Nutr Res Pract.  2012 Apr;6(2):113-119.

Lutein decreases oxidative stress and inflammation in liver and eyes of guinea pigs fed a hypercholesterolemic diet

Affiliations
  • 1Department of Nutritional Sciences, University of Connecticut, 3624 Horsebarn Rd ext, Storrs, CT 06269, USA. maria-luz.fernandez@uconn.edu

Abstract

Guinea pigs were fed a hypercholesterolemic diet (0.25 g/100 g cholesterol) and randomly allocated either to a Control group (n = 9) or to a Lutein (0.1 g/100 g) group (n = 10) for 12 weeks to evaluate oxidative stress and inflammation in both liver and eyes. Malondialdehyde (MDA) concentrations and inflammatory cytokines were measured as well as hepatic nuclear factor-kappaB (NF-kappaB) binding. Lutein concentrations were greater in eyes (P < 0.01) and liver (P < 0.001) in the Lutein group. All guinea pigs had high concentrations of hepatic cholesterol as well as high plasma ALT and AST levels indicative of liver injury. However, the Lutein group had 43% lower hepatic free cholesterol than the Controls (P < 0.05). Hepatic MDA and MDA in the eye were lower in the Lutein compared to the Control group (P < 0.05). Hepatic tumor necrosis factor-alpha was 32% lower in the Lutein group (P < 0.05). Lastly, the Lutein group presented lower NF-kappaB DNA binding activity than the Control group (P < 0.001). These results suggest that in the presence of high cholesterol, lutein exerts both antioxidant and anti-inflammatory effects, which can be explained by attenuated NF-kappaB DNA binding activity. Furthermore, results also suggest that lutein accumulates in the eyes of guinea pigs to protect against oxidative stress.

Keyword

Lutein; lipid peroxidation; inflammation; guinea pigs

MeSH Terms

Animals
Cholesterol
Cytokines
Diet
DNA
Eye
Guinea
Guinea Pigs
Inflammation
Lipid Peroxidation
Liver
Lutein
Malondialdehyde
NF-kappa B
Oxidative Stress
Plasma
Tumor Necrosis Factor-alpha
Cholesterol
Cytokines
DNA
Lutein
Malondialdehyde
NF-kappa B
Tumor Necrosis Factor-alpha

Figure

  • Fig. 1 Correlations between AST and free cholesterol (r = 0.57, P < 0.025) (Panel A) and ALT and free cholesterol (r = 0.66, P < 0.001) for 19 guinea pigs (n = 9, control and n = 10 for the lutein group). ALT and AST were determined by use of a COBAS C-111 analyzer.

  • Fig. 2 Malonaldehyde concentrations in liver and in eye of guinea pigs fed control (n = 9) or lutein (n = 10) diets. MDA concentrations were measured by thiobarbituric acid reactive substances (TBARS) *indicates P < 0.05.

  • Fig. 3 Concentrations of TNF-α, MCP-1 and IL-1β of liver and eye of guinea pigs fed control (n = 9) or lutein (n = 10) diets. Protein levels of cytokines were evaluated from homogenates of liver and eye using the MILLIPLEX MAP Mouse Cytokine PREMIXED Immunoassay kit *indicates P < 0.05.

  • Fig. 4 NF-kB p65 DNA binding activity of control and lutein treated guinea pigs. **P < 0.0001


