Protective mechanisms of Azadirachta indica against titanium dioxide nanoparticle-induced reproductive toxicity through antioxidant and endocrine axis regulation

Abstract

Muhammad Asif Latif*, Farhat Jabeen, Adeel Khalid, Zahid Iqbal, Muhammad Tayyab and Muhammad Imran

Aim: This study investigated the protective effects of Azadirachta indica (Neem) against Titanium Dioxide Nanoparticles (TiO₂-NPs)-induced reproductive toxicity in male Sprague Dawley rats.

Materials and Methods: A. indica leaves were extracted in methanol and the LC₅₀ was determined (‘2155.21 mg/kg’ BW). Rats were divided into six groups with eight rats in each group (n=8), including a control group, saline group, positive group (TiO₂-NPs, ‘120 mg/kg’ BW) and treatment groups receiving additional low (‘100 mg/kg’), medium (‘150 mg/kg’), or high (‘300 mg/kg’) doses of neem extract for ‘90 days’.

Results: TiO₂-NPs significantly reduced body weight, testicular somatic index and hormone levels and induced significant oxidative stress, while the plant extract dose-dependently attenuated these effects, with 300 mg/kg showing the strongest protective response and restoring antioxidant status toward control levels. While high-dose A. indica extract (300 mg/kg) markedly improved all parameters. TiO₂- NPs caused severe testicular damage, while high-dose mitigated structural abnormalities and restored tissue architecture.

Conclusion: High-dose A. indica extract effectively countered TiO₂-NPs-induced reproductive toxicity, highlighting its potential as a natural therapeutic agent for nanoparticle-related oxidative damage.