Effects of Low Protein Intake on the Development of the Remaining Kidney in Subtotally Nephrectomized Immature Rats: Apoptosis and Epidermal Growth Factor

Abstract

ABSTRACT. Effects of low protein intake on the development of the remaining kidney in subtotally (5/6) nephrectomized immature rats were examined. Three week-old weaning rats were kept on a diet containing either 12% (Lp rats) or 18% (Np rats) protein for 4 or 8 weeks after subtotal nephrectomy. Blood urea nitrogen (BUN) concentration was determined at 2, 4, 6, and 8 weeks after 5/6 nephrectomy. At 4 or 8 weeks after the operation, glomerular sclerosis and tubulointerstitial damage were assessed by a standard semiquantitative analysis and were expressed as the glomerular sclerosis index (GSI) and interstitial fibrosis score (IFS), respectively. The localization of DNA fragmented cells in the kidney was examined by the terminal deoxynucleotidyl transferase (TdT) -mediated d-UTPbiotin nick end labeling (TUNEL) method and the localization of the epidermal growth factor (EGF) by immunohistochemical methods. BUN concentration was significantly lower in the Lp rats compared with that in the Np rats. Both 4 and 8 weeks after subtotal nephrectomy, GSI and incidence of TUNEL positive cells in the distal tubules were significantly lower in the Lp rats than in the Np rats. Four weeks after the operation, IFS was significantly lower in the Lp rats than in the Np rats. Four and 8 weeks after the operation, EGF positive cells in the distal tubules were more observed in the Lp rats than in the Np rats. These findings reveal that protein restriction is effective in preventing renal tubular scarring in immature rats and that EGF is involved in the process of this prevention. KEY WORDS: EGF, immature rat, subtotal nephrectomy, TUNEL.J. Vet. Med. Sci. 69(3): 247-252, 2007 Subtotal (5/6) nephrectomy has been performed on laboratory animals to achieve a model for chronic renal failure [13,25]. The remaining kidney of 5/6 nephrectomized animals was utilized as a model for renal fibrosis [9,15,24] and a model for glomerular sclerosis [2,5]. In the remaining kidney glomerular sclerosis is observed following increased proliferative activity in glomeruli [2] and renal fibrosis is accompanied with apoptotic cells [12]. In this model, restriction of protein intake improves renal failure [6]. On the other hand, the epidermal growth factor (EGF) plays an important role in proliferative activity [16] and apoptosis [17] of the developing kidney in perinatal rats. These findings lead us to believe that both subtotal nephrectomy and restriction of protein intake greatly influence the developing kidney. Friedman and Pityer [3] have reported that low protein intake improves survival over normal protein intake in 3/4 nephrectomized immature rats. However, there is very little information available on the development of the remaining kidney in 5/6 nephrectomized immature rats. The present study was designed to clarify the effect of low protein intake on the development of the remaining kidney of subtotally nephrectomized immature rats with special reference to apoptosis and EGF. MATERIALS AND METHODS Animals and tissue processing:Three week-old m...

Effects of Maternal Renal Dysfunction on Fetal Development

“…It has been reported that a low protein intake improves survival over normal protein intake in 3/4 nephrectomized immature rats (Friedman & Pityer, 1986). Further, Mino et al (2007) have reported that a low protein diet induces a significant decrease in BUN, GSI, and IFS in 5/6 nephrectomized immature rats. These findings suggest that protein intake restriction is effective in preventing renal failure in immature animals, which is in accord with the results in adult rats.…”

“…The remaining kidney of 5/6 nephrectomized animals was utilized as a model for renal fibrosis (Johnson et al, 1997;Nangaku et al, 2002;Yang et al, 2001) and a model for glomerular sclerosis (Floege et al, 1992;Griffin et al, 1994). Since in immature rats as well as adult animals, 5/6 nephrectomy induces significant increases in BUN, glomerular sclerosis index (GSI), and interstitial fibrosis score (IFS), compared with sham-oprated ones (Mino et al, 2007), 5/6 nephrectomized immature animals are useful as animal model for renal failure.…”

“…Further, chronic renal failure caused by 5/6 nephrectomy is improved by extrinsic EGF (Moskowitz et al, 1992), and EGF accelerates the regeneration of tubular cells and ameliorates renal failure (Humes et al, 1989). Furthermore, in 5/6 nephrectomized immature rats, the incidence of TUNEL positive cells in distal tubules was lowered and more EGF-positive cells in the segments were observed after protein restriction (Mino et al, 2007). These findings reveal that protein restriction is effective in preventing renal tubular scarring in immature rats and that EGF is involved in the process of this prevention.…”

Effectiveness of Apoptotic Factors Expressed on the Wounds of Patients With Stage III Pressure Ulcers

“…11,12 Previous studies indicate that upregulation of apoptotic factors may occur in delayed healing of diabetic foot ulcers and malignant wounds. 10,13,14 Fu and colleagues 15 evaluated tissue samples taken from patients with diabetic foot ulcers and reported that apoptotic factors infl uenced production of granulation tissue, tissue remodeling, and scar formation. 3,15 We hypothesize that apoptotic processes also occur in PU healing.…”

Compensatory Renal Growth in Uninephrectomized Immature Rats: Proliferative Activity and Epidermal Growth Factor

“…The kidney is the organ next to the salivary glands in secreting a large amount of EGF [11]. EGF is involved in the process of preventing renal tubular scarring in 5/6 nephrectomized immature rats by protein restriction [17]. Addition of EGF to renal organ culture medium causes an increased uptake of bromodeoxyuridine (BrdU) [26].…”