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

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.

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The effect of maternal low-protein diet on the heart of adult offspring: role of mitochondria and oxidative stress

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2013-0452 ◽

2014 ◽

Vol 39 (8) ◽

pp. 880-887 ◽

Cited By ~ 28

Author(s):

Luciana Nascimento ◽

Cristiane M. Freitas ◽

Reginaldo Silva-Filho ◽

Ana Catarina R. Leite ◽

Alessandra B. Silva ◽

...

Keyword(s):

Oxidative Stress ◽

Oxidative Phosphorylation ◽

Protein Restriction ◽

Protein Diet ◽

Male Rats ◽

Low Protein Diet ◽

Adult Offspring ◽

Mitochondrial Oxidative Phosphorylation ◽

Low Protein ◽

And Oxidative Stress

Protein restriction during perinatal and early postnatal development is associated with a greater incidence of disease in the adult, such arterial hypertension. The aim in the present study was to investigate the effect of maternal low-protein diet on mitochondrial oxidative phosphorylation capacity, mitochondrial reactive oxygen species (ROS) formation, antioxidant levels (enzymatic and nonenzymatic), and oxidative stress levels on the heart of the adult offspring. Pregnant Wistar rats received either 17% casein (normal protein, NP) or 8% casein (low protein, LP) throughout pregnancy and lactation. After weaning male progeny of these NP or LP fed rats, females were maintained on commercial chow (Labina-Purina). At 100 days post-birth, the male rats were sacrificed and heart tissue was harvested and stored at −80 °C. Our results show that restricting protein consumption in pregnant females induced decreased mitochondrial oxidative phosphorylation capacity (51% reduction in ADP-stimulated oxygen consumption and 49.5% reduction in respiratory control ratio) in their progeny when compared with NP group. In addition, maternal low-protein diet induced a significant decrease in enzymatic antioxidant capacity (37.8% decrease in superoxide dismutase activity; 42% decrease in catalase activity; 44.8% decrease in glutathione-S-transferase activity; 47.9% decrease in glutathione reductase; 25.7% decrease in glucose-6 phosphate dehydrogenase) and glutathione level (34.8% decrease) when compared with control. From these findings, we hypothesize that an increased production of ROS and decrease in antioxidant activity levels induced by protein restriction during development could potentiate the progression of metabolic and cardiac diseases in adulthood.

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

Journal of the American Society of Nephrology ◽

10.1681/asn.v651379 ◽

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.

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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

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174416000647 ◽

2016 ◽

Vol 8 (2) ◽

pp. 178-187 ◽

Cited By ~ 7

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.

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Effect of prenatal programming and postnatal rearing on glomerular filtration rate in adult rats

AJP Renal Physiology ◽

10.1152/ajprenal.00593.2014 ◽

2015 ◽

Vol 308 (5) ◽

pp. F411-F419 ◽

Cited By ~ 13

Author(s):

German Lozano ◽

Ayah Elmaghrabi ◽

Jordan Salley ◽

Khurrum Siddique ◽

Jyothsna Gattineni ◽

...

Keyword(s):

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Protein Diet ◽

Low Protein Diet ◽

Control Group ◽

Adult Rats ◽

Pregnant Rats ◽

Mature Adult ◽

Low Protein

The present study examined whether a prenatal low-protein diet programs a decrease in glomerular filtration rate (GFR) and an increase in systolic blood pressure (BP). In addition, we examined whether altering the postnatal nutritional environment of nursing neonatal rats affected GFR and BP when rats were studied as adults. Pregnant rats were fed a normal (20%) protein diet or a low-protein diet (6%) during the last half of pregnancy until birth, when rats were fed a 20% protein diet. Mature adult rats from the prenatal low-protein group had systolic hypertension and a GFR of 0.38 ± 0.03 versus 0.57 ± 0.05 ml·min−1·100 g body wt−1 in the 20% group ( P < 0.01). In cross-fostering experiments, mothers continued on the same prenatal diet until weaning. Prenatal 6% protein rats cross-fostered to a 20% mother on day 1 of life had a GFR of 0.53 ± 0.05 ml·min−1·100 g body wt−1, which was not different than the 20% group cross-fostered to a different 20% mother (0.45 ± 0.04 ml·min−1·100 g body wt−1). BP in the 6% to 20% group was comparable with the 20% to 20% group. Offspring of rats fed either 20% or 6% protein diets during pregnancy and cross-fostered to a 6% mother had elevated BP but a comparable GFR normalized to body weight as the 20% to 20% control group. Thus, a prenatal low-protein diet causes hypertension and a reduction in GFR in mature adult offspring, which can be modified by postnatal rearing.

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

Clinical Science ◽

10.1042/cs0880029 ◽

1995 ◽

Vol 88 (1) ◽

pp. 29-37 ◽

Cited By ~ 10

Author(s):

Tsukasa Nakamura ◽

Mitsumine Fukui ◽

Isao Ebihara ◽

Shiori Osada ◽

Toshimasa Takahashi ◽

...

