You are here

ANTINOCICEPTIVE EFFECT OF WHEY PROTEIN AND ITS FRACTIONS IN SWISS ALBINO MICE

Journal Name:

Publication Year:

Abstract (2. Language): 
Background: Whey is a by-product of cheese production; it is one of the components which separate from milk after curdling, when rennet or an edible acidic substance is added. Whey protein (WP) is typically a mixture of beta-lacto globulin (p-lg) (~65%), alpha-lactalbumin (a-la) (~25%), and serum albumin (~8%), which are soluble in their native culture forms and it has the highest biological value of any known protein. Materials and Methods: Comparative studies were performed to assess the efficacy of WP, a-la and p-lg (100, 200 and 300 mg/Kg, Os) in tow animal models: hot plate-induced thermal pain and carrageenan-induced paw inflammation and antioxidant activities in rats. Results: Results revealed that the higher doses of WP, a-la and p-lg caused significant analgesic effect versus paracetamol (50 mg/Kg) especially after 3 hr-post treatment (potency: 3.01, 3.21 and 3.45, respectively). Whereas after 4hr., WP and a-la (300 mg/Kg) treatments had similar analgesic effect. While, P¬Ig (200 and 300 mg/Kg) was the most potent in its analgesic effect when compared with the paracetamol and the other treated groups. In acute anti-inflammatory activity, it was shown that the two doses of P-lg (100 and 200 mg /kg) significantly reduced paw oedema after 30 min (potency versus ketoprofen was: 1.11 and 1.13). While after 4 hr, the higher dose of a-la (300 mg/Kg) had similar effect to that induced by the two doses of P-lg (200 and 300 mg/Kg) treatment. The potency of the two doses (100 and 200 mg/Kg) of WP nearly had similar antiinflammatory effect (time dependent effect). All treatments caused significant antioxidant activity when compared with the control group. The increase in SOD value was dose dependent manner. In which, 300 mg/Kg showed remarkable increase in SOD level with the following rank, a-la > P-lg > WP > ketoprofen (5 mg/Kg) treated groups. These results indicated that P-lg produced powerful analgesic and anti-inflammatory activities than a-la and WP. As well as, a-la possess strong antioxidant activity than P-lg and WP treatments. Conclusion: It suggested that P-lg, a-la and WP could be used safely as natural analgesic and anti-inflammatory drug instead of NSAIDs, which have side effects when used for chronic disorders.
FULL TEXT (PDF): 
355-381

REFERENCES

References: 

