Ipconazole Induces Oxidative Stress, Cell Death, and Proinflammation in SH-SY5Y Cells

Ipconazole is an antifungal agrochemical widely used in agriculture against seed diseases of rice, vegetables, and other crops; due to its easy accumulation in the environment, it poses a hazard to human, animal, and environmental health. Therefore, we investigated the cytotoxic effect of ipconazole...

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Main Authors: Carlos Villaorduña, Mariano Mendoza-Carlos, Manuel Chuyma, Jhon Avilés, Ayda Avalos-Diaz, Ronald Lozano-Reategui, Juan Garcia-Ruiz, Nadia Panduro-Tenazoa, Jessy Vargas, Ysabel Moran-Quintanilla, José-Luis Rodríguez
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Toxics
Subjects:
Online Access:https://www.mdpi.com/2305-6304/11/7/566
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author Carlos Villaorduña
Mariano Mendoza-Carlos
Manuel Chuyma
Jhon Avilés
Ayda Avalos-Diaz
Ronald Lozano-Reategui
Juan Garcia-Ruiz
Nadia Panduro-Tenazoa
Jessy Vargas
Ysabel Moran-Quintanilla
José-Luis Rodríguez
author_facet Carlos Villaorduña
Mariano Mendoza-Carlos
Manuel Chuyma
Jhon Avilés
Ayda Avalos-Diaz
Ronald Lozano-Reategui
Juan Garcia-Ruiz
Nadia Panduro-Tenazoa
Jessy Vargas
Ysabel Moran-Quintanilla
José-Luis Rodríguez
author_sort Carlos Villaorduña
collection DOAJ
description Ipconazole is an antifungal agrochemical widely used in agriculture against seed diseases of rice, vegetables, and other crops; due to its easy accumulation in the environment, it poses a hazard to human, animal, and environmental health. Therefore, we investigated the cytotoxic effect of ipconazole on SH-SY5Y neuroblastoma cells using cell viability tests (MTT), ROS production, caspase3/7 activity, and molecular assays of the biomarkers of cell death (Bax, Casp3, APAF1, BNIP3, and Bcl2); inflammasome (NLRP3, Casp1, and IL1β); inflammation (NFκB, TNFα, and IL6); and antioxidants (NRF2, SOD, and GPx). SH-SY5Y cells were exposed to ipconazole (1, 5, 10, 20, 50, and 100 µM) for 24 h. The ipconazole, in a dose-dependent manner, reduced cell viability and produced an IC<sub>50</sub> of 32.3 µM; it also produced an increase in ROS production and caspase3/7 enzyme activity in SH-SY5Y cells. In addition, ipconazole at 50 µM induced an overexpression of Bax, Casp3, APAF1, and BNIP3 (cell death genes); NLRP3, Casp1, and IL1B (inflammasome complex genes); and NFκB, TNFα, and IL6 (inflammation genes); it also reduced the expression of NRF2, SOD, and GPx (antioxidant genes). Our results show that ipconazole produces cytotoxic effects by reducing cell viability, generating oxidative stress, and inducing cell death in SH-SY5Y cells, so ipconazole exposure should be considered as a factor in the presentation of neurotoxicity or neurodegeneration.
