Pub Date : 2024-10-26DOI: 10.1016/j.toxicon.2024.108152
Bernd Krock , Elizabeth M. Mudge , Annegret Müller , Stefanie Meyer , Jan Tebben , Pearse McCarron , Doris Abele , Urban Tillmann
Azaspiracid-59 (AZA-59) was detected in plankton in coastal waters of the Pacific Northwest USA. Given that bivalves metabolize and transform accumulated phycotoxins, a strain of Azadinium poporum isolated from the coast of Washington State that is a known producer of AZA-59 was used in a controlled feeding experiment with mussels (Mytilus edulis) to assess AZA-59 accumulation rates and transformation into shellfish metabolites. Mussels started feeding immediately after the addition of A. poporum. Mussels were generally healthy during the entire experimental exposure of 18 days with prevailingly high rates of clearance (approx. 100 mL per mussel per hour) and ingestion. Mussels were extracted after different exposure times and were analyzed by liquid chromatography coupled with low- and high-resolution mass spectrometry. In the course of the experiment a number of putative AZA-59 metabolites were detected including hydroxyl and carboxy analogues that corresponded with previously reported mussel metabolites of AZA-1. A significant formation of 3-OH fatty acid acyl esters relative to free AZAs was observed through the time course of the study, with numerous fatty acid ester variants of AZA-59 confirmed. These results illustrate the potential for metabolism of AZA-59 in shellfish and provide important information for local AZA monitoring and toxicity testing along the Northern Pacific US coast.
{"title":"Azaspiracid-59 accumulation and transformation in mussels (Mytilus edulis) after feeding with Azadinium poporum (Dinophyceae)","authors":"Bernd Krock , Elizabeth M. Mudge , Annegret Müller , Stefanie Meyer , Jan Tebben , Pearse McCarron , Doris Abele , Urban Tillmann","doi":"10.1016/j.toxicon.2024.108152","DOIUrl":"10.1016/j.toxicon.2024.108152","url":null,"abstract":"<div><div>Azaspiracid-59 (AZA-59) was detected in plankton in coastal waters of the Pacific Northwest USA. Given that bivalves metabolize and transform accumulated phycotoxins, a strain of <em>Azadinium poporum</em> isolated from the coast of Washington State that is a known producer of AZA-59 was used in a controlled feeding experiment with mussels (<em>Mytilus edulis</em>) to assess AZA-59 accumulation rates and transformation into shellfish metabolites. Mussels started feeding immediately after the addition of <em>A. poporum</em>. Mussels were generally healthy during the entire experimental exposure of 18 days with prevailingly high rates of clearance (approx. 100 mL per mussel per hour) and ingestion. Mussels were extracted after different exposure times and were analyzed by liquid chromatography coupled with low- and high-resolution mass spectrometry. In the course of the experiment a number of putative AZA-59 metabolites were detected including hydroxyl and carboxy analogues that corresponded with previously reported mussel metabolites of AZA-1. A significant formation of 3-OH fatty acid acyl esters relative to free AZAs was observed through the time course of the study, with numerous fatty acid ester variants of AZA-59 confirmed. These results illustrate the potential for metabolism of AZA-59 in shellfish and provide important information for local AZA monitoring and toxicity testing along the Northern Pacific US coast.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"251 ","pages":"Article 108152"},"PeriodicalIF":2.6,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-26DOI: 10.1016/j.toxicon.2024.108155
Grigorii V. Malykin, Peter V. Velansky, Timur Yu Magarlamov
We for the first time have recorded the presence of TTX and 11 of its analogues (TTXs) and determined the profile of these toxins by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) in Cephalothrix mokievskii, collected off the coast of Sakhalin Island and also revealed differences in the TTXs profile between C. mokievskii and sibling Cephalothrix cf, simula. We discuss the features of the TTXs profile in C. mokievskii, geographical distribution of TTX-containing nemerteans and its possible implication for toxification of marine bioresources.
