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Azaspiracids Increase Mitochondrial Dehydrogenases Activity in Hepatocytes: Involvement of Potassium and Chloride Ions.
- Source :
-
Marine drugs [Mar Drugs] 2019 May 08; Vol. 17 (5). Date of Electronic Publication: 2019 May 08. - Publication Year :
- 2019
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Abstract
- Background: Azaspiracids (AZAs) are marine toxins that are produced by Azadinium and Amphidoma dinoflagellates that can contaminate edible shellfish inducing a foodborne poisoning in humans, which is characterized by gastrointestinal symptoms. Among these, AZA1, -2, and -3 are regulated in the European Union, being the most important in terms of occurrence and toxicity. In vivo studies in mice showed that, in addition to gastrointestinal effects, AZA1 induces liver alterations that are visible as a swollen organ, with the presence of hepatocellular fat droplets and vacuoles. Hence, an in vitro study was carried out to investigate the effects of AZA1, -2, and -3 on liver cells, using human non-tumor IHH hepatocytes.<br />Results: The exposure of IHH cells to AZA1, -2, or -3 (5 × 10 <superscript>-12</superscript> -1 × 10 <superscript>-7</superscript> M) for 24 h did not affect the cell viability and proliferation (Sulforhodamine B assay and <superscript>3</superscript> H-Thymidine incorporation assay), but they induced a significant concentration-dependent increase of mitochondrial dehydrogenases activity (MTT reduction assay). This effect depends on the activity of mitochondrial electron transport chain complex I and II, being counteracted by rotenone and tenoyl trifluoroacetone, respectively. Furthermore, AZAs-increased mitochondrial dehydrogenase activity was almost totally suppressed in the K <superscript>+</superscript> -, Cl <superscript>-</superscript> -, and Na <superscript>+</superscript> -free media and sensitive to the specific inhibitors of K <subscript>ATP</subscript> and hERG potassium channels, Na <superscript>+</superscript> /K <superscript>+</superscript> , ATPase, and cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels.<br />Conclusions: These results suggest that AZA mitochondrial effects in hepatocytes derive from an imbalance of intracellular levels of K <superscript>+</superscript> and, in particular, Cl <superscript>-</superscript> ions, as demonstrated by the selective reduction of toxin effects by CFTR chloride channel inhibition.
- Subjects :
- Animals
Cell Line
Cell Survival drug effects
Chlorine
Cytoprotection drug effects
Electron Transport Complex I
Electron Transport Complex II
Hepatocytes drug effects
Hepatocytes metabolism
Humans
Mytilus edulis
Oxidoreductases metabolism
Potassium
Furans toxicity
Marine Toxins toxicity
Mitochondria drug effects
Oxidoreductases drug effects
Pyrans toxicity
Spiro Compounds toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1660-3397
- Volume :
- 17
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Marine drugs
- Publication Type :
- Academic Journal
- Accession number :
- 31072021
- Full Text :
- https://doi.org/10.3390/md17050276