Keyword(s):

Protein Diet ◽

Low Protein Diet ◽

Endothelin Receptors ◽

Glomerular Sclerosis ◽

Standard Diet ◽

Mrna Levels ◽

Puromycin Aminonucleoside ◽

Endothelin 1 ◽

Low Protein ◽

Focal Glomerular Sclerosis

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.

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

Cells ◽

10.3390/cells8091094 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1094 ◽

Cited By ~ 1

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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A maternal low-protein diet and neonatal overnutrition result in similar changes to glomerular morphology and renal cortical oxidative stress measures in male Wistar rats

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2018-0288 ◽

2019 ◽

Vol 44 (2) ◽

pp. 164-171 ◽

Cited By ~ 3

Author(s):

Anderson Pedroza ◽

Diorginis Soares Ferreira ◽

David F. Santana ◽

Pedro Thiago da Silva ◽

Francisco Carlos Amanajás de Aguiar Júnior ◽

...

Keyword(s):

Oxidative Stress ◽

Wistar Rats ◽

Renal Cortex ◽

Protein Diet ◽

Antioxidant Defenses ◽

Low Protein Diet ◽

Low Protein ◽

Oxidative Balance ◽

Male Wistar Rats ◽

Glomerular Morphology

There is a strong correlation between inadequate gestational and postpartum nutrition and the occurrence of cardiovascular diseases. The present study investigated the effects of a maternal low-protein diet and neonatal overfeeding on the oxidative balance and morphology of the renal cortex of male Wistar rats. Two independent protocols were used. First, pregnant Wistar rats received diets containing either 17% (normal protein) or 8% (low protein) casein throughout pregnancy and lactation. Second, the litter size was reduced by one-third on the third postnatal day to induce overnourishment in offspring. At 30 days, the oxidative balance and morphology of the renal cortex were analyzed. There was a small but significant increase in renal corpuscle area in the low protein (LP, 5%) and overnutrition (ON, 8%) groups. Glomerular tuft area also increased in LP (6%) and ON (9%), as did glomerular cellularity (LP, +11%; ON, +12%). In the oxidative stress analyses, both nutritional insults significantly elevated lipid peroxidation (LP, +18%; ON, +135%) and protein oxidation (LP, +40%; ON, +65%) while significantly reducing nonenzymatic antioxidant defenses, measured as reduced glutathione (LP, –32%; ON, –45%) and total thiol content (LP, –28%; ON, –24%). We also observed a decrease in superoxide dismutase (LP, –78%; ON, –51%), catalase (LP, –18%; ON, –61%), and glutathione S-transferase (only in ON, –44%) activities. Our results demonstrate that nutritional insults, even those of a very different nature, during perinatal development can result in similar changes in oxidative parameters and glomerular morphology in the renal cortex.

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Somatomedin-C and zinc status in rats as affected by Zn, protein and food intake

British Journal Of Nutrition ◽

10.1079/bjn19860096 ◽

1986 ◽

Vol 56 (1) ◽

pp. 163-169 ◽

Cited By ~ 23

Author(s):

Zafrallah T. Cossack

Keyword(s):

Food Intake ◽

Body Weight Gain ◽

Experimental Period ◽

Optimal Level ◽

Protein Diet ◽

Low Protein Diet ◽

Control Group ◽

Somatomedin C ◽

Low Protein ◽

Adequate Food

1. The objective of the present experiment was to study the level of plasma somatomedin-C (SM-C) and the status of zinc in rats as affected by three levels of Zn given in combinations with two levels of protein.2. Six groups of rats were fed, for 21 d, on six different diets based on combinations of two levels of dietary protein (low protein, 75 g/kg; high protein, 200 g/kg) and three levels of zinc (low Zn, 0.9 pglkg; moderate Zn, 55 pg/kg; high Zn, 110 pglkg). All groups were pair-fed with the group receiving the low-Zn-low-protein diet. An additional group of six rats served as an ad lib.-fed control group and was fed on a diet that contained 55 pg Zn/kg and 200 g protein/kg ad lib.3. Body-weight gain and food intake were recorded daily. Rats were killed at the end of the experimental period (21 d). Zn was assayed in plasma, tibia and liver by atomic absorption technique. Plasma SM-C was assayed by radioimmunoassay.4. In rats given the low-Zn-low-protein diet, the level of plasma SM-C increased in response to the increase in the amount of Zn or Zn and protein in the diet. However, no change was observed when the level of protein alone was increased.5. Among all groups tested, adlib.-fed rats showed the highest level of plasma SM-C. Thus it may be concluded that a balanced diet combined with adequate food intake is necessary to maintain an optimal level of plasma SM-C.

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