Exposure to the Natural Compound Climacostol Induces Cell Damage and Oxidative Stress in the Fruit Fly <i>Drosophila melanogaster</i>

The ciliate <i>Climacostomum virens</i> produces the metabolite climacostol that displays antimicrobial activity and cytotoxicity on human and rodent tumor cells. Given its potential as a backbone in pharmacological studies, we used the fruit fly <i>Drosophila melanogaster</i>...

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Main Authors: Elisabetta Catalani, Kashi Brunetti, Simona Del Quondam, Silvia Bongiorni, Simona Picchietti, Anna Maria Fausto, Gabriele Lupidi, Enrico Marcantoni, Cristiana Perrotta, Gabriele Achille, Federico Buonanno, Claudio Ortenzi, Davide Cervia
Format: Article
Language:English
Published: MDPI AG 2024-01-01
Series:Toxics
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Online Access:https://www.mdpi.com/2305-6304/12/2/102
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author Elisabetta Catalani
Kashi Brunetti
Simona Del Quondam
Silvia Bongiorni
Simona Picchietti
Anna Maria Fausto
Gabriele Lupidi
Enrico Marcantoni
Cristiana Perrotta
Gabriele Achille
Federico Buonanno
Claudio Ortenzi
Davide Cervia
author_facet Elisabetta Catalani
Kashi Brunetti
Simona Del Quondam
Silvia Bongiorni
Simona Picchietti
Anna Maria Fausto
Gabriele Lupidi
Enrico Marcantoni
Cristiana Perrotta
Gabriele Achille
Federico Buonanno
Claudio Ortenzi
Davide Cervia
author_sort Elisabetta Catalani
collection DOAJ
description The ciliate <i>Climacostomum virens</i> produces the metabolite climacostol that displays antimicrobial activity and cytotoxicity on human and rodent tumor cells. Given its potential as a backbone in pharmacological studies, we used the fruit fly <i>Drosophila melanogaster</i> to evaluate how the xenobiotic climacostol affects biological systems in vivo at the organismal level. Food administration with climacostol demonstrated its harmful role during larvae developmental stages but not pupation. The midgut of eclosed larvae showed apoptosis and increased generation of reactive oxygen species (ROS), thus demonstrating gastrointestinal toxicity. Climacostol did not affect enteroendocrine cell proliferation, suggesting moderate damage that does not initiate the repairing program. The fact that climacostol increased brain ROS and inhibited the proliferation of neural cells revealed a systemic (neurotoxic) role of this harmful substance. In this line, we found lower expression of relevant antioxidant enzymes in the larvae and impaired mitochondrial activity. Adult offsprings presented no major alterations in survival and mobility, as well the absence of abnormal phenotypes. However, mitochondrial activity and oviposition behavior was somewhat affected, indicating the chronic toxicity of climacostol, which continues moderately until adult stages. These results revealed for the first time the detrimental role of ingested climacostol in a non-target multicellular organism.
