Absorption and Effect of Azaspiracid-1 Over the Human Intestinal Barrier

Abal, Paula; Louzao, M. Carmen; Fraga-Corral, María; Vilariño, Natalia; Ferreiro, Sara F.; Vieytes, Mercedes R.; Botana, Luís M.

doi:10.1159/000480331

Cited by 15 publications

(16 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the contrary, AZAs caused accumulation of fat droplets in mice liver [30]. An involvement of autophagy can be hypothesized in digestive glands accumulating A. dexteroporum -AZAs, consistently with the regulation of neutral lipid metabolism upon food restriction [66] and the observation of autophagosomes in the cytoplasm of AZA-1 treated intestinal cells [29]. Autophagy has been also associated with destabilization of lysosomal membranes and accumulation of lipofuscin in the lysosomes [68,69], which were both observed in the digestive gland of A. dexteroporum -exposed mussels.…”

Section: Discussionmentioning

confidence: 94%

“…ovata , Gymnodinium catenatum and Prorocentrum lima ) [45,58,61,62,63], and in mice, where AZAs caused erosion and shortening of intestinal villi [30,50]. However, a direct role of AZAs on digestive tissue morphology is still controversial, since no structural damage to intestinal cells was demonstrated after in vitro treatment with these biotoxins [29]. Since the atrophy of digestive tubules is a typical symptom of reduced feeding or starvation in bivalves [61], a similar mechanism may be hypothesised in the mussels exposed to A. dexteroporum , as often observed in bivalves exposed to toxic microalgae [35,64,65].…”

Section: Discussionmentioning

confidence: 99%

“…The properties of a both lipophilic and charged molecule ensure AZAs broad capabilities to cross cell membranes and interact with biological structures. Indeed, in vitro exposures of mammalian cell cultures to AZAs revealed a wide variety of effects, including F-actin decrease and cytoskeleton disorganization, increase of cytosolic calcium and cAMP, inhibition of neuronal bioelectric activity, activation of apoptotic pathways, hERG (human ether-a-go-go-related gene) potassium channel blockage, alteration in cell–cell adhesion, damages to mitochondria, generation of autophagosomes, ATP depletion, upregulation of proteins involved in energy metabolism and Golgi apparatus disruption [20,21,22,23,24,25,26,27,28,29]. In vivo toxicological studies in rodents revealed that oral administration of AZAs induce extensive damages to several organs (intestine, liver, spleen and thymus) and gastrointestinal symptoms (dilation and fluid accumulation in the small intestine, exfoliation of duodenal villi, infiltration of leukocytes), while intravenous or intraperitoneal injection caused neurotoxicity (sluggishness, respiratory difficulties, spasms, progressive paralysis), cardiotoxicity (arrhythmias, functional and structural heart damage) and cardiovascular problems (altered arterial blood pressure) [20,30,31,32,33].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Biological Effects of the Azaspiracid-Producing Dinoflagellate Azadinium dexteroporum in Mytilus galloprovincialis from the Mediterranean Sea

et al. 2019

View full text Add to dashboard Cite

Azaspiracids (AZAs) are marine biotoxins including a variety of analogues. Recently, novel AZAs produced by the Mediterranean dinoflagellate Azadinium dexteroporum were discovered (AZA-54, AZA-55, 3-epi-AZA-7, AZA-56, AZA-57 and AZA-58) and their biological effects have not been investigated yet. This study aimed to identify the biological responses (biomarkers) induced in mussels Mytilus galloprovincialis after the bioaccumulation of AZAs from A. dexteroporum. Organisms were fed with A. dexteroporum for 21 days and subsequently subjected to a recovery period (normal diet) of 21 days. Exposed organisms accumulated AZA-54, 3-epi-AZA-7 and AZA-55, predominantly in the digestive gland. Mussels’ haemocytes showed inhibition of phagocytosis activity, modulation of the composition of haemocytic subpopulation and damage to lysosomal membranes; the digestive tissue displayed thinned tubule walls, consumption of storage lipids and accumulation of lipofuscin. Slight genotoxic damage was also observed. No clear occurrence of oxidative stress and alteration of nervous activity was detected in AZA-accumulating mussels. Most of the altered parameters returned to control levels after the recovery phase. The toxic effects detected in M. galloprovincialis demonstrate a clear biological impact of the AZAs produced by A. dexteroporum, and could be used as early indicators of contamination associated with the ingestion of seafood.

