Chronic Toxicity Study of Neosaxitoxin in Rats

Zepeda, Ramiro; Candiracci, Manila; Lobos, Nicolas; Lux, Sebastián; Miranda, Hugo F.

doi:10.3390/md12095055

Cited by 15 publications

(12 citation statements)

References 36 publications

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“…The kidneys and livers were immediately stored in 10% paraffin for histology. Paraffin sections were made and stained with hematoxylin and eosin for a thorough histopathological study [ 17 , 18 ]. Hematological analysis of the blood samples was performed using an automatic hematology analyzer.…”

Section: Methodsmentioning

confidence: 99%

Acute and Sub-Acute Toxicity Evaluation of the Methanolic Extract of Alstonia scholaris Stem Bark

et al. 2016

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Alstonia scholaris has been used by traditional medicine practitioners since the medieval ages for the treatment of diseases. The aim of this research was to evaluate the acute and sub-acute oral toxicity of its methanolic extract. The acute toxicity test was conducted using Sprague Dawley (SD) rats. The methanolic extract of Alstonia scholaris stem bark (ASME) was administrated in a single dose of 2000 mg/kg via oral gavage; and the animals were observed for any behavioral changes or mortality. In the sub-acute toxicity study, SD rats received three doses of ASME (250, 500 and 1000 mg/kg) for 28 days via oral gavage. During these 28 days of treatment, the rats were observed weekly for toxicity symptoms. Following the 28-day treatment, the rats were sacrificed for hematological, biochemical and histopathology studies. In the acute toxicity study, Alstonia scholaris was found to be non-toxic at a dose of 2000 mg/kg b.w. In the sub-acute toxicity study, significant variations in body weight, hematological and biochemical parameters were observed in the experimental groups at the dose of 500 and 1000 mg/kg with the death of two female rats being recorded at the highest dose (1000 mg/kg b.w.). Histopathological studies revealed slight degeneration (lesion) and centrilobular necrosis in the liver, which was most expressed in the highest-dose group. These results demonstrate that, while a single dose and short term oral intake of Alstonia scholaris bark extract caused no toxicity up to a dose of 2000 mg/kg b.w., toxic effects manifested in the long term treatment at the highest dose (500 and 1000 mg/kg). The long-term toxic effect was found to be associated with alterations in hematological compositions and end-organ damage to the liver. Thus, prolonged use of high doses of ASME orally should be discouraged and lower doses encouraged.

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Section: Methodsmentioning

confidence: 99%

Acute and Sub-Acute Toxicity Evaluation of the Methanolic Extract of Alstonia scholaris Stem Bark

et al. 2016

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“…Repeated exposure of rats to subacute doses of neoSTX for 12 weeks (6 µg/kg, once daily, subcutaneous) caused a reduction of body weight and food intake during the treatment period and the animals recovered quickly after the treatment was interrupted. No other behavioral changes were observed and no damage to several organs was detected by histological evaluation [ 16 ]. However, serum bilirubin, γ-glutamyltransferase (GGT) and aspartate aminotransferase (AST, formerly SGOT), three markers of liver damage, were elevated after 12 weeks of neoSTX treatment.…”

Section: Saxitoxinsmentioning

confidence: 99%

“…However, serum bilirubin, γ-glutamyltransferase (GGT) and aspartate aminotransferase (AST, formerly SGOT), three markers of liver damage, were elevated after 12 weeks of neoSTX treatment. These changes might reflect the detoxifying effort or be a consequence of the food intake reduction [ 16 ]. Lower doses (half and 1/6) had no effect at all.…”

Section: Saxitoxinsmentioning

confidence: 99%

Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection

Vilariño

Louzao

Abal

et al. 2018

Toxins

118

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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.

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“…No data on the short and long term repeated toxic effects of STX-group toxins in animals or humans were available in 2009 for the EFSA scientific opinion; a similar data gap could be highlighted at present, except for a paper from Zepeda et al (2014) which investigated the acute and chronic toxicity of NeoSTX by different routes of administration, showing that only the highest dose studied (6 µg NeoSTX/kg bw) when administered subcutaneously (not relevant for the dietary exposure) induced a reduction of weight and food consumption accompanied by a cholestasic pattern at the end of the treatment period. The effects were completely normalized with the drug withdrawal.…”

Section: Acute Toxicitymentioning

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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Chronic Toxicity Study of Neosaxitoxin in Rats

Cited by 15 publications

References 36 publications

Acute and Sub-Acute Toxicity Evaluation of the Methanolic Extract of Alstonia scholaris Stem Bark

Acute and Sub-Acute Toxicity Evaluation of the Methanolic Extract of Alstonia scholaris Stem Bark

Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection

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

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