Systémová enzymoterapie pro odborníky

Amelioration of the progressive course of chronic renal failure in subtotally nephrectomized rats by intraperitoneal enzyme therapy

K. SEBEKOVA¹, J. DAEMMRICH², L. PACZEK³, Z. GACIONG³, P. BLAZICEK⁴, V. SPUSTOVA¹ and A. HEIDLAND⁵

^l Clinic of Pharmacotherapy, Institute of Preventive and Clinical Medicine, Bratislava, Slovakia; ² Insitut für Pathologie, Universität Würzburg; ³The Transplantation Institute Warsaw, Poland; ⁴Military Hospital, Bratislava, Slovakia; ⁵Medizinische Fakultät, Universität Würzburg

Nieren- und Hochdruckkrankheiten, 1997, Jahrgang 26, Nr. 6/1997, S. 277-281

345 KA (5-08-1)

Abstract

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.


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Zánět a jeho ovlivnění SET Zvýšení využitelnosti antibiotik proteolytickými enzymy Angiologie, flebologie Gynekologie Chirurgie, traumatologie, ortopedie Imunologie Lymfologie ORL Pediatrie Revmatologie Sportovní medicína Stomatologie Urologie Literatura Časopisy s Impact faktorem Ostatní literatura SPC Wobenzym SPC Phlogenzym	Amelioration of the progressive course of chronic renal failure in subtotally nephrectomized rats by intraperitoneal enzyme therapy K. SEBEKOVA¹, J. DAEMMRICH², L. PACZEK³, Z. GACIONG³, P. BLAZICEK⁴, V. SPUSTOVA¹ and A. HEIDLAND⁵ ^l Clinic of Pharmacotherapy, Institute of Preventive and Clinical Medicine, Bratislava, Slovakia; ² Insitut für Pathologie, Universität Würzburg; ³The Transplantation Institute Warsaw, Poland; ⁴Military Hospital, Bratislava, Slovakia; ⁵Medizinische Fakultät, Universität Würzburg Nieren- und Hochdruckkrankheiten, 1997, Jahrgang 26, Nr. 6/1997, S. 277-281 345 KA (5-08-1) Abstract 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.
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