This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Kemi, M. Articles by Van Zwieten, M. J. Search for Related Content PubMed PubMed Citation Articles by Kemi, M. Articles by Van Zwieten, M. J. Social Bookmarking                         What's this?

The Relative Protective Effects of Moderate Dietary Restriction versus Dietary Modification on Spontaneous Cardiomyopathy in Male Sprague-Dawley Rats

Department of Safety Assessment, Banyu Pharmaceutical Co, Menuma, Japan,

Kevin P. Keenan

Department of Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania 19486, USA

Carol Mccoy

Department of Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania 19486, USA

Chao-Min Hoe

Biometrics, Merck Research Laboratories, West Point, Pennsylvania 19486, USA

Keith A. Soper

Biometrics, Merck Research Laboratories, West Point, Pennsylvania 19486, USA

Gordon C. Ballam

Purina Mills Inc, St Louis, Missouri 63116, USA

Matthew J. Van Zwieten

Department of Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania 19486, USA

The relative protective effects of modifying dietary protein, fat, fiber, and energy content vs moderate food or dietary restriction (DR) on spontaneous cardiomyopathy of Charles River male Sprague-Dawley (SD) rats was evaluated at 1 and 2 years. For 2 years, SD rats were fed Purina Rodent Chow 5002 (21.4% protein, 5.7% fat, 4.1% fiber, 3.1 kcal/g) or a modified rodent chow 5002-9 (13.6% protein, 4.6% fat, 15.7% crude fiber, 2.4 kcal/g) ad libitum (AL) or by moderate DR at approximately 65% of the caloric intake of the AL group fed the 5002 diet. Serum lipids, carcass composition, and organ weights were evaluated and hearts were qualitatively and quantitatively examined microscopically for male SD rats at 1 and 2 years. Cardiomyopathy was characterized by the colocalization of myocardial degeneration, the development of subepicardial, perivascular, subendocardial, and interstitial fibrosis, and mononuclear inflammatory cell infiltration that increased by incidence and severity in an age-dependent manner from 1 to 2 years. SD rats fed the 5002 diet AL had the greatest heart weights and the most severe cardiomyopathy, with the highest myocardial fibrotic index. These parameters were relatively decreased in the AL 5002-9 diet, the DR 5002 diet, and the DR 5002-9 diet rats at 1 and 2 years. Regardless of the type of diet fed, both AL groups had the most severe cardiomyopathy by 2 years. Moderate DR allowed isocaloric comparisons of the relative effects of modified diets on survival, obesity, and heart disease. Only slight improvements in the severity and progression of spontaneous cardiomyopathy were seen by modification of the protein, fiber, fat, and energy content of the diet if fed AL. However, moderate DR with either diet was more effective than changing the diet composition in preventing and controlling the progression of cardiomyopathy in male SD rats.

Key Words: Cardiomyopathy • myocardial fibrosis • dietary restriction • caloric restriction • dietary fiber • dietary protein • aging • Sprague-Dawley rats