{"title":"First data on tetrodotoxins in Cephalothrix mokievskii (palaeonemertea, nemertea) and possible involvement OF POISONOUS nemerteans in toxification of marine bioresources","authors":"Grigorii V. Malykin, Peter V. Velansky, Timur Yu Magarlamov","doi":"10.1016/j.toxicon.2024.108155","DOIUrl":"10.1016/j.toxicon.2024.108155","url":null,"abstract":"<div><div>We for the first time have recorded the presence of TTX and 11 of its analogues (TTXs) and determined the profile of these toxins by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) in <em>Cephalothrix mokievskii</em>, collected off the coast of Sakhalin Island and also revealed differences in the TTXs profile between <em>C</em>. <em>mokievskii</em> and sibling <em>Cephalothrix</em> cf, <em>simula</em>. We discuss the features of the TTXs profile in <em>C</em>. <em>mokievskii</em>, geographical distribution of TTX-containing nemerteans and its possible implication for toxification of marine bioresources.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"251 ","pages":"Article 108155"},"PeriodicalIF":2.6,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-25DOI: 10.1016/j.toxicon.2024.108154
Elizabeth M. Mudge , Alistair L. Wilkins , J. Sam Murray , Frode Rise , Christopher O. Miles
Gambierones are sulfated polyethers produced by benthic dinoflagellates in the genera Gambierdiscus, Coolia and Fukuyoa. While relative toxicity data for gambierones suggests they are low compared with ciguatoxin analogues, gambierones have been suggested for use as marker compounds for environmental monitoring programs for the presence of Gambierdiscus in marine waters. The published structure of gambierone and analogues of it, including 44-methylgambierone (44-MeGAM), have been reported to possess 1,2- and 4,5-cis diols, while only the 1,2- diol unit has been shown to undergo periodate oxidation. An in-depth analysis of previously reported NMR data for 44-MeGAM in CD3OD showed that the C-4 stereochemistry of 44-MeGAM and other gamberiones was mis-assigned, that the 4-CH2-CHOH-CH2OH and OH groups are equatorially and axially oriented, respectively, rather than vice versa as previously reported. This re-examination of existing 44-MeGAM NMR data also showed that its C-12 and C-13 assignments (and those for other gambierones) should be reversed. In an effort to better understand the C-4 stereochemical and periodate reaction characteristics of gambierones (C-4 is an epimerizable hemiacetal carbon), additional NMR data was acquired in D6-DMSO. Unexpectedly, progressive conversion of 44-MeGAM to a long-term stable ring-A furanoid analogue was observed. A subsequent series of microscale stability trials identified several solvents that affected the solution-stability of 44-MeGAM, and these findings should be taken into consideration during isolation, handling, storage and bioassay evaluations of gambierones in future studies.
