Evaluation on combinative toxicology of sodium perchlorate and sodium arsenate using zebrafish Danio rerio as a model

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Title: Evaluation on combinative toxicology of sodium perchlorate and sodium arsenate using zebrafish Danio rerio as a model
Author: Liu, Fujun
Abstract: Both perchlorate and arsenic are environmental contaminants , and their co -occurrence has been found in contaminated water . Perchlorate is a definitive thyroid disruptor , and thus affects antioxidant defense system . Arsenate is a pro -oxidant and cause oxidative stress . Arsenic is hypothesized as a thyroid disruptor . Ultimately , both chemicals cause damage on macromolecules . Theoretically , two chemicals have an additive interaction in thyrotoxicity and damage on macromolecules . To test this hypothesis , zebrafish Danio rerio were exposed to sodium arsenate (SA ) and sodium perchlorate (SP ) individually or in mixture in acute , sub -chronic , and chronic tests . The 96 -h LC50s of SA and SP were 272 and 1 ,365 mg /L , respectively , at larvae stage and 74 and 3 ,118 mg /L , respectively at juvenile stage . In the chronic toxicity test , we employed some endpoints to evaluate antioxidant (glutathione , GSH ) , thyrotoxicity (thyroid histopathology ) , and DNA damage (strand breaks , oxidative bases , and apoptosis ) . In addition , the toxicokinetics (uptake , accumulation , and depuration ) of both chemicals and their mixture was examined . Fish were exposed to SP (10 and 100 mg /L ) , SA (1 and 10 mg /L ) , and the mixture—SP+SA (10+1 and 100 +10 mg /L ) for up to 90 days . At day 10 , 30 , 60 , and 90 , fish were sampled and processed for endpoint assay . In the thyrotoxicity , the sensitivity of the following histopathological indicators for indicating thyroid perturbations by these two chemicals is , in descending order : epithelial cell height >percent of colloid area /follicle area >colloid area /follicular cell height >hyperplasia >angiogenesis >colloid area >follicle area . Models were applied to characterize the toxicokinetics of two chemicals . Two chemicals were taken up and depurated rapidly . Both chemicals reduced the uptake but enhanced the depuration of the other chemical from the zebrafish in mixture . Total and reduced GSH and the GSH status index were significantly altered by high concentrations of SA , SP , or their mixture . Damage to lipid and DNA was not as sensitive as expected . Two chemical displayed additive interactions in terms of some endpoints tested . In summary , this dissertation project explored the mechanism of these two chemicals and their interactions . This dissertation provides toxicological information for these two chemicals and clarifies their joint actions at different levels mechanistically .
URI: http : / /hdl .handle .net /2346 /10767
Date: 2006-05

Citation

Liu, Fujun Evaluation on combinative toxicology of sodium perchlorate and sodium arsenate using zebrafish Danio rerio as a model. Doctoral dissertation, Texas Tech University. Available electronically from http : / /hdl .handle .net /2346 /10767 .

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