Nijjar M S, Madhyastha M S
Department of Anatomy and Physiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Canada.
Mol Cell Biochem. 1997 Feb;167(1-2):179-85. doi: 10.1023/a:1006862311940.
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 other. 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.
软骨藻酸是一种贝类毒素，可引起胃肠道不适，随后出现头痛、意识混乱、定向障碍和短期记忆严重受损等神经症状。软骨藻酸是一种含有三个羧基和一个亚氨基的氨基酸，其溶解度、吸收速率和消除速率会因这些基团在不同pH值下的质子化情况而有所不同。我们认为软骨藻酸的毒性会随所施用的软骨藻酸溶液的pH值而变化。在小鼠体内，通过腹腔注射不同pH值的软骨藻酸后，以抓挠行为、癫痫活动和死亡的发作时间来衡量软骨藻酸的毒性。本研究结果表明，在pH 3.7时腹腔注射软骨藻酸后，抓挠行为、癫痫活动和死亡分别在12分钟、40分钟和55分钟出现。显然，这三种行为的发作时间相对较长，且彼此间隔明显。软骨藻酸毒性在pH 3.7时最低，在pH 7.4时最高，在其他pH值时毒性居中。在三种不同剂量下，抓挠行为的发作时间不受软骨藻酸溶液pH值的影响。相比之下，癫痫活动和死亡的发作时间受软骨藻酸pH值的显著影响，pH 7.4时的毒性高于pH 3.7时。随着软骨藻酸剂量的增加，pH对其毒性的影响减弱。事实上，在14.5 mg/kg剂量时，pH值为3.7和7.4时软骨藻酸的毒性相似。结论是，软骨藻酸的体内毒性随所施用溶液的pH值而变化。软骨藻酸在不同pH值下的毒性差异可能与其溶解度、吸收速率和消除速率有关，这取决于软骨藻酸分子的质子化程度。软骨藻酸的毒性还会因动物年龄、受体敏感性以及大脑不同区域的受体密度而有所不同。
