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Narasaki Y, Kalantar-Zadeh K, Rhee CM, Brunori G, Zarantonello D. Vegetarian Nutrition in Chronic Kidney Disease. Nutrients 2023; 16:66. [PMID: 38201898 PMCID: PMC10780746 DOI: 10.3390/nu16010066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 12/19/2023] [Accepted: 12/20/2023] [Indexed: 01/12/2024] Open
Abstract
There is rising interest globally with respect to the health implications of vegetarian or plant-based diets. A growing body of evidence has demonstrated that higher consumption of plant-based foods and the nutrients found in vegetarian and plant-based diets are associated with numerous health benefits, including improved blood pressure, glycemic control, lipid levels, body mass index, and acid-base parameters. Furthermore, there has been increasing recognition that vegetarian and plant-based diets may have potential salutary benefits in preventing the development and progression of chronic kidney disease (CKD). While increasing evidence shows that vegetarian and plant-based diets have nephroprotective effects, there remains some degree of uncertainty about their nutritional adequacy and safety in CKD (with respect to protein-energy wasting, hyperkalemia, etc.). In this review, we focus on the potential roles of and existing data on the efficacy/effectiveness and safety of various vegetarian and plant-based diets in CKD, as well as their practical application in CKD management.
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Affiliation(s)
- Yoko Narasaki
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90073, USA
- Tibor Rubin Veterans Affairs Long Beach Healthcare System, Long Beach, CA 90822, USA
| | - Kamyar Kalantar-Zadeh
- Tibor Rubin Veterans Affairs Long Beach Healthcare System, Long Beach, CA 90822, USA
- The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA
- Division of Nephrology, Hypertension, and Kidney Transplantation, University of California Irvine, Orange, CA 92868, USA
| | - Connie M. Rhee
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90073, USA
- Division of Nephrology, Hypertension, and Kidney Transplantation, University of California Irvine, Orange, CA 92868, USA
- Nephrology Section, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA
| | - Giuliano Brunori
- Department of Nephrology, Santa Chiara Hospital, APSS, 31822 Trento, Italy
- CISMed, University of Trento, 38122 Trento, Italy
| | - Diana Zarantonello
- Department of Nephrology, Santa Chiara Hospital, APSS, 31822 Trento, Italy
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Milovanova LY, Taranova MV, Volkov AV, Milovanova SY, Beketov VD. [Soy protein as part of a low-protein diet is a new direction in cardio- and nephroprotection in patients with 3B-4 stages of chronic kidney disease: prospective, randomized, controlled clinical study]. TERAPEVT ARKH 2022; 94:756-762. [PMID: 36286853 DOI: 10.26442/00403660.2022.06.201567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 08/04/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND It has been established that the use of a low-protein diet (LPD) in combination with ketoanalogues (KA) of essential amino acids can contribute to cardio- and nephroprotection in chronic kidney disease (CKD). Moreover, it has been shown that replacing part of the animal protein with soy protein (SP) in the diet contributed to more pronounced nephro- and cardioprotection in CKD, however, the data, available in the literature, are mainly represented by experimental studies. AIM To compare the effects of 2 types of diets on the main parameters of nephro- and cardioprotection in patients with CKD. MATERIALS AND METHODS We have conducted a prospective, randomized, controlled clinical study which included 85 patients with 3B4 stages of CKD, compliant to LPD (0.6 g of protein/kg body weight) + KA (1 tablet/5 kg body weight). 43 patients (Group 1) received LPD with replacing animal protein with soy (60% soy protein + 40% another vegetable proteins) + KA, and 42 patients (control group, Group 2) received LPD (60% animal protein + 40% vegetable protein) + KA, within 12 months. RESULTS The dietary substitution of animal protein with SP to a greater extent delayed the decrease in glomerular filtration rate (-5.9% vs -13.3%; p=0.048), the increase in left ventricular hypertrophy (+4.7% vs +12.3%; p=0.042), as well as the increase in central systolic blood pressure (+2.6% vs +13.0%; p=0.021), augmentation index (+7.6% vs +23.3%; p=0.010), slowed down the decrease in lean body mass in men (+0.9% vs -11.2%; p=0.017) and women (-1.8% vs -10.3%; p=0.024), increase in phosphorus (-10.3% vs +13.0%; p=0.029), cholesterol (-10.7% vs -3.4%; p=0.047) and urea (+6.3% vs +19.6%; p=0.035) serum levels. CONCLUSION The use of LPD with substitution of animal protein with soy protein + KA provides a more pronounced effect on nephro- and cardioprotection as well as maintenance of nutritional status, than conventional LPD + KA in patients with 3B4 stages of CKD.
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Affiliation(s)
- L Y Milovanova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - M V Taranova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - A V Volkov
- Sechenov First Moscow State Medical University (Sechenov University)
| | - S Y Milovanova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - V D Beketov
- Sechenov First Moscow State Medical University (Sechenov University)
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Ohta S, Asanoma M, Irie N, Tachibana N, Kohno M. Soy Phospholipids Exert a Renoprotective Effect by Inhibiting the Nuclear Factor Kappa B Pathway in Macrophages. Metabolites 2022; 12:metabo12040330. [PMID: 35448517 PMCID: PMC9031346 DOI: 10.3390/metabo12040330] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 04/01/2022] [Accepted: 04/02/2022] [Indexed: 12/14/2022] Open
Abstract
Complications associated with chronic kidney disease (CKD), which involves kidney inflammation, are a major health problem. Soy protein isolate (SPI) reportedly inhibits CKD exacerbation; however, its detailed action mechanism remains obscure. Therefore, the role of the polar lipid component of SPI in suppressing inflammation was investigated. Zucker fatty rats were divided into three groups and fed a diet containing casein, SPI, or casein + SPI ethanol extract (SPIEE) for 16 weeks. The isoflavones and phospholipids of SPIEE were evaluated for their anti-inflammatory effects. Rats in the SPI and casein + SPIEE groups showed reduced levels of the urinary N-acetyl-β-d-glucosaminidase and renal IL-1β mRNA (an inflammatory marker) compared with those in the casein group. In proximal tubular cells, genistein significantly inhibited monocyte chemoattractant protein-1 (MCP-1) expression induced by an IL-1β stimulus. In macrophages, soybean phospholipids suppressed lipopolysaccharide-induced IL-1β gene expression by inhibiting the phosphorylation of inhibitor κB and p65. Phosphatidylinositol (PI) was found to be essential for inhibition of IL-1β expression. SPIEE inhibited the exacerbation of kidney disease. Genistein and soybean phospholipids, especially soybean-specific phospholipids containing PI, effectively inhibited the inflammatory spiral in vitro. Hence, daily soybean intake may be effective for inhibiting chronic inflammation and slowing kidney disease progression.
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Affiliation(s)
- Satoshi Ohta
- Research Institute for Creating the Future, Fuji Oil Holdings Inc., 4-3 Kinunodai, Tsukubamirai-shi 300-2497, Ibaraki, Japan; (N.I.); (N.T.)
- Correspondence: ; Tel.: +81-297-52-6325
| | - Masashi Asanoma
- Soy Ingredients R&D Department, Fuji Oil Co., Ltd., 1 Sumiyoshicho, Izumisano-shi 598-8540, Osaka, Japan;
| | - Nao Irie
- Research Institute for Creating the Future, Fuji Oil Holdings Inc., 4-3 Kinunodai, Tsukubamirai-shi 300-2497, Ibaraki, Japan; (N.I.); (N.T.)
| | - Nobuhiko Tachibana
- Research Institute for Creating the Future, Fuji Oil Holdings Inc., 4-3 Kinunodai, Tsukubamirai-shi 300-2497, Ibaraki, Japan; (N.I.); (N.T.)
| | - Mitsutaka Kohno
- R&D Division Strategy Planning Department, Fuji Oil Co., Ltd., 1 Sumiyoshicho, Izumisano-shi 598-8540, Osaka, Japan;
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Kadowaki M, Kubota M, Watanabe R. Physiological Multifunctions of Rice Proteins of Endosperm and Bran. J Nutr Sci Vitaminol (Tokyo) 2020; 65:S42-S47. [PMID: 31619644 DOI: 10.3177/jnsv.65.s42] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Although it is considered a staple food, rice intake is under serious debate for its physiological usefulness, especially for diabetic patients, because of starch content. However, rice protein, the second major component of rice, has gained attention recently for its newly-discovered functions, which were previously unknown. Rice protein, a plant protein, shows multiple beneficial functions on lipid metabolism and diabetes and its complications, nephropathy, fatty liver and osteoporosis. Rice proteins of endosperm and bran, an ingredient of white rice and an unused product of brown rice, respectively, are valuable components for human health.
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Affiliation(s)
- Motoni Kadowaki
- Faculty of Agriculture, Niigata University.,Fuculty of Engineering, Niigata Institute of Technology
| | | | - Reiko Watanabe
- Department of Health and Nutrition, University of Niigata Prefecture
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Gluba-Brzozka A, Franczyk B, Rysz J. Cholesterol Disturbances and the Role of Proper Nutrition in CKD Patients. Nutrients 2019; 11:E2820. [PMID: 31752189 PMCID: PMC6893650 DOI: 10.3390/nu11112820] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Accepted: 11/10/2019] [Indexed: 12/21/2022] Open
Abstract
Chronic kidney disease (CKD) is a widespread disease with increasing prevalence in the modern society. Lipid disturbances are common in this group of patients. In most patients with CKD atherogenic dyslipidemia is observed. Dyslipidemia in patients with renal diseases increases the risk of cardiovascular diseases and it accelerates the progression of chronic kidney disease to its end stage. The amelioration of dyslipidemia and the lowering of oxidative stress, inflammatory processes, insulin sensitivity and remnant lipoproteins levels may lead to the reduction in cardiovascular burden. Nutritional interventions can strengthen the beneficial effect of treatment and they play an important role in the preservation of overall well-being of the patients with CKD since the aim of appropriate diet is to reduce the risk of cardiovascular events, prevent malnutrition, and hamper the progression of kidney disease. The management of dyslipidemia, regardless of the presence of chronic kidney disease, should be initiated by the introduction of therapeutic lifestyle changes. The introduction of diet change was shown to exert beneficial effect on the lipid level lowering that reaches beyond pharmacological therapy. Currently available evidence give the impression that data on dietary interventions in CKD patients is not sufficient to make any clinical practice guidelines and is of low quality.
