Hesperidin and naringenin mitigate titanium and magnesium alloy-induced toxicity by restoring mitochondrial redox homeostasis in human osteoblasts

Abstract

Titanium (Ti) and magnesium (Mg) can hinder the osseointegration of biomedical implants due to their toxicity, while flavonoids hesperidin (HD) and naringenin (NG) provide cytoprotection. This study evaluated the protection of HDs and NGs against metal-induced cytotoxicity in bone cells. Ti and Mg showed dose-dependent cytotoxicity, reduced cell viability, and induced genotoxicity, while NG and HD, particularly HD, improved osteoblast vmiability. At 300 and 600 µg/ml, Ti and Mg altered the secretion of procollagen type I peptides, osteocalcin, and alkaline phosphatase (ALP) and increased the proinflammatory cytokines IL-1, IL-6, and TNF-α. They also reduced ATP levels, the mitochondrial membrane potential, the activities of antioxidant enzymes (catalase and superoxide dismutase), and the expression of antioxidant genes (Nrf2 and HO-1) while increasing the expression of oxidative stress markers and apoptotic indicators. Cotreatment with 80 µM NG or HD significantly mitigated these effects, with advantages for HD, suggesting their potential to protect human osteoblasts and enhance Ti and Mg orthopedic implant performance by reducing inflammation and oxidative stress.