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Article ; Online: Cylindrospermopsin impairs zebrafish (Danio rerio) embryo development.

Moraes, A C N / Shah, S / Magalhães, V F / Habibi, H R

2022 Volume 175, Page(s) 105567

Abstract: Cyanotoxins are among common contaminants that can impair human, animal, and environmental health. Cylindrospermopsin (CYN) is an abundant form of cyanotoxins elevated following algal bloom in the water worldwide. Previous studies have described CYN ... ...

Abstract	Cyanotoxins are among common contaminants that can impair human, animal, and environmental health. Cylindrospermopsin (CYN) is an abundant form of cyanotoxins elevated following algal bloom in the water worldwide. Previous studies have described CYN effects on several organs in mammals. However, little is known about its toxicity mechanisms in other vertebrates. This study aims to characterize the developmental effects of CYN using zebrafish larvae as an aquatic model organism. A wide range of CYN concentrations (0-2000 μg/L) was tested using a morphometric approach for survival, hatching, various growth and developmental abnormalities. We also investigated the expression of genes related to oxidative stress, osmoregulation, and thyroid function. Exposure to CYN resulted in decreased growth, increased developmental abnormalities such as pericardial and yolk sac edema as well as swim bladder absence. In addition, CYN increased tr1a, and decreased dio1 and dio3 transcript levels which are involved in thyroid-mediated function. It also increased transcript levels related to oxidative stress, including hsp70, ahr1a, cyp1a, gpx and cat. Lastly, CYN exposure increased aqp3a and decreased dab2, which are involved in osmoregulation with a threshold of 10 μg/L. The present study demonstrates multiple effects of exposure to environmentally relevant CYN concentrations in zebrafish embryos.
MeSH term(s)	Alkaloids/metabolism ; Alkaloids/toxicity ; Animals ; Cyanobacteria Toxins ; Embryo, Nonmammalian ; Embryonic Development ; Zebrafish/metabolism
Chemical Substances	Alkaloids ; Cyanobacteria Toxins ; cylindrospermopsin (2JIZ556BA3)
Language	English
Publishing date	2022-01-31
Publishing country	England
Document type	Journal Article
ZDB-ID	1502505-6
ISSN	1879-0291 ; 0141-1136
ISSN (online)	1879-0291
ISSN	0141-1136
DOI	10.1016/j.marenvres.2022.105567
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Article: Cylindrospermopsin impairs zebrafish (Danio rerio) embryo development

Moraes, A.C.N. / Shah, S. / Magalhães, V.F. / Habibi, H.R.

Elsevier Ltd Marine environmental research. 2022 Mar., v. 175

2022

Abstract	Cyanotoxins are among common contaminants that can impair human, animal, and environmental health. Cylindrospermopsin (CYN) is an abundant form of cyanotoxins elevated following algal bloom in the water worldwide. Previous studies have described CYN effects on several organs in mammals. However, little is known about its toxicity mechanisms in other vertebrates. This study aims to characterize the developmental effects of CYN using zebrafish larvae as an aquatic model organism. A wide range of CYN concentrations (0–2000 μg/L) was tested using a morphometric approach for survival, hatching, various growth and developmental abnormalities. We also investigated the expression of genes related to oxidative stress, osmoregulation, and thyroid function. Exposure to CYN resulted in decreased growth, increased developmental abnormalities such as pericardial and yolk sac edema as well as swim bladder absence. In addition, CYN increased tr1a, and decreased dio1 and dio3 transcript levels which are involved in thyroid-mediated function. It also increased transcript levels related to oxidative stress, including hsp70, ahr1a, cyp1a, gpx and cat. Lastly, CYN exposure increased aqp3a and decreased dab2, which are involved in osmoregulation with a threshold of 10 μg/L. The present study demonstrates multiple effects of exposure to environmentally relevant CYN concentrations in zebrafish embryos.
Keywords	Danio rerio ; algal blooms ; cylindrospermopsin ; edema ; embryogenesis ; environmental health ; humans ; morphometry ; osmoregulation ; oxidative stress ; pericardium ; research ; swim bladder ; thyroid function ; toxicity ; yolk sac
Language	English
Dates of publication	2022-03
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1502505-6
ISSN	1879-0291 ; 0141-1136
ISSN (online)	1879-0291
ISSN	0141-1136
DOI	10.1016/j.marenvres.2022.105567
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Article ; Online: Cylindrospermopsin impairs tubular transport function in kidney cells LLC-PK1.