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Affiliation(s)
- Anna Gluba-Brzozka
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (B.F.); (J.R.)
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Ina S, Hamada A, Kumagai H, Yamaguchi Y. Bioactive Ingredients in Rice (Oryza sativa L.) Function in the Prevention of Type 2 Diabetes. J Nutr Sci Vitaminol (Tokyo) 2019; 65:S113-S116. [PMID: 31619608 DOI: 10.3177/jnsv.65.s113] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Diabetes mellitus (DM) greatly impacts human health worldwide as over 400 million patients suffer from DM-related symptoms. Type 2 DM accounts for more than 90% of DM and is caused mainly by unhealthy lifestyles, such as high-calorie and high-fat diets. Such undesirable eating habitats induce resistance to insulin resulting in high blood sugar levels that cause induction of various symptoms and complications of DM. Therefore, management of blood sugar levels is important for preventing DM. Our group has recently found that rice (Oryza sativa L.) contains anti-diabetes compounds. Here, we summarize the effect of the bioactive ingredients in rice on preventing type 2 DM.
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Affiliation(s)
- Shigenobu Ina
- Department of Chemistry and Life Science, Nihon University
| | - Aya Hamada
- Department of Chemistry and Life Science, Nihon University
| | - Hitomi Kumagai
- Department of Chemistry and Life Science, Nihon University
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Torre-Villalvazo I, Cervantes-Pérez LG, Noriega LG, Jiménez JV, Uribe N, Chávez-Canales M, Tovar-Palacio C, Marfil-Garza BA, Torres N, Bobadilla NA, Tovar AR, Gamba G. Inactivation of SPAK kinase reduces body weight gain in mice fed a high-fat diet by improving energy expenditure and insulin sensitivity. Am J Physiol Endocrinol Metab 2018; 314:E53-E65. [PMID: 29066461 DOI: 10.1152/ajpendo.00108.2017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) controls the activity of the electroneutral cation-chloride cotransporters (SLC12 family) and thus physiological processes such as modulation of cell volume, intracellular chloride concentration [Cl-]i, and transepithelial salt transport. Modulation of SPAK kinase activity may have an impact on hypertension and obesity, as STK39, the gene encoding SPAK, has been suggested as a hypertension and obesity susceptibility gene. In fact, the absence of SPAK activity in mice in which the activating threonine in the T loop was substituted by alanine (SPAK-KI mice) is associated with decreased blood pressure; however its consequences in metabolism have not been explored. Here, we fed wild-type and homozygous SPAK-KI mice a high-fat diet for 17 wk to evaluate weight gain, circulating substrates and hormones, energy expenditure, glucose tolerance, and insulin sensitivity. SPAK-KI mice exhibit resistance to HFD-induced obesity and hepatic steatosis associated with increased energy expenditure, higher thermogenic activity in brown adipose tissue, increased mitochondrial activity in skeletal muscle, and reduced white adipose tissue hypertrophy mediated by augmented whole body insulin sensitivity and glucose tolerance. Our data reveal a previously unrecognized role for the SPAK kinase in the regulation of energy balance, thermogenesis, and insulin sensitivity, suggesting that this kinase could be a new drug target for the treatment of obesity and the metabolic syndrome.
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Affiliation(s)
- Ivan Torre-Villalvazo
- Department of Nutrition Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Mexico City, Mexico
| | | | - Lilia G Noriega
- Department of Nutrition Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Mexico City, Mexico
| | - Jose V Jiménez
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Mexico City, Mexico
| | - Norma Uribe
- Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , México City, Mexico
| | - María Chávez-Canales
- Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Mexico City, Mexico
| | - Claudia Tovar-Palacio
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Mexico City, Mexico
| | - Braulio A Marfil-Garza
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Mexico City, Mexico
| | - Nimbe Torres
- Department of Nutrition Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Mexico City, Mexico
| | - Norma A Bobadilla
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Mexico City, Mexico
- Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Mexico City, Mexico
| | - Armando R Tovar
- Department of Nutrition Physiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Mexico City, Mexico
| | - Gerardo Gamba
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Mexico City, Mexico
- Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Mexico City, Mexico
- Tecnologico de Monterrey, Escuela de Medicina y de Ciencias de la Salud, Monterrey, Mexico
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Rafieian-Kopaei M, Beigrezaei S, Nasri H, Kafeshani M. Soy Protein and Chronic Kidney Disease: An Updated Review. Int J Prev Med 2017; 8:105. [PMID: 29416834 PMCID: PMC5760843 DOI: 10.4103/ijpvm.ijpvm_244_17] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 08/23/2017] [Indexed: 12/31/2022] Open
Abstract
Chronic kidney disease (CKD) is a serious universal problem that is the main risk for several diseases including cardiovascular disease. Dietary factors are important to prevent and control the kidney disease. Some evidence has shown that modifying the amount and the types of dietary protein exert a major effect on renal failure so limiting dietary protein and substituting animal protein with soy protein has suggested. However, there is a lot of controversy about it, especially in human. Thus, this paper will review the clinical trial studies conducted on the effects of soy protein intake on CKD in both animal and human and its effect mechanism.
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Affiliation(s)
| | - Sara Beigrezaei
- Department of Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hamid Nasri
- Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Marzieh Kafeshani
- Department of Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
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Vegetarian Diet in Chronic Kidney Disease-A Friend or Foe. Nutrients 2017; 9:nu9040374. [PMID: 28394274 PMCID: PMC5409713 DOI: 10.3390/nu9040374] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 03/10/2017] [Accepted: 04/05/2017] [Indexed: 12/17/2022] Open
Abstract
Healthy diet is highly important, especially in patients with chronic kidney disease (CKD). Proper nutrition provides the energy to perform everyday activities, prevents infection, builds muscle, and helps to prevent kidney disease from getting worse. However, what does a proper diet mean for a CKD patient? Nutrition requirements differ depending on the level of kidney function and the presence of co-morbid conditions, including hypertension, diabetes, and cardiovascular disease. The diet of CKD patients should help to slow the rate of progression of kidney failure, reduce uremic toxicity, decrease proteinuria, maintain good nutritional status, and lower the risk of kidney disease-related secondary complications (cardiovascular disease, bone disease, and hypertension). It has been suggested that plant proteins may exert beneficial effects on blood pressure, proteinuria, and glomerular filtration rate, as well as results in milder renal tissue damage when compared to animal proteins. The National Kidney Foundation recommends vegetarianism, or part-time vegetarian diet as being beneficial to CKD patients. Their recommendations are supported by the results of studies demonstrating that a plant-based diet may hamper the development or progression of some complications of chronic kidney disease, such as heart disease, protein loss in urine, and the progression of kidney damage. However, there are sparse reports suggesting that a vegan diet is not appropriate for CKD patients and those undergoing dialysis due to the difficulty in consuming enough protein and in maintaining proper potassium and phosphorus levels. Therefore, this review will focus on the problem as to whether vegetarian diet and its modifications are suitable for chronic kidney disease patients.
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Rice endosperm protein slows progression of fatty liver and diabetic nephropathy in Zucker diabetic fatty rats. Br J Nutr 2016; 116:1326-1335. [PMID: 27724997 DOI: 10.1017/s0007114516003512] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
We previously reported that rice endosperm protein (REP) has renoprotective effects in Goto-Kakizaki rats, a non-obese diabetic model. However, whether these effects occur in obese diabetes remains unclear. This study aimed to clarify the effects of REP on obese diabetes, especially on fatty liver and diabetic nephropathy, using the obese diabetic model Zucker diabetic fatty (ZDF) rats. In total, 7-week-old male ZDF rats were fed diets containing 20 % REP or casein (C) for 8 weeks. Changes in fasting blood glucose levels and urinary markers were monitored during the experimental period. Hepatic lipids and metabolites were measured and renal glomeruli were observed morphologically. HbA1c levels were significantly lower in rats fed REP, compared with C (P<0·05). Compared with C in the liver, REP prevented lipid accumulation (total lipid, TAG and total cholesterol, P<0·01). Liver metabolome analysis indicated that levels of metabolites associated with glycolysis, the pentose phosphate pathway and carnitine metabolism were significantly greater in the REP group than in the C group (P<0·05), suggesting activation of both glucose catabolism and fatty acid oxidation. The metabolite increases promoted by REP may contribute to suppression of liver lipid accumulation. Urinary excretion of albumin and N-acetyl-β-d-glucosaminidase was significantly reduced in rats fed REP for 8 weeks (P<0·01). In addition, there was a distinct suppression of mesangial matrix expansion and glomerular hypertrophy in response to REP (P<0·01). Thus, REP had preventive effects on obese diabetes, fatty liver and diabetic nephropathy.
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McGraw NJ, Krul ES, Grunz-Borgmann E, Parrish AR. Soy-based renoprotection. World J Nephrol 2016; 5:233-257. [PMID: 27152261 PMCID: PMC4848148 DOI: 10.5527/wjn.v5.i3.233] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Revised: 01/16/2016] [Accepted: 03/14/2016] [Indexed: 02/06/2023] Open
Abstract
Chronic kidney disease (CKD) is a significant public health problem as risk factors such as advanced age, obesity, hypertension and diabetes rise in the global population. Currently there are no effective pharmacologic treatments for this disease. The role of diet is important for slowing the progression of CKD and managing symptoms in later stages of renal insufficiency. While low protein diets are generally recommended, maintaining adequate levels of intake is critical for health. There is an increasing appreciation that the source of protein may also be important. Soybean protein has been the most extensively studied plant-based protein in subjects with kidney disease and has demonstrated renal protective properties in a number of clinical studies. Soy protein consumption has been shown to slow the decline in estimated glomerular filtration rate and significantly improve proteinuria in diabetic and non-diabetic patients with nephropathy. Soy’s beneficial effects on renal function may also result from its impact on certain physiological risk factors for CKD such as dyslipidemia, hypertension and hyperglycemia. Soy intake is also associated with improvements in antioxidant status and systemic inflammation in early and late stage CKD patients. Studies conducted in animal models have helped to identify the underlying molecular mechanisms that may play a role in the positive effects of soy protein on renal parameters in polycystic kidney disease, metabolically-induced kidney dysfunction and age-associated progressive nephropathy. Despite the established relationship between soy and renoprotection, further studies are needed for a clear understanding of the role of the cellular and molecular target(s) of soy protein in maintaining renal function.