References

• Allaben WT, Turturro A., Leakey Jea, Seng JE, Hart RW ( 1996). Variability within animal assays and the use of dietary restriction to achieve dietary control. Toxicol Pathol 24: 776-781.[Abstract/Free Full Text]
• Cornwell GG, Thomas BP, Snyder DL (1991). Myocardial fibrosis in aging germ-free and conventional Lobund-Wistar rats: The protective effect of diet restriction. J Gerontol B45: 167-170.
• Cusack BJ, Mushlin PS, Johnson CJ, Vestal RE, Olson RD (1996). Aging increases the cardiotoxicity of daunorubicin and daunorubicinol in the rat. J Gerontol 51A: B376-384.[Web of Science]
• Duffy PH, Feuers RJ, Leakey JA, Nakamura KD, Turtuorro A., Hart RW ( 1989). Effect of chronic restriction on physiological variables related to energy metabolism in the male Fischer 344 rat. Mech Ageing Dev 48: 117-133.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Duffy PH, Feuers RJ, Pipkin JL, Berg TF, Leakey Jea, Turturo A., Hart RW ( 1995). The effect of dietary restriction and aging on the physiological response of rodents to drugs. In: Dietary Restriction: Implications for the Design and Interpretation of Toxicity and Carcinogenicity Studies, Hart RW, Neumann DA, Robertson RT (eds). ILSI Press, Washington, DC, pp 125-140.
• Finch CE (1990). Longevity, Senescence and the Genome. University of Chicago Press, Chicago.
• Fishbein L (ed) (1991). Biological Effects of Dietary Restriction. Springer-Verlag, New York.
• Giknis ML, Clifford CB (1998). Spontaneous Neoplastic Lesions and Survival in Crl:CD® (SD)BR Rats Maintained on Dietary Restriction. Charles River Laboratories, Wilmington, Massachusetts.
• Gumprecht LA, Long CR, Soper KA, Smith PF, Hascheck-Hock WM, Keenan KP (1993). The early effects of dietary restriction on the pathogenesis of chronic renal disease in Sprague-Dawley rats at 12 months. Toxicol Pathol 21: 528-537.[Abstract/Free Full Text]
• Hart RW, Neumann DA, Robertson RT (eds) (1995). Dietary Restriction: Implications for the Design and Interpretation of Toxicity and Carcinogenicity Studies. ILSI Press, Washington, DC.
• Haseman JK, Rao Grf ( 1992). Effects of corn-oil, time-related changes and inter-laboratory variability on tumor occurrence in control Fischer 344 (F-344/N) rats. Toxicol Pathol 20: 52-60.[Abstract/Free Full Text]
• Herlihy JT, Kim SW ( 1994). Modulation of the aging cardiovascular system by dietary restriction. In: Modulation of Aging Processes by Dietary Restriction, Yu BP (ed). CRC Press, Boca Raton, Florida, pp 57-87.
• Hinglais N., Heudes D., Nicoletti A., Mandet C., Laurent M., Bariety J., Michel JB (1994). Colocalization of myocardial fibrosis and inflammatory cells in rats. Lab Invest 70: 286-294.[Web of Science][Medline] [Order article via Infotrieve]
• Iwaski K., Gleiser CA, Masoro EJ, McMahan CA, Seo EJ, Yu BP (1988). The influence of dietary protein source on longevity and age-related disease processes of Fischer rats. J Gerontol 43: B5-12.[Abstract]
• Keenan C., Barrett D., Knight E., Kimball J., Smith L., Powers W. (1998). The effects of ad libitum feeding, group housing and controlled feeding on body weight gain, longevity and pathology parameters of Sprague-Dawley rats. Toxicol Sci 42: 73.[Abstract/Free Full Text]
• Keenan KP, Ballam GC, Dixit R., Soper KA, Laroque P., Mattson BA, Adams SP, Coleman JB (1997). The effects of diet, overfeeding and moderate dietary restriction on Sprague-Dawley rat survival, disease and toxicology. J Nutr 127: 851S-856S.[Medline] [Order article via Infotrieve]
• Keenan KP, Laroque P., Ballam GC, Soper KA, Dixit R., Mattson BA, Adams SP, Coleman JB (1996). The effects of diet, ad libitum overfeeding, and moderate dietary restriction on the rodent bioassay: The uncontrolled variable in safety assessment. Toxicol Pathol 24: 757-768.[Abstract/Free Full Text]
• Keenan KP, Laroque P., Dixit R. (1998). Need for dietary control by caloric restriction in rodent toxicology and carcinogenicity studies. J Toxicol Environ Health B.1: 101-114.
• Keenan KP, Laroque P., Soper KA, Morrissey RE, Dixit R. (1996). The effects of overfeeding and moderate dietary restriction on Sprague-Dawley rat survival, pathology, carcinogenicity, and the toxicity of pharmaceutical agents. Exp Toxicol Pathol 48: 139-144.[Web of Science][Medline] [Order article via Infotrieve]
• Keenan KP, Smith PF, Hertzog P., Soper KA, Ballam GC, Clark RL (1994). The effects of overfeeding and dietary restriction on Sprague-Dawley rat survival and early pathology biomarkers of aging. Toxicol Pathol 22: 300-315.[Abstract/Free Full Text]
• Keenan KP, Smith PF, Soper KA (1994). The effects of dietary (caloric) restriction on rat aging, survival, pathology and toxicology. In: Pathobiology of The Aging Rat, Vol II, Mohr U, Dungworth DL, Capen CC (eds). ILSI Press, Washington, DC, pp 609-628.
