NEPHROTOXIC EFFECTS OF BACTERIAL RIBONUCLEASES IN THE ISOLATED-PERFUSED RAT-KIDNEY

Alterations of the renal function in the isolated perfused rat kidney system after application of two bacterial RNases, Bacillus intermedius RNase (binase) and ribonuclease produced by Bacillus amyloliquefacien s (barnase), were investigated with two different treatment regimens i n comparison with catalytically inactive derivatives of the enzymes, p hotooxidated at the active site His(101) binase and inactive mutant Hi s(102)Gln barnase. For the in vitro approach the test enzymes were dis solved in the perfusion media and applied to the kidney after removal from the animal. Alternatively, the test ribonucleases were administer ed to rats in vivo and the renal effects were assessed in the isolated perfused rat kidney 1 and 6 h after treatment. In the in vitro regime n both active enzymes induced time and concentration-dependent nephrot oxicity reflected in enhancement of urinary protein excretion, decline of glucose reabsorption, increase of gamma-glutamyltranspeptidase and alkaline phosphatase activities in urine. In vivo administration of a ctive binase induced functional impairment of the isolated perfused or gan in a similar way. None of the inactive RNases in both regimens and at all concentrations tested altered any renal parameter. The results suggest that RNA degradation may be involved in the nephrotoxic effec ts of bacillar RNases. (C) 1997 Elsevier Science Ireland Ltd.