The effect of oral protease administration in the rat remnant kidney model
Katarína Šebeková1, Jobst Dämmrich2, Zora Krivošíková1, August Heidland3
1 Clinic of Pharmacotherapy, Institute of Preventive and
Clinical Medicine, Bratislava, Slovakia
Res Exp Med (1999): 199, 177-188.
It has been demonstrated that intraperitoneal administration of proteolytic enzymes ameliorates the progression of renal diseases in various animal models. In the present study, we employed the rat remnant kidney model to study the effectiveness of oral administration of proteases. Twenty male Wistar rats underwent sham operation (CTRL), while 25 were subjected to 5/6 nephrectomy (5/6 NX). Rats were randomised into placebo (PL) (2 ml tap water/day by gavage), or Phlogenzym® (E; fixed mixture of trypsin 2.42 mg, bromelain 4.54 mg, and rutosid 5.04 mg added as antioxidant, in 2 ml tap water daily by gavage) treated group. Duration of the study was 45 days. Rats were pair-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 effectively (data at sacrifice: CTRL-PL 6.27±1.25, CTRL-E 9.27±0.99, 5/6 NX-PL 74.04±21.33, 5/6 NX-E 39.09±7.93 mg/ 24 h; P<0.01). Increased urinary excretion of the fibrogenic cytokine transforming growth factor (TGF-b 1) was improved, too (CTRL-PL 0.349±0.051, CTRL-E 0.693±0.230, 5/6 NX-PL 3.044±0.540, 5/6 NX-E 1.390±0.238 ng/m mol creatinine; P<0.05). At sacrifice, tubulointerstitial fibrosis was less pronounced in E-treated rats. Correspondingly, the volume fraction of tubulointerstitial tissue in the renal cortex was improved in 5/6 NX-E rats (CTRL-PL 9.9±0.2, CTRL-E 10.0±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 groups and a tendency towards lower values was observed after E treatment. Renal function as evaluated by serum creatinine and urea levels was not influenced by the enzyme therapy. No between-group differences in blood pressure were observed. In summary, oral administration of proteolytic enzymes improved proteinuria and urinary TGF-b 1 excretion, as well as the severity of tubulointerstitial fibrosis without signs of toxicity.
Key words: Rat remnant kidney model - Proteases - Renal fibrosis - TGF-b1 - Proteinuria
Datum aktualizace stránky: 19. 1. 2016