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spelling doaj.art-0ecfcdd936af4963b821d2834f209cd12024-02-23T15:36:19ZengMDPI AGToxics2305-63042024-01-0112210210.3390/toxics12020102Exposure to the Natural Compound Climacostol Induces Cell Damage and Oxidative Stress in the Fruit Fly <i>Drosophila melanogaster</i>Elisabetta Catalani0Kashi Brunetti1Simona Del Quondam2Silvia Bongiorni3Simona Picchietti4Anna Maria Fausto5Gabriele Lupidi6Enrico Marcantoni7Cristiana Perrotta8Gabriele Achille9Federico Buonanno10Claudio Ortenzi11Davide Cervia12Department for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), Università degli Studi della Tuscia, 01100 Viterbo, ItalyDepartment for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), Università degli Studi della Tuscia, 01100 Viterbo, ItalyDepartment for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), Università degli Studi della Tuscia, 01100 Viterbo, ItalyDepartment of Ecological and Biological Sciences (DEB), Università degli Studi della Tuscia, 01100 Viterbo, ItalyDepartment for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), Università degli Studi della Tuscia, 01100 Viterbo, ItalyDepartment for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), Università degli Studi della Tuscia, 01100 Viterbo, ItalySchool of Science and Technology, Section of Chemistry, Università degli Studi di Camerino, 62032 Camerino, ItalySchool of Science and Technology, Section of Chemistry, Università degli Studi di Camerino, 62032 Camerino, ItalyDepartment of Biomedical and Clinical Sciences (DIBIC), Università degli Studi di Milano, 20157 Milano, ItalyLaboratory of Protistology and Biology Education, Department of Education, Cultural Heritage, and Tourism (ECHT), Università degli Studi di Macerata, 62100 Macerata, ItalyLaboratory of Protistology and Biology Education, Department of Education, Cultural Heritage, and Tourism (ECHT), Università degli Studi di Macerata, 62100 Macerata, ItalyLaboratory of Protistology and Biology Education, Department of Education, Cultural Heritage, and Tourism (ECHT), Università degli Studi di Macerata, 62100 Macerata, ItalyDepartment for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), Università degli Studi della Tuscia, 01100 Viterbo, ItalyThe ciliate <i>Climacostomum virens</i> produces the metabolite climacostol that displays antimicrobial activity and cytotoxicity on human and rodent tumor cells. Given its potential as a backbone in pharmacological studies, we used the fruit fly <i>Drosophila melanogaster</i> to evaluate how the xenobiotic climacostol affects biological systems in vivo at the organismal level. Food administration with climacostol demonstrated its harmful role during larvae developmental stages but not pupation. The midgut of eclosed larvae showed apoptosis and increased generation of reactive oxygen species (ROS), thus demonstrating gastrointestinal toxicity. Climacostol did not affect enteroendocrine cell proliferation, suggesting moderate damage that does not initiate the repairing program. The fact that climacostol increased brain ROS and inhibited the proliferation of neural cells revealed a systemic (neurotoxic) role of this harmful substance. In this line, we found lower expression of relevant antioxidant enzymes in the larvae and impaired mitochondrial activity. Adult offsprings presented no major alterations in survival and mobility, as well the absence of abnormal phenotypes. However, mitochondrial activity and oviposition behavior was somewhat affected, indicating the chronic toxicity of climacostol, which continues moderately until adult stages. These results revealed for the first time the detrimental role of ingested climacostol in a non-target multicellular organism.https://www.mdpi.com/2305-6304/12/2/102secondary metabolite<i>Drosophila melanogaster</i>larvae developmentcell damageredox homeostasisgastrointestinal tract
spellingShingle Elisabetta Catalani
Kashi Brunetti
Simona Del Quondam
Silvia Bongiorni
Simona Picchietti
Anna Maria Fausto
Gabriele Lupidi
Enrico Marcantoni
Cristiana Perrotta
Gabriele Achille
Federico Buonanno
Claudio Ortenzi
Davide Cervia
Exposure to the Natural Compound Climacostol Induces Cell Damage and Oxidative Stress in the Fruit Fly <i>Drosophila melanogaster</i>
Toxics
secondary metabolite
<i>Drosophila melanogaster</i>
larvae development
cell damage
redox homeostasis
gastrointestinal tract
title Exposure to the Natural Compound Climacostol Induces Cell Damage and Oxidative Stress in the Fruit Fly <i>Drosophila melanogaster</i>
title_full Exposure to the Natural Compound Climacostol Induces Cell Damage and Oxidative Stress in the Fruit Fly <i>Drosophila melanogaster</i>
title_fullStr Exposure to the Natural Compound Climacostol Induces Cell Damage and Oxidative Stress in the Fruit Fly <i>Drosophila melanogaster</i>
title_full_unstemmed Exposure to the Natural Compound Climacostol Induces Cell Damage and Oxidative Stress in the Fruit Fly <i>Drosophila melanogaster</i>
title_short Exposure to the Natural Compound Climacostol Induces Cell Damage and Oxidative Stress in the Fruit Fly <i>Drosophila melanogaster</i>
title_sort exposure to the natural compound climacostol induces cell damage and oxidative stress in the fruit fly i drosophila melanogaster i
topic secondary metabolite
<i>Drosophila melanogaster</i>
larvae development
cell damage
redox homeostasis
gastrointestinal tract
url https://www.mdpi.com/2305-6304/12/2/102
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