Abstract
Domoic acid is a shellfish toxin which produces gastrointestinal distress, followed by neurological symptoms such as headache, confusion, disorientation and severe deficits in short-term memory. Domoic acid is an amino acid which contains three carboxylic groups, and one imino group, and its solubility, rate of absorption, and elimination would vary depending on the protonation of these groups at different pH's. We propose that domoic acid toxicity varies with pH of administered domoic acid solution. Domoic acid toxicity was measured in mice as the onset times for scratching behaviour, seizure activity, and death, after the intraperitoneal administration of domoic acid at different pH's. Results of the present study show that the scratching behaviour, seizure activity, and death, occurred at 12, 40, and 55 min, after intraperitoneal administration of domoic acid at pH 3.7. Apparently, the onset times for three types of behaviours were relatively long, and well separated from each ot her. Domoic acid toxicity was lowest at pH 3.7, and highest at pH 7.4, with intermediate toxicity at other pH's. The onset time of scratching behaviour was not influenced by pH of domoic acid solution at three different doses. In contrast, the onset times for seizure activity, and death were significantly affected by pH of domoic acid, toxicity being higher at pH 7.4 than at pH 3.7. The pH effect on domoic acid toxicity diminished as the dose of domoic acid was increased. In fact, at 14.5 mg/kg domoic acid toxicity was similar at both pH's of 3.7 and 7.4. It is concluded that in vivo toxicity of domoic acid varies depending on pH of the administered solution. The differential toxicity of domoic acid at different pH may be related to its solubility, rate of absorption, and elimination, depending on the degree of protonation of domoic acid molecule. Domoic acid toxicity would also vary depending on the age of animal, receptor sensitivity and density in different regions of brain. (Mol Ce ll Biochem 167: 179-185, 1997)
Similar content being viewed by others
References
Perl TM, Bedard L, Kosatsky T, Hockin J, Todd ECD, Remis RS: An outbreak of toxic encephalopathy caused by eating mussels contaminated with domoic acid. N Eng J Med 322: 1775–1780, 1990
Teitelbaum J, Zattore R, Carpenter S, Gendron D, Evans AC, Gjedde A, Cashman N: Neurologic sequelae of domoic acid intoxication due to ingestion of contaminated mussels. N Eng J Med 322: 1781–1787, 1990
Benet LZ, Kroetz DL, Sheiner LB: Pharmacokinetics: The dynamic of drug absorption, distribution, and elimination. In: JG Hardman, LE Limbird, PB Molinoff, RW Ruddon, AG Gilman, (eds). Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th edition, McGraw Hill, New York, 1996, pp 3–28
Wright JLC, Boyd RK, DeFreitas ASW, Falk M, Foxall RA, Jamieson WD, Laycock MV, McCulloch AW, McInnes AG, Odense P, Pathak VP, Quilliam MA, Ragan MA, Sim PG, Thibault P, Walter JA: Identification of domoic acid, a neuroexcitatory amino acid, in toxic mus-sels from eastern Prince Edward Island. Can J Chem 67: 481–490, 1990
Rao Subha DV, Quilliam MA, Pocklington R, Domoic acid – a neuro-toxic amino acid produced by the marine diatom Nitzschia pungens in culture. Can J Fish Aquat Sci 45: 2076–2079, 1988
Bates SS, Bird CJ, DeFreitas ASW, Foxall R, Gilgan MW, Hanic LA, Johnson GR, McCulloch AW, Odense P, Pocklington R, Quilliam MA, Sim PG, Smith JC, Subha Rao DV, Todd ECD, Walter JA, Wright JLC: Pennate diatom Nitzschia pungens as the primary source of domoic acid toxin in shellfish from eastern Prince Edward Island, Canada. Can J Fish Aquat Sci 46: 1203–1215, 1989
Tryphonas L, Truelove J, Todd E, Nera E, Iverson F: Experimental oral toxicity of domoic acid in cynomolgus monkeys (Macaca fascicularis) and rats. Food Chem Toxicol 28: 707–715, 1990
Todd ECD: Domoic acid and amnesic shellfish poisoning – A review. J. Food Protection 56: 69–83, 1993
Olney JW: Excitotoxicity: an overview. In: Proceedings of the Symposium on Domoic Acid Toxicity. Can Dis Weekly Rep. 16 suppl No. 1: 47–58, 1990
Nadler JV, Perry BW, Gentry C, Cotman CW: Degeneration of hip-pocampal CA 3 pyramidal cells induced by intraventricular kainic acid. J Comp Neurol 192: 333–359, 1980
Zaczek R, Coyle JT: Excitatory amino acid analogues: Neurotoxicity and seizures. Neuropharmacology 21: 15–26, 1984
Sperk G. Kainic acid seizures in the rat. Prog Neurobiol 42: 1–32, 1994
Strain SM, Tasker RAR: Hippocampal damage produced by systemic injections of domoic acid in mice. Neuroscience 44: 343–352, 1991