{"title":"Investigation of 44-methylgambierone reactivity with periodate: Structural reassignment, solvent instability and formation of a furanoid analogue","authors":"Elizabeth M. Mudge , Alistair L. Wilkins , J. Sam Murray , Frode Rise , Christopher O. Miles","doi":"10.1016/j.toxicon.2024.108154","DOIUrl":"10.1016/j.toxicon.2024.108154","url":null,"abstract":"<div><div>Gambierones are sulfated polyethers produced by benthic dinoflagellates in the genera <em>Gambierdiscus</em>, <em>Coolia</em> and <em>Fukuyoa</em>. While relative toxicity data for gambierones suggests they are low compared with ciguatoxin analogues, gambierones have been suggested for use as marker compounds for environmental monitoring programs for the presence of <em>Gambierdiscus</em> in marine waters. The published structure of gambierone and analogues of it, including 44-methylgambierone (44-MeGAM), have been reported to possess 1,2- and 4,5-<em>cis</em> diols, while only the 1,2- diol unit has been shown to undergo periodate oxidation. An in-depth analysis of previously reported NMR data for 44-MeGAM in CD<sub>3</sub>OD showed that the C-4 stereochemistry of 44-MeGAM and other gamberiones was mis-assigned, that the 4-CH<sub>2</sub>-CHOH-CH<sub>2</sub>OH and OH groups are equatorially and axially oriented, respectively, rather than vice versa as previously reported. This re-examination of existing 44-MeGAM NMR data also showed that its C-12 and C-13 assignments (and those for other gambierones) should be reversed. In an effort to better understand the C-4 stereochemical and periodate reaction characteristics of gambierones (C-4 is an epimerizable hemiacetal carbon), additional NMR data was acquired in D<sub>6</sub>-DMSO. Unexpectedly, progressive conversion of 44-MeGAM to a long-term stable ring-A furanoid analogue was observed. A subsequent series of microscale stability trials identified several solvents that affected the solution-stability of 44-MeGAM, and these findings should be taken into consideration during isolation, handling, storage and bioassay evaluations of gambierones in future studies.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"251 ","pages":"Article 108154"},"PeriodicalIF":2.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1016/j.toxicon.2024.108150
Ouafa Amrani , Mohamed Marghich , Ahmed Karim , Hassane Mekhfi , Abderrahim Ziyyat , Mohammed Aziz
Juniperus oxycedrus L. (J. oxycedrus) has a rich historical background in herbal remedies to treating digestive system abnormalities. However, no comprehensive evaluation of its potential toxic effects has been conducted. The current investigation aimed to evaluate the acute and subacute toxicity of an aqueous extract of J. oxycedrus (AEJO). AEJO was prepared by the conventional Moroccan methods by decoction the arial part of the plant. The acute and subacute toxicity tests were conducted in mice and rats, respectively. Acute toxicity tests showed that the extract was not toxic even at high doses of 5000 mg/kg. In the subacute study, no detectable indications of toxicity or mortality were observed and there were no notable deviations in food intake or water consumption among all rats. However, changes in body weight of animals treated with 1000 and 2000 mg/kg underwent a significant decrease. AEJO administration decreased platelet number, elevated levels of alanine aminotransferase and alkaline phosphatase, and reduced albumin levels. Histological examination revealed normal renal parenchyma despite increased creatinine. It also showed binucleation, and hepatocyte vacuolation. The results indicate that AEJO has considerable tolerance for consumption, but repeated use can affect hepatocytes and kidneys. Therefore, additional analyses, such as subchronic, chronic, and neurotoxic studies, are required before using this plant in clinical research.
