The effect of oral protease administration in the rat remnant kidney model

It has been demonstrated that intraperitoneal! administration of proteolyti c enzymes ameliorates the progression of renal diseases in various animal m odels. In the present study, we employed the rat remnant kidney model to st udy the effectiveness of oral administration of proteases. Twenty male Wist ar rats underwent sham operation (CTRL), while 25 were subjected to 5/6 nep hrectomy (5/6 NX). Rats were randomised into placebo (PL) (2 mi tap water/d ay by gavage), or Phlogenzym (E; fixed mixture of trypsin 2.42 mg, bromelai n 4.54 mg, and rutozid 5.04 mg added as antioxidant, in 2 ml tap water dail y by gavage) treated group. Duration of the study was 45 days. Rats were pa ir-fed. Enzyme treatment exerted salutary effects on various functional and morphological parameters. Proteinuria was higher in both 5/6 NX group rats throughout the study. Administration of proteases ameliorated its rise eff ectively (data at sacrifice: CTRL-PL 6.27+/-1.25, CTRL-E 9.27+/-0.99, 5/6 N X-PL 74.04+/-21.33, 5/6 NX-E 39.09+/-7.93 mg/24 h; P<0.01). Increased urina ry excretion of the fibrogenic cytokine transforming growth factor (TGF-bet a(1)) was improved, too (CTRL-PL 0.349+/-0.051, CTRL-E 0.693+/-0.230, 5/6 N X-PL 3.044+/-0.540, 5/6 NX-E 1.390+/-0.238 ng/mu mol creatinine; P<0.05). A t sacrifice, tubulointerstitial fibrosis was less pronounced in E-treated r ats. Correspondingly, the volume fraction of tubuloin terstitial tissue in the renal cortex was improved in 5/6 NX-E rats (CTRL-PL 9.9+/-0.2, CTRL-E 1 0.0+/-0.2, 5/6 NX-PL 17.9+/-1.8, 5/6 NX-E 13.8+/-0.9%; P<0.05), The protein /DNA ratio in isolated glomeruli and tubules, as an estimate of glomerular matrix accumulation and hypertrophy of tubules, was enhanced in 5/6 NX grou ps and a tendency towards lower values was observed after E treatment. Rena l function as evaluated by serum creatinine and urea levels was not influen ced by the enzyme therapy. No between-group differ differences in blood pre ssure were observed. In summary, oral administration of proteolytic enzymes improved proteinuria and urinary TGF-beta(1) excretion, as well as the sev erity of tubulointerstitial fibrosis without signs of toxicity.