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3-Nitropropionic Acid - Exogenous Animal Neurotoxin and Possible Human Striatal Toxin

Published online by Cambridge University Press:  18 September 2015

A.C. Ludolph ,
F. He ,
P.S. Spencer ,
J. Hammerstad  and
M. Sabri
A.C. Ludolph*
Affiliation:
Center for Research on Occupational and Environmental Toxicology, Portland, Oregon Department of Neurology, School of Medicine, Oregon Health Sciences University, Portland, Oregon
F. He
Affiliation:
Institute of Occupational Medicine, Chinese Academy of Preventive Medicine, Beijing, People's Republic of China
P.S. Spencer
Affiliation:
Center for Research on Occupational and Environmental Toxicology, Portland, Oregon Department of Neurology, School of Medicine, Oregon Health Sciences University, Portland, Oregon
J. Hammerstad
Affiliation:
Department of Neurology, School of Medicine, Oregon Health Sciences University, Portland, Oregon
M. Sabri
Affiliation:
Center for Research on Occupational and Environmental Toxicology, Portland, Oregon Department of Neurology, School of Medicine, Oregon Health Sciences University, Portland, Oregon
*
Center for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, Oregon, U.S.A. 97201
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Abstract:

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3-Nitropropionic acid (3-NPA) — a suicide inhibitor of succinate dehydrogenase — is a widely distributed plant and fungal neurotoxin known to induce damage to basal ganglia, hippocampus, spinal tracts and peripheral nerves in animals. Recent reports from Northern China indicate that 3-NPA is also likely to be responsible for the development of putaminal necrosis with delayed dystonia in children after ingestion of mildewed sugar cane. This article discusses the role of 3-NPA in the causation of the disease in China, its neurotoxic effects in animals and the potential role for this compound as a probe of selective neuronal vulnerability.

Type
Articles
Information
Canadian Journal of Neurological Sciences , Volume 18 , Issue 4 , November 1991 , pp. 492 - 498
Copyright
Copyright © Canadian Neurological Sciences Federation 1991

