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Hepatoprotective effects of whey protein isolate against acute liver toxicity induced by dimethylnitrosamine in rat

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Abstract

In order to investigate the hepatoprotective effects of whey protein isolate against acute liver toxicity induced by dimethylnitrosamine (DMN), a randomized experimental study was conducted. Forty-eight Sprague Dawley rats were randomly divided into three groups. Groups A and B consumed a diet containing casein, and group C received a diet containing whey protein isolate for 18 days. Group A was then given an intraperitoneal saline injection. It continued on the casein diet for another 4 days before being sacrificed. Each animal in groups B and C was given a single intraperitoneal injection of DMN (30 mg/kg) on the 18th day of the study. All groups continued their diets for 4 days before their euthanasia. The supply of whey protein diet resulted in a decrease in aspartate amino transferase, alanine amino transferase, alkaline phosphatase, total bilirubin, and malondialdehyde (MDA). Morphological and biochemical data suggested that a diet containing whey protein isolate decreased DMN-induced liver damage and, therefore, had beneficial effects on hepatic failure.

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References

  • Actis-Goretta L, Carrasqued F, Fraga CG (2004) The regular supplementation with an antioxidant mixture decreases oxidative stress in healthy humans. Clin Chim Acta 349:97–103

    Article  PubMed  CAS  Google Scholar 

  • Belfield A, Goldberg DM (1971) Revised assay for serum phenyl phosphatase activity using 4-amino-antipyrine. Enzyme 12:561–573

    PubMed  CAS  Google Scholar 

  • Bos C, Mahe S, Gaudichon C, Benamouzig R, Gausserès N, Luengo C, Ferrière F, Rautureau J, Tome D (1999) Assessment of postprandial protein utilization of 15N-labelled milk nitrogen in human subjects. Br J Nutr 81:221–226

    PubMed  CAS  Google Scholar 

  • Burtis CA, Ashwood ER, Bruns DE (2007) Tietz fundamentals of clinical chemistry, 6th edn. Saunders, Philadelphia

    Google Scholar 

  • Chang CY, Wu KC, Chiang SH (2007) Antioxidant properties and protein compositions of porcine haemoglobin hydrolysates. Food Chem 100:1537–1543

    Article  CAS  Google Scholar 

  • Eigel WN, Butler JE, Ernstrom CA, Farrel HM, Harwalkar VR, Jennes R, Whitney RM (1984) Nomenclature of proteins in cow’s milk. J Dairy Sci 67:1599–1631

    Article  CAS  Google Scholar 

  • Fehér J, Deák G, Müzes G, Láng I, Niederland V, Nékám K, Kárteszi M (1989) Liver- protective action of silymarin therapy in chronic alcoholic liver diseases. Orv Hetil 130:2723–2727

    PubMed  Google Scholar 

  • Fouillet H, Mariotti F, Gaudichon C, Bos C, Tomé D (2002) Peripheral and splanchnic metabolism of dietary nitrogen are differently affected by the protein source in humans as assessed by compartmental modeling. J Nutr 132:125–133

    PubMed  CAS  Google Scholar 

  • Fridrich I (1978) The biology of oxygen radicals. Science 201:875–880

    Article  Google Scholar 

  • George J, Chandrakasan G (2000) Biochemical abnormalities during the progression of hepatic fibrosis induced by dimethylnitrosamine. Clin Biochem 33:563–570

    Article  PubMed  CAS  Google Scholar 

  • George J, Rao KR, Stern R, Chandrakasan G (2001) Dimethylnitrosamine-induced liver injury in rats: the early deposition of collagen. Toxicology 156:129–138

    Article  PubMed  CAS  Google Scholar 

  • Ha E, Zemel MB (2003) Functional properties of whey, whey components, and essential amino acids: mechanisms underlying health benefits for active people. J Nutr Biochem 14:251–258

    Article  PubMed  CAS  Google Scholar 

  • Hakkak R, Korourian S, Shelnutt SR, Lensing S, Ronis MJ, Badger TM (2000) Diets containing whey or soy protein isolate protect against 7, 12-dimethylbenz(a)anthracene-induced mammary tumors in female rats. Cancer Epidemiol Biomarkers Prev 9:113–117

