Abstract
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.