References

REFERENCES

1.Fahn, S, Marsden, CD, Calne, DB. Classification and investigation of dystonia. In: Marsden, CD, Fahn, S, eds. Movement Disorders 2. London: Butterworth 1987; 332–353.Google Scholar
2.Langston, JW, Ballard, P, Tetrud, JW, et al. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1984; 219: 979–980.CrossRefGoogle Scholar
3.Ludolph, AC, Hugon, J, Dwivedi, MP, et al. Studies on the aetiology and pathogenesis of motor neuron diseases. I. Lathyrism: Clinical findings in established cases. Brain 1987; 110: 149–165.CrossRefGoogle ScholarPubMed
4.He, F, Zhang, S, Zhang, C, et al. Mycotoxin-induced encephalopathy and dystonia in children. In: Volans, GN, et al, eds. Basic Science in Toxicology. London: Taylor & Francis 1990; 596–604.Google Scholar
5.He, F, Zhang, S, Zhang, C, et al. Extrapyramidal lesions induced by mildewed sugar cane poisoning. Three case reports. Chin Med J 1987; 67: 395–396.Google Scholar
6.Hu, W. The isolation and structure identification of a toxic substance, 3-nitropropionic acid, produced by Arthrinium from mildewed sugar cane. Chin J Prev Med 1986; 20: 321–323.Google Scholar
7.Liu, X. Investigations on the etiology of mildewed sugar cane poisoning. A review. Chin J Prev Med 1986; 20: 306–308.Google Scholar
8.Liu, X. Studies on the mycology and mycotoxins in an outbreak of deteriorated sugar cane poisoning. Chin J Prev Med 1989; 23: 345–348.Google Scholar
9.Williams, MC, James LE Livestock poisoning from nitro-bearing Astragalus. In: Keeler, RF, Van Kampen, KR, James, LF, eds. Effects of Poisonous Plants on Livestock, New York: Academic Press 1978; 379–389.CrossRefGoogle Scholar
10.James, LF. Neurotoxins and other toxins from Astragalus and related genera. In: Keeler, RF, Tu, AT, eds. Handbook of Natural Toxins, Vol. 1 New York: Marcel Dekker 1983; 445–462.Google Scholar
11.Majak, W, Pass, MA. Aliphatic Nitrocompounds. In: Cheeke, PR, ed. Toxicants of Plant Origin. Vol. 11. Glycosides. Boca Raton: CRC Press 1990; 143–160.Google Scholar
12.James, LF, Hartley, J, Williams, MC, Van Kampen, KR. Field and experimental studies in cattle and sheep poisoned by nitro-bearing Astragalus or their toxins. J Am Vet Res 1980; 41: 377–382.Google ScholarPubMed
13.Pass, MA, Majak, W, Muir, AD, et al. Absorption of 3-nitropropanol and 3-nitropropionic acid from the digestive tract of sheep. Toxicol Lett 1984; 23: 1–7.CrossRefGoogle ScholarPubMed
14.Williams, MC, Barneby, RC. The occurrence of nitro-toxins in North American Astragalus (Fabaceae). Brittonia 1977; 29: 310–326.CrossRefGoogle Scholar
15.Williams, MC, Barneby, RC. The occurrence of nitro-toxins in Old World and South American Astragalus (Fabaceae). Brittonia 1977; 29: 327–331.CrossRefGoogle Scholar
16.Williams, MC. Nitro-compounds in foreign species of Astragalus. Weed Sci 1981; 29: 261–269.CrossRefGoogle Scholar
17.Williams, MC. 3-Nitropropionic acid and 3-nitropropanol in species of Astragalus. Can J Bot 1982; 60: 1956–1963.CrossRefGoogle Scholar
18.Williams, MC, Davies, AM. Nitro compounds in introduced Astragalus species. J Range Manage 1982; 35: 113–115.CrossRefGoogle Scholar
19.Shenk, JS, Risius, ML, Barnes, RF. Weaning meadow vole responses to crownvetch forage. Agron J 1974; 66: 386–389.CrossRefGoogle Scholar
20.Shenk, JS, Wangsness, PJ, Leach, RM, et al. Relationship between betanitropropionic acid content of crownvetch and toxicity in nonruminant animals. J Animal Sci 1976; 42: 616–621.CrossRefGoogle ScholarPubMed
21.Cooke, AR. The toxic constituent of Indigofera endecaphylla. Arch Biochem 1955; 55: 114–120.CrossRefGoogle ScholarPubMed
22.Morris, MP, Pagan, C, Wartlike, HE. Hiptagenic acid, a toxic component of Indigofera endecaphylla. Science 1954; 119: 322–323.CrossRefGoogle ScholarPubMed
23.Williams, MC. Toxic nitro compounds in Indigofera species. Agr J 1981;73:434–436.CrossRefGoogle Scholar
24.Murray, LR, Moore, T, Sharman, IM. The toxicity of Indigofera enneaphylla in rats. Aust J Agric Res 1965; 16: 713–720.CrossRefGoogle Scholar
25.Williams, MC. Toxic nitro compounds in Lotus. Agr J 1983; 75: 520–522.CrossRefGoogle Scholar
26.Gorter, K. Hiptagin, a new glucoside from Hiptage madablota. Gaertu Bull Jordin Bot Buitenzorg 1920; 2: 187–202.Google Scholar