Moraes, A C N / Freire, D S / Habibi, H / Lowe, J / Magalhães, V F

Toxicology letters

2021 Volume 344, Page(s) 26–33

Abstract: Cylindrospermopsin (CYN) has been involved in cases of poisoning in humans following ingestion. Studies have demonstrated that the kidney is the most affected organ. CYN exposure leads to low-molecular-weight proteinuria and increased excretions of the ... ...

Abstract	Cylindrospermopsin (CYN) has been involved in cases of poisoning in humans following ingestion. Studies have demonstrated that the kidney is the most affected organ. CYN exposure leads to low-molecular-weight proteinuria and increased excretions of the tubular enzymes in mice, suggesting the damage caused by CYN is mainly tubular. However, the mechanism involved in CYN nephrotoxicity remains unknown. Thus, in order to evaluate the effects of CYN exposure (0.1, 0.5 and 1.0 μg/mL) on tubular renal cells LLC-PK1 distinct mechanisms were analyzed by assessing cell death using flow cytometry, albumin uptake by fluorescence analysis, Na
MeSH term(s)	Albumins/metabolism ; Alkaloids/pharmacology ; Animals ; Biological Transport/drug effects ; Cell Death/drug effects ; Cell Line ; Epithelial Cells/drug effects ; Gene Expression Regulation, Enzymologic/drug effects ; Kidney Tubules, Proximal/cytology ; Sodium/metabolism ; Sodium-Potassium-Exchanging ATPase/genetics ; Sodium-Potassium-Exchanging ATPase/metabolism ; Swine
Chemical Substances	Albumins ; Alkaloids ; cylindrospermopsin (2JIZ556BA3) ; Sodium (9NEZ333N27) ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13)
Language	English
Publishing date	2021-03-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	433788-8
ISSN	1879-3169 ; 0378-4274
ISSN (online)	1879-3169
ISSN	0378-4274
DOI	10.1016/j.toxlet.2021.03.002
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Article ; Online: Cylindrospermopsin directly disrupts spermatogenesis in isolated male zebrafish testis.

Moraes, A C N / Fallah, H P / Magalhães, V F / Habibi, H R

General and comparative endocrinology

2021 Volume 313, Page(s) 113891

Abstract: Cylindrospermopsin (CYN) is a cytotoxin, and its documented effects in mammals include damage to several organs. CYN also has hormone-disrupting properties, including estrogenic activity, progesterone production inhibition, and apoptosis induction. While ...

Abstract	Cylindrospermopsin (CYN) is a cytotoxin, and its documented effects in mammals include damage to several organs. CYN also has hormone-disrupting properties, including estrogenic activity, progesterone production inhibition, and apoptosis induction. While CYN has been reported to exert reproductive toxicity in mice, little is known about its effect on fish reproductive function. Using ex vivo organ culture, we investigated the direct action of CYN on the male reproductive system. Isolated zebrafish testis was exposed to 250, 500, and 1000 µg/L CYN for 24 h and 7 d, followed by histo-morphological analysis. The results demonstrate that exposure to CYN led to a decrease in cell types from all three phases of spermatogenesis in zebrafish testis. There were also significant changes in fshr, lhr, and igf3 transcript levels, as well as testosterone secretion following exposure to CYN. In summary, this study provides novel information on the adverse effects of CYN on testicular spermatogenesis and male reproduction in zebrafish. These results provide a framework for a better understanding of CYN toxicity and the mechanism underlying the adverse action of CYN on male reproduction in fish.
MeSH term(s)	Alkaloids ; Animals ; Cyanobacteria Toxins ; Male ; Mice ; Spermatogenesis ; Testis/metabolism ; Zebrafish/metabolism
Chemical Substances	Alkaloids ; Cyanobacteria Toxins ; cylindrospermopsin (2JIZ556BA3)
Language	English
Publishing date	2021-08-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1851-x
ISSN	1095-6840 ; 0016-6480
ISSN (online)	1095-6840
ISSN	0016-6480
DOI	10.1016/j.ygcen.2021.113891
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Article ; Online: Renal tubular damage caused by cylindrospermopsin (cyanotoxin) in mice.

Moraes, A C N / Magalhães, V F

Toxicology letters

2018 Volume 286, Page(s) 89–95

Abstract: Cylindrospermopsin (CYN) is a cyanotoxin and a hydrophilic alkaloid of 415 Da. The principal effect of CYN is the inhibition of protein synthesis, and it can damage various organs. Studies have demonstrated that the kidney is the most affected organ. CYN ...

