Alleviative Effect of Lactoferrin Interventions Against the Hepatotoxicity Induced by Titanium Dioxide Nanoparticles

The current study was designed to investigate the alleviative effect of lactoferrin interventions against the hepatotoxicity induced by titanium dioxide nanoparticles (TiO₂-NPs). Thirty male Wistar rats were divided into six groups with 5 rats in each group. The first and second groups were intragastrically administered normal saline and TiO₂-NPs (100 mg/kg body weight) as the negative control (NC) and TiO₂-NP groups. The third, fourth, and fifth groups were intragastrically administered lactoferrin at concentrations of 100, 200, and 400 mg/kg body weight in addition to TiO₂-NPs (100 mg/kg body weight). The sixth group was intragastrically administered Fuzheng Huayu (FZHY) capsules at a concentration of 4.6 g/kg body weight in addition to TiO₂-NPs (100 mg/kg body weight) as the positive control group. After treatment for 4 weeks, the concentrations of lactoferrin were optimized based on the liver index and function results. Subsequently, the alleviative effects of lactoferrin interventions against TiO₂-NP-induced hepatotoxicity in rat liver tissues, including the effects on histological damage, oxidative stress-related damage, inflammation, fibrosis, DNA damage, apoptosis, and gene expression, were investigated using histopathological, biochemical, and transcriptomic assays. The results showed that 200 mg/kg lactoferrin interventions for 4 weeks not only ameliorated the liver dysfunction and histopathological damage caused by TiO₂-NP exposure but also inhibited the oxidative stress-related damage, inflammation, fibrosis, DNA damage, and apoptosis in the liver tissues of TiO₂-NP-exposed rats. The transcriptomic results confirmed that the alleviative effect of lactoferrin interventions against the TiO₂-NP exposure-induced hepatotoxicity was related to the activation of the PI3K/AKT signaling pathway.