Beneficial Effects of Hydrolysates of Whey Proteins in Spontaneously Hypertensive Rats

Eunju Park¹, Bo-Young Seo², Yoe-Chang Yoon³ and Seung-Min Lee^4,

¹Department of Food and Nutrition, Kyungnam University, Changwon, South Korea

²Department of Food and Nutrition, Chanshin University, Changwon, South Korea

³Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, South Korea

⁴Department of Food and Nutrition, College of Human Ecology, Yonsei University, Seoul, South Korea

Cite this paper:
Eunju Park, Bo-Young Seo, Yoe-Chang Yoon and Seung-Min Lee. Beneficial Effects of Hydrolysates of Whey Proteins in Spontaneously Hypertensive Rats. Journal of Food and Nutrition Research. 2017; 5(11):794-800. doi: 10.12691/jfnr-5-11-1

Abstract

We compared the effects of whey protein concentrate (WPC, control) with its hydrolystes either by protease M or protease S (the hydrolysates) in spontaneously hypertensive rats (SHR) in comparison to normotensive Wistar Kyoto rats (WKY). First, the hydrolysates demonstrated higher in vitro angiotensin converting enzyme (ACE) inhibition than WPC. In an 8 week of animal study, the hydrolysates decreased systolic blood pressure (SBP) and ACE activity in aorta with a greater reduction than WPC. A significant reduction in tail moment, an indicator of oxidative DNA damage was also detected in the hydrolysates compared to the WPC. Especially protease M-treated hydrolysate show low superoxide dismutase (SOD) activity. Our data indicated that the hydrolysates appeared to have greater blood pressure lowering effects than WPC possibly by greater inhibition of aorta ACE activity along with significant antioxidant roles.

Keywords:
hypertension whey protein concentrates whey protein hydrolysates angiotensin-converting enzyme inhibition chromosomal DNA damage antioxidants

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References:

[1]	Lenfant C., Chobanian A. V., Jones D. W., Roccella E. J., Joint National Committee on the Prevention D. E. and Treatment of High Blood P., "Seventh report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7): resetting the hypertension sails," Hypertension, vol 41(6):1178-1179, Jun 2003.
[2]	Majumder K. and Wu J., "Molecular targets of antihypertensive peptides: understanding the mechanisms of action based on the pathophysiology of hypertension," Int J Mol Sci, vol 16(1): 256-283, 2015.
[3]	Skeggs L. T., Jr., Kahn J. R. and Shumway N. P., "The preparation and function of the hypertensin-converting enzyme," J Exp Med, vol 103(3):295-299, Mar 1956.
[4]	Gavras H. and Gavras I., "Angiotensin converting enzyme inhibitors. Properties and side effects," Hypertension, vol 11(3 Pt 2): II37-41, Mar 1988.
[5]	Redon J., Oliva M. R., Tormos C., Giner V., Chaves J., Iradi A. and Saez G. T., "Antioxidant activities and oxidative stress byproducts in human hypertension," Hypertension, vol 41(5): 1096-1101, May 2003.
[6]	Wu L. and Juurlink B. H., "Increased methylglyoxal and oxidative stress in hypertensive rat vascular smooth muscle cells," Hypertension, vol 39(3): 809-814, Mar 2002.
[7]	Rodriguez-Iturbe B., Zhan C. D., Quiroz Y., Sindhu R. K. and Vaziri N. D., "Antioxidant-rich diet relieves hypertension and reduces renal immune infiltration in spontaneously hypertensive rats," Hypertension, vol 41(2):341-346, Feb 2003.
[8]	Nakazono K., Watanabe N., Matsuno K., Sasaki J., Sato T. and Inoue M., "Does superoxide underlie the pathogenesis of hypertension?," Proc Natl Acad Sci U S A, vol 88(22): 10045-10048, Nov 1991.
[9]	Tanito M., Nakamura H., Kwon Y. W., Teratani A., Masutani H., Shioji K., Kishimoto C., Ohira A., Horie R. and Yodoi J., "Enhanced oxidative stress and impaired thioredoxin expression in spontaneously hypertensive rats," Antioxid Redox Signal, vol 6(1): 89-97, Feb 2004.
[10]	Landmesser U., Cai H., Dikalov S., McCann L., Hwang J., Jo H., Holland S. M. and Harrison D. G., "Role of p47(phox) in vascular oxidative stress and hypertension caused by angiotensin II," Hypertension, vol 40(4):511-515, Oct 2002.
[11]	Colbert L. B. and Decker E. A., "Antioxidant Activity of an Ultrafiltration Permeate from Acid Whey," Journal of Food Science, vol 56(5): 1248-1250, 1991.
[12]	O'Keeffe M. B. and FitzGerald R. J., "Antioxidant effects of enzymatic hydrolysates of whey protein concentrate on cultured human endothelial cells," International Dairy Journal, vol 36(2): 128-135, Jun 2014.
[13]	Gutteridge J. M., Paterson S. K., Segal A. W. and Halliwell B., "Inhibition of lipid peroxidation by the iron-binding protein lactoferrin," Biochemical Journal, vol 199(1): 259-261, 1981.
[14]	Ostdal H., Daneshvar B. and Skibsted L. H., "Reduction of ferrylmyoglobin by beta-lactoglobulin," Free Radic Res, vol 24(6): 429-438, Jun 1996.
[15]	Mullally M. M., Meisel H. and FitzGerald R. J., "Angiotensin-I-converting enzyme inhibitory activities of gastric and pancreatic proteinase digests of whey proteins," International Dairy Journal, vol 7(5): 299-303, May 1997.
[16]	Wang X., Wang L., Cheng X., Zhou J., Tang X. and Mao X.-Y., "Hypertension-attenuating effect of whey protein hydrolysate on spontaneously hypertensive rats," Food Chemistry, vol 134(1): 122-126, 2012.
[17]	FitzGerald R. J. and Meisel H., "Lactokinins: whey protein-derived ACE inhibitory peptides," Nahrung, vol 43(3):165-167, Jun 1999.
[18]	FitzGerald R. J. and Meisel H., "Milk protein-derived peptide inhibitors of angiotensin-I-converting enzyme," Br J Nutr, vol 84 Suppl 1(S33-37), Nov 2000.
[19]	Yamamoto N., Akino A. and Takano T., "Antihypertensive effect of the peptides derived from casein by an extracellular proteinase from Lactobacillus helveticus CP790," J Dairy Sci, vol 77(4): 917-922, Apr 1994.
[20]	Maruyama S., Mitachi H., Awaya J., Kurono M., Tomizuka N. and Suzuki H., "Angiotensin I-converting enzyme inhibitory activity of the C-terminal hexapeptide of alpha (S1)-casein," Agricultural and Biological Chemistry (Japan), 1988.
[21]	Horwitz W., Chichilo P., Reynolds H., Official methods of analysis of the Association of Official Analytical Chemists, Washington, DC, USA: Association of Official Analytical Chemists, 1970.
[22]	Lawrence A., "The determination of lactose in milk products," Australian Journal of Dairy Technology, vol 23, 1968.
[23]	Cushman D. W. and Cheung H. S., "Spectrophotometric assay and properties of the angiotensin-converting enzyme of rabbit lung," Biochem Pharmacol, vol 20(7):1637-1648, Jul 1971.
[24]	Schmidt H. H., Warner T. D., Nakane M., Forstermann U. and Murad F., "Regulation and subcellular location of nitrogen oxide synthases in RAW264.7 macrophages," Mol Pharmacol, vol 41(4): 615-624, Apr 1992.
[25]	Green L. C., Wagner D. A., Glogowski J., Skipper P. L., Wishnok J. S. and Tannenbaum S. R., "Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids," Anal Biochem, vol 126(1): 131-138, Oct 1982.
[26]	Moshage H., Kok B., Huizenga J. R. and Jansen P., "Nitrite and nitrate determinations in plasma: a critical evaluation," Clinical Chemistry, vol 41(6):892-896, 1995.
[27]	Singh N. P., McCoy M. T., Tice R. R. and Schneider E. L., "A simple technique for quantitation of low levels of DNA damage in individual cells," Exp Cell Res, vol 175(1): 184-191, Mar 1988.
[28]	Kim M.-H., Lee N.-K., Kim S.-Y. and Yoon Y. C., "Chacteristics of whey protein hydrolysates from cheese whey, favors on various food application", 2014.
[29]	Hartmann R. and Meisel H., "Food-derived peptides with biological activity: from research to food applications," Curr Opin Biotechnol, vol 18(2): 163-169, Apr 2007.
[30]	Akpaffiong M. J. and Taylor A. A., "Antihypertensive and vasodilator actions of antioxidants in spontaneously hypertensive rats," Am J Hypertens, vol 11(12): 1450-1460, Dec 1998.
[31]	Arbos K. A., Claro L. M., Borges L., Santos C. A. and Weffort-Santos A. M., "Human erythrocytes as a system for evaluating the antioxidant capacity of vegetable extracts," Nutr Res, vol 28(7): 457-463, Jul 2008.
[32]	Bryszewska M., Zavodnik I. B., Niekurzak A. and Szosland K., "Oxidative processes in red blood cells from normal and diabetic individuals," Biochem Mol Biol Int, vol 37(2): 345-354, Oct 1995.
[33]	Pandey K. B. and Rizvi S. I., "Biomarkers of oxidative stress in red blood cells," Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, vol 155(2): 131-136, Jun 2011.
[34]	Zhou J., Keenan M. J., Losso J. N., Raggio A. M., Shen L., McCutcheon K. L., Tulley R. T., Blackman M. R. and Martin R. J., "Dietary whey protein decreases food intake and body fat in rats," Obesity (Silver Spring), vol 19(8):1568-1573, Aug 2011.