Abstract	Cylindrospermopsin (CYN) is a cyanotoxin and a hydrophilic alkaloid of 415 Da. The principal effect of CYN is the inhibition of protein synthesis, and it can damage various organs. Studies have demonstrated that the kidney is the most affected organ. CYN has played roles in at least two poisoning cases, i.e., the mysterious Palm Island disease in Australia and the event at Caruaru in Brazil. Therefore, we aimed to determine how CYN disrupts the renal tissue. Dose-response curves following single intraperitoneal injections of purified CYN (at 0, 16, 32, 64 and 128 μg CYN/kg body weight) were created in 10-week-old male BALB/C mice (n = 4). Renal physiology parameters were analyzed after 7 and 14 days. However, no alterations in the glomerular filtration rate (GFR) or nephrin expression (a crucial protein for glomerular integrity) were observed. We detected low-molecular-weight proteinuria and increased excretions of the tubular enzymes lactate dehydrogenase (LDH) and gamma-glutamyl transferase (GGT) at doses of 16, 32 and 64 μg CYN/kg body weight. Furthermore, we observed increases in the renal interstitial space and collagen deposition that indicated edema and fibrosis. The data seem to indicate that the damage is in the proximal tubule.
MeSH term(s)	Animals ; Bacterial Toxins/toxicity ; Biomarkers/urine ; Collagen/metabolism ; Dose-Response Relationship, Drug ; Edema/chemically induced ; Fibrosis ; Kidney Diseases/chemically induced ; Kidney Diseases/enzymology ; Kidney Diseases/pathology ; Kidney Diseases/urine ; Kidney Tubules, Proximal/drug effects ; Kidney Tubules, Proximal/enzymology ; L-Lactate Dehydrogenase/urine ; Male ; Mice, Inbred BALB C ; Proteinuria/chemically induced ; Proteinuria/urine ; Risk Assessment ; Time Factors ; Uracil/analogs & derivatives ; Uracil/toxicity ; gamma-Glutamyltransferase/urine
Chemical Substances	Bacterial Toxins ; Biomarkers ; cylindrospermopsin (2JIZ556BA3) ; Uracil (56HH86ZVCT) ; Collagen (9007-34-5) ; L-Lactate Dehydrogenase (EC 1.1.1.27) ; gamma-Glutamyltransferase (EC 2.3.2.2)
Language	English
Publishing date	2018-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	433788-8
ISSN	1879-3169 ; 0378-4274
ISSN (online)	1879-3169
ISSN	0378-4274
DOI	10.1016/j.toxlet.2017.12.028
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Article ; Online: Comparison of analytical tools and biological assays for detection of paralytic shellfish poisoning toxins.

Humpage, A R / Magalhaes, V F / Froscio, S M

Analytical and bioanalytical chemistry

2010 Volume 397, Issue 5, Page(s) 1655–1671

Abstract: The paralytic shellfish poisoning toxins (PSTs) were, as their name suggests, discovered as a result of human poisoning after consumption of contaminated shellfish. More recently, however, the same toxins have been found to be produced by freshwater ... ...

Abstract	The paralytic shellfish poisoning toxins (PSTs) were, as their name suggests, discovered as a result of human poisoning after consumption of contaminated shellfish. More recently, however, the same toxins have been found to be produced by freshwater cyanobacteria. These organisms have worldwide distribution and are common in our sources of drinking water, thus presenting another route of potential human exposure. However, the regulatory limits for PSTs in drinking water are considerably lower than in shellfish. This has increased the need to find alternatives to the mouse bioassay, which, apart from being ethically questionable, does not have a limit of detection capable of detecting the PSTs in water at the regulated concentrations. Additionally, the number of naturally occurring PSTs has grown substantially since saxitoxin was first characterised, markedly increasing the analytical challenge of this group of compounds. This paper summarises the development of chromatographic, toxicity, and molecular sensor binding methodologies for detection of the PSTs in shellfish, cyanobacteria, and water contaminated by these toxins. It then summarises the advantages and disadvantages of their use for particular applications. Finally it recommends some future requirements that will contribute to their improvement for these applications.
MeSH term(s)	Animals ; Bacterial Toxins/analysis ; Bacterial Toxins/toxicity ; Biological Assay/methods ; Chemistry Techniques, Analytical/methods ; Humans ; Marine Toxins/analysis ; Marine Toxins/toxicity ; Mice ; Microcystins/analysis ; Microcystins/toxicity ; Rats ; Saxitoxin/analysis ; Saxitoxin/toxicity ; Shellfish Poisoning/diagnosis
Chemical Substances	Bacterial Toxins ; Marine Toxins ; Microcystins ; cyanobacterial toxin ; Saxitoxin (35523-89-8)
Language	English
Publishing date	2010-07
Publishing country	Germany
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	201093-8
ISSN	1618-2650 ; 0016-1152 ; 0372-7920
ISSN (online)	1618-2650
ISSN	0016-1152 ; 0372-7920
DOI	10.1007/s00216-010-3459-4
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Article: Comparison of analytical tools and biological assays for detection of paralytic shellfish poisoning toxins

