Toxicity and uptake mechanism of cylindrospermopsin and lophyrotomin in primary rat hepatocytes

Chong, Matthew W.K.; Wong, Bryan S.F.; Lam, Patrick T.I.; Shaw, Glendon Reginald; Seawright, A. A.

doi:10.1016/s0041-0101(01)00228-8

Cited by 92 publications

(58 citation statements)

References 26 publications

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“…However, due to the small size of the molecule, a limited passive diffusion through biological membranes occurs, as indicated by in vitro studies, showing cytotoxic effects in a cell line, not expressing bile acid transport system (Chong et al, 2002). When [ 14 C]-CYN (0.2 mg/kg bw) was i.p.…”

Section: Admementioning

confidence: 99%

Review and analysis of occurrence, exposure and toxicity of cyanobacteria toxins in food

Testai

Buratti

Funari

et al. 2016

EFS3

102

125

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This report presents the extensive literature search conducted on 1) the occurrence of different cyanotoxins in food matrices; 2) the analytical methods for their detection; 3) their toxicological profile; 3) the environmental factors affecting toxicity of cyanobacterial population and 4) the combined effects of mixtures of cyanotoxins and other chemicals. It also includes a review of guidelines values or health-alert levels for cyanotoxins in food (or drinking water) adopted world-wide. The methodological aspects and the queries used in the extensive literature search, the collection and screening of retrieved papers and the inventory are briefly described in the report; all details are available in 3 supplementary appendices to this report. The analysis of collected papers indicated that most of them are focused on a single microcystin (MC) variant (MC-LR) out of the almost 100 MC known. Many studies on occurrence are affected by limited quality, due to analytical drawbacks in the detection methods and were not considered in the exposure assessment. Toxicity studies useful for the derivation of health based reference values are few, being many of them carried out using i.p. injection, which is poorly representative of actual human exposure. In addition, those toxicological studies carried out with poorly characterised cyanobacterial extracts or focused on single parameters, using a single dose, devoted to elucidation of mechanism of action, reporting qualitative description of effects were not used for data extraction. The relevant exposure scenarios are also described, although being the available data on exposure very limited, no definite conclusion on the health risks for the exposed population could be drawn. However, the possibility of risky exposure is evidenced for fish and shell-fish consumers and for blue-green algae supplements (BGAS) as well in relation to MC contamination. Finally, many data gaps were identified. © European Food Safety Authority, 2016Key words: Cyanobacteria, cyanotoxins, occurrence, toxicity, exposure, risk assessment, data gaps. Question number: EFSA-Q-2015-00141Correspondence:sc.secretariat@efsa.europa.eu Cyanotoxins in foodThe present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors.www.efsa.europa.eu/publications 2 EFSA Supporting publication 2016:EN-998NDisclaimer: The present document has been produced and adopted by the bodies identified above as author(s). This task has b...

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Section: Admementioning

confidence: 99%

Review and analysis of occurrence, exposure and toxicity of cyanobacteria toxins in food

Testai

Buratti

Funari

et al. 2016

EFS3

102

125

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“…However, the toxicity of CYN, particularly on fish, has been scarcely investigated. Regarding to CYN, it has been reported that it penetrates cells by passive diffusion (Chong et al 2002). CYN has been described as acting as a hepatotoxin even if other organs, mainly kidney and thymus, were also affected after intraperitoneal or oral administration Falconer et al 1999;Seawright et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Acute effects of pure cylindrospermopsin on the activity and transcription of antioxidant enzymes in tilapia (Oreochromis niloticus) exposed by gavage

et al. 2011

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The cyanobacterial toxin cylindrospermopsin (CYN) is a widely distributed contaminant of freshwater systems with the consequent risk for human and wildlife, particularly fish. However, CYN toxicity data on fish are still scarce. It is known that CYN inhibits glutathione synthesis and this could contribute to oxidative damage. In the present work tilapia (Oreochromis niloticus) were exposed by gavage to 200 and 400 μg/kg bw of pure CYN and sacrificed after 24 h. The activity and relative mRNA expression by real-time PCR of antioxidant enzymes glutathione peroxidase (GPx) and soluble glutathione-S-transferases (sGST) and the sGST protein abundance by Western blot analysis were evaluated in liver and kidney. Also the induction of lipid peroxidation (LPO) was assayed. Results show an increase of LPO products in both organs. Moreover, CYN altered the activity, gene expression and protein abundance of the enzymes, indicating the importance of GPx and sGST in CYN pathogenicity. This is the first time that CYN is reported to affect these enzymes in fish and they have shown to be responsive biomarkers of CYN toxicity.

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“…Genotoxic activity is caused by the ability of CYN to induce strand breaks at the DNA level and loss of whole chromosomes (Humpage et al, 2000). Beside the capacity of CYN to suppress glutathione and protein synthesis, probably by inhibiting ribosomal translation (Froscio et al, 2001), other mechanisms of actions have been assumed as an explanation for the severe liver injuries followed by CYN intoxication, although no protein phosphatase inhibition could be found (Runnegar et al, 1995;Chong et al, 2002). PSPs are potent blockers of voltage-dependent sodium-channels and therefore restrict transmission between neurons.…”

Section: Introductionmentioning

confidence: 99%

Occurrence and elimination of cyanobacterial toxins in two Australian drinking water treatment plants

Hoeger

Shaw²,

Hitzfeld

et al. 2004

Toxicon

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In Australian freshwaters, Anabaena circinalis, Microcystis spp. and Cylindrospermopsis raciborskii are the dominant toxic cyanobacteria. Many of these surface waters are used as drinking water resources. Therefore, the National Health and Medical Research Council of Australia set a guideline for MC-LR toxicity equivalents of 1.3 mg/l drinking water. However, due to lack of adequate data, no guideline values for paralytic shellfish poisons (PSPs) (e.g. saxitoxins) or cylindrospermopsin (CYN) have been set. In this spot check, the concentration of microcystins (MCs), PSPs and CYN were determined by ADDA-ELISA, cPPA, HPLC-DAD and/or HPLC-MS/MS, respectively, in two water treatment plants in Queensland/Australia and compared to phytoplankton data collected by Queensland Health, Brisbane. Depending on the predominant cyanobacterial species in a bloom, concentrations of up to 8.0, 17.0 and 1.3 mg/l were found for MCs, PSPs and CYN, respectively. However, only traces (,1.0 mg/l) of these toxins were detected in final water (final product of the drinking water treatment plant) and tap water (household sample). Despite the low concentrations of toxins detected in drinking water, a further reduction of cyanobacterial toxins is recommended to guarantee public safety. q

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Toxicity and uptake mechanism of cylindrospermopsin and lophyrotomin in primary rat hepatocytes

Cited by 92 publications

References 26 publications

Review and analysis of occurrence, exposure and toxicity of cyanobacteria toxins in food

Review and analysis of occurrence, exposure and toxicity of cyanobacteria toxins in food

Acute effects of pure cylindrospermopsin on the activity and transcription of antioxidant enzymes in tilapia (Oreochromis niloticus) exposed by gavage

Occurrence and elimination of cyanobacterial toxins in two Australian drinking water treatment plants

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