Effects of a Low-Protein Diet on Glomerular Endothelin Family Gene Expression in Experimental Focal Glomerular Sclerosis

1995 ◽  
Vol 88 (1) ◽  
pp. 29-37 ◽  
Author(s):  
Tsukasa Nakamura ◽  
Mitsumine Fukui ◽  
Isao Ebihara ◽  
Shiori Osada ◽  
Toshimasa Takahashi ◽  
...  

1. The present study was designed to assess whether glomerular expression of mRNAs for endothelin-1 and endothelin-3, as well as endothelin receptors A and B is affected by a low-protein diet during the course of focal glomerular sclerosis. 2. Focal glomerular sclerosis was induced in rats by injection of puromycin aminonucleoside on days 0, 27, 34 and 41 in conjunction with unilateral nephrectomy on day 22. Control rats were subjected to nephrectomy or sham operation on day 22. 3. Animals were divided into six groups. In group 1, the puromycin aminonucleoside-injected rats were fed a standard diet containing 22% protein. In group 2, the puromycin aminonucleoside-injected rats were fed a low-protein diet containing 6% protein, which was initiated on the day of the first puromycin aminonucleoside injection. In group 3, the nephrectomized rats without puromycin aminonucleoside were fed a standard diet. In group 4, the nephrectomized rats without puromycin aminonucleoside were fed a low-protein diet. In group 5, the sham-operated rats were fed a standard diet. In group 6, the sham-operated rats were fed a low-protein diet. 4. The percentage of sclerotic glomeruli in group 1 rats increased markedly with time, reaching 77% on day 80. 5. The glomerular mRNA levels for endothelin-1 and endothelin receptors A and B increased significantly as glomerular sclerosis progressed, whereas no endothelin-3 mRNA was detected in the glomeruli of any group. 6. The endothelin-1 production in isolated glomeruli from group 1 increased significantly as glomerular sclerosis progressed. 7. In group 2, the low-protein diet reduced the prevalence of glomerular sclerosis, attenuated the rise in mRNA levels for endothelin-1 and endothelin receptors A and B and reduced endothelin-1 production in glomeruli from rats with focal glomerular sclerosis. 8. These data indicate that increases in glomerular endothelin-1 and endothelin receptor mRNA levels are associated with the development of puromycin aminonucleoside-induced glomerular sclerosis. These effects are blunted by administration of a low-protein diet.

2009 ◽  
Vol 103 (4) ◽  
pp. 608-616 ◽  
Author(s):  
Xiang Gao ◽  
Jianxiang Wu ◽  
Zheyi Dong ◽  
Can Hua ◽  
Huimin Hu ◽  
...  

Dietary protein restriction is one major therapy in chronic kidney disease (CKD), and ketoacids have been evaluated in CKD patients during restricted-protein diets. The objective of the present study was to compare the efficacy of a low-protein diet supplemented with ketoacids (LPD+KA) and a low-protein diet alone (LPD) in halting the development of renal lesions in CKD. 5/6 Nephrectomy Sprague–Dawley rats were randomly divided into three groups, and fed with either 22 % protein (normal-protein diet; NPD), 6 % protein (LPD) or 5 % protein plus 1 % ketoacids (LPD+KA) for 24 weeks. Sham-operated rats were used as controls. Each 5/6 nephrectomy group included fifteen rats and the control group included twelve rats. Proteinuria, decreased renal function, glomerular sclerosis and tubulointerstitial fibrosis were found in the remnant kidneys of the NPD group. Protein restriction ameliorated these changes, and the effect was more obvious in the LPD+KA group after 5/6 nephrectomy. Lower body weight and serum albumin levels were found in the LPD group, indicating protein malnutrition. Lipid and protein oxidative products were significantly increased in the LPD group compared with the LPD+KA group. These findings indicate that a LPD supplemented with ketoacids is more effective than a LPD alone in protecting the function of remnant kidneys from progressive injury, which may be mediated by ketoacids ameliorating protein malnutrition and oxidative stress injury in remnant kidney tissue.