Humpage, A. R / Magalhaes, V. F / Froscio, S. M

Analytical and bioanalytical chemistry. 2010 July, v. 397, no. 5

2010

Abstract	The paralytic shellfish poisoning toxins (PSTs) were, as their name suggests, discovered as a result of human poisoning after consumption of contaminated shellfish. More recently, however, the same toxins have been found to be produced by freshwater cyanobacteria. These organisms have worldwide distribution and are common in our sources of drinking water, thus presenting another route of potential human exposure. However, the regulatory limits for PSTs in drinking water are considerably lower than in shellfish. This has increased the need to find alternatives to the mouse bioassay, which, apart from being ethically questionable, does not have a limit of detection capable of detecting the PSTs in water at the regulated concentrations. Additionally, the number of naturally occurring PSTs has grown substantially since saxitoxin was first characterised, markedly increasing the analytical challenge of this group of compounds. This paper summarises the development of chromatographic, toxicity, and molecular sensor binding methodologies for detection of the PSTs in shellfish, cyanobacteria, and water contaminated by these toxins. It then summarises the advantages and disadvantages of their use for particular applications. Finally it recommends some future requirements that will contribute to their improvement for these applications.
Keywords	enzyme-linked immunosorbent assay ; Cyanobacteria ; drinking water ; bioassays
Language	English
Dates of publication	2010-07
Size	p. 1655-1671.
Publisher	Springer-Verlag
Publishing place	Berlin/Heidelberg
Document type	Article
ISSN	1618-2642
DOI	10.1007/s00216-010-3459-4
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Article ; Online: Cylindrospermopsin effects on cell viability and redox milieu of Neotropical fish Hoplias malabaricus hepatocytes.

Silva, R C / Liebel, S / de Oliveira, H H P / Ramsdorf, W A / Garcia, J R E / Azevedo, S M F O / Magalhães, V F / Oliveira Ribeiro, C A / Filipak Neto, F

Fish physiology and biochemistry

2017

Abstract: Cylindrospermopsin (CYN) is a cyanotoxin that is cytotoxic to a wide variety of cells, particularly to the hepatocytes. In this study, the toxic effects of purified CYN were investigated in primary cultured hepatocytes of Neotropical fish Hoplias ... ...

Abstract	Cylindrospermopsin (CYN) is a cyanotoxin that is cytotoxic to a wide variety of cells, particularly to the hepatocytes. In this study, the toxic effects of purified CYN were investigated in primary cultured hepatocytes of Neotropical fish Hoplias malabaricus. After isolation, attachment, and recovery for 72 h, the cells were exposed for 72 h to 0, 0.1, 1.0, 10, and 100 μg l
Language	English
Publishing date	2017-04-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	292907-7
ISSN	1573-5168 ; 0920-1742
ISSN (online)	1573-5168
ISSN	0920-1742
DOI	10.1007/s10695-017-0367-y
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Article: Microcystin contamination in fish from the Jacarepaguá Lagoon (Rio de Janeiro, Brazil): ecological implication and human health risk.

Magalhães, V F / Soares, R M / Azevedo, S M

Toxicon : official journal of the International Society on Toxinology

2001 Volume 39, Issue 7, Page(s) 1077–1085

Abstract: Chronic and subchronic toxicity from exposure to microcystins, cyclic peptide liver toxins from certain cyanobacteria, poses an important hazard, which has received little study. No in vivo information exists on accumulation and transfer of microcystin ... ...