{"title":"Toxicological assessment of the aqueous extract of Juniperus oxycedrus L. on acute and subacute toxicities in rats","authors":"Ouafa Amrani , Mohamed Marghich , Ahmed Karim , Hassane Mekhfi , Abderrahim Ziyyat , Mohammed Aziz","doi":"10.1016/j.toxicon.2024.108150","DOIUrl":"10.1016/j.toxicon.2024.108150","url":null,"abstract":"<div><div><em>Juniperus oxycedrus</em> L. (<em>J. oxycedrus</em>) has a rich historical background in herbal remedies to treating digestive system abnormalities. However, no comprehensive evaluation of its potential toxic effects has been conducted. The current investigation aimed to evaluate the acute and subacute toxicity of an aqueous extract of <em>J. oxycedrus</em> (AEJO). AEJO was prepared by the conventional Moroccan methods by decoction the arial part of the plant. The acute and subacute toxicity tests were conducted in mice and rats, respectively. Acute toxicity tests showed that the extract was not toxic even at high doses of 5000 mg/kg. In the subacute study, no detectable indications of toxicity or mortality were observed and there were no notable deviations in food intake or water consumption among all rats. However, changes in body weight of animals treated with 1000 and 2000 mg/kg underwent a significant decrease. AEJO administration decreased platelet number, elevated levels of alanine aminotransferase and alkaline phosphatase, and reduced albumin levels. Histological examination revealed normal renal parenchyma despite increased creatinine. It also showed binucleation, and hepatocyte vacuolation. The results indicate that AEJO has considerable tolerance for consumption, but repeated use can affect hepatocytes and kidneys. Therefore, additional analyses, such as subchronic, chronic, and neurotoxic studies, are required before using this plant in clinical research.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"251 ","pages":"Article 108150"},"PeriodicalIF":2.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1016/j.toxicon.2024.108148
Mumtahin-ul Kousar , Mifftha Yaseen , Monisa Yousouf , Mudasir Ahmad Malik , Aarizoo Mushtaq , Taha Mukhtar , Rifat Javaid , Anam Aijaz , Abida Jabeen , Tawheed Amin
Aflatoxins are naturally produced toxins by specific molds, namely Aspergillus flavus and Aspergillus parasiticus. These toxins can be found in various agricultural products, including crops like maize, peanuts, cottonseed, and tree nuts. They have the potential to contaminate the food supply during different stages of production, processing, and storage. Aflatoxin is a very poisonous substance that has been linked to adverse health effects in both humans and animals. It is essential to detect and monitor aflatoxins to ensure the safety of food. Efficient and precise analytical techniques, such as chromatography and immunoassays, have been used to accurately measure the levels of aflatoxins in different substances. Regulatory bodies and worldwide associations have determined maximum permissible limits for aflatoxins in food and nourishment products to protect the well-being of the general public. Effectively addressing aflatoxin contamination necessitates a comprehensive approach that encompasses various strategies in agriculture, post-harvest practices, and regulatory measures. Continuous research and collaborative endeavors are crucial in order to minimize aflatoxin exposure and mitigate the associated risks. This review offers a comprehensive examination of the presence, health consequences, and elimination techniques associated with aflatoxins.
{"title":"Aflatoxins in cereal based products-an overview of occurrence, detection and health implication","authors":"Mumtahin-ul Kousar , Mifftha Yaseen , Monisa Yousouf , Mudasir Ahmad Malik , Aarizoo Mushtaq , Taha Mukhtar , Rifat Javaid , Anam Aijaz , Abida Jabeen , Tawheed Amin","doi":"10.1016/j.toxicon.2024.108148","DOIUrl":"10.1016/j.toxicon.2024.108148","url":null,"abstract":"<div><div>Aflatoxins are naturally produced toxins by specific molds, namely <em>Aspergillus flavus</em> and <em>Aspergillus parasiticus</em>. These toxins can be found in various agricultural products, including crops like maize, peanuts, cottonseed, and tree nuts. They have the potential to contaminate the food supply during different stages of production, processing, and storage. Aflatoxin is a very poisonous substance that has been linked to adverse health effects in both humans and animals. It is essential to detect and monitor aflatoxins to ensure the safety of food. Efficient and precise analytical techniques, such as chromatography and immunoassays, have been used to accurately measure the levels of aflatoxins in different substances. Regulatory bodies and worldwide associations have determined maximum permissible limits for aflatoxins in food and nourishment products to protect the well-being of the general public. Effectively addressing aflatoxin contamination necessitates a comprehensive approach that encompasses various strategies in agriculture, post-harvest practices, and regulatory measures. Continuous research and collaborative endeavors are crucial in order to minimize aflatoxin exposure and mitigate the associated risks. This review offers a comprehensive examination of the presence, health consequences, and elimination techniques associated with aflatoxins.