    PubMed  CAS  Google Scholar 

  • Hakkak R, Korourian S, Ronis MJ, Johnston JM, Badger TM (2001) Dietary whey protein protects against azoxymethane-induced colon tumors in male rats. Cancer Epidemiol Biomarkers Prev 10:555–558

    PubMed  CAS  Google Scholar 

  • Hara K, Ikeda M, Saito S, Matsumoto S, Numata K, Kato N, Tanaka K, Sekihara H (2002) Lactoferrin inhibits hepatitis B virus infection in cultured human hepatocytes. Hepatol Res 24:228

    Article  PubMed  CAS  Google Scholar 

  • Hasan FAM, Owyed S (2003) Interpretation of liver chemistry tests. Bull Kuwait Inst Med Spec 2:27–31

    Google Scholar 

  • Hoffman JR, Falvo MJ (2004) Protein—which is best? J Sports Sci Med 3:118–130

    Google Scholar 

  • Jin YL, Enzan H, Kuroda N, Hayashi Y, Nakayama H, Zhang YH, Toi M, Miyazaki E, Hiroi M, Guo LM, Saibara T (2003) Tissue remodeling following submassive hemorrhagic necrosis in rat livers induced by an intraperitoneal injection of dimethylnitrosamine. Virchows Arch 442:39--47

    PubMed  CAS  Google Scholar 

  • Kim EY, Kim EK, Lee HS, Sohn Y, Soh Y, Jung HS, Sohn NW (2007) Protective effects of Cuscutae semen against dimethylnitrosamine-induced acute liver injury in Sprague-Dawley rats. Biol Pharm Bull 30:1427--1431

    Article  PubMed  Google Scholar 

  • Kullisaar T, Songisepp E, Mikelsaar M, Zilmer K, Vihalemm T, Zilmer M (2003) Antioxidative probiotic fermented goats’ milk decreases oxidative stress-mediated atherogenicity in human subjects. Br J Nutr 90:449--456

    Article  PubMed  CAS  Google Scholar 

  • Kume H, Okazaki K, Sasaki H (2006) Hepatoprotective effects of whey protein on D-galactosamine-induce hepatitis and liver fibrosis in rats. Biosci Biotechnol Biochem 70:1281--1285

    Article  PubMed  CAS  Google Scholar 

  • Kusunose M, Qiu B, Cui T, Hamada A, Yoshikoa S, Ono M, Miyamura M, Kyotani S, Nishioka Y (2002) Effect of Sho-saiko-to extract on hepatic inflammation and fibrosis in Dimethylnitrosamine-induced liver injury in rats. Biol Pharm Bull 25:1417--1421

    Article  PubMed  CAS  Google Scholar 

  • Lukivskaya O, Lis R, Zwierz K, Buko V (2004) Effect of Nitric oxide donor and the Nitric oxide synthase inhibitor on the liver of rats with chronic hepatitis induced by Dimethylnitrosamine. Pol J Pharmacol 56:599--604

    PubMed  CAS  Google Scholar 

  • Marshall K (2004) Therapeutic applications of whey protein. Altern Med Rev 9:136--156

    PubMed  Google Scholar 

  • Mostafavipour Z, Zal F, Monabati A, Vessal M (2008) Protective effects of a combination of quercetin and vitamin E against cyclosporine A-induced oxidative stress and hepatotoxicity in rats. Hepatol Res 38:385--392

    Article  CAS  Google Scholar 

  • Okada Y, Okada M (1998) Scavenging effect of water soluble proteins in broad beans on free radicals and active oxygen species. J Agric Food Chem 46:401--406

    Article  PubMed  CAS  Google Scholar 

  • Pellet PL, Young VR (1980) Nutritional evaluation of protein foods. UNLI world hunger program. Food Nutr Bull 4:95–97

    Google Scholar 

  • Peňa-Ramos EA, Xiong YL, Artega GE (2004) Fractionation and characterization for antioxidant activity of hydrolysed whey protein. J Sci Food Agric 84:1908–1918