1. Marshall K: Therapeutic applications of whey protein. Altern. Med. Rev., 2004; 9: 136 - 156
2. Low PP, Rutherfurd KJ, Gill HS, and Cross ML: Effect of dietary whey protein concentrate on primary and secondary antibody responses in immunized BALB/c mice. Int. Immunopharmacol., 2003; 3: 393¬401
3. Brown EC, DiSilvestro RA, Babaknia A , and Devor ST: Soy versus whey protein bars: Effects on exercise training impact on lean body mass and antioxidant status . Nutr J., 2004; 3: 22- 26 .
4. Saito T: Antihypertensive peptides derived from bovine casein and whey proteins. Adv. Exp. Med. Biol., 2008; 606: 295 - 317.
5. Bounous G, Batist G, and Gold P: Whey proteins in cancer prevention Cancer Lett.,
1991; 57: 91- 94.
6. Neurath AR, Li YY, Strick N, and Jiang S: A herpesvirus inhibitor from bovine whey.Lancet, 1996; 347:1703 - 1704
7. Shah NP: Effects of milk-derived bioactives: an overview Br. J. Nutr., 2000;
84: (Suppl. 1), S3 -S10.
8. Hurrell RF, Lynch SR, Trinidad TP, Dassenko SA, and Cook JD: Iron absorption in humans as influenced by bovine milk proteins Am. J. Clin. Nutr., 1989; 49: 546 -
552
9. Yamaguchi M, Matsuura M, Kobayashi K, Sasaki H, Yajima T and Kuwata T: Lactoferrin Protects against Development of Hepatitis Caused by Sensitization of Kupffer Cells by Lipopolysaccharide. Clin. Diagn. Lab. Immunol., 2001; 8: 1234 - 1239
10. Yamaguchi M and Uchida M (2007). a-Lactalbumin suppresses interleukin-6 release after intestinal ischemia/reperfusion via nitric oxide in rats Inflammopharmacology, 15: 43 - 47
11. Hayashida K, Kaneko T, Takeuchi T, Shimizu H, Ando K., and Harada E: Oral administration of lactoferrin inhibits inflammation and nociception in rat adjuvant-induced arthritis. J. Vet. Med. Sci. 2004; 66: 149-154.
Available Online At www.ijprbs.com
Research Article
Hesham Eliwa, IJPRBS, 2012; Volume 1(6): 355-381
12. Smith HS: Arachidonic acid pathways in nociception. J. Support. Oncol., 2006; 4: 277
- 287
13. Yamakawa K, Matsunaga M, Isowa T, Kimura K, Kasugai K, Yoneda M, Kaneko H, and Ohira H: Transient responses of inflammatory cytokines in acute stress. Biol Psychol. May 14. [PMID: 19446599 [PubMed - as supplied by publisher]. 2009.
14. Clâria J and Romano M: Pharmacological intervention of cyclooxygenase-2 and 5-1ipoxygenase pathways. Impact on inflammation. Curr. Pharm. Des., 2005; 11:
3431- 3447.
15. Zimmermann M: Ethical guidelines for investigations of experimental pain in conscious animals. Pain, 1983; 16:109 -110.
16. Roszkowski A, Rooks WH, Tonolonis AJ, and Miller LM: Anti-inflammatoryand analgesic properties of Naproxien. J.Pharmacol. Exp.Thera., 1971; 179: 1.
17. Winter GA, Rislfy EA and Nuss GW:
Cargeenin induced oedema in hind paw of rats as assay for antiinflammatory drugs.
Proc. Soc. Exp. Biol. Med., 1962; 111: 121.
ISSN: 2277-8713
IJPRBS
18. Sharma J N, Samud AM and Asmawi MZ (2004). Comparison between plethysmometer and micrometer methods to measure acute paw oedema for screening anti-inflammatory activity in mice. Inflammopharmacology. 12; 1: 89 -
94 .
19. Suttle NF: Copper deficiency in ruminants, recent developments. The Veterinary Record, 1986; 119: 519 -522.
20. Hambrus L: Dietary assessments: how to validate primary data before conclusions can be drawn Leif Hambaeus. Scandinavian Journal of NutritinlNaringrforskning, 1998;
142:66-68.
21. Pillanto-Leppala A: Review: Bioactive peptides derived from whey proteins: Opioid and ace inhibitory peptides. Trends in Food Science and Technology. 2001; 11:
347 -356
22. Paakkari I, Jarvinen A, Anttila MJ, and Pihlanto- Leppala A: Opioid effects of the milk wehy-protein derived peptides a- and P- lactorphin in P-casomorphins and related peptides. Recent development (Brantl, V., Teschemacher, H.eds.). 1994: pp 33 -37, VCH, Weinheim.
Available Online At www.ijprbs.com
Research Article
Hesham Eliwa, IJPRBS, 2012; Volume 1(6): 355-381
ISSN: 2277-8713
IJPRBS
23. Pihlanto-Leppala A, Paakkari I, Rinta-Koski M, and Antila P: Bioactive peptide derived from in vitro proteolysis of bovine P-lactoglobulin and its effect on smooth muscle. J. Diary Res., 1997; 64: 149 - 155.
24. Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W,Lee L, and Isakson P: Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc. Natl. Acad. Sci. U.S.A., 1994; 91:
12013 - 12017.
25. Tantisira KG, John L, Jody S, Klanderman B , and Weiss ST: 5-Lipoxygenase pharmacogenetics in asthma: overlap with Cys-leukotriene receptor antagonist loci. Pharmacogenetics and Genomics, 2009; 19 : 244 - 247
