Publication Details |
| Category | Text Publication |
| Reference Category | Journals |
| DOI | 10.1016/j.hazadv.2025.100956 |
Licence  |
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| Title (Primary) | First evidence of CuPANotic cell death in fish gut upon environmentally relevant co-exposure to Copper and PVC microplastics |
| Author | Bakhasha, J.; Saxena, V.; Arya, N.; Kumar, P.; Yadav, K.K.; Kühnel, D.; Trivedi, A. |
| Source Titel | Journal of Hazardous Materials Advances |
| Year | 2026 |
| Department | ETOX |
| Volume | 21 |
| Page From | art. 100956 |
| Language | englisch |
| Topic | T9 Healthy Planet |
| Supplements | Supplement 1 |
| Keywords | Cuproptosis; PANoptosis; Microplastic-metal synergy; Programmed cell death pathways; Fish |
| Abstract | Microplastic-metal
interactions represent a critical but underexplored dimension of
aquatic ecotoxicology. Here, we provide the first validation of a novel
CuPANoptosis (Cuproptosis and PANoptosis) paradigm in fish, uncovering
how polyvinyl chloride microplastics (PVC-MPs) intensifies copper
(Cu²⁺)-induced toxicity in Channa punctatus. Fish were exposed
to environmentally relevant concentrations of PVC-MPs (0.5 mg/L) and
copper (0.85 mg/L), individually and in combination, for 60 days.
PVC-MPs acted as potent vectors, enhancing copper bioavailability,
tissue retention, and translocation across intestinal barriers,
resulting in exacerbated oxidative stress and mitochondrial dysfunction.
Mechanistically, FDX1-mediated Cu⁺ reduction accelerated abnormal
protein lipoylation and aggregation, collapsing TCA cycle function and
triggering cuproptosis. Strikingly, this cuproptotic activation
integrated with apoptotic, pyroptotic, and necroptotic pathways, forming
an interconnected programmed cell death circuitry ‘CuPANoptosis’. The
co-exposure group exhibited maximal ROS accumulation, lipid
peroxidation, GSH depletion, and severe disruption of intestinal
architecture, including vacuolization, villi detachment, and widespread
cellular damage, with all key alterations showing high statistical
significance (p < 0.05). Transcriptional and protein-level analyses revealed upregulation of key mediators including fdx1, dlat, dlst, bax, nlrp3, ripk1, and caspases,
validating synchronized activation of multiple cell death pathways.
These findings highlight that PVC-MPs act as dynamic carriers amplifying
copper-induced toxicity and unveil a previously unrecognized mechanism
of gut injury. Collectively, our study provides the first transformative
framework for understanding MP-metal synergy in aquatic systems,
emphasizing urgent ecological risks and the need for targeted mitigation
strategies. |
| Persistent UFZ Identifier | https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=31696 |
| Bakhasha, J., Saxena, V., Arya, N., Kumar, P., Yadav, K.K., Kühnel, D., Trivedi, A. (2026): First evidence of CuPANotic cell death in fish gut upon environmentally relevant co-exposure to Copper and PVC microplastics J. Hazard. Mater. Adv. 21 , art. 100956 10.1016/j.hazadv.2025.100956 |
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