Reference

1. Khachik F, Beecher GR, Smith JC Jr. Lutein, lycopene, and their oxidative metabolites in chemoprevention of cancer. J Cell Biochem Suppl. 1995. 22:236–246.
Article
2. Krinsky NI, Landrum JT, Bone RA. Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Annu Rev Nutr. 2003. 23:171–201.
Article
3. Donoso LA, Kim D, Frost A, Callahan A, Hageman G. The role of inflammation in the pathogenesis of age-related macular degeneration. Surv Ophthalmol. 2006. 51:137–152.
Article
4. Hollyfield JG, Bonilha VL, Rayborn ME, Yang X, Shadrach KG, Lu L, Ufret RL, Salomon RG, Perez VL. Oxidative damage-induced inflammation initiates age-related macular degeneration. Nat Med. 2008. 14:194–198.
Article
5. Dwyer JH, Navab M, Dwyer KM, Hassan K, Sun P, Shircore A, Hama-Levy S, Hough G, Wang X, Drake T, Merz CN, Fogelman AM. Oxygenated carotenoid lutein and progression of early atherosclerosis: the Los Angeles atherosclerosis study. Circulation. 2001. 103:2922–2927.
Article
6. Dwyer JH, Paul-Labrador MJ, Fan J, Shircore AM, Merz CN, Dwyer KM. Progression of carotid intima-media thickness and plasma antioxidants: the Los Angeles Atherosclerosis Study. Arterioscler Thromb Vasc Biol. 2004. 24:313–319.
Article
7. Sindhu ER, Firdous AP, Preethi KC, Kuttan R. Carotenoid lutein protects rats from paracetamol-, carbon tetrachloride- and ethanol-induced hepatic damage. J Pharm Pharmacol. 2010. 62:1054–1060.
Article
8. Sindhu ER, Preethi KC, Kuttan R. Antioxidant activity of carotenoid lutein in vitro and in vivo. Indian J Exp Biol. 2010. 48:843–848.
9. Jin XH, Ohgami K, Shiratori K, Suzuki Y, Hirano T, Koyama Y, Yoshida K, Ilieva I, Iseki K, Ohno S. Inhibitory effects of lutein on endotoxin-induced uveitis in Lewis rats. Invest Ophthalmol Vis Sci. 2006. 47:2562–2568.
Article
10. Kim JH, Na HJ, Kim CK, Kim JY, Ha KS, Lee H, Chung HT, Kwon HJ, Kwon YG, Kim YM. The non-provitamin A carotenoid, lutein, inhibits NF-kappaB-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase/PTEN/Akt and NF-kappaB-inducing kinase pathways: role of H(2)O(2) in NF-kappaB activation. Free Radic Biol Med. 2008. 45:885–896.
Article
11. Shanmugasundaram R, Selvaraj RK. Lutein supplementation alters inflammatory cytokine production and antioxidant status in F-line turkeys. Poult Sci. 2011. 90:971–976.
Article
12. He G, Karin M. NF-kappaB and STAT3 - key players in liver inflammation and cancer. Cell Res. 2011. 21:159–168.
Article
13. Luedde T, Schwabe RF. NF-kappaB in the liver--linking injury, fibrosis and hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2011. 8:108–118.
Article
14. Robinson SM, Mann DA. Role of nuclear factor kappaB in liver health and disease. Clin Sci (Lond). 2010. 118:691–705.
15. Fernandez ML. Guinea pigs as models for cholesterol and lipoprotein metabolism. J Nutr. 2001. 131:10–20.
Article
16. Roy S, Vega-Lopez S, Fernandez ML. Gender and hormonal status affect the hypolipidemic mechanisms of dietary soluble fiber in guinea pigs. J Nutr. 2000. 130:600–607.
Article
17. Torres-Gonzalez M, Shrestha S, Sharman M, Freake HC, Volek JS, Fernandez ML. Carbohydrate restriction alters hepatic cholesterol metabolism in guinea pigs fed a hypercholesterolemic diet. J Nutr. 2007. 137:2219–2223.
Article
18. Anstee QM, Goldin RD. Mouse models in non-alcoholic fatty liver disease and steatohepatitis research. Int J Exp Pathol. 2006. 87:1–16.
Article
19. Kim JE, Leite JO, DeOgburn R, Smyth JA, Clark RM, Fernandez ML. A lutein-enriched diet prevents cholesterol accumulation and decreases oxidized LDL and inflammatory cytokines in the aorta of guinea pigs. J Nutr. 2011. 141:1458–1463.