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"251 ","pages":"Article 108148"},"PeriodicalIF":2.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-21DOI: 10.1016/j.toxicon.2024.108134
C. David Malsawmtluanga, J. Lalbiaknunga, Lalawmpuia, C. Laldinkima
Misidentification and ingestion of poisonous mushrooms pose significant threats to food safety, particularly in Mizoram, India, where over ten fatalities due to mushroom poisoning have been reported in the past decade (2013–2023). This study aimed to address this critical issue by identifying and quantifying the cause of death due to consumption of wild mushroom from Champhai district, Mizoram, India and to test the reliability of HPLC-PDA for detection and quantification of amatoxins. HPLC-PDA confirmed the presence of α-amanitin in Amanita virosa and Amanita bisporigera in the samples. α-amanitin is a water-soluble, heat-stable, and highly toxic cyclic octapeptide present in the genus Amanita, which includes Amanita phalloides, Amanita verna, and Amanita virosa. Amanitin cytotoxicity arises from the inhibition of RNA polymerases, namely RNA polymerase II, which obstructs mRNA production in kidney and liver cells. Validation of the method demonstrated good precision and accuracy, with LOD and LOQ values of 88 ng g−1 and 210 ng g−1, respectively. The method was successfully applied to quantify α-amanitin in ten wild mushroom samples, revealing its presence only in Amanita virosa (1.17 mg g−1) and Amanita bisporigera (1.91 mg g−1) species. These findings underscore the importance of accurate α-amanitin detection methods in ensuring food safety and public health, particularly in regions prone to mushroom poisoning incidents. It is noteworthy that this study marks the initial exploration for detection and quantification of α-amanitin from poisonous mushrooms found in the wild regions of Champhai district in Mizoram, representing the first report of such in the area.
{"title":"Detection and quantification of Amatoxin in wild mushrooms from North-East India using HPLC-PDA method for food safety purposes","authors":"C. David Malsawmtluanga, J. Lalbiaknunga, Lalawmpuia, C. Laldinkima","doi":"10.1016/j.toxicon.2024.108134","DOIUrl":"10.1016/j.toxicon.2024.108134","url":null,"abstract":"<div><div>Misidentification and ingestion of poisonous mushrooms pose significant threats to food safety, particularly in Mizoram, India, where over ten fatalities due to mushroom poisoning have been reported in the past decade (2013–2023). This study aimed to address this critical issue by identifying and quantifying the cause of death due to consumption of wild mushroom from Champhai district, Mizoram, India and to test the reliability of HPLC-PDA for detection and quantification of amatoxins. HPLC-PDA confirmed the presence of α-amanitin in <em>Amanita virosa</em> and <em>Amanita bisporigera</em> in the samples. α-amanitin is a water-soluble, heat-stable, and highly toxic cyclic octapeptide present in the genus <em>Amanita</em>, which includes <em>Amanita phalloides</em>, <em>Amanita verna</em>, and <em>Amanita virosa</em>. Amanitin cytotoxicity arises from the inhibition of RNA polymerases, namely RNA polymerase II, which obstructs mRNA production in kidney and liver cells. Validation of the method demonstrated good precision and accuracy, with LOD and LOQ values of 88 ng g<sup>−1</sup> and 210 ng g<sup>−1</sup>, respectively. The method was successfully applied to quantify α-amanitin in ten wild mushroom samples, revealing its presence only in <em>Amanita virosa</em> (1.17 mg g<sup>−1</sup>) and <em>Amanita bisporigera</em> (1.91 mg g<sup>−1</sup>) species. These findings underscore the importance of accurate α-amanitin detection methods in ensuring food safety and public health, particularly in regions prone to mushroom poisoning incidents. It is noteworthy that this study marks the initial exploration for detection and quantification of α-amanitin from poisonous mushrooms found in the wild regions of Champhai district in Mizoram, representing the first report of such in the area.