    Article  Google Scholar 

  • Pihlanto A (2006) Anti oxidative peptides derived from milk proteins. Int Dairy J 16:1306–1314

    Article  CAS  Google Scholar 

  • Reitman S, Frankel S (1957) Colorimetric method for aspartate and alanine amino transferases. Am J Clin Pathol 28:56–63

    PubMed  CAS  Google Scholar 

  • Saleh ZA, El-Garawany GA, Assem F, El-Shibiny S (2007) Evaluation of the efficacy of whey protein to ameliorate the toxic effect of aflatoxin in rats. Inter Dair J 17:854–859

    Article  CAS  Google Scholar 

  • Shin JW, Son JY, Oh SM, Han SH, Wang JH, Cho JH, Cho CK, Yoo HS, Lee YW, Lee MM, Hu XP, Son CG (2006) An herbal formula, CGX, exerts hepato-therapeutic effects on dimethylnitrosamine-induced chronic liver injury model in rats. World J Gastroenterol 12:6142–6148

    PubMed  CAS  Google Scholar 

  • Smith AK, Circle SJ (1971) Soybeans: chemistry and technology. Vol. 1, proteins. AVI Publishing Company, Inc, Westport, pp 213–216

    Google Scholar 

  • Sukkar SG, Bounous G (2004) The role of whey protein in antioxidant defense. Rivista Italiana di Nutrizione Parenterale ed Enterale 22:193–200

    Google Scholar 

  • Tipton KD, Gurkin BE, Matin S, Wolfe RR (1999) Nonessential amino acids are not necessary to stimulate net muscle protein synthesis in healthy volunteers. J Nutr Biochem 10:89–95

    Article  PubMed  CAS  Google Scholar 

  • Tseng YM, Lin SK, Hsiao JK, Chen IJ, Lee JH, Wu SH, Tsai LY (2006) Whey protein concentrate promotes the production of glutathione (GSH) by GSH reductase in the PC12 cell line after acute ethanol exposure. Food Chem Toxicol 44:574–578

    Article  PubMed  CAS  Google Scholar 

  • Zommara M, Tachibana N, Sakono M, Suzuki Y, Oda T, Hashida H, Imaizumi K (1996) Whey from cultured skim milk decreases serum cholesterol and increases antioxidant enzymes in liver and red blood cells in rats. Nutr Res 16:293–302

    Article  CAS  Google Scholar 

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Acknowledgments

The authors are indebted to Dr. N. Tanideh, Director of the animal house of Shiraz University of Medical Sciences, and Dr. A. Farahnaki, Head of Department of Food Science, Shiraz University, for their assistance in all stages of this research. We would like to thank Arla Company, Osveh Company, and Razi Company for supplying us the WPI, vitamins, and minerals that were used in this study. We are also grateful for the financial support from Shiraz University of Medical Sciences.

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Authors and Affiliations

  1. Department of Pathology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

    Ahmad Oryan

  2. Department of Nutrition, School of Health and Nutrition, Research Centre for Health Sciences, Shiraz University of Medical Sciences, P.O. Box 111, Shiraz, 71645, I.R. of Iran

    Mohammad Hasan Eftekhari & Maryam Ershad

  3. Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohammad Reza Panjehshahin

  4. Department of Epidemiology, School of Health and Nutrition, Research Centre for Health Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

    Hamid Reza Tabatabaei

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  1. Ahmad Oryan
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  2. Mohammad Hasan Eftekhari
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  3. Maryam Ershad
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  4. Mohammad Reza Panjehshahin
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  5. Hamid Reza Tabatabaei
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Correspondence to Maryam Ershad.

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Oryan, A., Eftekhari, M.H., Ershad, M. et al. Hepatoprotective effects of whey protein isolate against acute liver toxicity induced by dimethylnitrosamine in rat. Comp Clin Pathol 20, 251–257 (2011). https://doi.org/10.1007/s00580-010-0986-5

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  • DOI: https://doi.org/10.1007/s00580-010-0986-5

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