The effect of intracellular antioxidant delivery (catalase) on hydrogen peroxide and proinflammatory cytokine synthesis: a new therapeutic horizon

Abstract

Reactive oxygen species synthesized by endothelial cells may be responsible for cell damage and altered physiologic function. After endotoxin stimulation, free radicals including H₂O₂ are produced. We have developed a method of intracellular drug delivery using albumin microcapsules. Catalase would be an excellent compound to alter H₂O₂ production. However, the large molecular size of catalase limits cellular penetration. Endothelial cells have been previously shown to readily phagocytoze albumin microcapsules.

Methods: Catalase was added to an albumin solution to form a 10% solution of catalase. Microspheres from 2 to 7 μm in size were formed using a Bucchi spray dryer. Human endothelial cells were incubated with varying concentrations of microencapsulated catalase. The cells were then exposed to Escherichia coli endotoxin to determine if increased intracellular penetration of catalase would inhibit H₂O₂, nitrate, and cytokine synthesis.

Results: There was a 7.2-fold increase in endothelial intracellular catalase after 48 h incubation. H₂O₂ was inhibited by 72%, nitrate 96%, TNF 90%, IL1 21%, IL6 42%.

Conclusions: These results demonstrate that inhibition of H₂O₂ as a result of increased intracellular delivery of catalase inhibits proinflammatory cytokine synthesis after endotoxin exposure.

Keywords::

• Antioxidants
• catalase
• TNF (tumor necrosis factor)
• hydrogen peroxide
• endotoxin
• nitric oxide
• interleukin 1

Acknowledgments

Declaration of interest: The author reports no conflict of interest. Funding was received by a non-profit group.