Copper oxide nanoparticles induced reactive oxygen species generation: A systematic review and meta-analysis

Copper oxide nanoparticles (CuO NPs) are widely employed in various industrial and biomedical applications owing to their enhanced physicochemical characteristics. However, concerns regarding their adverse effects on biological systems upon entering the environment remain unexplored. The generation of reactive oxygen species (ROS) is one of the primary mechanisms in CuO NPs induced toxicity. This meta-analysis was conducted to assess the associative link between CuO NPs exposure and ROS generation. A literature survey was performed in PubMed, Web of Science, Scopus, and Google Scholar, following PRISMA guidelines. After comprehensive initial and primary screening, 28 in vitro studies were selected for meta-analysis. Overall, our results show a substantial increase of ROS in the experimental group when compared to control (SMD = 3.3; 95 % CI: 2.82-3.77, p = 0.00001), with substantial heterogeneity (82 %). Subgroup analysis revealed that larger-sized NPs, higher dosages, and longer exposure duration were associated with ROS generation. Meta-regression analysis identified size, and dosage as significant factors influencing ROS levels. Sensitivity analysis revealed an outlier study and the funnel plot results suggested potential publication bias. Overall, our results provide valuable insights of CuO NPs induced ROS generation, and the relation of variables such as size, dose, and duration in nanotoxicity assessments.