Maeda M, Kodama T, Saito M, Tanaka T, Yoshizumi H, Nomotoa K, Fujita T: Neuromuscular action of insecticidal domoic acid on the American cockroach. Pesticide Biochem Physiol 28: 85–92, 1987
Tasker RAR, Connell BJ, Strain SM: Pharmacology of systemically administered domoic acid in mice. Can J Physiol Pharmaeol 69: 378–382, 1991
Chaimulera C, Costa S, Valerio E, Reggiani A: Domoic acid toxicity in rats and mice after intracerebroventricular administration: comparison with excitatory amino acid agonists. Pharmacol Toxicol 70: 115–120, 1992
Debonnel G, Beauehesne L, de Montigny C: Domoic acid, the alleged 'mussel toxin', might produce its neurotoxic effect through kainate receptor activation: an electrophysiological study in the rat dorsal hippocamapus. Can J Physiol Pharmacol 67: 29–33, 1989
Stewart GR, Zorumski CF, Price MT, Olney JW: Domoic acid: a de-mentia inducing excitotoxic food poison with kainic acid receptor specificity. Exp Neurol 110: 127–138, 1990
Dakshinamurti K, Sharma SK, Sundaram M, Watanabe T: Hippocampal changes in developing postnatal mice following intrauterine exposure to domoic acid. J Neurosci 13: 4486–4495, 1993
Grimmelt B, Nijjar MS, Brown J, MaeNair N, Wagner S, Johnson GR, Amend JF: Relationship between domoic acid levels in the blue mussel (Mytilus edulis) and toxicity in mice. Toxicon 28: 501–508, 1990
Zeevalk GD, Nicklas WJ: Nitric oxide in retina: relation to excitatory amino acids and excitotoxicity. Exp Eye Res 58: 343–350, 1994
Bowie D, Smart TG: Species dependent functional properties of non-NMDA receptors expressed in Xenopus laevis oocytes injected with mammalian and avian brain mRNA. Br J Pharmacol 111: 803–810, 1994
Scallet AC, Binienda Z, Caputo FA, Hall S, Paule MG, Rountree RL, Schmued L, Sobotka T, Slikker W Jr: Domoic acid-treated cynomolgus monkeys (M. fascicularis): effects of dose on hippocampal neuronal and terminal degeneration. Brain Res 627: 307–313, 1993
Pinsky C, Glavin GB, Bose R: Kynurenic acid protects against neurotoxicity and lethality of toxic extracts from contaminated Atlantic coast mussels. Prog Neuro Psychopharmacol Biol Psychiat 13: 595–598, 1989
Vrooman L, Jhamandas K, Boegman RJ, Beninger RJ: Picolinic acid modulates kainic acid-evoked glutamate release from the striatum in vitro. Brain Res 627: 193–198, 1993
Sharma SK, Dakshinamurti K: Suppression of domoic acid induced seizures by 8-(OH)-DPAT. J Neural Transm 93: 87–98, 1993
Khera KS, Whalen C, Angers G, Arnold DL: Domoic acid: A teratology and homeostatic study in rats. Bull Environ Contam Toxicol 53: 18–24, 1994
Nijjar MS, MacKenzie PM, Brown JA: A procedure for large-scale purification of domoic acid from toxic blue mussels (Mytilus edulis). Molec Cell Biochem 115: 213–217, 1992
Wozniak DF, Stewart GR, Miller JP, Olney JW: Age related sensitivity to kainate neurotoxicity. Exp Neurol 114: 250–253, 1991
Preston E, Hynie I: Transfer constants for blood-brain barrier permeation of the neuroexcitatory shellfish toxin, domoic acid. Can J Neurol Sci 18: 39–44, 1991
Suzuki XAM, Hierlihy SL: Renal clearance of domoic acid in the rat. Food Chem Toxic 31: 701–706, 1993
Falk M, Walter JA, Wiseman PW: Ultraviolet spectrum of domoic acid. Can J Chem 67: 1421–1425, 1989
Takemoto T, Daigo K: Constituents of Chondria armata. Chem. Pharm Bull 6: 578–580, 1958
Falk M, Seto PF, Walter JA: Solubility of domoic acid in water and in non aqueous solvents. Can J Chem 69: 1740–1744, 1991
Nicholls DG: The glutamatergic nerve terminal. Eur J Biochem 212: 613–631, 1993
Nijjar MS, Grimmelt B: Domoic acid inhibits adenylate cyclase activity in rat brain membranes. Molec Cell Biochem 136: 105–111, 1994
Chetkovich DM, Sweatt JD, NMDA receptor activation increases cyclic AMP in area CA1 of the hippocampus via calcium/calmodulin stimulation of adenylate cyclase. J Neurochem 61: 1933–1942, 1993
Olney JN: Neurotoxicity of excitatory amino acid neurotransmitters. In: EG McGeer, JW Olney, PL McGeer (eds). Kainic Acid as a Tool in Neurobiology. Raven Press, New York, 1978, pp 95–122, 1978
Nijjar MS: Effects of domoate, glutamate and glucose deprivation on calcium uptake by rat brain tissue in vitro. Biochem Pharmacol 46: 131–138, 1993
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nijjar, M., Madhyastha, M. Effect of pH on domoic acid toxicity in mice. Mol Cell Biochem 167, 179–185 (1997). https://doi.org/10.1023/A:1006862311940
Issue Date:
DOI: https://doi.org/10.1023/A:1006862311940