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spelling doaj.art-25d1be11dd8a4f97ab6c21b4142e47f62023-11-18T21:36:42ZengMDPI AGToxics2305-63042023-06-0111756610.3390/toxics11070566Ipconazole Induces Oxidative Stress, Cell Death, and Proinflammation in SH-SY5Y CellsCarlos Villaorduña0Mariano Mendoza-Carlos1Manuel Chuyma2Jhon Avilés3Ayda Avalos-Diaz4Ronald Lozano-Reategui5Juan Garcia-Ruiz6Nadia Panduro-Tenazoa7Jessy Vargas8Ysabel Moran-Quintanilla9José-Luis Rodríguez10Faculty of Pharmacy, Universidad Nacional Mayor de San Marcos, Lima 15021, PeruAgroforestry Department, Universidad Nacional Intercultural de la Amazonia, Pucallpa 25004, PeruAgroforestry Department, Universidad Nacional Intercultural de la Amazonia, Pucallpa 25004, PeruAgroforestry Department, Universidad Nacional Intercultural de la Amazonia, Pucallpa 25004, PeruAgroforestry Department, Universidad Nacional Intercultural de la Amazonia, Pucallpa 25004, PeruAgroforestry Department, Universidad Nacional Intercultural de la Amazonia, Pucallpa 25004, PeruAgroforestry Department, Universidad Nacional Intercultural de la Amazonia, Pucallpa 25004, PeruAgroforestry Department, Universidad Nacional Intercultural de la Amazonia, Pucallpa 25004, PeruAgroforestry Department, Universidad Nacional Intercultural de la Amazonia, Pucallpa 25004, PeruAgroforestry Department, Universidad Nacional Intercultural de la Amazonia, Pucallpa 25004, PeruFaculty of Veterinary, Universidad Complutense de Madrid, 28040 Madrid, SpainIpconazole is an antifungal agrochemical widely used in agriculture against seed diseases of rice, vegetables, and other crops; due to its easy accumulation in the environment, it poses a hazard to human, animal, and environmental health. Therefore, we investigated the cytotoxic effect of ipconazole on SH-SY5Y neuroblastoma cells using cell viability tests (MTT), ROS production, caspase3/7 activity, and molecular assays of the biomarkers of cell death (Bax, Casp3, APAF1, BNIP3, and Bcl2); inflammasome (NLRP3, Casp1, and IL1β); inflammation (NFκB, TNFα, and IL6); and antioxidants (NRF2, SOD, and GPx). SH-SY5Y cells were exposed to ipconazole (1, 5, 10, 20, 50, and 100 µM) for 24 h. The ipconazole, in a dose-dependent manner, reduced cell viability and produced an IC<sub>50</sub> of 32.3 µM; it also produced an increase in ROS production and caspase3/7 enzyme activity in SH-SY5Y cells. In addition, ipconazole at 50 µM induced an overexpression of Bax, Casp3, APAF1, and BNIP3 (cell death genes); NLRP3, Casp1, and IL1B (inflammasome complex genes); and NFκB, TNFα, and IL6 (inflammation genes); it also reduced the expression of NRF2, SOD, and GPx (antioxidant genes). Our results show that ipconazole produces cytotoxic effects by reducing cell viability, generating oxidative stress, and inducing cell death in SH-SY5Y cells, so ipconazole exposure should be considered as a factor in the presentation of neurotoxicity or neurodegeneration.https://www.mdpi.com/2305-6304/11/7/566ipconazoleoxidative stresscell deathneurotoxicity
spellingShingle Carlos Villaorduña
Mariano Mendoza-Carlos
Manuel Chuyma
Jhon Avilés
Ayda Avalos-Diaz
Ronald Lozano-Reategui
Juan Garcia-Ruiz
Nadia Panduro-Tenazoa
Jessy Vargas
Ysabel Moran-Quintanilla
José-Luis Rodríguez
Ipconazole Induces Oxidative Stress, Cell Death, and Proinflammation in SH-SY5Y Cells
Toxics
ipconazole
oxidative stress
cell death
neurotoxicity
title Ipconazole Induces Oxidative Stress, Cell Death, and Proinflammation in SH-SY5Y Cells
title_full Ipconazole Induces Oxidative Stress, Cell Death, and Proinflammation in SH-SY5Y Cells
title_fullStr Ipconazole Induces Oxidative Stress, Cell Death, and Proinflammation in SH-SY5Y Cells
title_full_unstemmed Ipconazole Induces Oxidative Stress, Cell Death, and Proinflammation in SH-SY5Y Cells
title_short Ipconazole Induces Oxidative Stress, Cell Death, and Proinflammation in SH-SY5Y Cells
title_sort ipconazole induces oxidative stress cell death and proinflammation in sh sy5y cells
topic ipconazole
oxidative stress
cell death
neurotoxicity
url https://www.mdpi.com/2305-6304/11/7/566
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