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Chen X, Wei G, Jalili T, Metos J, Giri A, Cho ME, Boucher R, Greene T, Beddhu S. The Associations of Plant Protein Intake With All-Cause Mortality in CKD. Am J Kidney Dis 2015; 67:423-30. [PMID: 26687923 DOI: 10.1053/j.ajkd.2015.10.018] [Citation(s) in RCA: 118] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2015] [Accepted: 10/10/2015] [Indexed: 01/29/2023]
Abstract
BACKGROUND Plant protein intake is associated with lower production of uremic toxins and lower serum phosphorus levels. Therefore, at a given total protein intake, a higher proportion of dietary protein from plant sources might be associated with lower mortality in chronic kidney disease. STUDY DESIGN Observational study. SETTINGS & PARTICIPANTS 14,866 NHANES III participants 20 years or older without missing data for plant and animal protein intake and mortality. PREDICTORS Plant protein to total protein ratio and total plant protein intake. Patients were stratified by estimated glomerular filtration rate (eGFR)<60 or ≥60mL/min/1.73m(2). OUTCOMES All-cause mortality. MEASUREMENTS Plant and total protein intakes were estimated from 24-hour dietary recalls. Mortality was ascertained by probabilistic linkage with National Death Index records through December 31, 2000. RESULTS Mean values for plant protein intake and plant protein to total protein ratio were 24.6±13.2 (SD) g/d and 33.0% ± 14.0%, respectively. The prevalence of eGFRs<60mL/min/1.73m(2) was 4.9%. There were 2,163 deaths over an average follow-up of 8.4 years. Adjusted for demographics, smoking, alcohol use, comorbid conditions, body mass index, calorie and total protein intake, and physical inactivity, each 33% increase in plant protein to total protein ratio was not associated with mortality (HR, 0.88; 95% CI, 0.74-1.04) in the eGFR≥60mL/min/1.73m(2) subpopulation, but was associated with lower mortality risk (HR, 0.77; 95% CI, 0.61-0.96) in the eGFR<60mL/min/1.73m(2) subpopulation. In sensitivity analyses, results were similar in those with eGFR<60mL/min/1.73m(2) defined by serum cystatin C level. LIMITATIONS Whether results are related to plant protein itself or to other factors associated with more plant-based diets is difficult to establish. CONCLUSIONS A diet with a higher proportion of protein from plant sources is associated with lower mortality in those with eGFR<60mL/min/1.73m(2). Future studies are warranted to determine the causal role of plant protein intake in reducing mortality in those with eGFR<60mL/min/1.73m(2).
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Affiliation(s)
- Xiaorui Chen
- Department of Nephrology, University of Utah School of Medicine, Salt Lake City, UT; Division of Nutrition, University of Utah, Salt Lake City, UT
| | - Guo Wei
- Department of Nephrology, University of Utah School of Medicine, Salt Lake City, UT
| | - Thunder Jalili
- Division of Nutrition, University of Utah, Salt Lake City, UT
| | - Julie Metos
- Division of Nutrition, University of Utah, Salt Lake City, UT
| | - Ajay Giri
- Department of Nephrology, University of Utah School of Medicine, Salt Lake City, UT
| | - Monique E Cho
- Department of Nephrology, University of Utah School of Medicine, Salt Lake City, UT; VA Healthcare System, Salt Lake City, UT
| | - Robert Boucher
- Department of Nephrology, University of Utah School of Medicine, Salt Lake City, UT
| | - Tom Greene
- VA Healthcare System, Salt Lake City, UT
| | - Srinivasan Beddhu
- Department of Nephrology, University of Utah School of Medicine, Salt Lake City, UT; VA Healthcare System, Salt Lake City, UT.
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Pandey G, Makhija E, George N, Chakravarti B, Godbole MM, Ecelbarger CM, Tiwari S. Insulin regulates nitric oxide production in the kidney collecting duct cells. J Biol Chem 2014; 290:5582-91. [PMID: 25533472 DOI: 10.1074/jbc.m114.592741] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
The kidney is an important organ for arterial blood pressure (BP) maintenance. Reduced NO generation in the kidney is associated with hypertension in insulin resistance. NO is a critical regulator of vascular tone; however, whether insulin regulates NO production in the renal inner medullary collecting duct (IMCD), the segment with the greatest enzymatic activity for NO production in kidney, is not clear. Using an NO-sensitive 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM) fluorescent dye, we found that insulin increased NO production in mouse IMCD cells (mIMCD) in a time- and dose-dependent manner. A concomitant dose-dependent increase in the NO metabolite (NOx) was also observed in the medium from insulin-stimulated cells. NO production peaked in mIMCD cells at a dose of 100 nm insulin with simultaneously increased NOx levels in the medium. At this dose, insulin significantly increased p-eNOS(Ser1177) levels in mIMCD cells. Pretreatment of cells with a PI 3-kinase inhibitor or insulin receptor silencing with RNA interference abolished these effects of insulin, whereas insulin-like growth factor-1 receptor (IGF-1R) silencing had no effect. We also showed that chronic insulin infusion to normal C57BL/6J mice resulted in increased endothelial NOS (eNOS) protein levels and NO production in the inner medulla. However, insulin-infused IRKO mice, with targeted deletion of insulin receptor from tubule epithelial cells of the kidney, had ∼50% reduced eNOS protein levels in their inner medulla along with a significant rise in BP relative to WT littermates. We have previously reported increased baseline BP and reduced urine NOx in IRKO mice. Thus, reduced insulin receptor signaling in IMCD could contribute to hypertension in the insulin-resistant state.
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Affiliation(s)
- Gaurav Pandey
- From the Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India and
| | - Ekta Makhija
- From the Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India and
| | - Nelson George
- From the Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India and
| | - Bandana Chakravarti
- From the Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India and
| | - Madan M Godbole
- From the Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India and
| | - Carolyn M Ecelbarger
- the Division of Endocrinology and Metabolism, Department of Medicine, Georgetown University, Washington, D. C. 2007
| | - Swasti Tiwari
- From the Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India and
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14
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Liu ZM, Ho SC, Chen YM, Tang N, Woo J. Effect of whole soy and purified isoflavone daidzein on renal function--a 6-month randomized controlled trial in equol-producing postmenopausal women with prehypertension. Clin Biochem 2014; 47:1250-6. [PMID: 24877660 DOI: 10.1016/j.clinbiochem.2014.05.054] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2014] [Revised: 05/14/2014] [Accepted: 05/15/2014] [Indexed: 01/12/2023]
Abstract
OBJECTIVES The aim of the study was to examine the long-term effect of commonly used whole soy foods (soy flour) and purified daidzein (one major isoflavone and the precursor of equol) on renal function among prehypertensive postmenopausal women who are also equol producers, a population most likely to benefit from soy intervention. DESIGN AND METHODS This was a 6-month double-blind, randomized, placebo-controlled trial. Two hundred seventy eligible Chinese women were randomized to either one of the three treatments: 40 g soy flour (whole soy group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group) or 40 g low-fat milk powder (placebo group) daily each for 6 months. Fasting blood and 24-h urine samples were collected at the beginning and end of trial. Serum creatinine, cystatin C, urea, angiotensin-converting enzyme, minerals and 24-h urinary creatinine and minerals were analyzed. Estimated glomerular filtration rate (eGFR) was calculated with the Cockcroft-Gault and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. RESULTS Two hundred fifty-three subjects completed the study according to the protocol. Urinary isoflavones indicated good compliance of participants. No significant changes were observed in most of renal parameters, however, there was a less decrease in eGFRcockcroft in 6-month change (p=0.044) and %change (p=0.031) with whole soy intake relative to milk placebo. Subgroup analysis among women with lowered renal function suggested whole soy consumption tended to improve markers of renal function relative to control. CONCLUSIONS Six-month consumption of whole soy tended to have a modest improvement of renal function in prehypertensive postmenopausal women with lowered renal function. Future trials in subjects with more declined renal function are necessary. TRIAL REGISTRATION The trial was registered in ClinicalTrials.gov with identifier of NCT01270737. (URL: http://clinicaltrials.gov/ct2/show/NCT01270737).
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Affiliation(s)
- Zhao-min Liu
- Department of Medicine &Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR
| | - Suzanne C Ho
- Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong SAR.
| | - Yu-ming Chen
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, PR China
| | - Nelson Tang
- Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR
| | - Jean Woo
- Department of Medicine &Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR.
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15
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Rice protein ameliorates the progression of diabetic nephropathy in Goto–Kakizaki rats with high-sucrose feeding. Br J Nutr 2013; 110:1211-9. [DOI: 10.1017/s0007114513000354] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The effect of rice protein (RP) on diabetic nephropathy in non-obese, spontaneous type 2 diabetic Goto–Kakizaki (GK) rats was investigated. GK rats at 7 weeks of age were fed 20 % RP or casein (C) in standard or high-sucrose diets for 10 weeks. Plasma total cholesterol, TAG, alkaline phosphatase (ALP), adiponectin, creatinine and urinary albumin excretion (UAE) were measured and renal histology was evaluated. Compared with C, RP lowered plasma TAG and improved plasma adiponectin levels in GK rats fed the standard diet (P< 0·05), and also lowered total cholesterol and ALP in high-sucrose-fed GK rats (P< 0·05). RP markedly suppressed the sharp increase in UAE when GK rats were fed high-sucrose diets (P< 0·05), and prevented glomerular mesangial matrix expansion in the deep renal cortex near the corticomedullary junction (P< 0·05). These results strongly indicate that dietary RP can ameliorate the progression of diabetic nephropathy at an early stage compared with C.
