Titanium implants enhance pulmonary nitric oxide production and lung injury in rats exposed to endotoxin

An increase in levels of elemental Ti in the blood and lung of rats with a Ti alloy implant has been demonstrated. However, the pathophysiological role of the elevated elemental Ti level in the circulation remains unclear. Rats were implanted with Ti alloy discs for 4 weeks. The levels of elemental Ti in the blood and lung were especially increased compared with other tissues. The Ti alloy implant enhanced lung injury related to endotoxin from Gram-negative bacteria (lipopolysaccharide, LPS), which was characterized by lung edema and other histological changes such as recruitment of neutrophils, interstitial edema, and alveolar hemorrhage in the lung. In the presence of endotoxin, an increase of nitrite production was shown in the plasma and bronchoalveolar lavage fluid of rats implanted with a Ti alloy. Moreover, the Ti alloy implant further enhanced the induction of inducible nitric oxide (NO) synthase (iNOS) protein expression induced by LPS in the lung. These endotoxin-related responses in the presence or absence of the Ti alloy implant could be inhibited by aminoguanidine (an iNOS inhibitor). These results provide the first experimental evidence that circulating Ti released from Ti alloy implants has an ability to affect pulmonary iNOS protein expression, and enhance the pathogenesis of acute lung injury during endotoxemia.