Prophylactic administration of carnosine and melatonin abates the incidence of apoptosis, inflammation, and DNA damage induced by titanium dioxide nanoparticles in rat livers

Although titanium dioxide nanoparticles (TDO-ns) are extensively used in the food, medicine, and cosmetic industries, discussions about the possible hazards of nanomaterials are just beginning to emerge. This study aimed to detect the inflammatory stress, oxidative stress, and apoptotic cell death induced in the livers of rats exposed to TDO-ns (600 mg/kg, particle size <= 100 nm). Furthermore, the modulation of these toxic effects by two potent naturally occurring antioxidants, carnosine (Carno) or melatonin (Melato), was evaluated. The co-administration of carnosine or melatonin to rats intoxicated with TDO-ns significantly attenuated the increases in serum tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), C-reactive protein (CRP), immunoglobulin G (IgG), vascular endothelial growth factor (VEGF), nitric oxide (NO), and alanine aminotransferase (ALT) levels. The two agents markedly ameliorated hepatic DNA damage and the alterations in hepatic malondialdehyde (MDA), glutathione (GSH), cytochrome P450, caspase-3, total phospholipid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin, and triglyceride (TG) levels. These results support the use of Carno or Melato as prophylactic agents against TDO-ns-induced liver damage.