Marine toxin domoic acid induces moderate toxicological response in non-target HepG2 cells
Domoic acid (DA) is a marine neurotoxin produced as a defence compound by diatom Pseudo-nitzschia. Although its toxicity is well known in marine mammals and fish, data on DA cyto/genotoxicity in human non-target cells is still limited. Hence, we aimed to study the effect of DA (0.001–10 µg/mL) on ce...
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Veröffentlicht in: | Toxicology (Amsterdam) 2022-03, Vol.470, p.153157-153157, Article 153157 |
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creator | Madunić, Josip Hercog, Klara Gerić, Marko Domijan, Ana-Marija Žegura, Bojana Gajski, Goran |
description | Domoic acid (DA) is a marine neurotoxin produced as a defence compound by diatom Pseudo-nitzschia. Although its toxicity is well known in marine mammals and fish, data on DA cyto/genotoxicity in human non-target cells is still limited. Hence, we aimed to study the effect of DA (0.001–10 µg/mL) on cell viability and proliferation kinetics of human hepatocellular carcinoma (HepG2) cells as well as DNA damage induction after 4, 24 and 72 h of exposure. The results revealed that DA up to 10 µg/mL did not elicit significant changes in HepG2 cell viability, proliferation and cell cycle at applied conditions. DA did not generate DNA double-strand breaks, while it exhibited significant dose- and time-dependent increase of DNA damage in the form of either DNA single-strand breaks or alkali labile sites. Additionally, increased malondialdehyde level after DA treatment indicated oxidative damage to lipids. Altogether, the results showed that neurotoxin DA induced only minor adverse genotoxic effects in non-target HepG2 cells that most probably occurred resulting from the oxidative stress. However, additional research is needed to further elucidate the mechanisms of DA toxicity, particularly in terms of chronic exposure, as well as to understand its potential influence on human non-target cells.
•Domoic acid showed no effects on cell viability and proliferation kinetics.•Domoic acid induced minor DNA damaging effect in non-target human liver cells.•Domoic acid did not induce DNA double-strand breaks.•Oxidative stress is implicated in domoic acid mechanism of toxicity.•Chronic low-level exposure deserves further research. |
doi_str_mv | 10.1016/j.tox.2022.153157 |
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•Domoic acid showed no effects on cell viability and proliferation kinetics.•Domoic acid induced minor DNA damaging effect in non-target human liver cells.•Domoic acid did not induce DNA double-strand breaks.•Oxidative stress is implicated in domoic acid mechanism of toxicity.•Chronic low-level exposure deserves further research.</description><identifier>ISSN: 0300-483X</identifier><identifier>EISSN: 1879-3185</identifier><identifier>DOI: 10.1016/j.tox.2022.153157</identifier><identifier>PMID: 35307467</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Animals ; Biotoxin ; Cyto/genotoxicity ; Diatoms - metabolism ; DNA - metabolism ; Domoic acid ; Harmful algae ; Hep G2 Cells ; Humans ; Kainic Acid - analogs & derivatives ; Kainic Acid - toxicity ; Mammals ; Marine Toxins - metabolism ; Marine Toxins - toxicity ; Neurotoxins - toxicity ; Non-target cells</subject><ispartof>Toxicology (Amsterdam), 2022-03, Vol.470, p.153157-153157, Article 153157</ispartof><rights>2022 Elsevier B.V.