Effect of Dietary Protein Restriction on Renal Purines and Purine-Metabolizing Enzymes in Adriamycin Nephrosis in Rats: A Mechanism for Protection against Acute Proteinuria Involving Xanthine Oxidase Inhibition

1990 ◽  
Vol 79 (6) ◽  
pp. 647-656 ◽  
Author(s):  
Gian Marco Ghiggeri ◽  
Fabrizio Ginevri ◽  
Giovanni Cercignani ◽  
Roberta Oleggini ◽  
Alessando Garberi ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Dietary Protein ◽  
Purine Nucleoside Phosphorylase ◽  
Protein Restriction ◽  
Purine Nucleoside ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Dietary Protein Restriction ◽  
Low Protein ◽  
Normal Protein Diet

1. A low protein diet prevents the development of proteinuria and glomerular damage in adriamycin experimental nephrosis without affecting renal haemodynamics. In this study the hypothesis was tested as to whether protein restriction is able to modulate the purine metabolic cycle and related enzymes such as xanthine oxidase, one of the putative effectors of adriamycin nephrotoxicity. 2. Renal activities of xanthine oxidase and purine nucleoside phosphorylase were markedly depressed in adriamycin-treated rats fed a 9% casein (low protein) diet compared with the group fed a 22% casein (normal protein) diet both 1 day after adriamycin administration and at the time of appearance of heavy proteinuria (day 15), whereas the activity of renal adenosine deaminase was unchanged. 3. The concentrations of the metabolic substrates of xanthine oxidase, i.e. hypoxanthine and xanthine, were constantly lower in renal homogenates of rats fed a low protein diet compared with those on a normal protein diet. In urine, uric acid, the product of hypoxanthine-xanthine transformation, was lower 1 day after adriamycin injection in protein-restricted rats compared with the group on a normal protein diet which showed a marked increase in its excretion. At the same time, the urinary efflux of adenosine 5′-monophosphate, which is the precursor nucleotide of the above-mentioned nucleosides and bases, was very high in rats fed a low protein diet, whereas it was absent in the group on a normal protein diet. 4. The progressive increment in proteinuria of glomerular origin (i.e. increased excretion of albumin and transferrin) typical of adriamycin-treated rats fed a normal protein diet was inhibited in the protein-restricted animals, which were normoproteinuric on day 10 and were only slightly proteinuric on day 15. 5. Like protein restriction, the pharmacological suppression of renal xanthine oxidase by dietary tungstate and the scavenging by dimethylthiourea of the putative free radical deriving from the action of xanthine oxidase, were associated with a similar (quantitative and qualitative) inhibition of glomerular proteinurea. 6. These data demonstrate that dietary protein restriction is associated with a block in purine metabolism within the kidney due to a marked reduction in the activities of two main enzymes of the cycle, i.e. purine nucleoside phosphorylase and xanthine oxidase, the latter being a putative effector of adriamycin nephrotoxicity. The partial reduction of proteinuria induced by a low protein diet is quantitatively and qualitatively comparable with the reduction induced by the specific block of renal xanthine oxidase or by the scavenging of OH · deriving from hypoxanthine and xanthine transformation. The crucial factor(s) determining protection against proteinuria in adriamycin nephrosis may be decreased xanthine oxidase activity in the kidney and inhibition of the O2 · and OH · production via the xanthine oxidase system.

scholarly journals Effects of Long-Term Dietary Protein Restriction on Intestinal Morphology, Digestive Enzymes, Gut Hormones, and Colonic Microbiota in Pigs

Animals ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 180 ◽  
Author(s):  
Defu Yu ◽  
Weiyun Zhu ◽  
Suqin Hang
Keyword(s):  
Growth Performance ◽  
Dietary Protein ◽  
Hormone Secretion ◽  
Protein Restriction ◽  
Intestinal Morphology ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Low Protein ◽  
Gut Hormone

Using protein-restriction diets becomes a potential strategy to save the dietary protein resources. However, the mechanism of low-protein diets influencing pigs’ growth performance is still controversial. This study aimed to investigate the effect of protein-restriction diets on gastrointestinal physiology and gut microbiota in pigs. Eighteen weaned piglets were randomly allocated to three groups with different dietary protein levels. After a 16-week trial, the results showed that feeding a low-protein diet to pigs impaired the epithelial morphology of duodenum and jejunum (p < 0.05) and reduced the concentration of many plasma hormones (p < 0.05), such as ghrelin, somatostatin, glucose-dependent insulin-tropic polypeptide, leptin, and gastrin. The relative abundance of Streptococcus and Lactobacillus in colon and microbiota metabolites was also decreased by extreme protein-restriction diets (p < 0.05). These findings suggested that long-term ingestion of a protein-restricted diet could impair intestinal morphology, suppress gut hormone secretion, and change the microbial community and fermentation metabolites in pigs, while the moderately low-protein diet had a minimal effect on gut function and did not impair growth performance.

scholarly journals Effects of dietary protein restriction on the progression of moderate renal disease in the Modification of Diet in Renal Disease Study.

