Free Radic Biol Med. 2025 Jul 3:S0891-5849(25)00810-X. doi: 10.1016/j.freeradbiomed.2025.07.006. Online ahead of print.
ABSTRACT
Globally, approximately 80% of wastewater is discharged into aquatic environments without proper treatment, introducing hazardous compounds into ecosystems. Pollutant interactions can cause synergistic toxicity in aquatic organisms; however, their combined effects remain poorly understood. Zebrafish (Danio rerio H.) were exposed to polystyrene (PS) microplastics and 17α-methyltestosterone (MT) for 21 d, followed by pathological analysis, enzyme activity assays, and quantitative real-time PCR to assess metabolism- and immunity-related gene expression. Integrated transcriptomic and metabolomic analyses were conducted to elucidate the molecular mechanisms of PS- and MT-induced toxicity in the liver and brain. In the liver tissue, dysregulation of lipid metabolism genes (CYP1A/3A, PPARα, and SREBP-1) led to excessive lipid accumulation and hepatic steatosis. In brain tissue, reduced glutathione peroxidase activity, coupled with elevated glutathione reductase and cytochrome P450 activities, exacerbated oxidative stress, compromising neuronal integrity. Exposure to PS and MT significantly upregulated inflammatory genes (TNF-α and IL-1β) and downregulated oxidative stress-related genes (GPx4b, Nrf2, and HO-1) in both tissues, intensifying oxidative damage and inflammatory responses. Combined analysis of liver metabolomics and brain transcriptomics revealed that PS and MT exposure significantly disrupted sphingolipid metabolism. Hepatic metabolic disorders may affect brain function via the liver-brain axis by activating neuroactive ligand-receptor interaction and calcium signaling pathways, thereby disrupting neurotransmitter homeostasis and causing neuronal damage.
PMID:40617460 | DOI:10.1016/j.freeradbiomed.2025.07.006