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      Domoic Acid Toxicologic Pathology: A Review

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          Abstract

          Domoic acid was identified as the toxin responsible for an outbreak of human poisoning that occurred in Canada in 1987 following consumption of contaminated blue mussels [ Mytilus edulis]. The poisoning was characterized by a constellation of clinical symptoms and signs. Among the most prominent features described was memory impairment which led to the name Amnesic Shellfish Poisoning [ASP]. Domoic acid is produced by certain marine organisms, such as the red alga Chondria armata and planktonic diatom of the genus Pseudo-nitzschia. Since 1987, monitoring programs have been successful in preventing other human incidents of ASP. However, there are documented cases of domoic acid intoxication in wild animals and outbreaks of coastal water contamination in many regions world-wide. Hence domoic acid continues to pose a global risk to the health and safety of humans and wildlife. Several mechanisms have been implicated as mediators for the effects of domoic acid. Of particular importance is the role played by glutamate receptors as mediators of excitatory neurotransmission and the demonstration of a wide distribution of these receptors outside the central nervous system, prompting the attention to other tissues as potential target sites. The aim of this document is to provide a comprehensive review of ASP, DOM induced pathology including ultrastructural changes associated to subchronic oral exposure, and discussion of key proposed mechanisms of cell/tissue injury involved in DOM induced brain pathology and considerations relevant to food safety and human health.

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          Most cited references227

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          Mechanisms of ischemic brain damage.

          In the United States stroke is the third leading cause of death and the leading cause of disability. Brain injury following stroke results from the complex interplay of multiple pathways including excitotoxicity, acidotoxicity, ionic imbalance, peri-infarct depolarization, oxidative and nitrative stress, inflammation and apoptosis. There are very few treatments for stroke and the development of new treatments requires a comprehensive understanding of the diverse mechanisms of ischemic brain damage that are responsible for neuronal death. Here, we discuss the underlying pathophysiology of this devastating disease and reveal the intertwined pathways that are the target of therapeutic intervention.
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            Mortality of sea lions along the central California coast linked to a toxic diatom bloom.

            Over 400 California sea lions (Zalophus californianus) died and many others displayed signs of neurological dysfunction along the central California coast during May and June 1998. A bloom of Pseudo-nitzschia australis (diatom) was observed in the Monterey Bay region during the same period. This bloom was associated with production of domoic acid (DA), a neurotoxin that was also detected in planktivorous fish, including the northern anchovy (Engraulis mordax), and in sea lion body fluids. These and other concurrent observations demonstrate the trophic transfer of DA resulting in marine mammal mortality. In contrast to fish, blue mussels (Mytilus edulus) collected during the DA outbreak contained no DA or only trace amounts. Such findings reveal that monitoring of mussel toxicity alone does not necessarily provide adequate warning of DA entering the food web at levels sufficient to harm marine wildlife and perhaps humans.
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              Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate.

              In newborn mice subcutaneous injectionis of monosodium glutamate induced acute neuronal necrosis in several regions of developing brain including the hypothanamus. As adults, treated animals showed stunted skeletal development, marked obesity, and female sterility. Pathological changes were also found in several organs associated with endocrine function. Studies of food consumption failed to demonstrate hyperphagia to explain the obesity. It is postulated that the aduls syndrome represents a multifacted nueroendocrine disturbance arising from the disruption of developing nueral centers concered in the mediation of endocrine function.
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                Author and article information

                Journal
                Mar Drugs
                MD
                Marine Drugs
                Molecular Diversity Preservation International
                1660-3397
                March 2008
                28 May 2008
                : 6
                : 2
                : 180-219
                Affiliations
                [1 ] Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, 251 Sir Frederick Banting Dr., 2202D2, Tunney’s Pasture, Ottawa, ON, Canada, K1A-0L2 E-Mail: Olga_Pulido@ 123456hc-sc.gc.ca
                [2 ] Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON, Canada; http://www.medicine.uottawa.ca/path/pulido.html, http://www.iatpfellows.org/
                Article
                md6020180
                10.3390/md20080010
                2525487
                18728725
                f3dcc7ed-e883-45e6-94c6-242f4d53808c
                Blood Transfus 2008:6 SIMTI Servizi Srl
                History
                : 4 December 2007
                : 16 May 2008
                : 16 May 2008
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                food safety,amnesic shellfish poisoning,neuropathology,glutamate receptors,excitotoxicity,domoic acid,neurotoxicology,toxicologic pathology

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