Amelioration of titanium dioxide nanoparticles-induced liver injury in mice: possible role of some antioxidants.
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 (TiO2 NPs) intoxicated mice. Nano-anatase TiO2 (21 nm) was administered (150 mg/kg/day) for 2 weeks followed by the aforementioned antioxidants either alone or in combination for 1 month. TiO2 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 TiO2 NPs. Additionally, these NPs effectively activated caspase-3 and caused liver DNA damage. Oral administration of idebenone (200mg/kg), carnosine (200mg/kg) and vitamin E (100mg/kg) alleviated the hazards of TiO2 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 TiO2 NPs-induced liver injury. The study also highlights the anti-inflammatory and the anti-apoptotic potentials of these antioxidants against the detrimental effects of TiO2 NPs.
Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: dr.samy_abdelfatah@hotmail.com.
Samy A Abdel
SA
Azim
Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: hebatallah.darwish@pharma.cu.edu.eg.
Hebatallah A
HA
Darwish
Therapeutic Chemistry Department, National Research Center, Dokki, Gizza, Egypt. Electronic address: maha-zaki_rizk@hotmail.com.
Maha Z
MZ
Rizk
Therapeutic Chemistry Department, National Research Center, Dokki, Gizza, Egypt. Electronic address: Sanaa_ahmedibrahim@yahoo.com.
Sanaa A
SA
Ali
Therapeutic Chemistry Department, National Research Center, Dokki, Gizza, Egypt. Electronic address: maiosman666@yahoo.com.
Mai O
MO
Kadry
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects*; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014025:Titanium / Q000633:toxicity*
D000975:Antioxidants; C009495:titanium dioxide; D014025:Titanium
Antioxidants; Apoptosis; Inflammation; Liver; Oxidative stress; Titanium dioxide nanoparticles