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16
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García IM, Mazzei L, Benardón ME, Oliveros L, Cuello-Carrión FD, Gil Lorenzo A, Manucha W, Vallés PG. Caveolin-1-eNOS/Hsp70 interactions mediate rosuvastatin antifibrotic effects in neonatal obstructive nephropathy. Nitric Oxide 2012; 27:95-105. [PMID: 22683596 DOI: 10.1016/j.niox.2012.05.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2012] [Revised: 05/26/2012] [Accepted: 05/29/2012] [Indexed: 11/29/2022]
Abstract
Evidence suggesting that statins may contribute to renoprotection has been provided in experimental and clinical studies. Statins restore endothelial nitric oxide (NO) levels by mechanisms including up-regulation of endothelial NO synthase (eNOS) expression. Caveolin-1/eNOS interaction is essential preventing inadequate NO levels. Here, we evaluated whether caveolin-1 associated with eNOS/Hsp70 expression may be involved in the mechanism by which rosuvastatin exerts tubulointerstitial fibrosis protection in neonatal unilateral ureteral obstruction (UUO). Neonatal rats subjected to UUO within 2 days of birth and controls were treated daily with vehicle or rosuvastatin (10 mg/kg/day) by oral gavage for 14 days. After UUO, morphometric evaluation of interstitial fibrosis showed increased interstitial volume (Vv) associated with reduced NO availability, increased mRNA and protein caveolin-1 expression as well as downregulation eNOS and heat shock protein 70 (Hsp70) expression. Conversely, rosuvastatin treatment attenuated the fibrotic response linked to high NO availability, decreased mRNA and protein caveolin-1 expression, and marked upregulation of eNOS and Hsp70 expression at transcriptional and posttranscriptional levels. Moreover, protein-protein interactions determined by immunoprecipitation and by immunofluorescence co-localization have shown decreased caveolin-1/eNOS as well as increased Hsp70/eNOS interaction, after rosuvastatin treatment. A dose dependent effect of rosuvastatin on decreased caveolin-1 expression was shown in control cortex. In conclusion, our data suggest that statins contribute to the protection against tubulointerstitial fibrosis injury in neonatal early kidney obstruction by increased NO availability, involving interaction of up-regulated eNOS/Hsp70 and down-regulated caveolin-1.
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Affiliation(s)
- Isabel Mercedes García
- Área de Fisiopatología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina
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17
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Asanoma M, Tachibana N, Hirotsuka M, Kohno M, Watanabe Y. Effects of soy protein isolate feeding on severe kidney damage in DOCA salt-treated obese Zucker rats. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2012; 60:5367-5372. [PMID: 22553937 DOI: 10.1021/jf300598a] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
This study assessed the effects of soy protein isolate (SPI) on severe kidney damage in deoxycorticosterone acetate (DOCA) salt-treated obese Zucker rats. These rats underwent heminephrectomy and were fed either casein or SPI diet for 12 weeks. From weeks 8 to 10 of the experiment, kidney damage was induced by biweekly injection of 25 mg/kg DOCA and administration of 0.5% NaCl (w/v) ad libitum. Urinary protein and N-acetyl-β-d-glucosaminidase excretions of SPI rats were much lower than those of casein rats at weeks 1 (p < 0.01) and 2 (p < 0.05) after DOCA treatment. Abnormal mineral excretions induced by DOCA treatment in casein rats were hardly detected in SPI rats. Severe atrophy of tubular epithelium and some flattened/detached renal tubules were also observed in casein rats, but not in SPI rats. These results indicate that consecutive treatment of SPI protects against renal dysfunction, particularly tubulointerstitial nephritis, in DOCA salt-treated obese Zucker rats.
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Affiliation(s)
- Masashi Asanoma
- Nutrition and Health Department, Food Science Research Institute, Fuji Oil Company Ltd., Izumisano-shi, Osaka 598-8540, Japan.
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18
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Whaley-Connell A, Pulakat L, DeMarco VG, Hayden MR, Habibi J, Henriksen EJ, Sowers JR. Overnutrition and the Cardiorenal Syndrome: Use of a Rodent Model to Examine Mechanisms. Cardiorenal Med 2011; 1:23-30. [PMID: 22258463 DOI: 10.1159/000322827] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Obesity has reached epidemic proportions with far-reaching health care and economic implications. Overnutrition, characterized by excess intake of carbohydrates and fats, has been associated with end-organ damage in several tissues, including the heart and the kidney. Furthermore, overnutrition is one of the most important modifiable and preventable causes of morbidity and mortality associated with cardiovascular and kidney diseases. Insulin resistance and compensatory hyperinsulinemia as well as associated mechanisms, including enhanced renin-angiotensin-aldosterone system activity, inflammation, and oxidative stress, have been implicated in obesity-related cardiorenal injury. In this review, the effect of overnutrition on heart and kidney disease is assessed in a rodent model of overnutrition and obesity, the Zucker obese rat.
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19
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Mima A, Ohshiro Y, Kitada M, Matsumoto M, Geraldes P, Li C, Li Q, White GS, Cahill C, Rask-Madsen C, King GL. Glomerular-specific protein kinase C-β-induced insulin receptor substrate-1 dysfunction and insulin resistance in rat models of diabetes and obesity. Kidney Int 2011; 79:883-96. [PMID: 21228767 DOI: 10.1038/ki.2010.526] [Citation(s) in RCA: 111] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Insulin resistance has been associated with the progression of chronic kidney disease in both diabetes and obesity. In order to determine the cellular mechanisms contributing to this, we characterized insulin signaling in renal tubules and glomeruli during diabetic and insulin-resistant states using streptozotocin-diabetic and Zucker fatty-insulin-resistant rats. Compared with nondiabetic and Zucker lean rats, the insulin-induced phosphorylation of insulin receptor substrate-1 (IRS1), Akt, endothelial nitric oxide synthase, and glycogen synthase kinase 3α were selectively inhibited in the glomeruli but not in the renal tubules of both respective models. Protein, but not mRNA levels of IRS1, was decreased only in the glomeruli of streptozotocin-diabetic rats likely due to increased ubiquitination. Treatment with the protein kinase C-β inhibitor, ruboxistaurin, enhanced insulin actions and elevated IRS1 expression. In glomerular endothelial cells, high glucose inhibited the phosphorylation of Akt, endothelial nitric oxide synthase, and glycogen synthase kinase 3α; decreased IRS1 protein expression and increased its association with ubiquitin. Overexpression of IRS1 or the addition of ruboxistaurin reversed the inhibitory effects of high glucose. Thus, loss of insulin's effect on endothelial nitric oxide synthase and glycogen synthase kinase 3α activation may contribute to the glomerulopathy observed in diabetes and obesity.
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Affiliation(s)
- Akira Mima
- Section of Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
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20
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Different effects of isoflavones on vascular function in premenopausal and postmenopausal smokers and nonsmokers: NYMPH study. Heart Vessels 2011; 26:590-5. [PMID: 21221602 DOI: 10.1007/s00380-010-0103-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2010] [Accepted: 11/05/2010] [Indexed: 10/18/2022]
Abstract
Isoflavone intake has been associated with a reduction in the risk of cardiovascular disease in postmenopausal women. The aim of the present study was to determine if the effects of isoflavones on vascular function differ between premenopausal and postmenopausal women and between women who smoke and those who do not. Women smokers and nonsmokers who consumed 50 mg of isoflavone/day as black soybean tea for a period of 2 months (n = 55, mean age 39) were enrolled in the present study. We examined endothelial function, which was assessed by the percent change in flow-mediated dilation (%FMD) and arterial wall stiffness using the cardio-ankle vascular index (CAVI), as well as by biochemical parameters of the blood. Neither premenopausal (p = 0.697) nor postmenopausal (p = 0.389) smokers experienced an increase in %FMD after daily consumption of isoflavones. However, both premenopausal (p = 0.004) and postmenopausal (p = 0.019) nonsmokers exhibited a marked elevation in %FMD. By contrast, isoflavone intake effectively reduced CAVI among both premenopausal smokers (p = 0.027) and nonsmokers (p = 0.013), but had no effect on CAVI among postmenopausal smokers (p = 0.169) or nonsmokers (p = 0.128). The women smokers and nonsmokers did not differ in age or %FMD at the time of enrollment in the study. Thus, isoflavones have different effects on vascular endothelial function and arterial wall stiffness in premenopausal and postmenopausal smokers and nonsmokers.
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21
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Hakkak R, Shaaf S, Jo CH, Macleod S, Korourian S. Effects of high-isoflavone soy diet vs. casein protein diet and obesity on DMBA-induced mammary tumor development. Oncol Lett 2010; 2:29-36. [PMID: 22870124 DOI: 10.3892/ol.2010.202] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2010] [Accepted: 10/21/2010] [Indexed: 01/11/2023] Open
Abstract
Obesity and elevated serum insulin growth factor-1 (IGF-1) level are major risk factors in the development of breast cancer. We investigated the long-term effects of high-isoflavone soy intake and obesity on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumor development and on serum IGF-1 and binding protein (IGFBP-3) levels. Lean and obese female Zucker rats fed casein or high-isoflavone soy protein were orally gavaged at age 50 days with DMBA and sacrificed after 147 days. The majority of lean casein-fed rats (69%) developed mammary tumors compared to 50% in lean soy-fed rats (P=0.176). In the obese groups, 76% of soy-fed rats developed mammary tumors compared to 15% of obese casein-fed rats (P<0.001). At age 43 days, IGFBP-3 was increased in the lean soy-fed rats compared to the lean casein-fed rats (P<0.05). At age 99 days, soy- and obese casein-fed rats exhibited increased serum IGF-1 compared to the lean rats and this increase was maintained for the rest of the experiment (P<0.05). Obese rats fed casein exhibited increased IGFBP-3 levels (P<0.001). However, obese rats fed soy exhibited a significant decrease in IGFBP-3 levels compared to the lean soy-fed rats (P<0.001) and a significant decrease in IGFBP-3 levels compared to the obese casein-fed rats (P<0.001). At age 197 days, IGFBP-3 levels were increased in obese casein-and soy-fed rats (P<0.001). The results suggest that female Zucker rats fed casein diets are protected against DMBA-induced mammary tumors, which is not the case for those on high-isoflavone soy diet, and changes in the concentration of serum IGFBP-3 may contribute to the incidence of DMBA-induced mammary tumors.
