FN Archimer Export Format
PT J
TI Azaspiracids Increase Mitochondrial Dehydrogenases Activity in Hepatocytes: Involvement of Potassium and Chloride Ions
BT 
AF Pelin, Marco
   Kilcoyne, Jane
   Florio, Chiara
   HESS, Philipp
   Tubaro, Aurelia
   Sosa, Silvio
AS 1:1;2:2;3:1;4:3;5:1;6:1;
FF 1:;2:;3:;4:PDG-ODE-DYNECO-PHYC;5:;6:;
C1 Department of Life Sciences, University of Trieste, Via A. Valerio 6, 34127 Trieste, Italy
   Marine Institute, Rinville, Oranmore, Co. H91 R673 Galway, Ireland
   IFREMER, Laboratoire Phycotoxines, Rue de l’Ile d’Yeu, 44311 Nantes, France
C2 UNIV TRIESTE, ITALY
   MARINE INST, IRELAND
   IFREMER, FRANCE
SI NANTES
SE PDG-ODE-DYNECO-PHYC
IN WOS Ifremer UPR
   DOAJ
   copubli-europe
IF 1.103
TC 8
UR https://archimer.ifremer.fr/doc/00494/60526/63989.pdf
LA English
DT Article
DE ;azaspiracids;hepatocytes;mitochondrial activity;mechanism of toxicity
AB 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. Results: The exposure of IHH cells to AZA1, -2, or -3 (5 × 10−12–1 × 10−7 M) for 24 h did not affect the cell viability and proliferation (Sulforhodamine B assay and 3H-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+-, Cl−-, and Na+-free media and sensitive to the specific inhibitors of KATP and hERG potassium channels, Na+/K+, ATPase, and cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels. Conclusions: These results suggest that AZA mitochondrial effects in hepatocytes derive from an imbalance of intracellular levels of K+ and, in particular, Cl− ions, as demonstrated by the selective reduction of toxin effects by CFTR chloride channel inhibition 
PY 2019
PD MAY
SO Marine Drugs
SN 1660-3397
PU MDPI
VL 17
IS 5
UT 000470964600029
DI 10.3390/md17050276
ID 60526
ER

EF