is an emerging field in reproductive toxicology. The condition decreases overall productivity through a reduction in reproductive efficiency, reduced weight gains, and lowered milk production. Reproduction in cattle may be further compromised by winter coat retention, increased susceptibility to high environmental temperatures, and light intolerance. Endocrine effects in steers associated with infected tall fescue include reduced prolactin and melatonin secretions and altered neurotransmitter metabolism in the hypothalamus, the pituitary, and pineal glands. Ewes have decreased prolactin and lengthened intervals from introduction of the ram until conception. The endophyte induces prolonged gestation, thickened placentas, large, weak foals, dystocia, and agalactia in pregnant mares. Ergot peptide alkaloids, produced by the endophyte, are suggested as the primary cause of fescue toxicosis. These compounds reduce prolactin, increase body temperatures, and have powerful vasoconstrictive effects. Neurohormonal imbalances of prolactin and melatonin, with restricted blood flow to internal organs, may be the principal causes of aberrant reproduction, growth, and maturation in livestock consuming endophyte-infected tall fescue.

Neuroendocrine measurements in steers grazed on endophyte-infected fescue.

Dopamine (DA), serotonin (5HT) and selected precursors and metabolites were measured in the anterior pituitary gland, hypothalamus and pineal gland, along with serum prolactin (PRL) and average daily gains (ADG), in steers (n = 6/group) grazing endophyte (Acremonium coenophialum)-infected and noninfected fescue (Festuca arundinacea Schreb). Paddocks (two/treatment) were designated 100F and 0F (100 and 0% infection, respectively). After 6 wk, three animals from one of the 100F paddocks were exchanged with three animals from one of the 0F paddocks, yielding 0F, 100F/0F, 0F/100F and 100F groups (n = 3). Compared to 0F steers, 100F steers had reduced serum PRL (9.23 vs 32.55 ng/ml, P less than or equal to .0001) and trial ADG (-.07 vs .28 kg, P less than or equal to .0002) but increased pituitary dihydroxyphenylacetic acid (DOPAC, a major metabolite of DA; 108 vs 59 ng/g, P less than or equal to .02) and 5-hydroxyindoleacetic acid (5HIAA, a major metabolite of 5HT; 265 vs 148 ng/g, P less than or equal to .04). Pituitary 5HIAA was greater in the steers rotated from the 0F to 100F paddocks than in steers maintained on the 0F paddocks (296 vs 148 ng/g, P less than or equal to .04). In addition pineal 5-hydroxytryptophan (5HTP, a precursor of 5HT) was increased (502 vs 280 ng/ml; P less than .08), whereas 5-methoxyindoleacetic acid (MIAA, a major metabolite of 5HIAA) and the 5HT/5HTP ratio were reduced (P less than .07) in 100F vs 0F steers. No differences among the treatment groups were observed in hypothalamic neurotransmitter and metabolite concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Fusarium moniliforme and corn associated with equine leukoencephalomalacia on rat neurotransmitters and metabolites.

Fusarium moniliforme (FM) is associated with equine leukoencephalomalacia (ELEM) and hepatotoxicities in horses and rats. The neurochemical effects of ELEM-associated corn naturally infected with FM and FM strain MRC 826 were studied in rats. Increases in brain 5-hydroxyindoleacetic acid (5-HIAA, major metabolite of serotonin, 5-HT) and 5-HIAA/5-HT ratios were observed in rats fed the ELEM-FM corn. These rats had reduced body weights (17%, P less than 0.01) and increased brain weight/body weight ratios (14%, P less than 0.01) as compared with controls that were fed commercial corn. Rats fed a rodent chow supplemented (16%, w/w) with corn cultures of FM (MRC 826) had brain 5-HT and 5-HIAA increased (11% and 60%, P less than 0.01, respectively). At 20% FM (MRC 826)-chow diet, the 5-HIAA levels were increased (18%, P less than 0.01). In both the 16% and 20% diets, brain 5-HIAA/5-HT ratios were increased (45%, P less than 0.01 and 10%, P less than 0.05), body weights reduced (30% and 18%, P less than 0.01) and brain weight/body weight ratios increased (40% and 16%, P less than 0.01), respectively. The incidences of microscopic liver lesions (particularly bile duct proliferations, hepatocellular hyperplasia, and focal necrosis) were consistent with rats fed the FM contaminated and FM-fortified diets. These results suggest a possible FM (ELEM-associated)-induced dysfunction in either 5-HT metabolism or 5-HIAA elimination in rat brains.