Effects of Flavonoid Supplementation on Nanomaterial-Induced Toxicity: A Meta-Analysis of Preclinical Animal Studies

Background: Nanomaterials, widely applied in various fields, are reported to have toxic effects on human beings; thus, preventive or therapeutic measures are urgently needed. Given the anti-inflammatory and antioxidant activities, supplementation with flavonoids that are abundant in the human diet has been suggested as a potential strategy to protect against nanomaterial-induced toxicities. However, the beneficial effects of flavonoids remain inconclusive. In the present study, we performed a meta-analysis to comprehensively explore the roles and mechanisms of flavonoids for animals intoxicated with nanomaterials. Methods: A systematic literature search in PubMed, EMBASE, and Cochrane Library databases was performed up to April 2022. STATA 15.0 software was used for meta-analyses. Results: A total of 26 studies were identified. The results showed that flavonoid supplementation could significantly increase the levels of antioxidative enzymes (superoxide dismutase, catalase, glutathione, glutathione peroxidase, and glutathione-S-transferase), reduce the production of oxidative agents (malonaldehyde) and pro-inflammatory mediators (tumor necrosis factor-alpha, interleukin-6, IL-1 beta, C-reactive protein, immunoglobulin G, nitric oxide, vascular endothelial growth factor, and myeloperoxidase), and alleviate cell apoptosis (manifested by decreases in the mRNA expression levels of pro-apoptotic factors, such as caspase-3, Fas cell surface death receptor, and Bax, and increases in the mRNA expression levels of Bcl2), DNA damage (reductions in tail length and tail DNA%), and nanomaterial-induced injuries of the liver (reduced alanine aminotransferase and aspartate aminotransferase activities), kidney (reduced urea, blood urea nitrogen, creatinine, and uric acid concentration), testis (increased testosterone, sperm motility, 17 beta-hydroxysteroid dehydrogenase type, and reduced sperm abnormalities), and brain (enhanced acetylcholinesterase activities). Most of the results were not changed by subgroup analyses. Conclusion: Our findings suggest that appropriate supplementation of flavonoids may be effective to prevent the occupational detriments resulting from nanomaterial exposure.