Toxic Effects of Orally Administered Titanum Dioxide on Brain, Lung And Liver of Adult Albino Rats ; Possible Mediation by Free Radical Damage

Abstract

Titanium dioxide (TiO2) has many applications nowadays. Due to its extreme whiteness and brightness,it is widely used as a white pigment in a variety of materials such as food additives, toothpastes,medicines, paints and coatings. However there is lack of knowledge about human health impacts, due totheir unique physical and chemical characteristics. The aim of this study was to assess the toxicity ofTiO2 nanoparticles on the brain, lung and liver in albino rats and its possible mediation by free radicaldamage. Thirty six adult female albino rats were used in this study. They were classified into three equalgroups. Group I : negative control. Group II : positive control administered 1ml 5% gum acacia solutionby oral gavage dialy. Group III : each rat was given Tio2 nanoparticles by oral gavage in a dailydose 600 mg/kg body weight suspended in 1 ml 5% gum acacia solution. Six rats were sacrificed fromeach group after 60 and 90 days. The brain, lung and liver of all rats were removed and subjected to histopathologicalexamination by light microscope and immunohistochemical staining for TNF-α. Also reducedglutathione (GSH) level in the blood and serum malondialdehyde (MDA) level were measured forall rats. The results revealed that TiO2 induced significant pathological changes in the brain mainly filamentousneuron, pyknotic nuclei, congested blood vessels and edema. The lung showed significant pathologicalchanges as thickened alveolar septa, emphysematous changes, cellular infiltrations, local lymphoidhyperplasia, and granulometus formation. The liver revealed hydropic degeneration, inflammatorycells infiltration, fatty degeneration and necrosis of hepatocytes. All histopathological changes were significantlyincreased depending on the duration of exposure. In addition, there was a duration-dependentincrease in TNF-α. activation which is a marker for inflammation and apoptosis; in the brain, lung andliver of rats treated with Tio2. Blood GSH level was reduced and serum MDA level was increased in ratsof TiO2 group at different duration of the study compared to controls. It is concluded that TiO2 NPs inducedtoxic effects on the brain; lung and liver which increase with increasing the duration of exposure,these effects may be mediated through inflammatory responses and oxidative damage. It is recommendedthat the use of TiO2 especially as food additive and coloring agent must be judged and its environmentallevel should be continuously monitored.