Evidence of an Oxidative Mechanism for the Hemolytic Activity of Silica Particles

Abstract

The formation of reactive oxygen species resulting from the interaction of silica dust particles with red blood cell membranes was investigated; particularly, the effect of surface hydroxyl (silanol) group concentration on the rate of formation of such reactive oxygen species was investigated. The rate of formation was measured indirectly through the effect of catalase, a hemoprotein peroxidase, on silica-induced hemolysis. It was found that the addition of exogenous catalase to erythrocytes markedly reduces the hemolysis caused by silica particles. Furthermore, the amount of catalase required for deactivation of silica per unit area of particle surface is lower for fumed silica particles and calcined crystalline particles than for uncalcined, crystalline silica, suggesting a correlation between the concentration of OH groups at the silica particle surface and its potential for generation of H202. The addition of albumin, a copper chelator, also decreases hemolysis. These results suggest that the hemolysis caused by silica particles is at least partly related to the formation of H202 at the particle surface and its subsequent reaction with Cu+ ions. The relationship between the concentration of surface silanol groups on the silica surface and the amount of catalase required to decrease hemolysis may also provide a method for testing potential fibrogenicity of respirable dusts.

In vitro toxicology of respirable Montserrat volcanic ash

“…These data correlate with those of a study by Razzaboni et al 22 where haemolysis induced by pure silica could not be decreased with a dose range of SOD from 10 to 300 μg/ml. From these results alone it would seem that most erythrocyte membrane damage caused by the ash samples was due to the production of superoxide.…”

“…Haemolytic activity of the particles was measured with a 10% erythrocyte solution using a modified method from Razzaboni et al 22. Sheep erythrocytes were obtained from the Scottish Antibody Production Unit (Carluke, UK) and were washed twice in 0.9% sodium chloride solution (Baxter, UK) and centrifuged at 90 g for 5 minutes.…”

Mesoporous Silica Nanoparticles for Reducing Hemolytic Activity Towards Mammalian Red Blood Cells

“…However, the low in vitro cytotoxicity offers no guarantee on the desired high biocompatibility in vivo. In fact, silica materials with amorphous particle morphology are known to cause the hemolysis of mammalian red blood cells (RBCs) 12–16. This kind of hemolytic behavior raised serious bio‐safety concerns regarding the application of amorphous silica for drug delivery involving intravenous administration and transport.…”

“…While the exact mechanism is still under investigation, most researchers agree that the hemolytic activity of silica is related to surface silanol groups 12–16. For example, a recent study by Murashov et al demonstrated that the hemolytic activity of amorphous silica is proportional to the concentration of surface silanol groups of these solid materials 15.…”

The role of nanoparticle size in hemocompatibility

“…As also particles with no positive surface charge like quartz particles induce clotting. Quartz particles are one of the best characterized particles including a lot of research work done yet (Hadnagy et al, 2003;Razzaboni and Bolsaitis, 1990). Also carbon nanotubes (single walled and multi walled) and carbon black particles are of great interest and examined concerning their biocompatibility (Zheng et al, 2007;Barlow et al, 2005;Meng et al, 2005), positive charge appears not to be the only decisive parameter.…”