27.Karakin, Carter J., the glucoside of Corynocarpus laevigata, and hiptagenic acid. Soc Chem Ind (London) 1943; 62: 238–240.Google Scholar
28.Moyer, BG, Pfeffer, PE, Valentine, KM, Gustine, DL. 3-Nitropropanoyl-D-glucopyranoses of Corynocarps laevigatus. Phytochemistry 1979; 18: 111–114.CrossRefGoogle Scholar
29.Alston, TA, Mela, L, Bright, HJ. 3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase. Proc Natl Acad Sci USA 1977; 74: 3161–3771.CrossRefGoogle ScholarPubMed
30.Coles, CJ, Edmondson, DE, Singer, TP. Inactivation of succinate dehydrogenase by 3-nitropropionate. J Biol Chem 1979; 254: 5161–5167.CrossRefGoogle ScholarPubMed
31.Porter, DJT, Bright, HJ. 3-Carbanionic substrate analogues bind very tightly to fumarase and aspartase. J Biol Chem 1980; 255: 4772–4880.CrossRefGoogle ScholarPubMed
32.Schloss, JV, Cleland, WW. Inhibition of isocitrate lyase by 3-nitropropionate, a reaction-intermediate analogue. Biochemistry 1982; 21: 4420–4427.CrossRefGoogle ScholarPubMed
33.Osman, MY, Effect of β-nitropropionic acid on rat brain acetylcholinesterase. Biochem Pharmacol 1982; 31: 4067–4072.CrossRefGoogle ScholarPubMed
34.Pass, MA, Muir, AD, Majak, W, et al. Effect of alcohol and aldehyde dehydrogenase inhibitors on the toxicity of 3-nitropropanol in rats. Toxicol Appl Pharmacol 1985; 78: 310–315.CrossRefGoogle ScholarPubMed
35.Matsumoto, H, Hylin, JW, Miyahara, A. Methemoglobinemia in rats injected with 3-nitropropionic acid, sodium nitrite, and nitroethane. Toxicol Appl Pharmacol 1961; 3: 493–499.CrossRefGoogle ScholarPubMed
36.Wilson, BJ. Miscellaneous Aspergillus toxins. In: Ciegler, A, Kadis, S, Ajl, SJ, eds. Microbial Toxins, Vol. 6. Fungal Toxins. New York: Academic Press 1971; 251–257.Google Scholar
37.Hamilton, BE, Gould, DH. Correlation of morphologic brain lesions with physiologic alterations and blood-brain barrier impairment in 3-nitropropionic acid toxicity in rats. Acta Neuropathol (Berlin) 1987; 74: 67–74.CrossRefGoogle ScholarPubMed
38.Williams, MC, Van Kampen, KR, Norris, FA. Timber milk vetch poisoning in chickens, rabbits, and cattle. Am J Vet Res 1969; 30: 2185–2190.Google Scholar
39.Williams, MC, James, LF, Bleak, AT. Toxicity of introduced nitrocontaining Astragalus to sheep, cattle, and chicks. J Range Manag 1976; 28: 260–263.CrossRefGoogle Scholar
40.Salyi, G, Sztojkov, V, Hilbertne Miklovics, M. A nutria tarka koronafürt (Coronilla varia L.) okozta mergezese. Magyar Allatorvosok Lapja 1988; 43: 313–316.Google Scholar
41.Gould, DH, Gustine, DL. Basal ganglia degeneration, myelin alterations, and enzyme inhibition induced in mice by the plant toxin 3-nitropropionic acid. Neuropathol Appl Neurobiol 1982; 8: 377–393.CrossRefGoogle Scholar
42.Gould, DH, Wilson, MP, Hamar, DW. Brain enzyme and clinical alterations induced in rats and mice by nitroaliphatic toxicants. Toxicol Lett 1985; 27: 83–89.CrossRefGoogle ScholarPubMed
43.Hamilton, BF, Gould, DH. Nature and distribution of brain lesions in rats intoxicated with 3-nitropropionic acid: a type of hypoxic (energy deficient) brain damage. Acta Neuropathol (Berl) 1987; 72: 286–297.CrossRefGoogle ScholarPubMed
44.Pass, MA, Majak, W, Yost, GS. Lack of a protective effect of thiamine on the toxicity of 3-nitropropanol and 3-nitropropionic acid in rats. Can J Anim Sci 1988; 68:315–320.CrossRefGoogle Scholar
45.McClean, DR, Jacobs, H, Mielke BW Methanol poisoning: a clinical and pathological study. Ann Neurol 1980; 8: 161–167.CrossRefGoogle Scholar
46.LeWitt, PA, Martin, SD. Dystonia and hyperkinesis with putaminal necrosis after methanol intoxication. Clin Neuropharmacol 1988; 11: 161–167.CrossRefGoogle Scholar
47.Guggenheim, MA, Couch, JR, Weinberg, W. Motor dysfunction as a permanent complication of methanol ingestion. Arch Neurol 1971; 24: 550–554.CrossRefGoogle ScholarPubMed
48.Potts, AM, Praglin, J, Farkas, L, et al. Studies on the visual toxicity of methanol: VII. Additional observations on methanol poisoning in the primate test object. Am J Ophthalmol 1955; 40: 76–82.CrossRefGoogle Scholar
