The hypothesis that C₆₀ fullerene nanoparticles (C₆₀) exert an antagonistic interactive effect on the toxicity of benzo[a]pyrene (BaP) has been supported by this investigation. Mussels were exposed to BaP (5, 50 & 100 μg/L) and C₆₀ (C₆₀–1 mg/L) separately and in combination. Both BaP and C₆₀ were shown to co-localize in the secondary lysosomes of the hepatopancreatic digestive cells in the digestive gland where they reduced lysosomal membrane stability (LMS) or increased membrane permeability, while BaP also induced increased lysosomal lipid and lipofuscin, indicative of oxidative cell injury and autophagic dysfunction. Combinations of BaP and C₆₀ showed antagonistic effects for lysosomal stability, mTORC1 (mechanistic target of rapamycin complex 1) inhibition and intralysosomal lipid (5 & 50 μg/L BaP). The biomarker data (i.e., LMS, lysosomal lipidosis and lipofuscin accumulation; lysosomal/cell volume and dephosphorylation of mTORC1) were further analysed using multivariate statistics. Principal component and cluster analysis clearly indicated that BaP on its own was more injurious than in combination with C₆₀. Use of a network model that integrated the biomarker data for the cell pathophysiological processes, indicated that there were significant antagonistic interactions in network complexity (% connectance) at all BaP concentrations for the combined treatments. Loss of lysosomal membrane stability probably causes the release of intralysosomal iron and hydrolases into the cytosol, where iron can generate harmful reactive oxygen species (ROS). It was inferred that this adverse oxidative reaction induced by BaP was ameliorated in the combination treatments by the ROS scavenging property of intralysosomal C₆₀, thus limiting the injury to the lysosomal membrane; and reducing the oxidative damage in the cytosol and to the nuclear DNA. The ROS scavenging by C₆₀, in combination with enhanced autophagic turnover of damaged cell constituents, appeared to have a cytoprotective effect against the toxic reaction to BaP in the combined treatments.

这项研究支持了C ₆₀富勒烯纳米颗粒（C ₆₀）对苯并[ a ] re（BaP）的毒性具有拮抗相互作用的假设。贻贝暴露于的BaP（5，50 100微克/升）和C ₆₀（C ₆₀ -1 mg / L的）中单独或组合。已证明BaP和C ₆₀共同位于消化腺肝胰腺消化细胞的次级溶酶体中，在那里它们降低了溶酶体膜稳定性（LMS）或增加了膜通透性，而BaP也诱导了溶酶体脂质和脂褐素的增加。氧化细胞损伤和自噬功能障碍。BaP和C _60的组合表现出对溶酶体稳定性，mTORC1（雷帕霉素复合物1的机械靶标）抑制和溶酶体脂质（5和50μg/ L BaP）具有拮抗作用。使用多变量统计数据进一步分析了生物标记数据（即LMS，溶酶体脂质增生和脂褐素积聚；溶酶体/细胞体积和mTORC1的去磷酸化）。主成分和聚类分析清楚地表明，BaP本身比与C ₆₀结合使用更有害。使用整合了细胞病理生理过程生物标志物数据的网络模型，表明在联合治疗的所有BaP浓度下，网络复杂性（％连接性）均存在明显的拮抗作用。溶酶体膜稳定性的丧失可能导致溶酶体中的铁和水解酶释放到细胞质中，在那里铁会产生有害的活性氧（ROS）。可以推断，结合酶处理后，溶酶体C ₆₀的ROS清除性能改善了BaP诱导的不良氧化反应，从而限制了溶酶体膜的损伤。并减少细胞质和核DNA的氧化损伤。C ₆₀清除ROS，与受损细胞成分的自噬更新增强相结合，在联合治疗中似乎具有针对BaP毒性反应的细胞保护作用。