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Affiliation(s)
- Reza Hakkak
- Department of Dietetics and Nutrition, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
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22
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Siow RCM, Mann GE. Dietary isoflavones and vascular protection: activation of cellular antioxidant defenses by SERMs or hormesis? Mol Aspects Med 2010; 31:468-77. [PMID: 20837051 DOI: 10.1016/j.mam.2010.09.003] [Citation(s) in RCA: 81] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2010] [Accepted: 09/02/2010] [Indexed: 12/14/2022]
Abstract
During the past decade nutrigenomic studies in humans, animal models and cultured cells have provided important and novel insights into the mechanisms by which dietary isoflavones afford protection against vascular dysfunction through the amelioration of oxidative modifications and upregulation of endogenous antioxidant signaling pathways. In this review, we highlight that increased generation of nitric oxide (NO) and reactive oxygen species (ROS) in the vessel wall in response to dietary isoflavones enhance the activity of antioxidant defense enzymes in endothelial and smooth muscle cells. The estrogenic properties of isoflavones are likely to contribute to the molecular mechanisms by which these compounds activate signal transduction pathways involved in sustaining endothelial function and transcriptional activation of antioxidant defense genes in vascular cells. We evaluate the recent literature that estrogenic and hormetic properties of phytoestrogens are of benefit for the maintenance of vascular function, and conclude that dietary isoflavones can protect against cardiovascular diseases by virtue of their ability to activate signaling pathways leading to increased NO bioavailability and regulation of phase II and antioxidant enzyme expression via the redox sensitive transcription factor Nrf2. In context of epigenetics and the developmental origins of adult disease, it is noteworthy that exposure to dietary soy during fetal development reduces the susceptibility to CVD and obesity in adulthood. Thus, the Nrf2/Keap1 defense pathway provides a key mechanism by which isoflavones can act as hormetic agents to modulate intracellular redox signaling in the vasculature to prolong healthspan and reduce the incidence of age-related cardiovascular diseases.
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Affiliation(s)
- Richard C M Siow
- Cardiovascular Division, British Heart Foundation Centre of Research Excellence, School of Medicine, King's College London, 150 Stamford Street, London SE1 9NH, UK
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23
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Schreihofer DA, Deutsch C, Lovekamp-Swan T, Sullivan JC, Dorrance AM. Effect of high soy diet on the cerebrovasculature and endothelial nitric oxide synthase in the ovariectomized rat. Vascul Pharmacol 2010; 52:236-42. [PMID: 20197113 PMCID: PMC2921790 DOI: 10.1016/j.vph.2010.02.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2009] [Revised: 01/21/2010] [Accepted: 02/24/2010] [Indexed: 10/19/2022]
Abstract
High soy (HS) diets are neuroprotective and promote vascular dilatation in the periphery. We hypothesized that an HS diet would promote vascular dilatation in the cerebrovasculature by mimicking estradiol's actions on the endothelial nitric oxide synthase (eNOS) system including increasing eNOS expression and decreasing caveolin-1 expression to increase nitric oxide (NO) production. Ovariectomized rats were fed HS or a soy-free diet (SF)+/-low physiological estradiol (E2) for 4weeks. Neither E2 nor HS altered middle cerebral artery (MCA) structure or vascular responses to acetylcholine, serotonin, or phenylephrine. Estradiol enhanced bradykinin-induced relaxation in an eNOS-dependent manner. Although E2 and HS increased eNOS mRNA expression in the brain and cerebrovasculature, they had no effect on eNOS protein expression or phosphorylation in the MCA. However, E2 decreased caveolin-1 protein in the MCA. In MCAs neither E2 nor HS altered estrogen receptor (ER) alpha expression, but E2 did reduce ER beta levels. These data suggest that HS diets have no effect on vascular NO production, and that E2 may modulate basal NO production by reducing the expression of caveolin-1, an allosteric inhibitor of NOS activity. However, the effects of E2 and HS on the cerebrovasculature are small and may not underlie their protective actions in pathological states.
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Affiliation(s)
- Derek A Schreihofer
- Department of Physiology, Medical College of Georgia, Augusta, GA 30912-3000, USA.
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24
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Jang EH, Ko JH, Ahn CW, Lee HH, Shin JK, Chang SJ, Park CS, Kang JH. In vivo and in vitro application of black soybean peptides in the amelioration of endoplasmic reticulum stress and improvement of insulin resistance. Life Sci 2010; 86:267-74. [PMID: 20045417 DOI: 10.1016/j.lfs.2009.12.012] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2009] [Revised: 12/04/2009] [Accepted: 12/17/2009] [Indexed: 12/16/2022]
Abstract
AIMS Hepatic endoplasmic reticulum (ER) stress plays a key role in the development of obesity-induced insulin resistance. This study evaluated the effects of peptides from black soybean (BSP) on ER stress and insulin signaling in vitro and in vivo. MAIN METHODS Using C2C12 myotubes or HepG2 cells, we evaluated the effects of BSP on the expression of proteins involved in insulin signaling and in the ER stress response in insulin-sensitive or insulin-resistant cells. BSP was given orally to db/db mice for 5weeks to investigate its antidiabetic effects in vivo and the underlying mechanisms. KEY FINDINGS BSP increased GLUT4 translocation and glucose transport in myotubes and stimulated Akt-mediated glycogen synthase kinase-3beta (GSK-3beta) and Foxo1 phosphorylation in HepG2 cells. BSP significantly restored the suppression of insulin-mediated Akt phosphorylation in insulin-resistant cells. BSP significantly inhibited the activation of ER stress-responsive proteins by thapsigargin. BSP also significantly reduced blood glucose and improved glucose tolerance in db/db mice. The serum lipid profile (triglyceride and high-density lipoprotein concentrations) improved concomitantly with the BSP-induced downregulation of hepatic fatty acid synthase expression in db/db mice. Consistent with the results observed in HepG2 cells, BSP downregulated the elevated hepatic ER stress response in diabetic mice concomitantly with an increased expression of phospho-Foxo1. SIGNIFICANCE A peptide mixture, BSP, showed beneficial effects through multiple mechanisms involving the suppression of hepatic ER stress and restoration of insulin resistance, suggesting that it has potential as an antidiabetic agent.
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Affiliation(s)
- Eun-Hee Jang
- Department of Pharmacology and Medicinal Toxicology Research Center, Inha Research Institute for Medical Sciences, College of Medicine, South Korea
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25
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Kwon DY, Daily JW, Kim HJ, Park S. Antidiabetic effects of fermented soybean products on type 2 diabetes. Nutr Res 2010; 30:1-13. [PMID: 20116654 DOI: 10.1016/j.nutres.2009.11.004] [Citation(s) in RCA: 220] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2009] [Revised: 11/12/2009] [Accepted: 11/15/2009] [Indexed: 12/15/2022]
Abstract
Historically, the incidence of type 2 diabetes has been lower in Asian populations compared with those in Western countries. One possible reason for the lower incidence among Asians is that they consume fermented soybean products, which are unique to the traditional Asian diet. Some have hypothesized that dietary phytoestrogens and soy peptides in fermented soybean foods consumed in traditional Asian diets may help prevent and slow the progression of type 2 diabetes. This review evaluates the existing evidence from animal studies and clinical and epidemiologic investigations on fermented soybeans in the prevention and treatment of type 2 diabetes. Nutritional studies performed in animals and intervention studies with humans suggest that the ingestion of soy protein with isoflavones improves glucose control and reduces insulin resistance. Korean fermented soybean products such as doenjang, kochujang, and chungkookjang contain alterations in the structures and content of isoflavonoids and small bioactive peptides, which are produced during fermentation. Several studies revealed improvements in insulin resistance and insulin secretion with the consumption of these fermented products. Therefore, fermented soybean products may help prevent or attenuate the progression of type 2 diabetes. Although the lack of human intervention trials does not permit definitive conclusions, the evidence does suggest that fermented soy products may be better for preventing or delaying the progression of type 2 diabetes compared with nonfermented soybeans.
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Affiliation(s)
- Dae Young Kwon
- Emerging Innovative Technology Research Division, Korean Food Research Institutes, Sungnam, Korea
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26
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Mann GE, Bonacasa B, Ishii T, Siow RCM. Targeting the redox sensitive Nrf2–Keap1 defense pathway in cardiovascular disease: protection afforded by dietary isoflavones. Curr Opin Pharmacol 2009; 9:139-45. [DOI: 10.1016/j.coph.2008.12.012] [Citation(s) in RCA: 125] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2008] [Accepted: 12/11/2008] [Indexed: 12/30/2022]
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27
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McCarty MF. Isoflavones Made Simple – Agonist Activity for the Beta-Type Estrogen Receptor May Mediate Their Health Benefits. COMPLEMENTARY AND ALTERNATIVE THERAPIES AND THE AGING POPULATION 2009:475-522. [DOI: 10.1016/b978-0-12-374228-5.00024-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Yang HY, Chen JR. Renoprotective effects of soy protein hydrolysates in N(omega)-nitro-L-arginine methyl ester hydrochloride-induced hypertensive rats. Hypertens Res 2008; 31:1477-83. [PMID: 18957819 DOI: 10.1291/hypres.31.1477] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Pepsin-digested soy protein hydrolysate (SPH) has been reported to be responsible for many of the physiological benefits associated with soy protein consumption. In the present study, we investigated the effects of SPH with angiotensin-converting enzyme (ACE) inhibitory potential on blood pressure and renal injuries in rats with N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertension. Rats were fed a diet containing L-NAME (50 mg/kg body weight) with or without SPH (at 1%, 3%, or 5%) for 6 weeks. We found that ingestion of SPH ameliorated the development of hypertension during the 6-week experimental period. SPH was also found to ameliorate renal function by decreasing urinary protein excretion and elevating the creatinine clearance rate. The levels of kidney ACE activity, malonaldehyde, tumor necrosis factor-a and plasminogen activator inhibitor-1, and the expression of CYP4A decreased in the 5% SPH group. Consumption of 5% SPH also ameliorated renal damage according to the histopathological analysis. These findings suggest that SPH might ameliorate the elevation of blood pressure and show renoprotective effects in nitric oxide (NO)-deficient rats, and one possible mechanism might be mediation via its ACE inhibitory activity.