1986 ◽  
Vol 23 (5) ◽  
pp. 610-618 ◽  
Author(s):  
P. H. Berry

Hypophyses of four groups of 50 female rats (F0—nulliparous, F0—multiparous, F1—standard diet, and F1—low protein) were examined by light microscopy and immunocytochemistry by the avidin-biotin complex method. In pituitary glands of rats fed a low protein diet, the incidence of neoplasms of the pars distalis, the number of multifocal tumors, and the degree of neoplastic cellular atypia were significantly reduced. Pituitary adenomata in rats fed a low protein diet also caused significantly less brain compression at the time of necropsy than in rats fed a standard diet. All but two neoplastic foci from the 83 tumors stained for prolactin, and 14 of these also stained for growth hormone. No differences were found in the frequency of hemorrhagic or solid patterns of tumor. These findings may reflect a reduction in pituitary tumor initiation, promotion, and/or progression in rats fed a low protein diet.


1983 ◽  
Vol 65 (4) ◽  
pp. 399-406 ◽  
Author(s):  
A. M. El-Nahas ◽  
H. Paraskevakou ◽  
S. Zoob ◽  
A. J. Rees ◽  
D. J. Evans

1. We have examined the effect of a low protein diet on the development of glomerular sclerosis and progressive renal failure after subtotal nephrectomies in rats. 2. Two groups of male Sprague-Dawley rats were studied after five-sixths nephrectomy; group 1 were maintained on a normal diet (13.5 g day−1 kg−1 body weight) and group 2 were fed with a low protein diet (6 g day−1 kg−1 body weight). 3. Rats maintained on a low protein diet survived for longer, and had significantly less glomerular sclerosis and significantly greater glomerular filtration rates when the experiment ended after 7 months. 4. We conclude that dietary protein influences favourably the development of glomerular scarring and renal failure after subtotal nephrectomy in rats.


Author(s):  
Martin den Heijer ◽  
Gerard M J Bos ◽  
Ingeborg A Brouwer ◽  
Wim B J Gerrits ◽  
Henk J Blom

The methionine loading test is used for the diagnosis of impaired methionine/homocysteine metabolism, in particular the transsulfuration pathway. Usually this test is performed on a low protein diet to control the intake of methionine. However, this is inconvenient and relatively expensive. In this study we compared the effects of a low protein diet and a standard diet on methionine loading test in 28 subjects (crossover design). The mean difference in homocysteine concentration after methionine loading between the two diets was 1.3 [confidence interval (CI) 95%-1.0–3.6]μmol/L which demonstrates that a special low protein diet is not essential in the performance of the methionine loading test. We also observed that 3 weeks after the first methionine loading test, fasting serum concentration of folate was higher and vitamin B12 concentration was lower.


Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4305-4315 ◽  
Author(s):  
C. Fournier ◽  
R. Rizzoli ◽  
P. Ammann

Abstract Peak bone mass acquisition is influenced by environmental factors including dietary intake. A low-protein diet delays body and skeletal growth in association with a reduction in serum IGF-1 whereas serum FGF21 is increased by selective amino acid deprivation. Calcium (Ca) and phosphorous (P) are also key nutrients for skeletal health, and inadequate intakes reduce bone mass accrual in association with calciotropic hormone modulation. Besides, the effect of calcium supplementation on bone mass in prepubertal children appears to be influenced by protein intake. To further explore the interaction of dietary protein and Ca-P intake on bone growth, 1-month-old female rats were fed with an isocaloric 10%, 7.5%, or 5% casein diet containing normal or low Ca-P for an 8-week period (6 groups). Changes in tibia geometry, mineral content, microarchitecture, strength, and intrinsic bone quality were analyzed. At the hormonal level, serum IGF-1, fibroblast growth factor 21 (FGF21), PTH, 1,25-dihydroxyvitamin D3 (calcitriol), and FGF23 were investigated as well as the Ghr hepatic gene expression. In normal dietary Ca-P conditions, bone mineral content, trabecular and cortical bone volume, and bone strength were lower in the 5% casein group in association with a decrease in serum IGF-1 and an increase in FGF21 levels. Unexpectedly, the low-Ca-P diet attenuated the 5% casein diet-related reduction of serum IGF-1 and Ghr hepatic gene expression, as well as the low-protein diet-induced decrease in bone mass and strength. However, this was associated with lower cortical bone material level properties. The low-Ca-P diet increased serum calcitriol but decreased FGF23 levels. Calcitriol levels positively correlated with Ghr hepatic mRNA levels. These results suggest that hormonal modulation in response to a low-Ca-P diet may modify the low-protein diet-induced effect on Ghr hepatic mRNA levels and consequently the impact of low protein intakes on IGF-1 circulating levels and skeletal growth.


