Partial ureteropelvic regional stenosis of the epidermal growth factor and hepatocyte growth factor to investigate experimentally the effects on renal damage

Purpose: Obstructive nephropathy is the damage of the kidneys due to an abnormality of the urine outflow in the urinary tract. Many congenital and acquired diseases of urinary tract cause an obstructive nephropathy during childhood. Even though the urinary obstruction may be disappeared with surgical techniques kidney damage can be progressive and renal failure may occur. Tubulointerstitial fibrosis is the characteristic finding of the obstructive nephropathy and it has been demonstrated that oxidative stress have an important role in the ethiopathogenesis of the obstructive nephropathy. Clinical and experimental studies have demonstrated that EGF and HGF have an antioxidant, antifibrotic and cytoprotective effect, immunomodülator and antiapoptotic effects. The aim of this study was to investigate the effect of EGF and HGF on bilateral kidneys in the rats with unilateral ureteral obstruction.Materials and Methods: 48 rats divided into 6 groups as Control, UPD, Gelatin, EGF, HGF and EGF + HGF groups. According to experiment groups, uncharged gelatin strips and, 2 micrograms HGF and 2 micrograms EGF absorbed gelatin strips were prepared by Middle East Technical University Department of Chemistry. Single-sided UPJ obstruction model was performed by the method of guidewire through the 7/0 prolene ligation. Strips of gelatin were wrapped around of both kidneys after unilateral ureteral obstruction. At the end of 3-week experimental period, the rats were sacrificed and both kidneys were removed. NO, MDA and GSH levels were measured biochemically. The tubular atrophy with H & E staining and tubulointersititial fibrosis with Masson trichrome staining were detected. Endothelin-1 and TGF-ß1 staining degree were detected immunohistochemically. Statistical analysis were performed with the Kruskal-Wallis one-way analysis and binary comparisons between the groups with Bonferroni test.Results: MDA and NO levels in the treatment groups were significantly lower than those of obstruction groups (p<0.05). GSH levels of treatment groups were significantly higher than those of obstruction groups (p<0.05). EGF had more improving effect than HGF treatment. When the histopathological findings were compared with other groups, tubulointersititial fibrosis and tubular atrophy of the EGF groups were significantly decreased (p<0.05). TGF-ß1 and endothelin-1 staining degree of EGF treatment groups were found to be decreased when compared with those of HGF group (p<0.05). TGF-ß1 staining of contralateral kidney in the treatment groups was increased (p<0.05).Conclusion: EGF showed more protective effect than HGF treatment against tissue damage in the unilateral obstructive nephropathy. EGF plus HGF did not create a significant difference compared to EGF alone. Our results show that both the obstruction and also the treatment lead to changes in contralateral kidney.Our study showed that EGF was more protective effect against tissue damage in unilateral obstructive nephropathy than HGF treatment.Key words: UPJ, obstruction, experimental, EGF, HGF, NO, MDA, GSH, TGF-ß1 and Endothelin -1