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Affiliation(s)
- Hsin-Yi Yang
- College of Pharmacy, Taipei Medical University, Taipei, Taiwan
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Trujillo J, Cruz C, Tovar A, Vaidya V, Zambrano E, Bonventre JV, Gamba G, Torres N, Bobadilla NA. Renoprotective mechanisms of soy protein intake in the obese Zucker rat. Am J Physiol Renal Physiol 2008; 295:F1574-82. [PMID: 18815216 DOI: 10.1152/ajprenal.90385.2008] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
We previously showed that long-term consumption of a soy protein diet (SoyP) reduces renal damage in obese Zucker (ObeseZ) rats by restoring urinary NO2 and NO3 excretion (UNO2/NO3V), suggesting that nitric oxide (NO) deficiency may contribute to the renal progression observed in this model. In addition, there is compelling evidence that hyperleptinemia produced deleterious effects on the kidney through its interaction with the short leptin receptor (ObRa). This study was designed to evaluate the contribution of the NO/endothelial NO synthase (eNOS) system, renal oxidative stress, and ObRa expression to the renoprotection conferred by the consumption of a SoyP in ObeseZ rats. Ten lean and ten male ObeseZ rats were included. One-half of each group was fed with a 20% SoyP and the other half with a 20% casein protein diet (CasP) over the course of 160 days. eNOS protein levels and phosphorylation, renal lipoperoxidation (rLPO), and antioxidant enzyme activity were assessed. In addition, renal ObRa, TGF-beta, and kidney injury molecule (Kim-1) mRNA levels, as well as urinary Kim-1 levels, were measured. Renal injury observed in ObeseZ rats fed with CasP was not associated with changes in eNOS expression or phosphorylation. However, this group did present with increased rLPO, reduced catalase activity, and upregulation of ObRa, TGF-beta1, and Kim-1. In contrast, ObeseZ rats fed with a SoyP exhibited a reduction in NOS-Thr495 phosphorylation and rLPO, as well as an enhanced catalase activity. These findings were associated with a significant reduction of ObRa, TGF-beta1, and Kim-1 mRNA levels and urinary Kim-1 protein. Our results show that renoprotection by SoyP in ObeseZ rats is in part mediated by increased NO availability secondary to a reduction in eNOS-T495 phosphorylation and oxidative stress, together with a significant reduction in ObRa and TGF-beta expression.
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Affiliation(s)
- Joyce Trujillo
- Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico
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Effects of N-hexacosanol on nitric oxide synthase system in diabetic rat nephropathy. Mol Cell Biochem 2008; 315:169-77. [DOI: 10.1007/s11010-008-9804-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2008] [Accepted: 05/23/2008] [Indexed: 12/20/2022]
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Jang EH, Moon JS, Ko JH, Ahn CW, Lee HH, Shin JK, Park CS, Kang JH. Novel black soy peptides with antiobesity effects: activation of leptin-like signaling and AMP-activated protein kinase. Int J Obes (Lond) 2008; 32:1161-70. [PMID: 18414417 DOI: 10.1038/ijo.2008.60] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To investigate the mechanisms underlying the antiobesity effects of a novel isoflavone-free peptide mixture (BSP) derived from black soybean. DESIGN Long-term effects of BSP were evaluated in diet-induced obese (DIO) mice fed a high-fat (HF) diet without or with BSP (2, 5 or 10% of energy) for 13 weeks, or for 8 weeks in combination with exercise. Acute effects of BSP on food intake and body weight in rats and leptin-deficient ob/ob mice were evaluated. Cell culture models or tissue extracts were used to investigate the mechanisms underlying the antiobesity effect. MEASUREMENT Total food intake, body weight gain, white adipose tissue (WAT) mass, plasma concentrations of leptin, adiponectin, cholesterol and triglyceride were measured. Janus kinase 2 (JAK2)-dependent signal transducers and activators of the transcription 3 (STAT3) phosphorylation and AMP-activated protein kinase (AMPK) activity were determined using Western-blot in cultured cells or tissue extracts. RESULTS DIO mice fed an HF diet with BSP (2, 5 or 10%) for 13 weeks gained less body weight (21.4, 19.8 or 17.1 g, respectively) than the mice fed an HF diet without BSP (22.6 g) concurrent with inhibition of total food intake in a dose-dependent manner. BSP also significantly decreased food intake in rats and leptin-deficient ob/ob mice. The highest dose of BSP (10%) significantly elevated the plasma adiponectin and decreased plasma triglyceride. BSP activated JAK2-dependent STAT3 in a cell model, and elevated the level of hypothalamic phospho-STAT3 in ob/ob mice. BSP also phosphorylated AMPK and acetyl-CoA carboxylase of C2C12 myocytes in a dose-dependent manner. The antiobesity effect was augmented by low-intensity wheel-based exercise. In exercised mice, BSP significantly decreased periepididymal WAT mass and body weight gain. CONCLUSION These results provided evidences that BSP decreased appetite and HF diet-induced body weight gain particularly in combination with exercise, through leptin-like STAT3 phosphorylation and AMPK activation.
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Affiliation(s)
- E-H Jang
- Department of Pharmacology and Medicinal Toxicology Research Center, Inha Research Institute for Medical Sciences, College of Medicine, Inha University, Incheon, South Korea
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Hwang SY, Taylor CG, Zahradka P, Bankovic-Calic N, Ogborn MR, Aukema HM. Dietary soy protein reduces early renal disease progression and alters prostanoid production in obese fa/fa Zucker rats. J Nutr Biochem 2007; 19:255-62. [PMID: 17656081 DOI: 10.1016/j.jnutbio.2007.03.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2006] [Revised: 03/08/2007] [Accepted: 03/27/2007] [Indexed: 12/21/2022]
Abstract
With the rising incidence of obesity and the metabolic syndrome, obesity-associated nephropathy also has increased. One of the earliest pathologies in the development of this nephropathy is glomerular hyperfiltration and hypertrophy. Dietary soy protein (SP) ameliorates disease progression in several models of renal disease, and vegetable sources of protein, as compared to animal sources of protein, alter renal hemodynamics. Therefore, the effect of dietary SP on early renal disease and prostanoid production was examined in the obese fa/fa Zucker rat. Rats, 6 weeks of age, were given diets containing 17% protein from either SP or egg white (EW) for 8 weeks. Feed consumption and body and kidney weights were significantly greater in fa/fa rats as compared to lean rats. The fa/fa rats also had 139% more proteinuria and kidneys with 43% larger glomeruli. SP feeding did not alter body weights or proteinuria but did result in 6% lower kidney weights (g/100 g body weight) and 16% smaller glomeruli in fa/fa rats. Cyclooxygenase activity as determined by 6-keto prostaglandin F(1alpha) (6-keto PGF(1alpha)) synthesis was lower in fa/fa rats given SP-based diets as compared to those given EW-based diets. Ratios of renal thromboxane (TX) B(2)/6-keto PGF(1alpha) and PGE(2)/6-keto PGF(1alpha) were higher, while TXB(2)/PGE(2) levels were not different in rats given SP diets as compared to those given EW diets, also indicating that dietary SP reduced renal 6-keto PGF(1alpha) levels. These findings suggest that attenuation of early glomerular hypertrophy in young obese fa/fa rats by dietary SP may be mediated by the lower levels of 6-keto PGF(1alpha) since this would be expected to reduce glomerular hyperfiltration.
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Affiliation(s)
- Sun-Young Hwang
- Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada
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Sankaran D, Bankovic-Calic N, Cahill L, Yu-Chen Peng C, Ogborn MR, Aukema HM. Late dietary intervention limits benefits of soy protein or flax oil in experimental polycystic kidney disease. Nephron Clin Pract 2007; 106:e122-8. [PMID: 17622740 DOI: 10.1159/000104836] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2006] [Accepted: 03/14/2007] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND/AIMS Dietary soy protein and flax oil retard kidney disease progression when initiated in the early stages of disease in several experimental models, including the Han:SPRD-cy rat. However, individuals with kidney disease often do not become aware of their condition until injury to the kidney is extensive. The objective of this study was to determine whether initiating these interventions in established disease would alter further progression of renal injury. METHODS Two-month-old adult male Han:SPRD-cy rats were given either a flax oil diet (7% flax oil), a soy protein diet (20% soy protein) or a control diet (7% corn oil, 20% casein) for 4 months. Renal disease progression was assessed by examining morphological, immunohistochemical and biochemical parameters. RESULTS Compared to controls, there was 21-24% less staining of proliferating cells, 21-24% less oxidative damage and 13-15% less renal inflammation in kidneys from rats given dietary soy protein and flax oil. Renal cystic growth and fibrosis and serum creatinine levels were not altered by these dietary treatments. CONCLUSIONS Late intervention with dietary soy protein and flax oil reduces some disease-associated pathologies in established renal disease in Han:SPRD-cy rats. The potential benefits of the antioxidant and anti-inflammatory effects on ultimate renal disease outcome in the long term remains to be determined.
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Affiliation(s)
- Deepa Sankaran
- Departments of Human Nutritional Sciences, University of Manitoba, Winnipeg, Man., Canada
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Bernstein AM, Treyzon L, Li Z. Are High-Protein, Vegetable-Based Diets Safe for Kidney Function? A Review of the Literature. ACTA ACUST UNITED AC 2007; 107:644-50. [PMID: 17383270 DOI: 10.1016/j.jada.2007.01.002] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2006] [Indexed: 12/16/2022]
Abstract
In individuals with chronic kidney disease, high-protein diets have been shown to accelerate renal deterioration, whereas low-protein diets increase the risk of protein malnutrition. Vegetarian diets have been promoted as a way to halt progression of kidney disease while maintaining adequate nutrition. We review the literature to date comparing the effects of animal and vegetable protein on kidney function in health and disease. Diets with conventional amounts of protein, as well as high-protein diets, are reviewed. The literature shows that in short-term clinical trials, animal protein causes dynamic effects on renal function, whereas egg white, dairy, and soy do not. These differences are seen both in diets with conventional amounts of protein and those with high amounts of protein. The long-term effects of animal protein on normal kidney function are not known. Although data on persons with chronic kidney disease are limited, it appears that high intake of animal and vegetable proteins accelerates the underlying disease process not only in physiologic studies but also in short-term interventional trials. The long-term effects of high protein intake on chronic kidney disease are still poorly understood. Several mechanisms have been suggested to explain the different effects of animal and vegetable proteins on normal kidney function, including differences in postprandial circulating hormones, sites of protein metabolism, and interaction with accompanying micronutrients.
