Ameliorative effects of zinc oxide and vitamin C quaternized oligochitosan on rat ovarian dysfunction caused by titanium dioxide nanoparticles
摘要
Titanium dioxide nanoparticles (TiO₂ NPs), found in food additives and cosmetics, are linked to reproductive health issues. This study examines TiO₂ NPs’ impact on ovarian structure and fertility, showing potential to cause follicular atresia. We evaluated zinc oxide and vitamin C-loaded oligochitosan nanoparticles (ZVC@OCNPs) in mitigating TiO₂-induced ovarian toxicity in rats. Six groups of female rats (10 rats each), were utilized: the first group (G1) served as a control, the second group (G2) was administered ZVC@OCNP (200 mg/kg of ZnO and 150 mg/kg of VC), the third group (G3) received 100 mg/kg of TiO2 NPs, the fourth group (G4) was given 150 mg/kg of TiO2 NPs, and the fifth group (G5) was treated with 100 mg/kg of TiO2 NPs followed by ZVC@OCNP. The sixth group (G6) was administered 150 mg/kg of TiO2 nanoparticles followed by ZVC@OCNP. ZVC@OCNPs showed high encapsulation efficiency for ZnO (79.9 ± 1.8%, 23.1 ± 1.1%) and VC (68.7 ± 1.3%, 17.9 ± 0.7%). TiO₂ NPs reduced FSH and LH levels, causing tissue damage and increased ovarian collagen. ZVC@OCNPs treatment mitigated these effects at higher TiO₂ doses, reducing collagen 33–40% and improving hormone levels 33–43%. The enhancements show ZVC@OCNPs preserve ovarian activity by regulating inflammatory and oxidative pathways. Molecular investigation via immunohistochemistry showed downregulation of NFκB-p65 and IL-1β after ZVC@OCNP therapy, indicating reduced inflammatory signaling. Molecular docking studies showed ZnO/VC had higher binding affinity to inflammatory receptors than ibuprofen, indicating enhanced anti-inflammatory properties based on binding energy with GLN-284 and LYS-252 of NFκB-p65 and GLU-194 of IL-1 receptor (ID: 1IRA). These findings underscore the potential of ZVC@OCNPs as a novel therapeutic strategy to protect ovarian function through improvements at Immunohistochemistry, Biochemistry, Histology, and Ultrastructure levels. Further research is needed to explore long-term effects. In conclusion, ZVC@OCNPs as a dual-delivery nanocarrier may provide a promising approach to mitigate reproductive risks from TiO₂ NP exposure, with implications for reproductive health outcomes.