Amelioration of the progressive course of chronic renal failure in
subtotally nephrectomized rats by intraperitoneal enzyme therapy
Sebekova K.1,
Daemmrich J.2, Paczek L.3, Gaciong Z.3,
Blazicek P.4, Spustova V.1
Heidland A.5. Amelioration of the progressive
course of chronic renal failure in subtotally nephrectomized rats by
intraperitoneal enzyme therapy. Nieren- und Hochdruckkrankheiten
1997, Jahr. 26, No. 6/1997, s. 277-281. 345 KA (5-08-1)
1 Clinic of Pharmacotherapy, Institute of Preventive and Clinical
Medicine, Bratislava, Slovakia; 2 Insitut für Pathologie,
Universität Würzburg; 3 The Transplantation Institute Warsaw,
Poland; 4 Military Hospital, Bratislava, Slovakia; 5 Medizinische
Fakultät, Universität Würzburg.
Amelioration of the
progressive course of chronic renal failure in subtotally
nephrectomized rats by intraperitoneal enzyme therapy. Aim of the
present study was to investigate whether sustained systemic
treatment with proteases ameliorates the progressive course of a
nonimmune-mediated renal disease. Subtotal nephrectomy in rat was
used as a model of chronic renal failure.
Phlogenzym (a fixed combination of trypsin, bromelain, and rutin)
was used as a model substance. On day 1 after 5/6 nephrectomy, the
male Wistar rats were randomized into 2 groups: 1: placebo (P), n =
7, administered daily 2 ml of sterile 0.9% NaCl solution i.p., and
2: verum group (E), n = 7, injected with 12 mg of phlogenzym in the
same vehiculum. After 6 weeks the enzyme-treated animals showed
lower proteinuria (P: 19.6 ± 9.l versus E: 10.2 ± 6.2 mg/24 h, p <
0.05).
Their plasma creatinine levels were lower (P: 106.7 ± 33.9 vs E:
76.0 ± 6.3 mmol/l, p < 0.01 ), due to higher creatinine clearance
(P: 192.3 ± 99.4 vs E: 300.5 ± 47.9 ml/min/100 g, p < 0.05). The
groups did not differ by serum urea concentration, although the urea
clearance tended to be higher in the enzyme-treated rats. Decreased
urinary TGF-b excretion (P: 0.363 ± 0.183 vs E: 0.232 ± 0.085 ng/mg
creatinine, p < 0.05) reflected the hindered cytokine formation in
renal tissue. Histomorphologically, cellular infiltration with
mononuclear cells was lower in the E-treated rats, and a decline in
interstitial fibrosis was observed (expressed as volume fraction of
cortical interstitium; P: 17.2 ± 1.4, E: 12.3 ± 0.5%, p < 0.001).
Moreover, the activities of lysosomal proteinases (cathepsin B, L+B,
and H), which are decreased in the remnant kidney model, were
significantly higher in both isolated glomeruli and tubules of the
E-treated rats. In summary: for the first time evidence for
beneficial effects of systemic enzyme treatment in a nonimmune-mediated
renal disease was given. In the rat model of subtotal nephrectomy
treatment with enzymes ameliorated the development of
tubulointerstitial fibrosis and the progression of chronic renal
failure.
This study was also published in other journals, which have the following
reviews on this website::
Inter. Journal of Tissue Reactions 1997, Vol. XIX, No. 1/2, pp 97 -
abstract
Mineral and Electrolyte Metabol. 1997: 23, pp 291-295. 344 KA
(17-05-1)
(Full Text)