Astaxanthin Attenuates Chlorpyrifos-Induced Pulmonary Cytotoxicity by Modulating Mitochondrial Redox and Inflammatory Pathways

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dc.contributor.authorOkudan Altindas, Mediha Demet
dc.contributor.authorGuner, Adem
dc.date.accessioned2026-04-25T14:20:27Z
dc.date.available2026-04-25T14:20:27Z
dc.date.issued2025
dc.departmentSinop Üniversitesi
dc.description.abstractChlorpyrifos (CPF), an organophosphate pesticide, is known to induce pulmonary toxicity through oxidative stress, mitochondrial dysfunction, and inflammation. Astaxanthin (ASX), a xanthophyll carotenoid derived primarily from marine microalgae (Haematococcus pluvialis), possesses strong antioxidant properties and has demonstrated cellular protective effects in numerous oxidative stress studies. However, its efficacy against CPF-induced lung cell damage remains uncharacterized. This study revealed the protective role of ASX, as a pretreatment and co-treatment, against CPF-induced cytotoxicity in human A549 lung adenocarcinoma cells by assessing cell viability, intracellular reactive oxygen species (IROS), total oxidative status (TOS), total antioxidant capacity (TAC), mitochondrial membrane potential (MMP), intracellular calcium ions (Ca2+), lactate dehydrogenase (LDH) release, malondialdehyde (MDA) levels, glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, DNA fragmentation, and apoptosis/inflammation-associated gene expression. CPF treatment significantly decreased cell viability and TAC, while elevating IROS, TOS, MMP, intracellular Ca2+, and LDH release. CPF also increased MDA levels and suppressed GPx and SOD activities. DNA fragmentation and quantitative polymerase chain reaction (qPCR) analysis revealed upregulation of pro-apoptotic and inflammatory markers such as BCL2-associated X protein (BAX), caspase-3 (CASP3), tumor protein p53 (TP53), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), nuclear factor kappa B (NF kappa B), and voltage-dependent anion-selective channel protein 1 (VDAC1) and suppression of anti-apoptotic B-cell lymphoma 2 (BCL2) and antioxidant defense genes nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). ASX treatment, particularly when administered as a pretreatment, significantly reversed CPF-induced oxidative and inflammatory responses by restoring SOD, GPx, and TAC levels, reducing IROS, TOS, MDA, and LDH release, and downregulating apoptotic and inflammatory gene expressions. ASX pretreatment notably decreased MMP and intracellular Ca2+ levels, indicating protection against mitochondrial dysfunction and calcium dysregulation. ASX upregulated Nrf2 and HO-1 expression and restored the BCL2/BAX balance, suggesting inhibition of mitochondrial-mediated apoptosis. Additionally, ASX significantly attenuated CPF-induced anti-angiogenic effects in the in ovo Hen's Egg Test Chorioallantoic Membrane (HET-CAM) assay. These findings demonstrate, for the first time, that ASX exerts a broad spectrum of protective effects against CPF-induced cytotoxicity in lung cells, mainly through the stabilization of mitochondrial redox status and modulation of apoptosis- and inflammation-related gene pathways, highlighting ASX as a promising candidate for further therapeutic development. Furthermore, the pronounced efficacy observed in the pretreatment regimen suggests that ASX can be evaluated as a potential nutritional preventive strategy in high-risk populations with occupational or environmental CPF exposure.
dc.identifier.doi10.3390/cimb47080663
dc.identifier.issn1467-3037
dc.identifier.issn1467-3045
dc.identifier.issue8
dc.identifier.orcid0000-0003-3295-3538
dc.identifier.pmid40864817
dc.identifier.scopus2-s2.0-105014495920
dc.identifier.scopusqualityQ3
dc.identifier.urihttps://doi.org/10.3390/cimb47080663
dc.identifier.urihttps://hdl.handle.net/11486/8583
dc.identifier.volume47
dc.identifier.wosWOS:001557356400001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherMdpi
dc.relation.ispartofCurrent Issues in Molecular Biology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20260420
dc.subjectastaxanthin
dc.subjectchlorpyrifos
dc.subjectlung
dc.subjectmitochondrial dysfunction
dc.subjectoxidative stress
dc.subjecttoxicity
dc.titleAstaxanthin Attenuates Chlorpyrifos-Induced Pulmonary Cytotoxicity by Modulating Mitochondrial Redox and Inflammatory Pathways
dc.typeArticle

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