Inhibition of puromycin-induced renal injury by a superoxide dismutase derivative with prolonged in vivo half-life.

To know the possible involvement of reactive oxygen species and the site(s) of their action in puromycin aminonucleoside (PAN)-induced renal injury, two types of superoxide dismutase (SOD) derivatives were synthesized: one (SM-SOD) circulates bound to albumin with a half-life of 6 h and the other (AH-SOD) linked with hexamethylenediamines rapidly undergoes glomerular filtration and accumulates in renal proximal tubule cells without being excreted in urine. When injected intravenously to the rat, PAN induced a marked proteinuria, increased plasma levels of cholesterol and triglyceride, and suppressed the growth of animals. Intravenously administered SM-SOD significantly inhibited such changes induced by PAN. However, native SOD which rapidly undergoes urinary excretion failed to inhibit the renal injury caused by PAN. Though AH-SOD markedly accumulated in renal proximal tubule cells, it also failed to inhibit the renal injury. These results suggested that superoxide and/or its hazardous metabolite(s) in and around the renal glomerulus, but not in tubule cells, may play critical roles in the pathogenesis of PAN-induced renal injury.