1996 ◽  
Vol 7 (12) ◽  
pp. 2616-2626 ◽  
Keyword(s):  
Renal Disease ◽  
Beneficial Effect ◽  
Dietary Protein ◽  
Protein Intake ◽  
Diet Group ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Dietary Protein Restriction ◽  
Low Protein ◽  
Gfr Decline

The Modification of Diet in Renal Disease (MDRD) Study consisted of two randomized controlled trials to determine the effects of dietary protein restriction and strict blood pressure control. In 255 patients with advanced renal disease (baseline GFR, 13 to 24 mL/min per 1.73 m2; Study B), secondary analyses demonstrated a correlation between achieved protein intake and rate of decline in GFR, consistent with a beneficial effect of a low-protein diet. In 585 patients with moderate renal disease (baseline GFR, 25 to 55 mL/min per 1.73 m2; Study A), the primary analysis of the effect of the low-protein diet was inconclusive because of a nonlinear GFR decline and limited duration of follow-up. A meta-analysis of recent controlled trials, including MDRD Study A, demonstrated a beneficial effect of a low-protein diet on the incidence of renal failure. The objective of these secondary analyses is to explore further the effect of dietary protein restriction in Study A. In these analyses, a total of 585 patients were randomly assigned to follow either a low-protein diet (0.58 g/kg per day) or a usual-protein diet (1.3 g/kg day). Outcomes included the rate of GFR decline, incidence of renal failure or death, and change in urine protein excretion. Analyses included comparisons of randomized groups and correlations of outcomes with achieved protein intake. The comparisons of randomized groups revealed a faster GFR decline during the first 4 months after assignment to the low-protein diet but no difference in the variability in GFR decline between the diet groups, indicating a uniform short-term effect of the low-protein diet on GFR, probably as a result of hemodynamic adjustments. After 4 months, the mean decline in GFR in the low-protein diet group was slower, and the variability of the rate of decline was smaller, than in the usual-protein diet group (ratio of standard deviations, 0.73; 95% confidence interval, 0.55 to 0.91; P < 0.01). This suggests a greater beneficial effect of the low-protein diet in patients with a more rapid GFR decline. The net effect of the low-protein diet on GFR decline over 3 yr was no significant change in mean GFR decline, but reduced variability of the decline (ratio of standard deviations, 0.76; 95% confidence interval, 0.60 to 0.92; P < 0.01). Correlational analyses revealed trends similar to the comparisons of randomized groups. During the first 4 months, patients with a greater decline in protein intake (irrespective of diet group) had a greater decline in GFR; thereafter, patients with a lower protein intake had a slower GFR decline. Over 3 yr, there was no significant correlation between GFR decline and achieved protein intake. The correlation of protein intake with GFR decline after 4 months was less strong than observed in Study B. The relative risk of death or renal failure was 0.65 (95% confidence interval, 0.38 to 1.10; P = 0.10) in patients assigned to the low-protein diet group compared with the usual-protein diet group, which is similar to that observed in the meta-analysis. During follow-up, the increase in urine protein excretion was delayed in the low-protein diet group (P = 0.008) and in patients with lower achieved protein intake (P = 0.005). In summary, the absence of a significant difference between the diet groups in the mean change in GFR from baseline to 3 yr precludes a definitive conclusion of a beneficial effect of the diet intervention based solely on MDRD Study A. However, these secondary analyses are consistent with a beneficial effect of the low-protein diet to slow the GFR decline in patients with the most rapidly declining GFR and to reduce urine protein excretion. These results, together with the results of the recent meta-analysis (including MDRD Study A), provide some support for the hypothesis that dietary protein restriction slows the progression of moderate renal disease.

scholarly journals Survival on dialysis among chronic renal failure patients treated with a supplemented low-protein diet before dialysis.