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"251 ","pages":"Article 108134"},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Some of the most commonly identified freshwater toxins are anatoxin-a (ATX-a), cylindrospermopsin (CYN), and microcystin-LR (MC-LR). The aim of this paper was to compare different methods of extracting and concentrating these cyanotoxins and check the impact of selected physical factors on the accumulation of biomass of Dolichospermum flos-aquae, Microcystis aeruginosa, and Raphidiopsis raciborskii. The effect of different cyanobacteria cultivation conditions on the amount of cyanotoxins synthesized showed no significant changes over time in the average concentration of all tested toxins in the medium compared to the control. Mixing cultures increases the intracellular content of ATX-a. Aerating also positively affects the concentration of MC-LR intracellularly. In order to optimize the solid phase extraction (SPE) process of toxins, the C18 phase or activated carbon was used. In general, higher toxin recoveries were achieved when using the C18 phase. The best result was achieved for ATX-a, 94% recovery with elution using methanol with 0.1% trifluoroacetic acid (TFA). For MC-LR, the best recovery was 59%, and for CYN 22%. The study evaluated the various methods to release cyanotoxins from cyanobacteria showed that: the highest ATX-a concentration (0.60 μg/mg d.w) was obtained using MilliQ water and microwave treatment for 10–15 s. For MC-LR, the highest extracted amount (6.73 μg/mg d.w) resulted from methanol treatment and boiling at 100 °C for 15 min. CYN extraction was the most effective by using MilliQ water and alternative freezing/thawing (1.54 μg/mg d.w). In conclusion, changing the optimal parameters of cyanobacterial cultivation, only slightly affects the increase in biomass accumulation and synthesis of cyanobacterial toxins. In the case of ATX, the key is the use of the TFA additive in the SPE process. No single method has been identified as the ideal approach for isolating various intracellular cyanotoxins.
{"title":"Optimization of isolation and concentration of the common freshwater cyanobacterial toxins ATX-a, CYN and MC-LR using standard techniques, optimization of cyanobacteria growth","authors":"Saravana Kumar Selvaraj , Bartosz Lelito , Michal Adamski , Ariel Kaminski","doi":"10.1016/j.toxicon.2024.108137","DOIUrl":"10.1016/j.toxicon.2024.108137","url":null,"abstract":"<div><div>Some of the most commonly identified freshwater toxins are anatoxin-a (ATX-a), cylindrospermopsin (CYN), and microcystin-LR (MC-LR). The aim of this paper was to compare different methods of extracting and concentrating these cyanotoxins and check the impact of selected physical factors on the accumulation of biomass of <em>Dolichospermum flos-aquae, Microcystis aeruginosa,</em> and <em>Raphidiopsis raciborskii</em>. The effect of different cyanobacteria cultivation conditions on the amount of cyanotoxins synthesized showed no significant changes over time in the average concentration of all tested toxins in the medium compared to the control. Mixing cultures increases the intracellular content of ATX-a. Aerating also positively affects the concentration of MC-LR intracellularly. In order to optimize the solid phase extraction (SPE) process of toxins, the C18 phase or activated carbon was used. In general, higher toxin recoveries were achieved when using the C18 phase. The best result was achieved for ATX-a, 94% recovery with elution using methanol with 0.1% trifluoroacetic acid (TFA). For MC-LR, the best recovery was 59%, and for CYN 22%. The study evaluated the various methods to release cyanotoxins from cyanobacteria showed that: the highest ATX-a concentration (0.60 μg/mg d.w) was obtained using MilliQ water and microwave treatment for 10–15 s. For MC-LR, the highest extracted amount (6.73 μg/mg d.w) resulted from methanol treatment and boiling at 100 °C for 15 min. CYN extraction was the most effective by using MilliQ water and alternative freezing/thawing (1.54 μg/mg d.w). In conclusion, changing the optimal parameters of cyanobacterial cultivation, only slightly affects the increase in biomass accumulation and synthesis of cyanobacterial toxins. In the case of ATX, the key is the use of the TFA additive in the SPE process. No single method has been identified as the ideal approach for isolating various intracellular cyanotoxins.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"251 ","pages":"Article 108137"},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-21DOI: 10.1016/j.toxicon.2024.108149