Abstract	Chronic and subchronic toxicity from exposure to microcystins, cyclic peptide liver toxins from certain cyanobacteria, poses an important hazard, which has received little study. No in vivo information exists on accumulation and transfer of microcystin from the food chain to humans. This paper present results of a 3-year study that demonstrates bioaccumulation of microcystins by fish and potential rates of microcystin ingestion by humans. The study was carried out in a shallow coastal lagoon in the city of Rio de Janeiro (Jacarepaguá Lagoon). Fish (Tilapia rendalli) were collected every 2 weeks from August 1996 to November 1999. Microcystins were analyzed by HPLC in phytoplankton, fish liver and viscera while fish muscle tissue was analyzed by enzyme linked immunosorbant assay (ELISA). Phytoplankton samples, dominated by the genus Microcystis, were confirmed to contain microcystins as were fish livers, viscera and muscle tissue. During the entire study period, including times of low water bloom densities, fish muscle tissue contained concentrations of microcystins close to or above the recommended limit for human consumption (0.04 microg x kg(-1) day). Our findings demonstrate that microcystins can accumulate in fish tissue used for human consumption. Rates of ingestion routinely exceed the TDI guidelines as set by the WHO for drinking water. Appropriate epidemiology and risk assessment should be undertaken so that an acceptable TDI and appropriate risk management decisions can be made for human consumption of fish which are harvested from cyanobacterial blooms that contain cyanotoxins.
MeSH term(s)	Animals ; Brazil/epidemiology ; Chromatography, High Pressure Liquid ; Ecology ; Foodborne Diseases/epidemiology ; Liver/chemistry ; Marine Toxins/analysis ; Marine Toxins/metabolism ; Marine Toxins/toxicity ; Microcystins ; Peptides, Cyclic/analysis ; Peptides, Cyclic/metabolism ; Peptides, Cyclic/toxicity ; Plankton/chemistry ; Risk Assessment ; Seasons ; Tilapia/metabolism
Chemical Substances	Marine Toxins ; Microcystins ; Peptides, Cyclic ; microcystin (77238-39-2)
Language	English
Publishing date	2001-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	204479-1
ISSN	1879-3150 ; 0041-0101
ISSN (online)	1879-3150
ISSN	0041-0101
DOI	10.1016/s0041-0101(00)00251-8
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Article: Accumulation and depuration of microcystins (cyanobacteria hepatotoxins) in Tilapia rendalli (Cichlidae) under laboratory conditions

Soares, R.M / Magalhaes, V.F / Azevedo, S.M.F.O

Aquatic toxicology. 2004 Oct. 18, v. 70, issue 1

2004

Abstract: In order to understand accumulation and depuration of microcystins (MCYSTs) in Tilapia rendalli, three experiments with juveniles were done. The experiments simulated the fish diet during a Microcystis aeruginosa bloom in three different situations. In ... ...

Abstract	In order to understand accumulation and depuration of microcystins (MCYSTs) in Tilapia rendalli, three experiments with juveniles were done. The experiments simulated the fish diet during a Microcystis aeruginosa bloom in three different situations. In the first one each fish received daily, during 15 days, fish food plus toxic cells of M. aeruginosa (20.4 micrograms MCYSTs fish -1 day -1). In the following 15 days they were fed without toxic cells. In the second experiment, fish were fed only with toxic cells during 28 days (14.6 micrograms MCYSTs fish -1 day -1) and in the third experiment, during 42 days, fish were fed with fish food plus toxic cells (29.2 micrograms MCYSTs fish -1 day -1) previously disrupted (to simulate a senescent bloom). MCYSTs analyses were done by enzyme-linked immunosorbent assay (ELISA) in liver and muscle samples in all experiments and in faeces in the first one (only in the depuration period). The results demonstrated different profiles of MCYSTs accumulation in liver and muscle of T. rendalli. Comparing the experiments, the highest MCYSTs accumulation in the liver (2.8 micrograms g -1) occurred in the second one, where fish had only toxic cells as feeding source. In the first experiment, the highest MCYSTs accumulation in liver (0.6 micrograms MCYSTs g -1) was observed during the accumulation period, while in muscle, interestingly, the highest concentration (0.05 micrograms MCYSTs g -1) occurred in the depuration period. In this same period, it was also observed elimination of toxins through faeces. The second and third experiments showed almost the same average concentrations in tissues although fish have received more MCYSTs in third one. With respect to implications of the fish comsumption, MCYSTs accumulation in muscle of T. rendalli in all three experiments reached concentrations that would represent an intake of these toxins above the tolerable limit for humans and these results confirmed our previous observations from a field study. In conclusion, in this study it was observed that T. rendalli is able to accumulate MCYSTs and the availability of other feeding sources, besides toxic cells, probably interferes with the accumulation rate. Therefore, the occurrence of toxic cyanobacterial blooms produncing MCYSTs in aquaculture ponds could represent a risk to the quality of fish to the consumers.
Keywords	Tilapia (Cichlidae) ; tilapia (common name) ; juveniles ; fish ponds ; eutrophication ; fish culture ; food quality ; microcystins ; bacterial toxins ; Microcystis aeruginosa ; animal pathogenic bacteria ; fish feeding ; bioaccumulation ; excretion ; laboratory techniques ; enzyme-linked immunosorbent assay ; liver ; muscles ; feces ; food contamination ; food pathogens ; human health ; Brazil
Language	English
Dates of publication	2004-1018
Size	p. 1-10.
Document type	Article
ZDB-ID	782699-0
ISSN	1879-1514 ; 0166-445X
ISSN (online)	1879-1514
ISSN	0166-445X
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