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      Various Dietary Protein Intakes and Progression of Renal Failure in Spontaneously Hypercholesterolemic Imai Rats

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          Abstract

          Background/Aim: Dietary protein restriction is known to be beneficial in the preservation of the renal function in patients with chronic renal failure. Recently, the effect of varying quantity and quality of dietary protein intakes was also studied. This study investigates the effects of different dietary animal proteins on renal function in spontaneously hypercholesterolemic Imai rats that exhibit renal lesions similar to human focal and segmental glomerulosclerosis. The sources of proteins were from casein, pork, and fish. Primary concern was the effect of fish meat protein, because the effects of fish oil are well reported. To examine whether remnants of fish oil affect the experimental results, semi-defatted fish meat and fully defatted fish meat were prepared for these experiments. Methods: Forty-two Imai rats were placed on diets containing casein, defatted pork meat, semi-defatted fish meat, or defatted fish meat as a protein sources from 10 to 22 weeks of age. Twenty-four hour urine collections were obtained along with measurements of systolic blood pressure and drawing blood from the tail artery every 4 weeks. Finally, the kidneys were removed and prepared for histological study. Results: The semi-defatted fish meat diet retarded the rise of plasma cholesterol, virtually completely prevented the development of hypertriglyceridemia, and slowed the progression of proteinuria, renal function failure, and glomerular injury as compared with the control casein diet. However, the fully defatted fish meat diet led to renal failure at the same rate as the casein diet. The defatted pork diet group exhibited a higher creatinine clearance at the end of the experiments as compared with the casein and the fully defatted fish meat diet groups. Conclusions: These data suggest that an important determinant of the protective effects of the semi-defatted fish meat diet was related to the prevention of hypercholesterolemia and hypertriglyceridemia by the remaining fish oil. Fish meat protein itself did not indicate superior beneficial effects in the regression of the renal function in Imai rats as compared with casein protein, and defatted pork showed better results than casein and fully defatted fish meat.

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          Most cited references 20

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          Mesangial immune injury, hypertension, and progressive glomerular damage in Dahl rats.

          Hypertension frequently accompanies chronic glomerulonephritis. Mesangial injury and glomerulosclerosis are common in glomerulonephritis and are often harbingers of progressive glomerular destruction. Thus, in a model of mesangial immune injury we studied the relationship between hypertension, mesangial injury, and glomerulosclerosis. We induced mesangial ferritin-antiferritin immune complex disease (FIC) in Dahl salt-sensitive (S) and salt-resistant (R) rats. S and R rats with FIC were fed chow containing 0.3% NaCl until 14 weeks of age and then switched to 8.0% NaCl chow until 28 weeks of age. Groups of control S and R rats (no FIC) were either fed 0.3% NaCl for 28 weeks or switched to 8.0% NaCl chow at 14 weeks of age. Blood pressure, serum creatinine, urinary protein, and glomerular injury (assessed by semiquantitative morphometric analysis) were determined at 14 and 28 weeks of age. R rats with or without FIC did not develop hypertension; mesangial injury was minimal. At 14 weeks of age, only S FIC rats developed hypertension, proteinuria, significant mesangial expansion and early glomerulosclerosis. At 28 weeks of age, proteinuria, mesangial expansion, and glomerulosclerosis were significantly more severe in hypertensive S rats with FIC than in those without FIC. These studies show that despite a normal salt intake, mesangial injury hastened the onset of hypertension, but only in rats genetically predisposed to hypertension (S FIC at 14 weeks). High dietary salt further aggravated hypertension, which, in turn, magnified both mesangial injury and glomerulosclerosis. Clinically, the different rates of progression of human glomerulonephritis associated with hypertension may be in part dependent on similar mechanisms.
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            LKPNM: a prodrug-type ACE-inhibitory peptide derived from fish protein.