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Biological Effects of the Azaspiracid-Producing Dinoflagellate Azadinium dexteroporum in Mytilus galloprovincialis from the Mediterranean Sea

et al. 2019

View full text Add to dashboard Cite

show abstract

“…There are no pharmacokinetics data in humans. Intestinal absorption has been demonstrated in vivo in mice and in vitro in human intestinal cell cultures [ 197 , 198 ]. AZA1 is widely distributed after absorption, being detected in several organs including spleen, kidney, lung, heart and liver, and only trace amounts in the brain [ 198 ].…”

Section: Azaspiracidsmentioning

confidence: 99%

Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection

Vilariño

Louzao

Abal

et al. 2018

Toxins

Self Cite

114

View full text Add to dashboard Cite

Marine biotoxins are produced by aquatic microorganisms and accumulate in shellfish or finfish following the food web. These toxins usually reach human consumers by ingestion of contaminated seafood, although other exposure routes like inhalation or contact have also been reported and may cause serious illness. This review shows the current data regarding the symptoms of acute intoxication for several toxin classes, including paralytic toxins, amnesic toxins, ciguatoxins, brevetoxins, tetrodotoxins, diarrheic toxins, azaspiracids and palytoxins. The information available about chronic toxicity and relative potency of different analogs within a toxin class are also reported. The gaps of toxicological knowledge that should be studied to improve human health protection are discussed. In general, gathering of epidemiological data in humans, chronic toxicity studies and exploring relative potency by oral administration are critical to minimize human health risks related to these toxin classes in the near future.

show abstract

“…Figure 1.3 Chemical structures of AZA toxins 1, 2 and 3 (Twiner et al, 2012a) AZA consumption results in increased permeability of the intestine, leading to fluid accumulation in the small intestine and diarrhoea. The mode of action of AZA is unclear, studies conducted on Caco-2 cells that model the human intestine found that exposure to AZA-1 interfered with the protein occludin, and leading to disruption in paracellular permeability (Abal et al, 2017). A further observation of AZA-1 exposure to Caco-2 cells was a disorganisation of actin cytoskeleton and a decrease in adherence, this could be a factor involved in increased intestinal permeability (Vilariño et al, 2006, Vilariño, 2008.…”

Section: Figure 12mentioning

confidence: 99%

Prospecting the insect model, Galleria mellonella, for gut-related pathobiology

Emery¹

View full text Add to dashboard Cite

Animal research has contributed immensely to medical and scientific advances over the last century, and continues to play important roles in enhancing our understanding of infectious and non-communicable disease development, and the search for treatments. The mouse, for example, shares ~95% of human genes and is the most widespread vertebrate model in use. Since the late 1980s, there has been several UK and EU directives (e.g., 2010/63/EU) to improve the welfare of animals considered essential for experimentation, and to link directly with the principle of the 3Rs, to Replace, Reduce and Refine animal use. Additionally, animal maintenance, husbandry, compliance with legislation and licencing, and staff training are costly and time-consuming. Hence, there is much to gain from developing alternative in vivo models and complementary in vitro, in chemico and in silico tools. Larvae of the wax moth Galleria mellonella represent one such surrogate to rodents, and have been used successfully to study microbial isolates for virulence traits, putative antibiotic therapies, and more recently, toxicological assessment. There is an abundance of practical and biological advantages to selecting G. mellonella over rodents and traditional non-mammalian fruit flies and nematodes (which are described in Chapter 1), but one area lacking in knowledge is their applicability for studies of gut pathobiology. Therefore, the aim of this thesis was to evaluate the usefulness and accuracy of G. mellonella larvae as a model for gut specific toxins and pathogens when administered through an oral route (gavage). A series of whole-organism (phenotype), cellular, biochemical, microbiological and microscopy methods were used to interrogate the gastrointestinal tract of G. mellonella in the absence and presence of chemicals and microbes known to cause gastropathy in rodents and humans. First, the transferability of the indomethacin restraint/ulcer assay was established in G. mellonella, with levels of tissue deterioration and enhanced leakiness reminiscent of rodents (Chapter 2). Second, the rearing of insects on nutraceuticals Cordyceps sinensis and bovine colostrum alleviated gut damage caused by indomethacin, and improved survival outcomes when challenged with the enteric pathogen Campylobacter jejuni (Chapter 3). Third, oral administration of shellfish poisoning toxins (okadaic acid and azaspiracids 1-3) to G. mellonella, interfered with tissue integrity and microbial stability of the gastrointestinal tract, and produced comparable LD50 levels to their rodent counterparts (Chapter 4). The results presented here go beyond establishing synonymous damage phenomena between G. mellonella larvae and vertebrates (Chapter 5), but adds new knowledge to the structure and function of the lepidopteran alimentary canal, the cytopathology of emerging marine toxins, and how diet invariably influences a host’s capacity to recover from subacute chemical and microbial disruptors.

show abstract

Absorption and Effect of Azaspiracid-1 Over the Human Intestinal Barrier

Cited by 15 publications

References 40 publications

Biological Effects of the Azaspiracid-Producing Dinoflagellate Azadinium dexteroporum in Mytilus galloprovincialis from the Mediterranean Sea

Biological Effects of the Azaspiracid-Producing Dinoflagellate Azadinium dexteroporum in Mytilus galloprovincialis from the Mediterranean Sea

Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection

Prospecting the insect model, Galleria mellonella, for gut-related pathobiology

Contact Info

Product

Resources

About