• Keenan KP, Soper KA, Hertzog PR, Gumprecht LA, Smith PF, Mattson BA, Ballam GC, Clark RL (1995). Diet, overfeeding and moderate dietary restriction in control Sprague-Dawley rats. II. Effects on age-related proliferative and degenerative lesions. Toxicol Pathol 23: 287-302.[Abstract/Free Full Text]
• Keenan KP, Soper KA, Smith PF, Ballam GC, Clark RL (1995). Diet, overfeeding and moderate dietary restriction in control Sprague-Dawley rats: I. Effects on spontaneous neoplasms. Toxicol Pathol 23: 269-286.[Abstract/Free Full Text]
• Kemi M., Matsumoto H., Nomura Y., Takahashi R. (1996). Early myocardial lesions induced by cardiotoxic compounds in Sprague-Dawley rats. J Vet Med Sci 58: 699-702.[Web of Science][Medline] [Order article via Infotrieve]
• Klinger MM, MacCarter GO, Boozer CN (1996). Body weight and composition in the Sprague-Dawley rat: Comparison of three out-bred sources. Lab Anim Sci 46: 67-70.[Web of Science][Medline] [Order article via Infotrieve]
• Klurfeld DM, Welch CB, Davis MJ, Kritchevsky D. (1989). Determination of degree of energy restriction necessary to reduce DMBA-induced mammary tumorigenesis in rats during the promotion phase. J Nutr 119: 286-291.[Abstract/Free Full Text]
• Knight EV, Barrett DS, Keenan CM, Kimball JP, Eitzen BH, Bryant S., Smith LN, Szot RJ, Powers WJ (1998). Influence of origin or controlled feeding on longevity of Sprague-Dawley rats. Int J Toxicol 17(suppl 2): 57-78.[Abstract/Free Full Text]
• Kritchevsky D. (1993). Energy restriction and carcinogenesis. Food Res Int 26: 289-295.[CrossRef]
• Kritchevsky D. (1994). The role of fat, calories and fiber in disease. In: Nutritional Toxicology, Kotsonis FN, Mackey M, Hjelle J (eds). Raven Press, New York, pp 67-93.
• Lakatta EG (1995). Cardiovascular system. In: Handbook of Physiology, Section 11, Aging, Masoro EJ (ed). American Physiological Society, Oxford University Press, New York, pp 413-474.
• Lang PL (1991). Changes in life span of research animals leading to questions about validity of toxicologic studies. Chem Regul Rep 14: 1518-1520.
• Laroque P., Keenan KP, Soper KA, Dorian C., Gerin G., Hoe CM, Duprat P. (1997). Effect of initial body weight and moderate dietary restriction on survival in Sprague-Dawley rats. Exp Toxicol Pathol 49: 459-465.[Web of Science][Medline] [Order article via Infotrieve]
• Lewis DJ (1992). Nonneoplastic lesions in the cardiovascular system. In: Pathobiology of the Aging Rat, Vol I, Mohr U, Dungworth DL, Capen CC (eds). ILSI Press, Washington, DC, pp 301-309.
• Maeda H., Gleiser CA, Masoro EJ, Murata I., McMahan CA, Yu BP (1985). Nutritional influences on aging of Fischer 344 rats. II. Pathology. J Gerontol 40: 671-688.[Abstract/Free Full Text]
• Manson JE, Willett WC, Stampfer MJ, Colditz DJ, Hunter SE, Hankinson CH, Hennekens CH, Speizer FF (1995). Body weight and mortality among women. N Engl J Med 333: 677-685.[Abstract/Free Full Text]
• Masoro EJ (1991). Physiological consequences of dietary restriction: An overview. In: Biological Effects of Dietary Restriction, Fishbein L (ed). Springer-Verlag, New York, pp 115-122.
• Masoro EJ (ed) (1995). Handbook of Physiology, Section 11, Aging. American Physiological Society, Oxford University Press, New York.
• Masoro EJ (1996). Possible mechanisms underlying the antiaging actions of caloric restriction. Toxicol Pathol 24: 738-741.[Abstract/Free Full Text]
• Masoro EJ, Iwasaki K., Gleiser CA, McMahan CA, Seo EJ, Yu BP (1989). Dietary modulation of the progression of nephropathy in aging rats: An evaluation of the importance of protein. Am J Clin Nutr 48: 1217-1227.
• Masoro EJ, Shimokawa I., Yu BP (1991). Retardation of the aging process in rats by food restriction. Ann NY Acad Sci 621: 337-352.[Web of Science][Medline] [Order article via Infotrieve]
• Maynard LA, Loosli JK, Hintz HF, Warner RG (1979). Animal Nutrition. McGraw-Hill, New York, pp 186-219.
• McCay C., Crowell M., Maynard L. (1935). The effect of retarded growth upon the length of the life span and upon the ultimate size. J Nutr 10: 63-79.[Abstract/Free Full Text]
• McGinnis JM Foege WH (1993). Actual causes of death in the United States. J Am Med Assoc 270: 2207-2212.[Abstract/Free Full Text]
• Merry BJ, Holehan AM (1994). Effects of diet on aging. In: Physiological Basis of Aging and Geriatrics, 2nd ed, Timiras PS (ed). CRC Press, Boca Raton, Florida, pp 285-310.
• Murtagh-Mark CM, Reiser KM, Harris R., McDonald RB (1995). Source of dietary carbohydrate affects lifespan of Fischer 344 rats independent of caloric restriction. J Gerontol 50A: B148-B154.[Web of Science]
• National Research Council, Committee on Rodents ( 1996). Husbandry. In: Laboratory Animal Management. National Academy Press, Washington, DC, pp 44-84.