1995 ◽  
Vol 6 (5) ◽  
pp. 1379-1385
Author(s):  
J Coresh ◽  
M Walser ◽  
S Hill
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Mortality Rate ◽  
Serum Creatinine ◽  
Dietary Treatment ◽  
Mortality Rates ◽  
Protein Restriction ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Low Protein

Concerns have been raised about the possibility of protein restriction resulting in malnutrition and poor subsequent survival on dialysis. However, no studies have examined patients treated with protein restriction to determine their subsequent survival on dialysis. This study prospectively monitored 67 patients with established chronic renal failure (mean initial serum creatinine of 4.3 mg/dL) who were treated with a very low-protein diet (0.3 g/kg per day) supplemented with either essential amino acids or a ketoacid-amino acid mixture and observed closely for clinical complications. Forty-four patients required dialysis. Once dialysis was started, dietary treatment was no longer prescribed. The cumulative mortality rate during the first 2 yr after starting dialysis was 7% (95% confidence interval, 0 to 16%). During this period, only two deaths occurred compared with 11.5 deaths expected on the basis of national mortality rates adjusted for age, sex, race, and cause of renal disease (P = 0.002). However, the protective effect was limited to the first 2 yr on dialysis. Thereafter, mortality rates increased, resulting in a total of 10 deaths during 96.4 person-years of follow-up, which was not significantly lower than the 14.9 deaths expected (P = 0.25). Extrapolation of sequential serum creatinine measurements made before dietary treatment suggests that the improved survival cannot be due to the early initiation of dialysis. Although the lack of an internal control group and data on dialysis lends uncertainty, the large difference in mortality rate between these patients and the nationwide experience indicates that protein restriction and close clinical monitoring predialysis does not worsen and may substantially improve survival during the first 2 yr on dialysis. These findings point out the importance of studying predialysis treatments as a means for lowering mortality on dialysis.

Green tea extract intake during lactation modified cardiac macrophage infiltration and AMP-activated protein kinase phosphorylation in weanling rats from undernourished mother during gestation and lactation

2016 ◽  
Vol 8 (2) ◽  
pp. 178-187 ◽  
Author(s):  
E. Matsumoto ◽  
S. Kataoka ◽  
Y. Mukai ◽  
M. Sato ◽  
S. Sato
Keyword(s):  
Protein Kinase ◽  
Green Tea ◽  
Control Diet ◽  
Protein Restriction ◽  
Protein Diet ◽  
Macrophage Infiltration ◽  
Low Protein Diet ◽  
Low Protein ◽  
Tea Extract ◽  
Amp Activated Protein Kinase

Maternal dietary restriction is often associated with cardiovascular disease in offspring. The aim of this study was to investigate the effect of green tea extract (GTE) intake during lactation on macrophage infiltration, and activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and serine-threonine kinase Akt (Akt) in the hearts of weanlings exposed to maternal dietary protein restriction. Pregnant Wistar rats were fed control (C) or low-protein diets (LP) throughout gestation. Following delivery, the dams received a control or a GTE-containing control diet during lactation: control diet during gestation and lactation (CC), low-protein diet during gestation and lactation (LPC), low-protein diet during gestation and 0.12% GTE-containing low-protein diet during lactation (LPL), and low-protein diet during gestation and 0.24% GTE-containing low-protein diet during lactation (LPH). The female offspring were sacrificed at day 22. Biochemical parameters in the plasma, macrophage infiltration, degree of fibrosis and expression levels of AMPK and Akt were examined. The plasma insulin level increased in LPH compared with LPC. Percentage of the fibrotic areas and the number of macrophages in LPC were higher than those in CC. Conversely, the fibrotic areas and the macrophage number in LPH were smaller (21 and 56%, respectively) than those in LPC. The levels of phosphorylated AMPK in LPL and LPH, and Akt in LPH were greater than those in LPC. In conclusion, maternal protein restriction may induce macrophage infiltration and the decrease of insulin levels. However, GTE intake during lactation may suppress macrophage infiltration and restore insulin secretion function via upregulation of AMPK and insulin signaling in weanlings.

scholarly journals Insulin-like growth factor-I, but not growth hormone, is dependent on a high protein intake to increase nitrogen balance in the rat

1999 ◽  
Vol 81 (2) ◽  
pp. 145-152 ◽  
Author(s):  
Myriam Sanchez-Gomez ◽  
Kjell Malmlöf ◽  
Wilson Mejia ◽  
Antonio Bermudez ◽  
Maria Teresa Ochoa ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Dietary Protein ◽  
Protein Diet ◽  
N Balance ◽  
Low Protein Diet ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Low Protein ◽  
Igf I

