Abstract
Effects of single subcutaneous doses of sodium 2,4-dichlorophenoxyacetate (2,4-D-Na) on biogenic amines and their acidic metabolites in rat brain and cerebrospinal fluid (CSF) were analyzed by high pressure liquid chromatography. After 200 mg/kg 2,4-D-Na, the cerebral concentration of 5-hydroxytryptamine (5-HT) was increased slightly and that of 5-hydroxyindoleacetic acid (5-HIAA) roughly 3-fold between 1 and 8 h after the administration. There was also a tendency towards slightly lowered dopamine (DA) levels. No statistically significant changes in brain concentrations of noradrenaline (NA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) or tryptophan (TRY) were found. At the same time, however, the maximal increase in DOPAC, HVA and 5-HIAA concentrations in the CSF was 2.3–5.8-fold. The dependency of biogenic amines and metabolites on 2,4-D-Na dose was studied by injecting s.c. 0, 10, 30 and 100 mg/kg and sacrificing the rats at 2 h. In the brain, there was a dose-dependent increase in concentrations of 5-HIAA (at the two highest doses) and HVA (at the highest dose) while in the CSF those of all three acidic metabolites increased at the two highest doses. The 10 mg/kg dose had no effect. The results agree with the hypothesis that 2,4-D inhibits the organic acid transport out of the brain, which should then result in increased cerebral levels of acidic metabolites of biogenic amines, but it may also have effects on the activity of serotoninergic and dopaminergic neurones.
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References
Curzon G, Hutson PH, Kantamaneni BD, Sahakian BJ, Sarna GS (1985) 3,4-Dihydroxyphenylethylamine and 5-hydroxytryptamine metabolism in the rat: acidic metabolites in cisternal cerebrospinal fluid before and after giving probenecid. J Neurochem 45: 508–513
Dedek J, Baumes R, Tien-Duc N, Gomeni R, Korf J (1979) Turnover of free and conjugated (sulphonyloxy) dihydroxyphenylacetic acid and homovanillic acid in rat striatum. J Neurochem 33: 687–695
Desi I, Sos J, Olasz J, Sule F, Markus V (1962) Nervous system effects of a chemical herbicide. Arch Environ Health 4: 95–102
Elo HA, Ylitalo P (1979) Distribution of 2-methyl-4-chlorophenoxyacetic acid and 2,4-dichlorophenoxyacetic acid in male rats: evidence for the involvement of the central nervous system in their toxicity. Toxicol Appl Pharmacol 51: 439–446
Elo HA, Hervonen H, Ylitalo P (1988) Comparative study on cerebrovascular injuries by three chlorophenoxyacetic acids (2,4-D, 2,4,5-T and MCPA). Comp Biochem Physiol 90C: 65–68
Hill EV, Carlisle H (1947) Toxicity of 2,4-dichlorophenoxyacetic acid for experimental animals. J Industr Hyg Toxicol 29: 85–95
Hutson PH, Sarna GS, Kantamaneni BD, Curzon G (1984) Concurrent determination of brain dopamine and 5-hydroxytryptamine turnovers in individual freely moving rats using repeated sampling of cerebrospinal fluid. J Neurochem 43: 151–159
Jones DIR, Knight AG, Smith AJ (1967) Attempted suicide with herbicide containing MCPA. Arch Environ Health 14: 363–366
Kim CS, O'Tuama LA (1981) Choroid plexus transport of 2,4-dichlorophenoxyacetic acid: interaction with the organic acid carrier. Brain Res 224: 209–212
Kim CS, O'Tuama LA, Mann JD, Roe CR (1983) Saturable accumulation of the anionic herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), by rabbit choroid plexus: early developmental origin and interaction with salicylates. J Pharmacol Exp Ther 225: 699–704
Kim CS, Keizer RF, Ambrose WW, Breese GR (1987) Effects of 2,4,5-trichlorophenoxyacetic acid and quinolinic acid on 5-hydroxy-3-indoleacetic acid transport by the rabbit choroid plexus: pharmacology and electron microscopic cytochemistry. Toxicol Appl Pharmacol 90: 436–444
Lewander T, Sjöden PO, Söderberg U (1974) Effekten av fenoxisyror (2,4,5-T) på halten av tryptofan, tyrosin samt dessas metaboliter hos råtta. Report to the National Swedish Environmental Protection Board, 5 pp
Lorenzo AV, Spector R (1973) Transport of salicylic acid by the choroid plexus in vitro. J Pharmacol Exp Ther 184: 465–471
McKinney SE, Peck HM, Bochey JM, Byham BB, Schuchardt GS, Beyer KH (1951) Benemid, p-(dl-n-propylsulfamyl)benzoic acid: toxicological properties. J Pharmacol Exp Ther 102: 208–214
Mefford IN (1981) Application of high performance chromatography with electrochemical detection to neurochemical analysis: measurement of catecholamines, serotonin and metabolites in rat brain. J Neurosci Methods 3: 207–224
Mohammad FK, St Omer VEV (1985) Developing rat brain monoamine levels following in utero exposure to a mixture of 2,4-dichlorophenoxyacetic and 2,4,5-trichlorophenoxyacetic acids. Toxicol Lett 29: 215–223
Prescott LF, Park J, Darrien I (1979) Treatment of severe 2,4-D and mecoprop intoxication with alkaline diuresis. Br J Clin Pharmacol 7: 111–116
Pritchard JB (1980) Accumulation of anionic pesticides by rabbit choroid plexus in vitro. J Pharmacol Exp Ther 212: 354–359
Rowe VK, Hymas TA (1954) Summary of toxicological information on 2,4-D and 2,4,5-T type herbicides and an evaluation of the hazards to livestock associated with their use. Am J Vet Res 15: 622–629
Sjöden PO, Söderberg U (1978) Phenoxyacetic acids: sublethal effects. In: Ramel C (ed) Chlorinated phenoxy acids and their dioxins. Ecol Bull (Stockholm) 27: 149–164
Ylitalo P, Heikkinen ER, Myllylä VV (1976) Evaluation of successive collection of cisternal cerebrospinal fluid in rats, rabbits, and cats. Exp Neurol 50: 330–336
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Elo, H.A., MacDonald, E. Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on biogenic amines and their acidic metabolites in brain and cerebrospinal fluid of rats. Arch Toxicol 63, 127–130 (1989). https://doi.org/10.1007/BF00316434
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DOI: https://doi.org/10.1007/BF00316434