• National Research Council, Subcommittee of Laboratory Animal Nutrition (1995). Nutrient requirements of the laboratory rat. In: Nutrient Requirements of Laboratory Animals, 4th rev ed. National Academy Press, Washington, DC, pp 11-79.
• Newberne PM, Sotnikov AV (1996). Diet: The neglected variable in chemical safety evaluations. Toxicol Pathol 24: 746-756.[Abstract/Free Full Text]
• Pedrozo H., Bertrand HA, Herlihy JT (1994). Caloric restriction alters arterial blood pressure and baroreflex responsiveness of the spontaneous hypertensive rat. Age 17: 23-27.[CrossRef][Web of Science]
• Peterson AD, Baumgardt BR (1971). Food and energy intake of rats fed diets varying in energy concentration and density. J Nutr 101: 1057-1068.[Abstract/Free Full Text]
• Peterson AD, Baumgardt BR (1971). Influence of level of energy demand on the ability of rats to compensate for diet dilution. J Nutr 101: 1069-1074.[Abstract/Free Full Text]
• Rao GN, Edmondson J., Ewell MR (1993). Influence of dietary protein concentration on severity of nephropathy in Fischer-344 (F-344/N) rats. Toxicol Pathol 21: 353-361.[Web of Science][Medline] [Order article via Infotrieve]
• Rao GN, Hasemen JK, Grumbein S., Crawford DD, Eustis SL (1990). Growth, body weight, survival, and tumor trends in F-344/ N rats during an eleven-year period. Toxicol Pathol 18:61-70.[Web of Science][Medline] [Order article via Infotrieve]
• Rimm EB, Ascherio A., Giovannucci E., Spiegelman D., Stampfer MJ, Willett WC (1996). Vegetable, fruit, and cereal fiber intake and risk of coronary heart disease among men. J Am Med Assoc 275: 447-451.[Abstract/Free Full Text]
• Roberts J., Snyder DL, Friedman E. (1996). Handbook of Pharmacology of Aging. CRC Press, Boca Raton, Florida.
• Roe Fjc (1994). Historical histopathological control data for laboratory rodents: Valuable treasure or worthless trash. Lab Anim 28: 148-154.[Abstract/Free Full Text]
• Roe Fjc, Lee PN, Conybeare G., Kelly D., Matter B., Prentice D., Tobin G. (1995). The Biosure Study: Influence of composition of diet and food consumption on longevity, degenerative disease and neoplasia in Wistar rats studies for up to 30 months post weaning. Food Chem Toxicol 33(suppl 1): 1S-100S.[Medline] [Order article via Infotrieve]
• Rosenbaum M., Leibel RL, Hirsch J. (1997). Obesity. N Engl J Med 337: 396-407.[Free Full Text]
• Ross M. (1976). Nutrition and longevity in experimental animals. In: Nutrition and Aging, Winick M (ed). Wiley and Sons, New York, pp 23-41.
• Schaffer SW (1998). Effect of obesity on myocardial metabolism, morphology, and function in the obese (fa/fa) Zucker rat. In: The Heart and Lung in Obesity, Alpert AM, Alexander JK (eds). Futura, Armonk, NY, pp 11-24.
• Sohal RS, Agarwal S., Candas M., Forster MJ, Lal H. ( 1994). Effect of age and caloric restriction on DNA oxidative damage in different tissues of C57BL/6 mice. Mech Ageing Dev 76: 215-224.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Sohal RS, Ku HH, Agarwal S., Forster MJ, Lal H. ( 1994). Oxidative damage, mitochondrial oxidant generation and antioxidant defences during aging and in response to food restriction in the mouse. Mech Ageing Dev 74: 121-133.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Sohal RS, Weindruch R. (1996). Oxidative stress, caloric restriction, and aging. Science 273: 59-63.[Abstract]
• Stark A., Nyska A., Madar Z. (1996). Metabolic and morphometric changes in small and large intestine in rats fed high-fiber diets. Toxicol Pathol 24: 166-171.[Abstract/Free Full Text]
• Tukey JW, Ciminera JL, Heyse JF (1985) Testing the statistical certainty of a response to increasing doses of a drug. Biometrics 41: 259-301.
• Turturro A., Duffy P., Hart RW ( 1995). The effect of caloric modulation on toxicity studies. In: Dietary Restriction: Implications for the Design and Interpretation of Toxicity and Carcinogenicity Studies, Hart RW, Neumann DA, Robertson RT (eds). ILSI Press, Washington, DC, pp 79-97.
• Vandewoude Mfj, Buyssens N. (1992). Effect of aging and malnutrition on rat myocardium. I. The myocyte. Virchows Archiv A Pathol Anat 421: 179-188.[CrossRef]
• Weindruch R. (1996). The retardation of aging by caloric restriction: Studies in rodents and primates. Toxicol Pathol 24: 742-745.[Abstract/Free Full Text]
• Weindruch R., Sohal RS (1997). Caloric intake and aging. N Engl J Med 337: 986-994.[Free Full Text]
• Weindruch R., Walford RL (1988). The Retardation of Aging and Disease by Dietary Restriction. Charles C Thomas, Springfield, Illinois.
• Westfall PH, Young SS (1993). Resampling-based multiple testing: Examples and methods for p-value adjustment. Wiley and Sons, New York.
• Willet W. (1990). Nutritional Epidemiology. Oxford University Press, New York.
• Yu BP (ed) (1993). Free Radicals in Aging. CRC Press, Boca Raton, Florida.
• Yu BP (ed) (1994). Modulation of Aging Processes by Dietary Restriction CRC Press, Boca Raton, Florida.

