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.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors*; D001798:Blood Proteins / Q000378:metabolism; D003959:Diamines / Q000493:pharmacokinetics / Q000494:pharmacology*; D006207:Half-Life; D007275:Injections, Intravenous; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D011137:Polystyrenes / Q000493:pharmacokinetics / Q000494:pharmacology*; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism*; D011692:Puromycin Aminonucleoside / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000493:pharmacokinetics / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D001798:Blood Proteins; D003959:Diamines; D008055:Lipids; D011137:Polystyrenes; D011692:Puromycin Aminonucleoside; D013482:Superoxide Dismutase; C068153:superoxide dismutase-poly(styrene co-maleic acid butyl ester); C007297:1,6-diaminohexane