Proteolytic enzymes in attenuation of tubulointerstitial fibrosis in
various models of non-immune mediated renal disease
Sebekova K.1,
Fierlbeck W.2, Krivosikova Z.1, Schinzel R.3,
Dämmrich J.4, Galbavy S. 5, Blazicek P.6,
Syrova D.6, Heidland A.7
1Clinic of Pharmacotherapy. Institut of Preventive and
Clinical Medicine. Bratislava. Slovakia
2C!inic of Internal Medicine,IV. University Erlangen-Nuernberg,
Germany.
3Department of Physiological Chemistry. Biozentrum;
University Wuerzburg. Germany.
4Institute of Pathology. University Wuerzburg . Germany:
5Institute of Pathology Commenius University, Bratislava.
Slovakia
6Department of Clinical Chemistry. Military Hospital.
Bratislava. Slovakia
7C!inic of Internal Medicine, Department of Nephrology,
University Wuerzburg . Germany
Biomedical subedition Folia Medica Cassoviensia 1999, č. 5 -
Transactions of the Universities of Košice
In renal hypertrophy (RH) accumulation of
extracellular matrix and intracellular proteins is a consequence of
enhanced proteosynthesis and decreased protein degradation. If
impaired activities of proteolytic enzymes participate in the RH,
administration of proteases should exert beneficial effects. This
hypothesis was studied in 3 different rat models of progressive
renal disease: renovascular hypertension, remnant kidney model, and
unilateral ureteral obstruction (UUO) model. The effect of
Phlogenzym® ( a fixed mixture of trypsin, bromelain, and
rutosid) in dose of 12 mg/d administered through 14-45 days was
compared to that of the placebo (and angiotensin II receptor 1
antagonist losartan, UUO model). Sham operated healthy rats served
as controls. Systemic treatment with proteolytic enzymes showed
beneficial effects on renal function (amelioration of proteinuria
and partial prevention in rise of serum creatinine), slowed down the
development of tubulointerstitial fibrosis and accumulation of
collagen in renal cortex, and partially prevented the rise in
pro-fibrotic factors, such as urinary TGF-b 1 excretion,
and accumulation of advanced glycation end products and markers of
lipid peroxidation.