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Affiliation(s)
- Adam M Bernstein
- Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA
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Davis J, Higginbotham A, O'Connor T, Moustaid-Moussa N, Tebbe A, Kim YC, Cho KW, Shay N, Adler S, Peterson R, Banz W. Soy protein and isoflavones influence adiposity and development of metabolic syndrome in the obese male ZDF rat. ANNALS OF NUTRITION AND METABOLISM 2007; 51:42-52. [PMID: 17356265 DOI: 10.1159/000100820] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2006] [Accepted: 06/01/2006] [Indexed: 12/18/2022]
Abstract
BACKGROUND/AIMS Previously, we demonstrated that soy protein ameliorates the diabetic phenotype in several rodent models of obesity and metabolic syndrome (MS). This study was designed to further elucidate factors related to adiposity, glycemic control, and renal function in male Zucker Diabetic Fatty (ZDF/Lepr(fa)) rats. METHODS Animals were randomly assigned to one of four diets: control, casein (C); low isoflavone (LIS) soy protein; high isoflavone (HIS) soy protein, or casein + rosiglitazone (CR) for 11 weeks. At sacrifice, physiological, biochemical, and molecular parameters were determined. RESULTS Body weight and total adiposity were higher in LIS and CR diet groups despite lower food intake. Additionally, these animals exhibited differential regulation of adipose-specific proteins (PPAR-gamma and GLUT4) and enzyme activity (FAS and GPDH). HIS-fed animals had reduced total and liver adiposity. Glycemic control was prolonged in both soy-based and rosiglitazone (RGZ) groups. Renal dysfunction was significantly reduced in soy-fed and RGZ-treated rodents as demonstrated by lower levels of proteinuria and dilated tubules with proteinaceous casts. CONCLUSION Collectively, these data provide evidence that soy protein with low or high isoflavone content may have therapeutic significance in reducing severity of diabetes, MS, and renal disease as demonstrated in this preclinical model.
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Affiliation(s)
- Jeremy Davis
- Southern Illinois University, Carbondale, IL 62901-4317, USA
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36
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Cahill LE, Peng CYC, Bankovic-Calic N, Sankaran D, Ogborn MR, Aukema HM. Dietary soya protein during pregnancy and lactation in rats with hereditary kidney disease attenuates disease progression in offspring. Br J Nutr 2007; 97:77-84. [PMID: 17217562 DOI: 10.1017/s0007114507250470] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Dietary soya protein substitution for casein initiated at weaning slows disease progression in animal models of chronic renal disease. As there is increasing evidence that fetal programming can have a significant impact on kidney physiology and function in offspring, the objective of the current study was to determine whether exposure to soya protein in the diet earlier than weaning would have further benefits. Han:SPRD-cy (cy/+) breeder rats were fed a casein-based or soya protein-based diet 2 weeks prior to mating, throughout pregnancy and during lactation. Following this maternal period, 3-week-old pups were given either the same or the alternate diet for a 7-week weaning period. Dietary soya protein compared with casein in the maternal or weaning period both independently resulted in less renal inflammation (macrophage infiltration lower by 24% (P=0.0003) and 32% (P<0.001), respectively). When soya protein was given in both feeding periods, the effect was additive. Soya protein substitution for casein resulted in less oxidative damages as indicated by 28% lower oxidized-LDL staining (P=0.013) when present in the maternal period, or in the weaning period (by 56%, P<0.0001). Renal cell proliferation was reduced by 29-33% (P<0.05) in rats given soya protein whether the exposure was during the maternal or weaning period. Soya protein compared with casein in the maternal period also resulted in 33% (P=0.0013) less proteinuria, indicating superior renal function. Dietary soya protein during pregnancy and lactation represents a potential preventative approach in treating for those with congenital kidney diseases.
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Affiliation(s)
- Leah E Cahill
- Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada
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Osman MM, Khalil A, Ahmed MH. Chloroquine-induced nitric oxide: new treatment for an emerging epidemic of obesity-related glomerulopathy. Diabetes Technol Ther 2006; 8:691-2. [PMID: 17109602 DOI: 10.1089/dia.2006.8.691] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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38
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Ahmed MH, Khalil A, Osman MM. Nitric oxide as treatment for an emerging epidemic of obesity-related glomerulopathy. Diabetes Res Clin Pract 2006; 74:207-8. [PMID: 16787680 DOI: 10.1016/j.diabres.2006.05.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2006] [Accepted: 05/17/2006] [Indexed: 11/24/2022]
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Abstract
PURPOSE OF REVIEW Recent studies have reported an alarming increase in the incidence of obesity-related glomerulopathy, in a context of a worldwide spread of obesity. RECENT FINDINGS Several epidemiological investigations have confirmed that obesity is a significant risk factor for the appearance of proteinuria and end-stage renal disease in a normal population. Obesity-induced hemodynamic changes and glomerular deposition of lipids (partly mediated by sterol regulatory element-binding proteins) play an important role in the pathogenesis of obesity-related renal disease. In addition, the renin-angiotensin-aldosterone system is markedly activated in obesity, adipocytes being an important source of these hormones. Weight loss induces a marked reduction in all renin-angiotensin-aldosterone system components. Patients with reduced renal mass of any origin appeared to be particularly susceptible to the detrimental influence of obesity: body mass index was the most important risk factor for the development of proteinuria and renal insufficiency in patients with unilateral renal agenesis, unilateral nephrectomy and remnant kidneys. Weight loss induces a very important reduction in proteinuria in chronic proteinuric nephropathies of different etiologies. SUMMARY Prevention and treatment of obesity should be a first-line objective in the therapeutic approach of patients with diabetic and nondiabetic chronic renal diseases.
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Affiliation(s)
- Manuel Praga
- Nephrology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
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Torres N, Torre-Villalvazo I, Tovar AR. Regulation of lipid metabolism by soy protein and its implication in diseases mediated by lipid disorders. J Nutr Biochem 2006; 17:365-73. [PMID: 16481155 DOI: 10.1016/j.jnutbio.2005.11.005] [Citation(s) in RCA: 141] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2005] [Revised: 09/30/2005] [Accepted: 11/01/2005] [Indexed: 01/24/2023]
Abstract
Soybeans have a high-quality protein that has been consumed for approximately 5000 years in Oriental countries. The awareness that soy products are healthy has increased their consumption in Western countries. Substantial data from epidemiological surveys and nutritional interventions in humans and animals indicate that soy protein reduces serum total and low-density lipoprotein (LDL) cholesterol and triglycerides as well as hepatic cholesterol and triglycerides. This review examines the evidence on the possible mechanisms for which soy protein has beneficial effects in diabetes, obesity and some forms of chronic renal disease. Consumption of soy protein due to low methionine content reduces serum homocysteine concentration, decreasing the risk of acquiring a cardiovascular disease. On the other hand, soy protein reduces the insulin/glucagon ratio, which in turn down-regulates the expression of the hepatic transcription factor sterol regulatory element binding protein (SREBP)-1. The reduction of this factor decreases the expression of several lipogenic enzymes, decreasing in this way serum and hepatic triglycerides as well as LDL cholesterol and very LDL triglycerides in diabetes and obesity, reducing lipotoxicity in the liver. Soy protein intake also reduces hepatic lipotoxicity by maintaining the number of functional adipocytes, preventing the transfer of fatty acids to extra adipose tissues. Furthermore, soy protein isoflavones stimulate the transcription factor SREBP-2, increasing serum cholesterol clearance. The reduction of serum cholesterol and triglyceride concentrations by soy protein intake produces beneficial effects in the kidney preventing the inflammatory response, increasing the renal flow by releasing endothelial nitric oxide (NO) synthase from the caveolae, facilitating the synthesis of NO. Thus, soy protein consumption may reduce the clinical and biochemical abnormalities in diseases mediated by lipid disorders.
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Affiliation(s)
- Nimbe Torres
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico, DF 14000, Mexico
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Dietary soy modulates endothelium-dependent relaxation in aged male rats: Increased agonist-induced endothelium-derived hyperpolarising factor and basal nitric oxide activity. Free Radic Biol Med 2006; 41:731-9. [PMID: 16895793 DOI: 10.1016/j.freeradbiomed.2006.05.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2006] [Revised: 05/04/2006] [Accepted: 05/15/2006] [Indexed: 11/28/2022]
Abstract
We examined the effects of dietary soy on the contributions of endothelium-derived hyperpolarising factor (EDHF), nitric oxide (NO), and oxidative stress to vascular tone in isolated aortic rings and small mesenteric and pulmonary arteries in vitro. Male Wistar rats were either continuously fed a soy-deficient diet (SD) or switched from a soy-deficient diet to a soy-rich one for 6 months (SW). Contractile responses were generally smaller in arteries from SW rats. In mesenteric arteries, this difference was blunted by L-NAME, but not by charybdotoxin and apamin. Preconstricted SW mesenteric arteries were more sensitive to acetylcholine (ACh) than SD ones. This difference was unaffected by L-NAME but was abolished by charybdotoxin and apamin. Exogenous superoxide dismutase (SOD) and catalase induced powerful relaxations in aortic rings, which were smaller in those from SW rats. In mesenteric and pulmonary arteries, however, they partially inhibited ACh-mediated relaxation, and enhanced PGF(2alpha)-mediated contraction, respectively. Our results suggest that feeding aging male rats a soy-rich diet results in improved agonist-mediated EDHF production and a generalized reduction in contractile force, which is partly due to elevated basal NO. Our data also suggest a prorelaxant role for endogenous H(2)O(2) in small arteries, which is modulated by a soy diet.
