Immunomodulatory Effects of Domoic Acid Differ Between In vivo and In vitro Exposure in Mice

Levin, Milton; Leibrecht, Heather; Ryan, James C.; Dolah, Frances Van; Guise, Sylvain De

doi:10.3390/md6040636

Cited by 15 publications

(8 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additional transcriptomic analyses (together with other omic approaches) of mussels exposed to DSP toxins will be critical to elucidate the mechanisms by which these toxins affect marine invertebrates in vivo . Overall, the differences observed between in vitro and in vivo studies are in agreement with previous studies [ 35 ], where the synergistic interactions between OA and other DSP toxins might be responsible for higher levels of toxicity [ 3 , 36 ] and/or different toxicological effects [ 37 ].…”

Section: Discussionsupporting

confidence: 90%

Early Genotoxic and Cytotoxic Effects of the Toxic Dinoflagellate Prorocentrum lima in the Mussel Mytilus galloprovincialis

Prego-Faraldo

Valdiglesias

Laffón

et al. 2016

Toxins

View full text Add to dashboard Cite

Okadaic acid (OA) and dinophysistoxins (DTXs) are the main toxins responsible for diarrhetic shellfish poisoning (DSP) intoxications during harmful algal blooms (HABs). Although the genotoxic and cytotoxic responses to OA have been evaluated in vitro, the in vivo effects of these toxins have not yet been fully explored. The present work fills this gap by evaluating the in vivo effects of the exposure to the DSP-toxin-producing dinoflagellate Prorocentrum lima during the simulation of an early HAB episode in the mussel Mytilus galloprovincialis. The obtained results revealed that in vivo exposure to this toxic microalgae induced early genotoxicity in hemocytes, as a consequence of oxidative DNA damage. In addition, the DNA damage observed in gill cells seems to be mainly influenced by exposure time and P. lima concentration, similarly to the case of the oxidative damage found in hemocytes exposed in vitro to OA. In both cell types, the absence of DNA damage at low toxin concentrations is consistent with the notion suggesting that this level of toxicity does not disturb the antioxidant balance. Lastly, in vivo exposure to growing P. lima cell densities increased apoptosis but not necrosis, probably due to the presence of a high number of protein apoptosis inhibitors in molluscs. Overall, this work sheds light into the in vivo genotoxic and cytotoxic effects of P. lima. In doing so, it also demonstrates for the first time the potential of the modified (OGG1) comet assay for assessing oxidative DNA damage caused by marine toxins in marine invertebrates.

show abstract

Section: Discussionsupporting

confidence: 90%

Early Genotoxic and Cytotoxic Effects of the Toxic Dinoflagellate Prorocentrum lima in the Mussel Mytilus galloprovincialis

Prego-Faraldo

Valdiglesias

Laffón

et al. 2016

Toxins

View full text Add to dashboard Cite

show abstract

“…The study further found that the elevated eosinophils were associated with more sensitive indicators of functional immune status, such as decreased T-lymphocyte proliferation and increased neutrophil phagocytosis. Similarly, California sea lions with clinical symptoms of DA toxicity had elevated eosinophil counts [80], which is further supported by the observed immunomodulatory effects of DA on mammalian WBCs [81], [82]. As such, the results from this study support the hypothesis that DA caused an immunomodulatory response in these dolphins, although the implications for an individual survival outcome and/or a population level health effect require further elucidation.…”