The aim of the present study was to investigate the influence of dietary protein level on the protein anabolic effects of growth hormone (GH) and insulin-like growth factor-I (IGF-I). Female growing rats were fed on either a high- or a low-protein diet with crude protein contents of 222 and 83 g/kg respectively. The diets contained the same amount of metabolizable energy (15·1 MJ/kg) and were given during a 14 d period. During the same time, three groups of rats (n 8) on each diet received subcutaneous infusions of either saline, recombinant human GH (rhGH) or recombinant human IGF-I (rhIGF-I). rhGH and rhIGF-I were given in doses of 360 and 500 μg/d respectively. The low-protein diet alone reduced significantly (P < 0·05) IGF-I concentrations in serum and in tissue taken from the gastrocnemius muscle as well as IGF-I mRNA from the same muscle. The responses to rhGH and rhIGF-I in terms of muscle IGF-I and its mRNA were variable. However, when rhIGF-I was infused into rats on the high-protein diet, significantly elevated levels of IGF-I in muscle tissues could be observed. This was associated with a significantly (P < 0·05) increased N balance, whereas rhGH significantly (P < 0·05) enhanced the N balance in rats on the low-protein diet. Thus, it can be concluded that the level of dietary protein ingested regulates not only the effect of IGF-I on whole-body N economy but also the regulation of IGF-I gene expression in muscles. The exact mechanism by which GH exerts its protein anabolic effect, however, remains to be elucidated.

scholarly journals Serum metabolites associated with dietary protein intake: results from the Modification of Diet in Renal Disease (MDRD) randomized clinical trial

2019 ◽  
Vol 109 (3) ◽  
pp. 517-525 ◽  
Author(s):  
Casey M Rebholz ◽  
Zihe Zheng ◽  
Morgan E Grams ◽  
Lawrence J Appel ◽  
Mark J Sarnak ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Amino Acid ◽  
Dietary Protein ◽  
Protein Intake ◽  
Filtration Rate ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Dietary Protein Intake ◽  
Low Protein ◽  
P 16

ABSTRACT Background Accurate assessment of dietary intake is essential, but self-report of dietary intake is prone to measurement error and bias. Discovering metabolic consequences of diets with lower compared with higher protein intake could elucidate new, objective biomarkers of protein intake. Objectives The goal of this study was to identify serum metabolites associated with dietary protein intake. Methods Metabolites were measured with the use of untargeted, reverse-phase ultra-performance liquid chromatography–tandem mass spectrometry quantification in serum specimens collected at the 12-mo follow-up visit in the Modification of Diet in Renal Disease (MDRD) Study from 482 participants in study A (glomerular filtration rate: 25–55 mL · min−1 · 1.73 m−2) and 192 participants in study B (glomerular filtration rate: 13–24 mL · min−1 · 1.73 m−2). We used multivariable linear regression to test for differences in log-transformed metabolites (outcome) according to randomly assigned dietary protein intervention groups (exposure). Statistical significance was assessed at the Bonferroni-corrected threshold: 0.05/1193 = 4.2 × 10−5. Results In study A, 130 metabolites (83 known from 28 distinct pathways, including 7 amino acid pathways; 47 unknown) were significantly different between participants randomly assigned to the low-protein diet compared with the moderate-protein diet. In study B, 32 metabolites (22 known from 8 distinct pathways, including 4 amino acid pathways; 10 unknown) were significantly different between participants randomly assigned to the very-low-protein diet compared with the low-protein diet. A total of 11 known metabolites were significantly associated with protein intake in the same direction in both studies A and B: 3-methylhistidine, N-acetyl-3-methylhistidine, xanthurenate, isovalerylcarnitine, creatine, kynurenate, 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE (P-16:0/20:4), 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (P-18:0/20:4), 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC (P-16:0/20:4), sulfate, and γ-glutamylalanine. Conclusions Among patients with chronic kidney disease, an untargeted serum metabolomics platform identified multiple pathways and metabolites associated with dietary protein intake. Further research is necessary to characterize unknown compounds and to examine these metabolites in association with dietary protein intake among individuals without kidney disease. This trial was registered at clinicaltrials.gov as NCT03202914.

scholarly journals Proximal tubule glutamine synthetase expression is necessary for the normal response to dietary protein restriction