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McCarty MF. Isoflavones made simple - genistein's agonist activity for the beta-type estrogen receptor mediates their health benefits. Med Hypotheses 2006; 66:1093-114. [PMID: 16513288 DOI: 10.1016/j.mehy.2004.11.046] [Citation(s) in RCA: 111] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2004] [Accepted: 11/24/2004] [Indexed: 02/06/2023]
Abstract
Soy isoflavones, the focus of much research and controversy, are often referred to as "weak estrogens". In fact, genistein is a relatively potent agonist for the recently characterized beta isoform of the estrogen receptor (ERbeta). The low nanomolar serum concentrations of unconjugated free genistein achieved with high-nutritional intakes of soy isoflavones are near the binding affinity of genistein for this receptor, but are about an order of magnitude lower than genistein's affinity for the "classical" alpha isoform of the estrogen receptor (ERalpha). Moreover, these concentrations are far too low to inhibit tyrosine kinases or topoisomerase II, in vitro activities of genistein often cited as potential mediators of its physiological effects. The thesis that these physiological effects are in fact mediated by ERbeta activation provides a satisfying rationale for genistein's clinical activities. Hepatocytes do not express ERbeta; this explains why soy isoflavones, unlike oral estrogen, neither modify serum lipids nor provoke the prothrombotic effects associated with increased risk for thromboembolic disorders. The lack of uterotrophic activity of soy isoflavones reflects the fact that ERalpha is the exclusive mediator of estrogen's impact in this regard. Vascular endothelium expresses both ERalpha and ERbeta, each of which has the potential to induce and activate nitric oxide synthase; this may account for the favorable influence of soy isoflavones on endothelial function in postmenopausal women and ovariectomized rats. The ERbeta expressed in osteoblasts may mediate the reported beneficial impact of soy isoflavones on bone metabolism. Suggestive evidence that soy-rich diets decrease prostate cancer risk, accords well with the observation that ERbeta appears to play an antiproliferative role in healthy prostate. In the breast, ERalpha promotes epithelial proliferation, whereas ERbeta has a restraining influence in this regard - consistent with the emerging view that soy isoflavones do not increase breast cancer risk, and possibly may diminish it. Premenopausal women enjoy a relative protection from kidney failure; since ERbeta is an antagonist of TGF-beta signaling in mesangial cells, soy isoflavones may have nephroprotective potential. Estrogen also appears to protect women from left ventricular hypertrophy, and recent evidence suggests that this effect is mediated by ERbeta. In conjunction with reports that isoflavones may have a modestly beneficial impact on menopausal symptoms - perhaps reflecting the presence of ERbeta in the hypothalamus - these considerations suggest that soy isoflavone regimens of sufficient potency may represent a safe and moderately effective alternative to HRT in postmenopausal women. Further clinical research is required to characterize the impact of optimal genistein intakes on endothelial and bone function in men. Studies with ERbeta-knockout mice could be helpful for clarifying whether ERbeta does indeed mediate the chief physiological effects of low nanomolar genistein. S-equol, a bacterial metabolite of daidzein, has an affinity for ERbeta nearly as high as that of genistein; whether this compound contributes meaningfully to the physiological efficacy of soy isoflavones in some individuals is still unclear.
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Douglas G, Armitage JA, Taylor PD, Lawson JR, Mann GE, Poston L. Cardiovascular consequences of life-long exposure to dietary isoflavones in the rat. J Physiol 2006; 571:477-87. [PMID: 16410278 PMCID: PMC1796799 DOI: 10.1113/jphysiol.2005.104125] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Dietary soy intake in man is proposed to provide cardiovascular protection, but it is not established whether this property is attributable to the soy protein per se or to associated dietary isoflavones. This investigation aimed to establish whether the dietary isoflavones in soy protein affect cardiovascular function. Ten days prior to mating, male and female Wistar rats were habituated to either a soy based isoflavone rich diet (plasma concentration 1.87 micromol l(-1) isoflavones) or the same diet after isoflavone elution (plasma isoflavone not detectable). Offspring were weaned onto and maintained on the same diet as their dam and sire for 6 months. Blood pressure, and constrictor and dilator responses in the aorta and mesenteric resistance arteries were assessed at 3 and 6 months of age. There was no effect of isoflavone removal from the diet on blood pressure, heart rate, aortic function or mesenteric artery contractile function, at either 3 or 6 months of age. Resistance mesenteric arteries from 6-month-old female rats fed the isoflavone rich diet demonstrated a modest increase in arterial distensibility compared with those fed the depleted diet, and mesenteric arteries from male and female rats fed the isoflavone rich diet showed increased sensitivity to acetylcholine. In summary, the isoflavone content of soy protein has no influence on blood pressure in healthy rats fed a diet based on soy protein, but influences small artery function.
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Affiliation(s)
- G Douglas
- Division of Reproductive Health, Endocrinology and Development, Medical School of Guy's, King's and St Thomas' Hospital, King's College LondonLondon, UK
| | - J A Armitage
- Division of Reproductive Health, Endocrinology and Development, Medical School of Guy's, King's and St Thomas' Hospital, King's College LondonLondon, UK
| | - P D Taylor
- Division of Reproductive Health, Endocrinology and Development, Medical School of Guy's, King's and St Thomas' Hospital, King's College LondonLondon, UK
| | - J R Lawson
- Special Diets ServicesPO Box 705, Witham, Essex, UK
| | - G E Mann
- Cardiovascular Division, King's College London, New Hunts HouseGuy's Campus, London, UK
| | - L Poston
- Division of Reproductive Health, Endocrinology and Development, Medical School of Guy's, King's and St Thomas' Hospital, King's College LondonLondon, UK
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Pérez-Rojas JM, Derive S, Blanco JA, Cruz C, Martínez de la Maza L, Gamba G, Bobadilla NA. Renocortical mRNA expression of vasoactive factors during spironolactone protective effect in chronic cyclosporine nephrotoxicity. Am J Physiol Renal Physiol 2005; 289:F1020-30. [PMID: 15998842 DOI: 10.1152/ajprenal.00166.2005] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
We showed that spironolactone reduced structural damage and prevented renal dysfunction in chronic cyclosporine (CsA) nephrotoxicity. These findings evidenced an aldosterone renal vascular effect under this condition. To investigate aldosterone’s role in modulating renal vascular tone, renocortical vasoactive pathways mRNA levels in chronic CsA nephrotoxicity as well as spironolactone’s effect on renal function in acute CsA nephrotoxicity were evaluated. Two experimental sets were designed. For chronic nephrotoxicity, rats fed with low-sodium diet were divided into groups receiving vehicle, spironolactone (Sp), CsA, and CsA+Sp, for 21 days. Creatinine clearance, survival percentage, and renocortical mRNA levels of pro-renin, angiotensinogen (Ang), angiotensin receptors (AT1A, AT1B, and AT2), preproendothelin, endothelin receptors (ETA, ETB), cyclooxygenase-2 (COX-2), and adenosine receptors (Ad1, Ad2A, Ad2B, and Ad3) were analyzed. For acute nephrotoxicity, similar groups fed with a standard chow diet for 7 days were included. Serum potassium and sodium, glomerular filtration rate (GFR), and renal blood flow (RBF) were determined. In chronic model, CsA produced pro-renin and ET upregulation, altered adenosine receptors expression, and reduced Ang, AT1A, AT1B, ETB, and COX-2 mRNA levels. Spironolactone protective effect in chronic nephrotoxicity was associated with prevention of pro-renin upregulation and increased AT2, together with ETBreduction. In acute nephrotoxicity, spironolactone completely prevented GFR and RBF reduction induced by CsA. Our results suggest that aldosterone contributes to renal vasoconstriction observed in CsA nephrotoxicity and that renoprotection conferred by spironolactone was related to modification of renocortical vasoactive pathways expression, in which pro-renin normalization was the most evident change in chronic nephropathy. Finally, our data point to spironolactone as a potential treatment to reduce CsA nephrotoxicity in transplant patients.
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Affiliation(s)
- Jazmin M Pérez-Rojas
- Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico
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Locati D, Morandi S, Cupisti A, Ghiadoni L, Arnoldi A. Characterization and quantification of soy isoflavone metabolites in serum of renal transplanted patients by high-performance liquid chromatography/electrospray ionization mass spectrometry. RAPID COMMUNICATIONS IN MASS SPECTROMETRY : RCM 2005; 19:3473-81. [PMID: 16261643 DOI: 10.1002/rcm.2222] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
During a dietary intervention study on 16 renal transplanted patients, in which 25 g/day of animal proteins were replaced with 25 g of soy proteins, the metabolic profile of soy isoflavones in serum was characterized. This paper describes a reliable and fast liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) method, in negative ion mode, allowing the characterization and simultaneous quantification of several soy isoflavone metabolites. Six metabolites were identified and quantified: daidzein ([M-H](-) at m/z 252.8), dihydrodaidzein (DHD, [M-H](-) at m/z 254.8), equol ([M-H](-) at m/z 240.9), O-desmethylangolensin (O-DMA, [M-H](-) at m/z 256.8), genistein ([M-H](-) at m/z 268.8), and dihydrogenistein (DHG, ([M-H(+)](-) at m/z 270.8). Quantification was assessed using two deuterated internal standards, D(3)-daidzein and D(4)-genistein. This method permitted a limit of quantification (LOQ, S/N = 10) and a limit of detection (LOD, S/N = 3) of 0.05 microM and 0.005 microM for all analytes, except for genistein, where the LOQ and LOD were 0.005 microM and 0.001 microM, respectively. The linearity ranges were from 0.005 to 1.5 microM for genistein, from 0.05 to 1.5 microM for DHG, and from 0.05 to 0.7 microM for the other metabolites. The relative standard deviations (RSDs) were between 0.19% and 13.9% at the LOQ concentration for all metabolites, and between 0.6% and 4.8% at the maximum concentration. On the basis of the results obtained in the dietary intervention study, it was possible to split the patients into five groups characterized by different metabolic pathways.
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Affiliation(s)
- Daniela Locati
- Department of Agri-Food Molecular Sciences, Laboratory of Food Chemistry and Mass Spectrometry, University of Milan, Via Celoria 2, 20133 Milan, Italy.
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