Malignant nephrosclerosis in Goldblatt hypertensive rats: amelioration by systemic enzyme therapy
Heidland A.1, Sebekova K.2, Dämmrich J.1,
Paczek L.3, Fierlbeck W.4, Krivosikova Z.2,
Gaciong Z.3. Malignant nephrosclerosis in Goldblatt
hypertensive rats: amelioration by systemic enzyme therapy. Int J
Tiss Reac Vol. XIX, No. 1/2, pp. 89 - 90, 1997 - abstract 109 SO 112
(19-04-2).
1 University of Wuerzburg, Germany. 2 Institute of Preventive and
Clinical Medicine, Bratislava, Slovakia
3 Transplantation Institute, Warsaw, Poland. 4 University Erlangen-Nuernberg,
Germany.
7th Interscience World Conference on Inflammation, Antirheumatics,
Analgesics,
Immunomodulators, Geneva, Switzerland. 19-21 May 97.
Abstract
In various models of nephrosclerosis, glomerulosclerosis and
tubulointerstitial fibrosis, impaired activities of proteolytic
enzymes (cathepsins, metalloproteases, plasmin) and/or elevated
levels of protease inhibitors have been demonstrated. In the current
study we investigated the effect of systemic administration of an
oral enzyme combination in the model of hypertension induced renal
injury (2-kidney-1-clip hypertension) in rats. Phlogenzym®
(trypsin, bromelin, rutosid) was administered to the test group of
2KlC rats (n=9) intraperitoneally in a dose of 12mg/2 ml of .9% NaCl
daily during 7 weeks. The placebo treated group (n=7) received the
vehicle only, sham operated rats (n=5) served as controls. Blood
pressure rose from 92.2±2.5 to 191.4±7.6 mm Hg at 7 weeks in the
placebo group, and from 92.0±2.3 to 180.5±6.5 mm Hg in the enzyme
treated group (difference not significant). Morphologically,
malignant nephrosclerosis was demonstrated in 57% of placebo treated
rats, but only in 11 % of enzyme treated animals. The volume index
of the cortical interstitial tissue was lower in the enzyme group
(13.4±0.5%) versus placebo group 15.5±0.8%, p<.05 (sham operated
rats: 9.3±0.3%).
It is assumed, that the administered enzyme combination preparation
modulates various amplificatory mechanisms involved in the
hypertension induced renal injury, probably by cleavage of adhesion
molecules (CD44, CD4, B7-1), enhanced formation of prostacyclin, and
enhanced removal of cytokines due to the binding to an activated
a2-macroglobulin-protease complex.