Section: Discussionsupporting

confidence: 75%

Concurrent Exposure of Bottlenose Dolphins (Tursiops truncatus) to Multiple Algal Toxins in Sarasota Bay, Florida, USA

et al. 2011

View full text Add to dashboard Cite

Sentinel species such as bottlenose dolphins (Tursiops truncatus) can be impacted by large-scale mortality events due to exposure to marine algal toxins. In the Sarasota Bay region (Gulf of Mexico, Florida, USA), the bottlenose dolphin population is frequently exposed to harmful algal blooms (HABs) of Karenia brevis and the neurotoxic brevetoxins (PbTx; BTX) produced by this dinoflagellate. Live dolphins sampled during capture-release health assessments performed in this region tested positive for two HAB toxins; brevetoxin and domoic acid (DA). Over a ten-year study period (2000–2009) we have determined that bottlenose dolphins are exposed to brevetoxin and/or DA on a nearly annual basis (i.e., DA: 2004, 2005, 2006, 2008, 2009; brevetoxin: 2000, 2004, 2005, 2008, 2009) with 36% of all animals testing positive for brevetoxin (n = 118) and 53% positive for DA (n = 83) with several individuals (14%) testing positive for both neurotoxins in at least one tissue/fluid. To date there have been no previously published reports of DA in southwestern Florida marine mammals, however the May 2008 health assessment coincided with a Pseudo-nitzschia pseudodelicatissima bloom that was the likely source of DA observed in seawater and live dolphin samples. Concurrently, both DA and brevetoxin were observed in common prey fish. Although no Pseudo-nitzschia bloom was identified the following year, DA was identified in seawater, fish, sediment, snails, and dolphins. DA concentrations in feces were positively correlated with hematologic parameters including an increase in total white blood cell (p = 0.001) and eosinophil (p<0.001) counts. Our findings demonstrate that dolphins within Sarasota Bay are commonly exposed to two algal toxins, and provide the impetus to further explore the potential long-term impacts on bottlenose dolphin health.

show abstract

“…The agreement between studies indicates that in vitro cytokine release may be a useful parameter in mechanistic studies of substances causing direct effects on the immune system. This notion is in accordance with published literature (Gennari et al, 2005;Lankveld et al, 2010;Levin et al, 2008).…”

Section: Immunotoxicity Of Dietary Toxicants In Vitrosupporting

confidence: 93%

In vitro cytokine release from human peripheral blood mononuclear cells in the assessment of the immunotoxic potential of chemicals

Stølevik

Nygaard

Granum

et al. 2011

Toxicology in Vitro

View full text Add to dashboard Cite

Alternative methods to the use of animals in testing of chemicals are needed. We investigated if the immunotoxic potential of 12 dietary toxicants could be predicted from effects on cytokine release from human peripheral blood mononuclear cells (PBMC) after in vitro exposure. Nine cytokines were selected to reflect different types of immune responses. The toxicants were classified as immunotoxic or non-immunotoxic substances according to the published in vivo data. Isolated human PBMC were exposed for 20 h to three concentrations of each of the 12 substances in the presence of human liver S9 fraction. After further incubation of PBMC in fresh medium containing the mitogen phytohemagglutinin (PHA, 10 μg/ml) for 48 h, release of the nine selected cytokines into the supernatant as well as cell proliferation were measured by Luminex technology™ and the BrdU incorporation assay, respectively. All 12 substances investigated affected the release of one or more cytokines, and each of the substances showed different cytokine release patterns. Within the limitations of the study design, the present study suggests that the effect of the substances on mitogen-induced cytokine release from PBMC cannot predict their immunotoxic potential, but may be useful in mechanistic studies.

show abstract

Immunomodulatory Effects of Domoic Acid Differ Between In vivo and In vitro Exposure in Mice

Cited by 15 publications

References 66 publications

Early Genotoxic and Cytotoxic Effects of the Toxic Dinoflagellate Prorocentrum lima in the Mussel Mytilus galloprovincialis

Early Genotoxic and Cytotoxic Effects of the Toxic Dinoflagellate Prorocentrum lima in the Mussel Mytilus galloprovincialis

Concurrent Exposure of Bottlenose Dolphins (Tursiops truncatus) to Multiple Algal Toxins in Sarasota Bay, Florida, USA

In vitro cytokine release from human peripheral blood mononuclear cells in the assessment of the immunotoxic potential of chemicals

Contact Info

Product

Resources

About