title: Hormonal and organ-specific dysfunction induced by the interaction between titanium dioxide nanoparticles and salicylic acid in male mice.
abstract: BACKGROUND
  Nanomaterials coating gained much concern in orthopedic implants and cosmetics. Drug combination may be a promising strategy for treating multi-factorial diseases. Titanium dioxide (TDN) nanoparticles are being widely used in many industries as well as in medicine and pharmacology. Therefore, increased human and environmental exposure can be expected, which has put TDN under toxicological scrutiny, and it is necessary to address the potential health and safety implications of nanomaterials used in nanomedicine. The toxicity of titanium oxide nanoparticles (TDN) and salicylic acid (SA) separately or in combination was studied for 21 days.
  
  
  METHODS
  The liver and kidney biomarker were determined, and hormones and oxidative stress levels were detected in mice.
  
  
  RESULTS
  The intraperitoneal (i.p.) injection of TDN and SA in combination had a potential toxicological effect on major organs and hormonal homeostasis of mice. TDN and SA could antagonistically interact to affect the liver and kidney functions. No synergistic damage was observed in the liver function of mice that were treated with both TDN and SA as compared to the SA group. TDN acted as a synergistic agent to SA in the case of total cholesterol and total proteins levels. SA acted as antagonistic to the effect of TDN when injected together in mice because the effect on kidney functions is less than that predicted on the basis of the additive. The effect of co-administration of SA and TDN on the following hormones; triiodothyronine, thyroxine, estradiol II and insulin various among additive, potentiation, antagonistic and no effect, respectively as compared to TDN group. The interaction of TDN and SA was also found to induce oxidative stress as indicated by the increase in lipid peroxidation (LPO) levels. The decrease in the level of the reduced glutathione in the co-treated group indicated that there were no synergistic damages. SA and TDN co-administration could induce a potential increase in LPO levels in liver, kidney, and spleen but not in heart tissue. These results have not suggested that TDN and SA have a synergistic sub-chronic toxicity in mice after i.p. administration. SA may decrease the toxicity of TDN to some degree that could be related to the potentiation chemical reaction between SA and TDN.
  
  
  CONCLUSIONS
  Our results suggested that the damage observed in mice treated with TDN and SA is organ-specific and associated with hormonal homeostasis and oxidative damage.
authors.forename: Nahla S
authors.initials: NS
authors.lastname: El-Shenawy
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Al-Harbi
authors.forename: Fatimah F E
authors.initials: FF
authors.lastname: Al Hamayani
mesh_terms: D000818:Animals; D004347:Drug Interactions; D005978:Glutathione / Q000378:metabolism; D006728:Hormones / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000009:adverse effects*; D049329:Nanostructures / Q000009:adverse effects; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D020156:Salicylic Acid / Q000009:adverse effects*; D014025:Titanium / Q000009:adverse effects*
chemical_list: D006728:Hormones; C009495:titanium dioxide; D014025:Titanium; D005978:Glutathione; D020156:Salicylic Acid