Amelioration of titanium dioxide nanoparticles-induced liver injury in mice: Possible role of some antioxidants

Abstract This study investigates the efficacy of idebenone, carnosine and vitamin E in ameliorating some of the biochemical indices induced in the liver of titanium dioxide nanoparticles (TiO 2 NPs) intoxicated mice. Nano-anatase TiO 2 (21 nm) was administered (150 mg/kg/day) for 2 weeks followed by the aforementioned antioxidants either alone or in combination for 1 month. TiO 2 NPs significantly increased serum liver function enzyme activities, liver coefficient and malondialdehyde levels in hepatic tissue. They also suppressed hepatic glutathione level and triggered an inflammatory response via the activation of macrophages and the enhancement of tumor necrosis factor-α and interleukin-6 levels. Moreover, the mRNA expression of nuclear factor-erythroid-2-related factor 2, nuclear factor kappa B and Bax was up-regulated whereas that of Bcl-2 was down-regulated following TiO 2 NPs. Additionally, these NPs effectively activated caspase-3 and caused liver DNA damage. Oral administration of idebenone (200 mg/kg), carnosine (200 mg/kg) and vitamin E (100 mg/kg) alleviated the hazards of TiO 2 NPs with the combination regimen showing a relatively higher effect. The histopathological examination reinforced these findings. In conclusion, oxidative stress could be regarded as a key player in TiO 2 NPs-induced liver injury. The study also highlights the anti-inflammatory and the anti-apoptotic potentials of these antioxidants against the detrimental effects of TiO 2 NPs.