1993 ◽  
Vol 3 (7) ◽  
pp. 1387-1397
Author(s):  
I Ebihara ◽  
S Suzuki ◽  
T Nakamura ◽  
M Fukui ◽  
Y Yaguchi ◽  
...  

This study was designed to assess how the expression of genes for components of the extracellular matrix is altered in a model of focal glomerular sclerosis. In this model, a unilateral nephrectomy combined with injections of puromycin aminonucleoside induces a much higher incidence of focal glomerular sclerosis. Rats received puromycin aminonucleoside on days 0, 27, 34, and 41 and underwent unilateral nephrectomy on day 22. Control rats received physiologic saline injections with and without unilateral nephrectomy. Rats from each group were killed on days 48, 60, and 80. The steady-state levels of glomerular mRNA encoding type IV collagen, the B1 and B2 chains of laminin, heparan sulfate proteoglycan, and type I and type III collagens were compared in both the puromycin aminonucleoside-treated and the control glomeruli. The mRNA levels encoding type IV collagen and laminin B1 and B2 were increased three-, two-, and twofold, respectively, on day 48 of focal glomerular sclerosis. These transcripts were further increased eight-, seven-, and eightfold, respectively, on day 80 compared with the control glomeruli (P < 0.01). In contrast, heparan sulfate proteoglycan mRNA levels were not increased on day 48 when the animals had marked proteinuria. However, the heparan sulfate proteoglycan mRNA levels did become elevated by day 60 and remained elevated thereafter. The expression of type I and type III collagen mRNA was increased 12- and 7-fold, respectively (P < 0.01), on day 80 in focal glomerular sclerosis rats compared with the controls. An immunofluorescence study revealed the accumulation of immunoglobulin M, C3, type IV collagen, laminin, heparan sulfate proteoglycan, and type I and type III collagens in the sclerotic area. These data indicate that changes in the mRNA levels for components of the basement membrane and interstitial collagen are associated with the development of glomerular sclerosis.


2015 ◽  
Vol 10 (3) ◽  
pp. 505
Author(s):  
Malgorzata Elzbieta Knapik-Czajka

<p>Multienzyme 2-oxoglutarate complex (2-OGDH) together with branched chain α-ketoacid dehydrogenase (BCKDH) and pyruvate dehydrogenase  belong to the family of mitochondrial 2-oxoacid dehydrogenases. Hypolipidemic drugs, bezafibrate and fenofibrate, up-regulate liver BCKDH. The present study has been undertaken to determine the effect of low doses of bezafibrate and fenofibrate on liver 2-OGDH. Fibrates were administrated to rats fed low-protein diet at 5, 10 or 20 mg/kg. In rats treated with increasing doses of bezafibrate 2-OGDH activity increased by 7, 35 and 42%, while in rats administered with fenofibrate by 8, 18, and 56% (p&lt;0.05 for bezafibrate 10 and 20, and fenofibrate 20 mg/kg). Changes in 2-OGDH activity did not correspond with changes in mRNA levels of the complex enzymes. Moreover, mRNA levels of PPARα remained unaltered. It is conceivable that stimulation of 2-OGDH activity by low doses of fibrates is the result of post-transcriptional events and may have a significant effect on liver metabolism.</p><p> </p>


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