Shihui Xie , Shuo Han , Jietao Gong , Zhiyuan Feng , Yang Sun , Hong Yao , Peiying Shi
It has been confirmed that bee venom (BV) can inhibit tumor metastasis of lung cancer cells induced by epidermal growth factor, suggesting the inhibitory role of BV on the regulation of epidermal growth factor receptor (EGFR), and may synergistically promote the anti-lung cancer effect of EGFR tyrosine kinase inhibitor gefitinib. This paper aims to ascertain the therapeutic potentials of BV combined with gefitinib against non-small cell lung cancer (NSCLC) in vitro. As results, the content of the main component melittin in air-dried BV was determined by HPLC. Subsequently, it was found that BV significantly inhibited the proliferation of NSCLC PC-9 and NCI-H1299 cells, but not generated apparent toxicity to human normal lung epithelial BEAS-2B cells. Meanwhile, the combination of BV and gefitinib also significantly inhibited the proliferation of these two cells, and suppressed the migration and invasion of PC-9 cells. By bioinformatics analysis and molecular docking, it was predicted that the main component melittin in BV could act on the cell membrane and transmembrane protein EGFR. Ultimately, Western blot assays showed BV alone or combined with gefitinib significantly decreased the protein expression of phosphorylated EGFR (p-EGFR) and the protein expression ratio of p-EGFR to EGFR, and increased the protein expression ratio of LC3-II to LC3-I in PC-9 cells or epidermal growth factor-activated PC-9 cells. The results demonstrated that BV could prompt the inhibition of gefitinib on proliferation, migration, and invasion of NSCLC cells via EGFR-mediated autophagy, showing the synergistic anti-NSCLC potential when combined with gefitinib.
{"title":"Bee venom prompts the inhibition of gefitinib on proliferation, migration, and invasion of non-small cell lung cancer cells via EGFR-mediated autophagy","authors":"Shihui Xie , Shuo Han , Jietao Gong , Zhiyuan Feng , Yang Sun , Hong Yao , Peiying Shi","doi":"10.1016/j.toxicon.2024.108149","DOIUrl":"10.1016/j.toxicon.2024.108149","url":null,"abstract":"<div><div>It has been confirmed that bee venom (BV) can inhibit tumor metastasis of lung cancer cells induced by epidermal growth factor, suggesting the inhibitory role of BV on the regulation of epidermal growth factor receptor (EGFR), and may synergistically promote the anti-lung cancer effect of EGFR tyrosine kinase inhibitor gefitinib. This paper aims to ascertain the therapeutic potentials of BV combined with gefitinib against non-small cell lung cancer (NSCLC) <em>in vitro</em>. As results, the content of the main component melittin in air-dried BV was determined by HPLC. Subsequently, it was found that BV significantly inhibited the proliferation of NSCLC PC-9 and NCI-H1299 cells, but not generated apparent toxicity to human normal lung epithelial BEAS-2B cells. Meanwhile, the combination of BV and gefitinib also significantly inhibited the proliferation of these two cells, and suppressed the migration and invasion of PC-9 cells. By bioinformatics analysis and molecular docking, it was predicted that the main component melittin in BV could act on the cell membrane and transmembrane protein EGFR. Ultimately, Western blot assays showed BV alone or combined with gefitinib significantly decreased the protein expression of phosphorylated EGFR (p-EGFR) and the protein expression ratio of p-EGFR to EGFR, and increased the protein expression ratio of LC3-II to LC3-I in PC-9 cells or epidermal growth factor-activated PC-9 cells. The results demonstrated that BV could prompt the inhibition of gefitinib on proliferation, migration, and invasion of NSCLC cells via EGFR-mediated autophagy, showing the synergistic anti-NSCLC potential when combined with gefitinib.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"251 ","pages":"Article 108149"},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-20DOI: 10.1016/j.toxicon.2024.108132