            It has been previously documented that the thermolysin-digest of "Katsuo-bushi", a Japanese traditional food processed from dried bonito possesses potent inhibitory activity against angiotensin I-converting enzyme (ACE). The present authors isolated eight kinds of ACE-inhibitory peptides from it. Of these isolated peptides, LKPNM (IC50 = 2.4 microM) was found to be hydrolyzed by ACE to produce LKP (IC50 = 0.32 microM) with 8-fold higher ACE-inhibitory activity relative to the parent peptide or LKPNM, suggesting that LKPNM can be regarded as a prodrug-type ACE-inhibitory peptide. For assessment of relative antihypertensive activities of LKPNM and LKP to that of captopril, they were orally administered to SHR rats to monitor time-course changes of blood pressures, whereby it was evidenced that both LKPNM and captopril showed maximal decrease of blood pressure 4 h after oral administration and their efficacies lasted until 6 h post-administration. In sharp contrast, however, maximal reduction of blood pressure occurred as early as 2 h after administration of LKP. Minimum effective doses of LKPNM, LKP and captopril were 8, 2.25 and 1.25 mg/kg, respectively. When compared on molar basis, antihypertensive activities of LKPNM and LKP accounted for 66% and 91% relative to that of captopril, respectively, whereas in vitro ACE-inhibitory activities of LKPNM and LKP were no more than 0.92% and 7.73% compared with that of captopril (IC50 = 0.022 microM). It is of interest to note that both of these peptides exert remarkably higher antihypertensive activities in vivo despite weaker in vitro ACE-inhibitory effects, which was ascertained by using captopril as the reference drug.
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              Renal, metabolic and hormonal responses to ingestion of animal and vegetable proteins.

              Renal and hormonal responses were studied in a group of healthy individuals fed, in random order, for three weeks, a vegetable protein diet (N = 10), an animal protein diet (N = 10), or an animal protein diet supplemented with fiber (N = 7), all containing the same amount of total protein (chronic study). In seven additional subjects the acute renal, metabolic and hormonal response to ingestion of a meat or soya load of equivalent total protein content was investigated (acute study). In the chronic study GRF, RPF and fractional clearance of albumin and IgG were significantly higher on the animal than the vegetable protein diets (GFR: 121 +/- 4 vs. 111 +/- 4 ml/min/1.73 m2, P less than 0.001; RPF: 634 +/- 29 vs. 559 +/- 26 ml/min/1.73 m2, P less than 0.001; theta alb: 19.5 +/- 3.1 vs. 10.2 +/- 1.6 x 10(-7), P less than 0.01; theta IgG: 11.6 +/- 3.1 vs. 7.5 +/- 1.7 x 10(-7), P less than 0.05). Renal vascular resistance was lower on the animal than vegetable protein diet (82 +/- 5 vs. 97 +/- 5 mmHg/min/liter; P less than 0.001). Fiber supplementation to APD did not have any effect on the renal variables measured which were indistinguishable from APD. In the acute study, GFR and RPF both rose significantly by approximately 16% (P less than 0.005) and approximately 14% (P less than 0.05), respectively, after the meat load, while RVR fell by approximately 12% (P less than 0.05). There were no significant changes in these parameters following the soya load.(ABSTRACT TRUNCATED AT 250 WORDS)
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                Author and article information

                Journal
                NEE
                Nephron Exp Nephrol
                10.1159/issn.1660-2129
                Cardiorenal Medicine
                S. Karger AG
                1660-2129
                2007
                March 2007
                07 March 2007
                : 105
                : 4
                : e98-e107
                Affiliations
                aDepartment of Nephrology, Qilu Hospital of Shandong University, and bTeaching Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China; cDepartment of Nephrology and Blood Purification Medicine, Wakayama Medical University, and dRyoshukai Wakayama Kidney Disease Clinic, Wakayama, eDepartment of Nutrition, Siebold University of Nagasaki, Nagasaki, and
                Article
                100491 Nephron Exp Nephrol 2007;105:e98–e107
                10.1159/000100491
                17347583
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 7, Tables: 3, References: 28, Pages: 1
                Categories
                Original Paper

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