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. 2021 Jan 8;19(1):23.
doi: 10.3390/md19010023.

DSP Toxin Distribution across Organs in Mice after Acute Oral Administration

M Carmen Louzao  1 , Paula Abal  1 , Celia Costas  1 , Toshiyuki Suzuki  2 , Ryuichi Watanabe  2 , Natalia Vilariño  1 , Ana M Botana  3 , Mercedes R Vieytes  4 , Luis M Botana  1
Affiliations

DSP Toxin Distribution across Organs in Mice after Acute Oral Administration

M Carmen Louzao et al. Mar Drugs. .

Abstract

Okadaic acid (OA) and its main structural analogs dinophysistoxin-1 (DTX1) and dinophysistoxin-2 (DTX2) are marine lipophilic phycotoxins distributed worldwide that can be accumulated by edible shellfish and can cause diarrheic shellfish poisoning (DSP). In order to study their toxicokinetics, mice were treated with different doses of OA, DTX1, or DTX2 and signs of toxicity were recorded up to 24 h. Toxin distribution in the main organs from the gastrointestinal tract was assessed by liquid chromatography-mass spectrometry (LC/MS/MS) analysis. Our results indicate a dose-dependency in gastrointestinal absorption of these toxins. Twenty-four hours post-administration, the highest concentration of toxin was detected in the stomach and, in descending order, in the large intestine, small intestine, and liver. There was also a different toxicokinetic pathway between OA, DTX1, and DTX2. When the same toxin doses are compared, more OA than DTX1 is detected in the small intestine. OA and DTX1 showed similar concentrations in the stomach, liver, and large intestine tissues, but the amount of DTX2 is much lower in all these organs, providing information on DSP toxicokinetics for human safety assessment.

Keywords: LC/MS/MS; dinophysistoxin-1; dinophysistoxin-2; okadaic acid; toxicokinetic.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Total ion chromatogram of OA, DTX1, and DTX2 of the stomach, small intestine, and large intestine samples.
Figure 2
Figure 2
Toxin concentration in different tissues of the digestive organs (ng/g) according to oral dose administered to mice: (A) okadaic acid, (B) dinophysistoxin-1, and (C) dinophysistoxin-2, reported as mean ± SEM.
Figure 3
Figure 3
Total toxin (ng) detected in different contents of the digestive organs according to oral dose administered to mice: (A) okadaic acid, (B) dinophysistoxin-1, and (C) dinophysistoxin-2, reported as mean ± SEM.
Figure 4
Figure 4
Time course of OA, DTX1, or DTX2 cumulatively excreted (ng) in urine (A) and feces (B): mice received a dose of 1000 µg/kg of each toxin.
Figure 5
Figure 5
Plasma amount of toxins in mice 24 h after oral gavage administration of each dose of OA or DTX1.
Figure 6
Figure 6
Toxin recovery: % OA, DTX1, or DTX2 detected 24 h after administration of the dose indicated.
See this image and copyright information in PMC

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