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dc.contributor.authorMottalebi, Abbasali
dc.contributor.authorPourahmad, Jalal
dc.contributor.authorShahraki, J.
dc.contributor.authorZarshenas, Gh.
dc.coverage.spatialIranen_US
dc.coverage.spatialPersian Gulfen_US
dc.coverage.spatialOman Seaen_US
dc.date.accessioned2018-07-22T04:22:46Z
dc.date.available2018-07-22T04:22:46Z
dc.date.issued2013
dc.identifier.urihttp://hdl.handle.net/1834/13315
dc.description.abstractIn this research, we investigated and compared the cytotoxic mechanisms of aqueous extract of C.polykricoides responsible for a severe and widespread HAB in the Persian Gulf and Gulf of Oman (2008-2009) in both isolated rat and trout liver hepatocytes. In addition, the role of oxidative stress and mitochondria in the induction of apoptosis were also investigated. Isolated hepatocytes were obtained by collagenase perfusion of the rat liver. To determine the hepatocyte “ROS” generation, dichlorofluorescin diacetate was used as the reagent. The uptake of the cationic fluorescent dye, rhodamine 123, has been used for the determination of hepatocytes mitochondrial membrane potential. Redistribution of lysosomotropic probe, acridine orange from lysosomes into cytosol was used for determination of lysosomal membrane damage. GSH and GSSG were determined using spectrofluorometric method. Caspase-3 activity and apoptosis phenotype were also determined using ‘‘Sigma’s caspase-3 assay kit and Sigma–Aldrich apoptosis detection kit, respectively. Incubation of algal extract with isolated rat hepatocytes caused hepatocyte membrane lysis, reactive oxygen species formation (ROS), glutathione depletion, collapse of mitochondrial membrane potential, ATP depletion and increase in ADP/ATP ratio, cytochrome c release in to the hepatocyte cytosol, activation of caspases cascade and appearance of apoptosis phenotype. antioxidants (α-tocopherol succinate and BHT), hydroxyl radical scavenger (mannitol and DMSO), Mitochondrial permeability transition (MPT) pore sealing agents (cyclosporine A, carnitine and trifluoperazine), NADPH P450 reductase inhibitor (Diphenyliodonium chloride), CYP2E1 inhibitors (Phenylimidazole and 4-Methylpyrazole) and ATP generators (L-glutamine, Fructose and Xylitol) inhibited the activation of caspase-3 and cell death. Our data showed, that algal extract activate apoptosis signaling via oxidative stress and mitochondrial pathway. ROS formation could directly be involved in mitochondrial MPT pore opening and activation of caspases cascade leading to toxic effect of C.polykricoides extract on both rat and trout hepatocytes. These findings contribute to a better understanding of C.polykricoides-toxic effects on mammalian and aquatic liver cells. Our findings revealed that trout hepatocytes are much more sensitive ( more than two hundred folds) to toxic effects of C.polykricoides extract than rat hepatocytes. On the other hand the algal extract induced lysosomal membrane damage only in trout but not rat hepatocytes.en_US
dc.description.sponsorshipIranian Fisheries Science Research Instituteen_US
dc.language.isofaen_US
dc.publisherIranian Fisheries Science Research Instituteen_US
dc.relation.ispartofseries40839;
dc.titleA search for cellular and molecular cytotoxic mechanisms of Cochlodinium Polykricoides in isolated rat and fish hepatocytesen_US
dc.typeReporten_US
dc.description.statusPublisheden_US
dc.format.pages45pp.en_US
dc.publisher.placeTehran, Iranen_US
dc.subject.asfaC.polykricoidesen_US
dc.subject.asfaCytotoxicen_US
dc.subject.asfaRat and trouten_US
dc.subject.asfaCellularen_US
dc.subject.asfaMolecularen_US
dc.subject.asfaCochlodinium Polykricoidesen_US
dc.subject.asfaGenerationen_US
dc.subject.asfaGSHen_US
dc.subject.asfaApoptosis phenotypeen_US
dc.subject.asfaL-glutamineen_US
dc.type.refereedRefereeden_US
refterms.dateFOA2021-01-30T18:48:32Z


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