EFFECT OF PH ON DOMOIC ACID TOXICITY IN MICE

Domoic acid is a shellfish toxin which produces gastrointestinal distr ess, followed by neurological symptoms such as headache, confusion, di sorientation and severe deficits in short-term memory. Domoic acid is an amino acid which contains three carboxylic groups, and one imino gr oup, and its solubility, rate of absorption, and elimination would var y depending on the protonation of these groups at different pH's. We p ropose 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 th e intraperitoneal administration of domoic acid at different pH's. Res ults of the present study show that the scratching behaviour, seizure activity, and death, occurred at 12, 40, and 55 min, after intraperito neal administration of domoic acid at pH 3.7. Apparently, the onset ti mes for three types of behaviours were relatively long, and well separ ated from each other. Domoic acid toxicity was lowest at pH 3.7, and h ighest 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 s olution at three different doses. In contrast, the onset times for sei zure activity, and death were significantly affected by pH of domoic a cid, 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 increas ed. 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 aci d varies depending on pH of the administered solution. The differentia l toxicity of domoic acid at different pH may be related to its solubi lity, rate of absorption, and elimination, depending on the degree of protonation of domoic acid molecule. Domoic acid toxicity would also v ary depending on the age of animal, receptor sensitivity and density i n different regions of brain.