Laís Sousa do Nascimento Monteiro , Rosemary Matias , Carlos Eurico Fernandes , Jeandre Augusto Otsubo Jaques , Igor Leal Brito , Ademir Kleber Morbeck de Oliveira , Gilberto Gonçalves Facco , Carla Letícia Gediel Rivero-Wendt
Norantea guianensis Aubl., commonly referred to as the parrot flower or macaw-tail vine, is a plant species found in the Brazilian Amazon, Caatinga, and Cerrado biomes. It is used in folk medicine for its anxiolytic properties, as well as its ability to alleviate headaches and reduce fever. Nevertheless, despite its therapeutic benefits, the impact on embryonic development has yet to be fully explained. The objective of this study was to evaluate chemical constituents by HPLC-DAD, UV–visible and classical phytochemistry and the LC50 of ethanolic extracts from the stem and leaves of N. guianensis in Danio rerio after 96 h and to investigate their effect on developmental morphology. The findings were then related to both Acetylcholinesterase (AChE) activity and the plant's chemical composition. Zebrafish embryos were exposed to 0, 20, 40, 60, 80 and 100 mg/L concentrations of stem and leaves extracts. Phytochemical analysis revealed that the stem extract contained predominantly phenolic compounds, tannins, and anthraquinones, while the leaf extract contained alkaloids and flavonoids. The LC50 values for the stem and leaf extracts were 64.55 mg/L and 7.16 mg/L, respectively, being the stem extract was more toxic than the leaf extract. Induced malformations and alterations in the zebrafish development in different concentrations for both extract including pericardial edema, increased heart rate, spinal malformation and equilibrium disruption. Unlike to stem extract, the leaf extract delayed larval hatching and inhibited AChE activity. The findings indicate that the leaf extract possesses higher embryotoxicity and its use should be avoided during pregnancy.
{"title":"Evaluation of chemical constituents in Norantea guianensis aubl. Extracts, embryotoxicity, and acetylcholinesterase inhibitory potential in Danio rerio","authors":"Laís Sousa do Nascimento Monteiro , Rosemary Matias , Carlos Eurico Fernandes , Jeandre Augusto Otsubo Jaques , Igor Leal Brito , Ademir Kleber Morbeck de Oliveira , Gilberto Gonçalves Facco , Carla Letícia Gediel Rivero-Wendt","doi":"10.1016/j.toxicon.2024.108132","DOIUrl":"10.1016/j.toxicon.2024.108132","url":null,"abstract":"<div><div><em>Norantea guianensis</em> Aubl., commonly referred to as the parrot flower or macaw-tail vine, is a plant species found in the Brazilian Amazon, Caatinga, and Cerrado biomes. It is used in folk medicine for its anxiolytic properties, as well as its ability to alleviate headaches and reduce fever. Nevertheless, despite its therapeutic benefits, the impact on embryonic development has yet to be fully explained. The objective of this study was to evaluate chemical constituents by HPLC-DAD, UV–visible and classical phytochemistry and the LC50 of ethanolic extracts from the stem and leaves of N. guianensis in <em>Danio rerio</em> after 96 h and to investigate their effect on developmental morphology. The findings were then related to both Acetylcholinesterase (AChE) activity and the plant's chemical composition. Zebrafish embryos were exposed to 0, 20, 40, 60, 80 and 100 mg/L concentrations of stem and leaves extracts. Phytochemical analysis revealed that the stem extract contained predominantly phenolic compounds, tannins, and anthraquinones, while the leaf extract contained alkaloids and flavonoids. The LC50 values for the stem and leaf extracts were 64.55 mg/L and 7.16 mg/L, respectively, being the stem extract was more toxic than the leaf extract. Induced malformations and alterations in the zebrafish development in different concentrations for both extract including pericardial edema, increased heart rate, spinal malformation and equilibrium disruption. Unlike to stem extract, the leaf extract delayed larval hatching and inhibited AChE activity. The findings indicate that the leaf extract possesses higher embryotoxicity and its use should be avoided during pregnancy.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"251 ","pages":"Article 108132"},"PeriodicalIF":2.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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