This present study was conducted to provide evidence and an explanation for the apoptosis that occurs in the marine rotifer Brachionus plicatilis when facing 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) stress. Metabolomics analysis showed that aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, and arginine biosynthesis were the top three sensitive pathways to BDE-47 exposure, which resulted in the reduction in the amino acid pool level. Pyrimidine metabolism and purine metabolism pathways were also significantly influenced, and the purine and pyrimidine content were obviously reduced in the low (0.02 mg/L) and middle (0.1 mg/L) concentration groups while increased in the high (0.5 mg/L) concentration group, evidencing the disorder of nucleotide synthesis and decomposition in B. plicatilis. The biochemical detection of the key enzymes in purine metabolism and pyrimidine metabolism showed the downregulation of Glutamine Synthetase (GS) protein expression and the elevation of Xanthine Oxidase (XOD) activity, which suggested the impaired DNA repair and ROS overproduction. The content of DNA damage biomarker (8-OHdG) increased in treatment groups, and the p53 signaling pathway was found to be activated, as indicated by the elevation of the p53 protein expression and Bax/Bcl-2 ratio. The ROS scavenger (N-acetyl-L-cysteine, NAC) addition effectively alleviated not only ROS overproduction but also DNA damage as well as the activation of apoptosis. The combined results backed up the speculation that purine metabolism and pyrimidine metabolism alteration play a pivotal role in BDE-47-induced ROS overproduction and DNA damage, and the consequent activation of the p53 signaling pathway led to the observed apoptosis in B. plicatilis.

Polybrominated diphenyl ethers (PBDEs) are classic and emerging pollutants that are potentially harmful to the human immune system. Research on their immunotoxicity and mechanisms suggests that they play an important role in the resulting pernicious effects of PBDEs. 2,2′,4,4′-Tetrabrominated biphenyl ether (BDE-47) is the most biotoxic PBDE congener, and, in this study, we evaluated its toxicity toward RAW264.7 cells of mouse macrophages. The results show that exposure to BDE-47 led to a significant decrease in cell viability and a prominent increase in apoptosis. A decrease in mitochondrial membrane potential (MMP) and an increase in cytochrome C release and caspase cascade activation thus demonstrate that cell apoptosis induced by BDE-47 occurs via the mitochondrial pathway. In addition, BDE-47 inhibits phagocytosis in RAW264.7 cells, changes the related immune factor index, and causes immune function damage. Furthermore, we discovered a significant increase in the level of cellular reactive oxygen species (ROS), and the regulation of genes linked to oxidative stress was also demonstrated using transcriptome sequencing. The degree of apoptosis and immune function impairment caused by BDE-47 could be reversed after treatment with the antioxidant NAC and, conversely, exacerbated by treatment with the ROS-inducer BSO. These findings indicate that oxidative damage caused by BDE-47 is a critical event that leads to mitochondrial apoptosis in RAW264.7 macrophages, ultimately resulting in the suppression of immune function.

The ionic properties of strontium (Sr), a significant artificial radionuclide in the marine environment, were estimated using a stable nuclide-substituting experimental system under controlled laboratory conditions. The bio-accumulation of Sr and its impacts, as well as any possible hidden mechanisms, were evaluated based on the physiological alterations of the sentinel blue mussel Mytilus edulis. The mussels were exposed to a series of stress-inducing concentrations, with the highest solubility being 0.2 g/L. No acute lethality was observed during the experiment, but sublethal damage was evident. Sr accumulated in a tissue-specific way, and hemolymph was the target, with the highest accumulating concentration being 64.46 µg/g wet weight (ww). At the molecular level, increases in the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and changes in ROS components (H₂O₂, O²⁻, and -OH) and antioxidant system activity indicated that the redox equilibrium state in hemocytes was disturbed. Furthermore, the rise in the hemocyte micronucleus (MN) rate (4‰ in the high-concentration group) implied DNA damage. At the cellular level, the structures of hemocytes were damaged, especially with respect to lysosomes, which play a crucial role in phagocytosis. Lysosomal membrane stability (LMS) was also affected, and both acid phosphatase (ACP) and alkaline phosphatase (AKP) activities were reduced, resulting in a significant decline in phagocytosis. The hemolymph population structure at the organ level was disturbed, with large changes in hemocyte number and mortality rate, along with changes in component ratios. These toxic effects were evaluated by employing the adverse outcome pathway (AOP) framework. The results suggested that the disruption of intracellular redox homeostasis is a possible explanation for Sr-induced toxicity in M. edulis.

We had evidenced that oxidative stress, driven by excessive reactive oxygen species (ROS) accumulation, constituted a central mechanism governing the toxicity of polybrominated diphenyl ethers (PBDEs) in marine organisms, and autophagy had been postulated as a potential cytoprotective countermeasure. However, the precise role remained unclear. To address this gap, in vitro studies based on the large yellow croaker (Larimichthys crocea) kidney cell line (PCK) were conducted to delineate the underlying molecular pathways. Results showed that 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) induced concentration-dependent cytotoxicity, including lactate dehydrogenase (LDH) release, organelle damage, and loss of membrane integrity. ROS (including O_-2, H₂O₂, and ·OH) levels were significantly elevated, leading to lipid peroxidation and protein carbonylation, while upregulating total antioxidant capacity (T-AOC) by 5.3-fold at 15 μM BDE-47. Antioxidant enzymes (SOD, CAT, GSH) were upregulated as a compensatory response to mitigate oxidative damage. Notably, we observed and confirmed autophagy induction though multiple biological levels: autophagosome formation, increased expression of key autophagy-related proteins (LC3B-II, Beclin1, and Atg5), and enhanced autophagic flux. Inhibition of autophagy by 3-methyladenine (3-MA) elevated MDA content, exacerbating oxidative damage, while simultaneously increasing LDH release and enhancing cell death. These results indicate that BDE-47-induced autophagy could alleviate oxidative stress and subsequent cytotoxicity, providing new insights into the protective role of autophagy in PBDE-mediated toxicity in marine organisms.