</rights><rights>Copyright © 2022 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c283t-87677277066d5b20effd9a22e4c76653e6a393ffa962916b98c947fbd810da603</citedby><cites>FETCH-LOGICAL-c283t-87677277066d5b20effd9a22e4c76653e6a393ffa962916b98c947fbd810da603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0300483X22000695$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35307467$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Madunić, Josip</creatorcontrib><creatorcontrib>Hercog, Klara</creatorcontrib><creatorcontrib>Gerić, Marko</creatorcontrib><creatorcontrib>Domijan, Ana-Marija</creatorcontrib><creatorcontrib>Žegura, Bojana</creatorcontrib><creatorcontrib>Gajski, Goran</creatorcontrib><title>Marine toxin domoic acid induces moderate toxicological response in non-target HepG2 cells</title><title>Toxicology (Amsterdam)</title><addtitle>Toxicology</addtitle><description>Domoic acid (DA) is a marine neurotoxin produced as a defence compound by diatom Pseudo-nitzschia. Although its toxicity is well known in marine mammals and fish, data on DA cyto/genotoxicity in human non-target cells is still limited. Hence, we aimed to study the effect of DA (0.001–10 µg/mL) on cell viability and proliferation kinetics of human hepatocellular carcinoma (HepG2) cells as well as DNA damage induction after 4, 24 and 72 h of exposure. The results revealed that DA up to 10 µg/mL did not elicit significant changes in HepG2 cell viability, proliferation and cell cycle at applied conditions. DA did not generate DNA double-strand breaks, while it exhibited significant dose- and time-dependent increase of DNA damage in the form of either DNA single-strand breaks or alkali labile sites. Additionally, increased malondialdehyde level after DA treatment indicated oxidative damage to lipids. Altogether, the results showed that neurotoxin DA induced only minor adverse genotoxic effects in non-target HepG2 cells that most probably occurred resulting from the oxidative stress. However, additional research is needed to further elucidate the mechanisms of DA toxicity, particularly in terms of chronic exposure, as well as to understand its potential influence on human non-target cells.
•Domoic acid showed no effects on cell viability and proliferation kinetics.•Domoic acid induced minor DNA damaging effect in non-target human liver cells.•Domoic acid did not induce DNA double-strand breaks.•Oxidative stress is implicated in domoic acid mechanism of toxicity.•Chronic low-level exposure deserves further research.</description><subject>Animals</subject><subject>Biotoxin</subject><subject>Cyto/genotoxicity</subject><subject>Diatoms - metabolism</subject><subject>DNA - metabolism</subject><subject>Domoic acid</subject><subject>Harmful algae</subject><subject>Hep G2 Cells</subject><subject>Humans</subject><subject>Kainic Acid - analogs & derivatives</subject><subject>Kainic Acid - toxicity</subject><subject>Mammals</subject><subject>Marine Toxins - metabolism</subject><subject>Marine Toxins - toxicity</subject><subject>Neurotoxins - toxicity</subject><subject>Non-target cells</subject><issn>0300-483X</issn><issn>1879-3185</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kD1PwzAURS0EoqXwA1iQR5YEfyR2IiZUQYtUxAISYrEc-6VylcTFThH8e1KlMDK95dyjdy9Cl5SklFBxs0l7_5UywlhKc05zeYSmtJBlwmmRH6Mp4YQkWcHfJugsxg0hhPFMnKIJzzmRmZBT9P6kg-sADyLXYetb7wzWxlnsOrszEHHrLQTdj4jxjV87oxscIG59F2HgcOe7pNdhDT1ewnbBsIGmiefopNZNhIvDnaHXh_uX-TJZPS8e53erxLCC90khhZRMSiKEzStGoK5tqRmDzEghcg5C85LXtS4FK6moysKUmawrW1BitSB8hq5H7zb4jx3EXrUu7j_QHfhdVExkNCdCFnJA6Yia4GMMUKttcK0O34oStZ9UbdRQU-0nVeOkQ-bqoN9VLdi_xO-GA3A7AjCU_HQQVDQOOgPWBTC9st79o_8Bz_6G3A</recordid><startdate>20220330</startdate><enddate>20220330</enddate><creator>Madunić, Josip</creator><creator>Hercog, Klara</creator><creator>Gerić, Marko</creator><creator>Domijan, Ana-Marija</creator><creator>Žegura, Bojana</creator><creator>Gajski, Goran</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20220330</creationdate><title>Marine toxin domoic acid induces moderate toxicological response in non-target HepG2 cells</title><author>Madunić, Josip ; Hercog, Klara ; Gerić, Marko ; Domijan, Ana-Marija ; Žegura, Bojana ; Gajski, Goran</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c283t-87677277066d5b20effd9a22e4c76653e6a393ffa962916b98c947fbd810da603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Biotoxin</topic><topic>Cyto/genotoxicity</topic><topic>Diatoms - metabolism</topic><topic>DNA - metabolism</topic><topic>Domoic acid</topic><topic>Harmful algae</topic><topic>Hep G2 Cells</topic><topic>Humans</topic><topic>Kainic Acid - analogs & derivatives</topic><topic>Kainic Acid - toxicity</topic><topic>Mammals</topic><topic>Marine Toxins - metabolism</topic><topic>Marine Toxins - toxicity</topic><topic>Neurotoxins - toxicity</topic><topic>Non-target cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Madunić, Josip</creatorcontrib><creatorcontrib>Hercog, Klara</creatorcontrib><creatorcontrib>Gerić, Marko</creatorcontrib><creatorcontrib>Domijan, Ana-Marija</creatorcontrib><creatorcontrib>Žegura, Bojana</creatorcontrib><creatorcontrib>Gajski, Goran</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Toxicology (Amsterdam)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Madunić, Josip</au><au>Hercog, Klara</au><au>Gerić, Marko</au><au>Domijan, Ana-Marija</au><au>Žegura, Bojana</au><au>Gajski, Goran</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Marine toxin domoic acid induces moderate toxicological response in non-target HepG2 cells</atitle><jtitle>Toxicology (Amsterdam)</jtitle><addtitle>Toxicology</addtitle><date>2022-03-30</date><risdate>2022</risdate><volume>470</volume><spage>153157</spage><epage>153157</epage><pages>153157-153157</pages><artnum>153157</artnum><issn>0300-483X</issn><eissn>1879-3185</eissn><abstract>Domoic acid (DA) is a marine neurotoxin produced as a defence compound by diatom Pseudo-nitzschia. Although its toxicity is well known in marine mammals and fish, data on DA cyto/genotoxicity in human non-target cells is still limited. Hence, we aimed to study the effect of DA (0.001–10 µg/mL) on cell viability and proliferation kinetics of human hepatocellular carcinoma (HepG2) cells as well as DNA damage induction after 4, 24 and 72 h of exposure. The results revealed that DA up to 10 µg/mL did not elicit significant changes in HepG2 cell viability, proliferation and cell cycle at applied conditions. DA did not generate DNA double-strand breaks, while it exhibited significant dose- and time-dependent increase of DNA damage in the form of either DNA single-strand breaks or alkali labile sites. Additionally, increased malondialdehyde level after DA treatment indicated oxidative damage to lipids. Altogether, the results showed that neurotoxin DA induced only minor adverse genotoxic effects in non-target HepG2 cells that most probably occurred resulting from the oxidative stress. However, additional research is needed to further elucidate the mechanisms of DA toxicity, particularly in terms of chronic exposure, as well as to understand its potential influence on human non-target cells.
•Domoic acid showed no effects on cell viability and proliferation kinetics.•Domoic acid induced minor DNA damaging effect in non-target human liver cells.•Domoic acid did not induce DNA double-strand breaks.•Oxidative stress is implicated in domoic acid mechanism of toxicity.•Chronic low-level exposure deserves further research.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>35307467</pmid><doi>10.1016/j.tox.2022.153157</doi><tpages>1</tpages></addata></record> |
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subjects | Animals Biotoxin Cyto/genotoxicity Diatoms - metabolism DNA - metabolism Domoic acid Harmful algae Hep G2 Cells Humans Kainic Acid - analogs & derivatives Kainic Acid - toxicity Mammals Marine Toxins - metabolism Marine Toxins - toxicity Neurotoxins - toxicity Non-target cells |
title | Marine toxin domoic acid induces moderate toxicological response in non-target HepG2 cells |
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