Toxicologic Pathology, Vol. 28, No. 2, 285-296 (2000)
DOI: 10.1177/019262330002800208


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				E. I. Dedkov, W. Zheng, L. P. Christensen, R. M. Weiss, F. Mahlberg-Gaudin, and R. J. Tomanek Preservation of coronary reserve by ivabradine-induced reduction in heart rate in infarcted rats is associated with decrease in perivascular collagen Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H590 - H598. [Abstract] [Full Text] [PDF]

				D. B. Walker Serum Chemical Biomarkers of Cardiac Injury for Nonclinical Safety Testing Toxicol Pathol, January 1, 2006; 34(1): 94 - 104. [Abstract] [Full Text] [PDF]

				K. P. Keenan, C.-M. Hoe, L. Mixson, C. L. Mccoy, J. B. Coleman, B. A. Mattson, G. A. Ballam, L. A. Gumprecht, and K. A. Soper Diabesity: A Polygenic Model of Dietary-Induced Obesity from Ad Libitum Overfeeding of Sprague-Dawley Rats and Its Modulation by Moderate and Marked Dietary Restriction Toxicol Pathol, October 1, 2005; 33(6): 650 - 674. [Abstract] [Full Text] [PDF]

				S.-K. Park and T. A. Prolla Gene expression profiling studies of aging in cardiac and skeletal muscles Cardiovasc Res, May 1, 2005; 66(2): 205 - 212. [Abstract] [Full Text] [PDF]

				M. C. Capogrossi Cardiac Stem Cells Fail With Aging: A New Mechanism for the Age-Dependent Decline in Cardiac Function Circ. Res., March 5, 2004; 94(4): 411 - 413. [Full Text] [PDF]

				C.-K. Lee, D. B. Allison, J. Brand, R. Weindruch, and T. A. Prolla Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts PNAS, November 12, 2002; 99(23): 14988 - 14993. [Abstract] [Full Text] [PDF]

				G. N. Rao Diet and Kidney Diseases in Rats Toxicol Pathol, October 1, 2002; 30(6): 651 - 656. [Abstract] [PDF]

				J. B. Nold, K. P. Keenan, A. Nyska, and M. E. Cartwright Society of Toxicologic Pathology Position Paper: Diet as a Variable in Rodent Toxicology and Carcinogenicity Studies Toxicol Pathol, August 1, 2001; 29(5): 585 - 586. [PDF]

				Letters to the Editor Toxicol Pathol, February 1, 2001; 29(2): 274 - 276. [PDF]

This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Kemi, M. Articles by Van Zwieten, M. J. Search for Related Content PubMed PubMed Citation Articles by Kemi, M. Articles by Van Zwieten, M. J. Social Bookmarking                         What's this?