Renal clearance of domoic acid in the rat

Suzuki, C; Hierlihy, S. L.

doi:10.1016/0278-6915(93)90140-t

Cited by 86 publications

(49 citation statements)

References 13 publications

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“…Further, since the dicarboxylate excitatory amino acid analogs are mainly eliminated by glomerular filtration [62] and no alterations in the glomeruli and renal tubules have been characterized [21], the renal clearance of KA is unlikely to be altered in PTGS-2 deficient mice. Additionally, we found that the time to onset of seizure activity was not different between PTGS-2 deficient and wild type mice, suggesting no alteration in either the absorption of KA from the peritoneum nor in its distribution to the brain.…”

Section: Discussionmentioning

confidence: 99%

Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice

Toscano

Ueda

Tomita

et al. 2008

Brain Research Bulletin

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Excitotoxicity involves over activation of brain excitatory glutamate receptors and has been implicated in neurological, neurodegenerative and neuropsychiatric diseases. Metabolism of arachidonic acid (AA) through the phospholipase A 2 (PLA 2 )/ prostaglandin-endoperoxide synthase (PTGS) pathway is increased after excitotoxic stimulation. However, the individual roles of the PTGS isoforms in this process are not well established. We assessed the role of the PTGS isoforms in the process of excitotoxicity by exposing mice deficient in either PTGS-1 (PTGS-1 -/-) or PTGS-2 (PTGS-2 -/-) to the rototypic excitotoxin, kainic acid (KA). Seizure intensity and neuronal damage were significantly elevated in KA-exposed PTGS-2 -/-, but not in PTGS-1 -/-, mice. The increased susceptibility was not associated with an alteration in KA receptor binding activity or mediated through the CB1 endocannabinoid receptor. The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) was decreased in the CA1 pyramidal neurons of PTGS-2 -/-mice, suggesting an alteration of GABAergic function. In wild-type mice, six weeks treatment with the PTGS-2 selective inhibitor celecoxib recapitulated the increased susceptibility to KA-induced excitotoxicity observed in PTGS-2 -/-mice, further supporting the role of PTGS-2 in the excitotoxic process. The increased susceptibility to KA was also associated with decreased brain levels of PGE 2 , a biomarker of PTGS-2 activity. Our results suggest that PTGS-2 activity and its specific products may modulate neuronal excitability by affecting GABAergic neurotransmission. Further, inhibition of PTGS-2 but not PTGS-1, may increase the susceptibility to seizures.

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Section: Discussionmentioning

confidence: 99%

Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice

Toscano

Ueda

Tomita

et al. 2008

Brain Research Bulletin

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“…[23][24][25][26] There is limited information about the effects of DA on the kidney; however, oral dosing in coho salmon has shown that the kidney is a primary site of DA accumulation in this species, and studies in rodents have shown that renal excretion is the exclusive route of systemic DA elimination. 27,28 Examination of sea lions after DA poisoning has also revealed some evidence of interstitial nephritis, renal edema, and elevated BUN, although the exact cause of these findings cannot be definitively attributed to DA toxicity. 29,30 Furthermore, sea lions with acute DA toxicosis seem to have an elevated hematocrit, 31 suggesting that water reabsorption or red blood cell production could be affected, both of which are functions of the kidney.…”

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confidence: 99%

Characterization of Renal Toxicity in Mice Administered the Marine Biotoxin Domoic Acid

Funk

Janech

Dillon

et al. 2014

Journal of the American Society of Nephrology

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Domoic acid (DA), an excitatory amino acid produced by diatoms belonging to the genus Pseudo-nitzschia, is a glutamate analog responsible for the neurologic condition referred to as amnesic shellfish poisoning. To date, the renal effects of DA have been underappreciated, although renal filtration is the primary route of systemic elimination and the kidney expresses ionotropic glutamate receptors. To characterize the renal effects of DA, we administered either a neurotoxic dose of DA or doses below the recognized limit of toxicity to adult Sv128/Black Swiss mice. DA preferentially accumulated in the kidney and elicited marked renal vascular and tubular damage consistent with acute tubular necrosis, apoptosis, and renal tubular cell desquamation, with toxic vacuolization and mitochondrial swelling as hallmarks of the cellular damage. Doses$0.1 mg/kg DA elevated the renal injury biomarkers kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, and doses$0.005 mg/kg induced the early response genes c-fos and junb. Coadministration of DA with the broad spectrum excitatory amino acid antagonist kynurenic acid inhibited induction of c-fos, junb, and neutrophil gelatinase-associated lipocalin. These findings suggest that the kidney may be susceptible to excitotoxic agonists, and renal effects should be considered when examining glutamate receptor activation. Additionally, these results indicate that DA is a potent nephrotoxicant, and potential renal toxicity may require consideration when determining safe levels for human exposure.

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“…Experimental studies have determined serum half-lives of approximately 20 min for rats (Suzuki & Hierlihy 1993, Truelove & Iverson 1994 and approximately 2 h for Cynomolgus monkeys (Truelove & Iverson 1994). Although the rate of clearance of DA in sea lions is not known, it can be estimated using interspecies scaling (Edwards 1975).…”

Section: Discussionmentioning

confidence: 99%

Exposure assessment of the biotoxin domoic acid in California sea lions: application of a bioenergetic model

Bejarano¹,

Dolah²,

Gulland³

et al. 2007

Mar. Ecol. Prog. Ser.

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The biotoxin domoic acid (DA), produced by diatoms of the genus Pseudo-nitzschia, has caused massive California sea lion Zalophus californianus mortalities and live strandings along the California coast. Since quantifying the field DA dose that causes toxic effects in sea lions is logistically difficult, a bioenergetic model that uses age/sex-specific energy requirements was developed to estimate DA doses, assuming ingestion of 2 important vector species: anchovies Engraulis mordax and sardines Sardinops sagax. In this model, uncertainty and variability were incorporated by assigning sampling distributions to each model variable. Variables included: (1) vector energy density and assimilation efficiency of gross fish energy; (2) sea lion weight and energy requirements adjusted for energy expenditures associated with foraging, growth and reproduction; and (3) DA concentration in the vector species. Model outputs were analyzed relative to thresholds that cause adverse effects in other mammal species (1 and 2.71 mg DA kg -1 body weight). Based on DA concentrations measured in fish during a previous Pseudo-nitzschia bloom, consumption of anchovies versus sardines as 20% of the sea lions' daily intake would result in a 4-fold increase in risk of non-lethal toxic effects. Across age classes, the median DA dose in pups (7 to 12 mo old) was twice that estimated for juveniles and was between 2 and 4 times greater than for adults. In DA dose estimates most of the variability resulted from the uncertainty associated with the energy density of the vector species and DA concentration in sardines rather than from the uncertainty associated with sea lions. Finally, we highlight the most relevant areas of research needed for determining a definitive risk of sea lion exposure to DA. KEY WORDS: Domoic acid · Exposure assessment · California sea lion · Probabilistic modelResale or republication not permitted without written consent of the publisher

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Renal clearance of domoic acid in the rat

Cited by 86 publications

References 13 publications

Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice

Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice

Characterization of Renal Toxicity in Mice Administered the Marine Biotoxin Domoic Acid

Exposure assessment of the biotoxin domoic acid in California sea lions: application of a bioenergetic model

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