Uremic concentrations of guanidino compounds inhibit neutrophil superoxide production

Abstract

Uremic concentrations of guanidino compounds inhibit neutrophil superoxide production. Background In Uremia, diminished reactive oxygen intermediate (ROI) production is an important consequence of impaired neutrophil function. We have studied the effect of guanidino compounds, known uremic toxins, on neutrophil ROI production in vitro. Methods Neutrophils from healthy volunteers were exposed for three hours to individual or mixed guanidino compounds (GCmix) at concentrations encountered in uremic plasma. After removal of guanidino compounds, neutrophils were activated by adhesion, N-formyl-methionyl-leucyl-phenyalanine (fMLP), phorbol 12-myristate 13-acetate (PMA), or opsonized zymosan, and superoxide production was measured by lucigenin chemiluminescence (CL). The direct effect of guanidino compounds on superoxide production in activated neutrophils was also measured. The energy staus (ATP and creatine phosphate), antioxidant status (total gluathione), and glycolytic flux (lactate production) were measured.