26. Anderson GD, Hauser SD, McGarity KL, Bremer ME, Isakson PC, and Gregory SA: Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin 6 in rat adjuvant arthritis., J. Clin. Invest., 1996; 97:
2672 - 2679
27. Schmelzer KR, Inceoglu B, Kubala L, Kim IH, Jinks SL, Eiserich JP, and Hammock BD:
Enhancement of antinociception by coadministration of nonsteroidal anti-inflammatory drugs and soluble epoxide hydrolase inhibitors. Proc. Natl. Acad. Sci.
U.S.A., 2006; 103: 13646 - 13651
28. Stichtenoth DO: Mini Rev. The second generation of COX-2 inhibitors: clinical pharmacological point of view. Med. Chem.,
2004; 4: 617- 624
29. Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, and Schnitzer TJ: Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients with Rheumatoid
Arthritis. N. Engl. J. Med., 2000; 343: 1520 -1528.
30. Gilroy DW, Colville-Nash PR, Willis D,
Chivers J, Paul-Clark MJ, and Willoughby DA: Inducible cyclooxygenase may have anti-inflammatory properties. Nat. Med.,
1999; 5: 698-701.
31. Yamaguchi M, Yoshida K, and Uchida M: Novel Functions of Bovine Milk-Derived a-Lactalbumin: Anti-nociceptive and Anti-inflammatory Activity Caused by Inhibiting
Available Online At www.ijprbs.com
Research
Article
Hesham
Eliwa, IJPRBS, 2012; Volume 1(6): 355-381
Cyclooxygenase-2 and Phospholipase A2. Biol. Pharm. Bull. 2009; 32: 3, 366- 371.
32. Ushida Y, Shimokawa Y, Toida T, Matsui H, and Takase M : Bovine UMactalbumin Stimulates Mucus Metabolism in Gastric Mucosa, J. Dairy Sci., 2007; 90: 541 - 546
33. Ghosh S and Playford RJ: Bioactive natural compounds for the treatment of gastrointestinal disorders. Clinical Science. 2003; 104: 547-556
34. Stern M, Pang KY, and Walker WA: Food proteins and gut mucosal barrier. II. Differential Interaction of Cow's Milk Proteins with the Mucous Coat and the Surface Membrane of Adult and Immature Rat Jejunum. Pediatric Research. 1984; 18:1252-1257.
35. Brune K: Safety of anti-inflammatory treatment--new ways of thinking. Rheumatology Oxford. 2004; 43: 16-20.
36. Bonizzi G, Piette J, Schoonbroodt S, Greimers R, Havard L, Merville MP, and Bours V: Reactive oxygen intermediate-dependent NF-kappaB activation by interleukin-1beta requires 5-lipoxygenase or NADPH oxidase activity. Mol. Cell Biol., 1999; 19:1950 - 60.
ISSN: 2277-8713
IJPRBS
37. Chou TC, Chang LP, Li CY, Wong CS, and Yang SP: The Antiinflammatory and Analgesic Effects of Baicalin in Carrageenan-Evoked Thermal Hyperalgesia, Anesth. Analg., 2003; 97: 1724 - 1729.
38. Arunachalam G, Chattopadhyay D, Chatterjee S, Mandal AB, Sur TK, and Mandal SC: Evaluation of anti-inflammatory activity of Alstonia macrophylla Wall. ex A.DC. leaf extract, Phytomedicine, 2002; 9:
632- 635.
39. Kwon MS, Shim EJ, Seo YJ, Choi SS, Lee JY, Lee HK, and Suh HW: Effect of aspirin and acetaminophen on proinflammatory cytokine-induced. Pharmacology, 2005;
74:152-156
40. Burd AN, Tang JE, Moore DR, and Phillips SM: Exercise training and protein metabolism: influences of contraction, protein intake, and sex-based differences J Appl Physiol. 2009; 106: 1692-1701.
41. Lönnerdal B and Lien EL: Nutritional and physiologic significance of alpha lactalbumin in infants. Nutr Rev., 2003; 61:
295-305.
42. El-Zahar Kh., Sitohy M , Choiset Y, Metro FQ, Haertle T, and Chobert JM : Peptic
Available Online At www.ijprbs.com
Research Article
Hesham Eliwa, IJPRBS, 2012; Volume 1(6): 355-381
ISSN: 2277-8713
IJPRBS
hydrolysis of ovine b-lactoglobulin and a-lactalbumin Exceptional susceptibility of native ovine b-lactoglobulin to pepsinolysis. International Dairy Journal 2005; 15: 17-27.
43. Futagami A, Ishizaki M, Fukuda Y, Kawana S, and Yamanaka N: Wound healing involves induction of cyclooxygenase-2 expression in rat skin. Lab. Invest. 2002;
82:1503-13.
44. Wang XM, Wu TX, Hamza M, Ramsay ES, Wahl SM and Dionne RA: Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007; 128: 136¬147.
45. White CW, Avraham KB, Shanley PF, and Groner Y: Transgenic mice with expression
of elevated levels of copper-zinc superoxide dismutase in the lungs are resistant to pulmonary oxygen toxicity. J Clin Invest.,
1991; 87:2162-68.
46. Fakhrzadeh L, Laskin JD, Gardner CR, and Laskin DL: Superoxide dismutase-over expressing mice are resistant to ozone-induced tissue injury and increases in nitric oxide and tumor necrosis factor-alpha. Am.
J. Respir. Cell Mol Biol. 2004; 30:280 -7.
47. Wong D, Wang M, Cheng Y, and FitzGerald GA: Cardiovascular hazard and non-steroidal anti-inflammatory drugs. Curr Opin Pharmacol. 2005; 5: 204 -10.
48. Hayasawa H, Toida T, Shimokawa Y, and Matsumoto H: Antiulcer agent. U.S. Patent,
6815419. 2004.

Thank you for copying data from http://www.arastirmax.com