49.Martin-Amat, G, McMartin, KE, Hayreh, SS, et al. Methanol poisoning: ocular toxicity produced by formate. Toxicol Appl Pharmacol 1978; 45: 201–208.CrossRefGoogle ScholarPubMed
50.Nicholls, P. Formate as an inhibitor of cytochrome c oxidase. Biochem Biophys Res Commun 1975; 67: 610–616.CrossRefGoogle ScholarPubMed
51.Nicholls, P. The effect of formate on cytochrome aa3 and on electron transport in the intact respiratory chain. Biochim Biophys Acta 1976; 430: 13–29.CrossRefGoogle ScholarPubMed
52.Carella, F, Grassi, MP, Savoiardo, M, et al. Dystonic-Parkinsonian syndrome after cyanide poisoning: clinical and MRI findings. J Neurol Neurosurg Psychiatry 1988; 51: 1345–1348.CrossRefGoogle ScholarPubMed
53.Uitti, RJ, Rajput, AH, Ashenhurst, EM, et al. Cyanide-induced Parkinsonism: a clinicopathologic report. Neurology 1985; 35: 921–925.CrossRefGoogle ScholarPubMed
54.Finelli, PF. Changes in the basal ganglia following cyanide poisoning. J Comput Assist Tomogr 1981; 5: 755–756.CrossRefGoogle ScholarPubMed
55.Whelan, DT, Hill, RE, McClorry, S. Fumaric aciduria: a new organic aciduria, associated with mental retardation and speech impairment. Clinica Chimica Acta 1983; 132: 301–308.CrossRefGoogle ScholarPubMed
56.Robinson, BH. Lactic acidemia. In: Scriver, CR, Beaudet, AL, Sly, WS, Valle, D, eds. The Metabolic Basis of Inherited Disease. New York: McGraw Hill 1989; 869–888.Google Scholar
57.Walker, V, Mills, GA, Hall, MA, et al. A fourth case of fumarase deficiency. J Inher Metab Dis 1989; 12: 331–332.CrossRefGoogle ScholarPubMed
58.Gellera, MS, Uziel, G, Rimoldi, M, et al. Fumarase deficiency is an autosomal recessive encephalopathy affecting both the mito-chondrial and the cytosolic enzymes. Neurology 1990; 40: 495–499.CrossRefGoogle Scholar
59.Brierley, JB, Graham, DI. Hypoxia and vascular disorders of the central nervous system. In: Adams, JH, Corsellis, JAN, Duchen, LW, eds. Greenfield’s Neuropathology, 4th ed. New York: John Wiley 1984; 125–207.Google Scholar
60.Brierley, JB, Brown, AW, Calverley, J. Cyanide intoxication in the rat: physiological and neuropathological aspects. J Neurol Neurosurg Psychiatry 1976; 9: 122–140.Google Scholar
61.Brierley, JB, Prior, PF, Calverley, J, et al. Cyanide intoxication in Macaca mulatta-physiological and neuropathological aspects. J Neurol Sci 1977; 31: 133–157.CrossRefGoogle Scholar
62.Olney, JW, Fuller, T, De Gubareff, T. Acute dendrotoxic changes in the hippocampus of kainate-treated rats. Brain Res 1979; 176: 91–100.CrossRefGoogle ScholarPubMed
63.Hennebery, RC, Novelli, A, Cox, JA, et al. Neurotoxicity at the Nmethyl-D-aspartate receptor in energy-compromised neurons: An hypothesis for cell death in aging and disease. Ann NY Acad Sci 1989; 568: 225–233.Google Scholar
64.Novelli, A, Reilly, JA, Lysko, PG, et al. Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced. Brain Res 1988; 451: 205–212.CrossRefGoogle ScholarPubMed
65.Bush, MT, Touster, O, Brockman, JE. The production of beta-nitropropionic acid by a strain of Aspergillus flavus. J Biol Chem 1951; 188: 685–693.CrossRefGoogle ScholarPubMed
66.Nakamura, S, Shimoda, C. Studies on an antibiotic substance oryzacidin, produced by Asp. oryzae. Part 5. Existence of 3-nitropropionic acid. J Agr Chem Soc Japan 1954; 28: 909–913.Google Scholar
67.Raistrick, H, Stössl, A. Studies in the biochemistry of micro-organisms. 104. Metabolites of Penicillium atrovenetum G. Smith: β-nitropropionic acid, a major metabolite. Biochem J 1958; 68: 647–653.CrossRefGoogle Scholar
68.Anzai, K, Suzuki, S. A new antibiotic bovinocidin, identified as β-nitropropionic acid. J Antibiotics (Tokyo) 1960; 13: 133–136.Google ScholarPubMed
69.Iwasaki, T, Koskowski, FV. Production of P-nitropropionic acid in foods. J Food Sci 1973; 38: 1162–1165.CrossRefGoogle Scholar
70.Kinosita, R, Ishiko, T, Sugiyama, S, et al. Mycotoxins in fermented food. Cancer Res 1968; 28: 2296–2311.Google ScholarPubMed
71.Woods, AH, Pendleton, L. Fourteen simultaneous cases of an acute degenerative striatal disease. Arch Neurol Psych 1925; 13: 549–568.CrossRefGoogle Scholar
72.Verhaart, WJC. Symmetrical degeneration of the neostriatum in Chinese infants. Arch Dis Child 1938; 13: 225–234.CrossRefGoogle ScholarPubMed