2017 ◽  
Vol 313 (1) ◽  
pp. F116-F125 ◽  
Author(s):  
Hyun-Wook Lee ◽  
Gunars Osis ◽  
Mary E. Handlogten ◽  
Jill W. Verlander ◽  
I. David Weiner
Keyword(s):  
Glutamine Synthetase ◽  
Proximal Tubule ◽  
Dietary Protein ◽  
Acid Production ◽  
Protein Intake ◽  
Ammonia Excretion ◽  
Protein Restriction ◽  
Protein Diet ◽  
Acid Excretion ◽  
Dietary Protein Restriction

Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion changes in parallel during changes in dietary protein intake. Dietary protein restriction decreases endogenous acid production and decreases urinary ammonia excretion, a major component of net acid excretion. Glutamine synthetase (GS) catalyzes the reaction of [Formula: see text] and glutamate, which regenerates the essential amino acid glutamine and decreases net ammonia generation. Because renal proximal tubule GS expression increases during dietary protein restriction, this could contribute to the decreased ammonia excretion. The purpose of the current study was to determine the role of proximal tubule GS in the renal response to protein restriction. We generated mice with proximal tubule-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Cre-negative (Control) and PT-GS-KO mice in metabolic cages were provided 20% protein diet for 2 days and were then changed to low-protein (6%) diet for the next 7 days. Additional PT-GS-KO mice were maintained on 20% protein diet. Dietary protein restriction caused a rapid decrease in urinary ammonia excretion in both genotypes, but PT-GS-KO blunted this adaptive response significantly. This occurred despite no significant genotype-dependent differences in urinary pH or in serum electrolytes. There were no significant differences between Control and PT-GS-KO mice in expression of multiple other proteins involved in renal ammonia handling. We conclude that proximal tubule GS expression is necessary for the appropriate decrease in ammonia excretion during dietary protein restriction.

scholarly journals A low-protein diet supplemented with ketoacids plays a more protective role against oxidative stress of rat kidney tissue with 5/6 nephrectomy than a low-protein diet alone

2009 ◽  
Vol 103 (4) ◽  
pp. 608-616 ◽  
Author(s):  
Xiang Gao ◽  
Jianxiang Wu ◽  
Zheyi Dong ◽  
Can Hua ◽  
Huimin Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Tissue ◽  
Protein Restriction ◽  
Protein Malnutrition ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Glomerular Sclerosis ◽  
Control Group ◽  
Stress Injury ◽  
Low Protein

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.

scholarly journals Maternal Protein Restriction Modulates Angiogenesis and AQP9 Expression Leading to a Delay in Postnatal Epididymal Development in Rat

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1094 ◽  
Author(s):  
Talita de Mello Santos ◽  
Marilia Martins Cavariani ◽  
Dhrielly Natália Pereira ◽  
Bruno César Schimming ◽  
Luiz Gustavo de Almeida Chuffa ◽  
...  
Keyword(s):  
Well Being ◽  
Protein Restriction ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Pregnant Rats ◽  
Low Protein ◽  
Maternal Protein Restriction ◽  
Aqp1 Expression ◽  
In The Beginning ◽  
Endothelial Growth Factor

The maternal nutritional status is essential to the health and well-being of the fetus. Maternal protein restriction during the perinatal stage causes sperm alterations in the offspring that are associated with epididymal dysfunctions. Vascular endothelial growth factor (VEGF) and its receptor, VEGFr-2, as well as aquaporins (AQPs) are important regulators of angiogenesis and the epididymal microenvironment and are associated with male fertility. We investigated the effects of maternal protein restriction on epididymal angiogenesis and AQP expression in the early stages of postnatal epididymal development. Pregnant rats were divided into two experimental groups that received either a normoprotein (17% protein) or low-protein diet (6% protein) during gestation and lactation. At postnatal day (PND)7 and PND14, male offspring were euthanized, the epididymides were subjected to morphometric and microvascular density analyses and to VEGF-A, VEGF-r2, AQP1 and AQP9 expression analyses. The maternal low-protein diet decreased AQP9 and VEGFr-2 expression, decreased epididymal microvascularity and altered the morphometric features of the epididymal epithelium; no changes in AQP1 expression were observed at the beginning of postnatal epididymal development. Maternal protein restriction alters microvascularization and affects molecules involved in the epidydimal microenvironment, resulting in morphometric alterations related to a delay in the beginning of epididymis postnatal development.

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