Article
20. Fernandez ML, McNamara DJ. Regulation of cholesterol and lipoprotein metabolism in guinea pigs mediated by dietary fat quality and quantity. J Nutr. 1991. 121:934–943.
Article
21. Clark RM, Herron KL, Waters D, Fernandez ML. Hypo- and hyperresponse to egg cholesterol predicts plasma lutein and beta-carotene concentrations in men and women. J Nutr. 2006. 136:601–607.
Article
22. Carr TP, Andresen CJ, Rudel LL. Enzymatic determination of triglyceride, free cholesterol, and total cholesterol in tissue lipid extracts. Clin Biochem. 1993. 26:39–42.
Article
23. Schäffer MW, Sinha Roy S, Mukherjee S, Das SK. Identification of lutein, a dietary antioxidant carotenoid in guinea pig tissues. Biochem Biophys Res Commun. 2008. 374:378–381.
Article
24. Lin EC, Fernandez ML, McNamara DJ. Dietary fat type and cholesterol quantity interact to affect cholesterol metabolism in guinea pigs. J Nutr. 1992. 122:2019–2029.
Article
25. Shanmugasundaram R, Selvaraj RK. Dietary lutein and fish oil interact to alter atherosclerotic lesions in a Japanese quail model of atherosclerosis. J Anim Physiol Anim Nutr (Berl). 2011. 95:762–770.
Article
26. Puri P, Baillie RA, Wiest MM, Mirshahi F, Choudhury J, Cheung O, Sargeant C, Contos MJ, Sanyal AJ. A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology. 2007. 46:1081–1090.
Article
27. Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, Sterling RK, Luketic VA, Shiffman ML, Clore JN. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology. 2001. 120:1183–1192.
Article
28. Nair S, V PC, Arnold C, Diehl AM. Hepatic ATP reserve and efficiency of replenishing: comparison between obese and nonobese normal individuals. Am J Gastroenterol. 2003. 98:466–470.
Article
29. McClain CJ, Mokshagundam SP, Barve SS, Song Z, Hill DB, Chen T, Deaciuc I. Mechanisms of non-alcoholic steatohepatitis. Alcohol. 2004. 34:67–79.
Article
30. Janero DR. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med. 1990. 9:515–540.
Article
31. Young AJ, Lowe GM. Antioxidant and prooxidant properties of carotenoids. Arch Biochem Biophys. 2001. 385:20–27.
Article
32. Ribaya-Mercado JD, Blumberg JB. Lutein and zeaxanthin and their potential roles in disease prevention. J Am Coll Nutr. 2004. 23:567S–587S.
Article
33. Debril MB, Renaud JP, Fajas L, Auwerx J. The pleiotropic functions of peroxisome proliferator-activated receptor gamma. J Mol Med (Berl). 2001. 79:30–47.
Article
34. Selvaraj RK, Shanmugasundaram R, Klasing KC. Effects of dietary lutein and PUFA on PPAR and RXR isomer expression in chickens during an inflammatory response. Comp Biochem Physiol A Mol Integr Physiol. 2010. 157:198–203.
Article
35. Mai J, Shen X, Shi D, Wei Y, Shen H, Wu M. Effect of lutein on relieving oxidative stress in mice induced by D-galatose. Wei Sheng Yan Jiu. 2010. 39:430–432.
36. Ruhl CE, Everhart JE. Relation of elevated serum alanine aminotransferase activity with iron and antioxidant levels in the United States. Gastroenterology. 2003. 124:1821–1829.
Article
37. Preethi KC, Kuttan R. Hepato and reno protective action of Calendula officinalis L. flower extract. Indian J Exp Biol. 2009. 47:163–168.
38. Catala A. Lipid peroxidation of membrane phospholipids in the vertebrate retina. Front Biosci (Schol Ed). 2011. 3:52–60.
Article
39. Ham WT Jr, Mueller HA, Sliney DH. Retinal sensitivity to damage from short wavelength light. Nature. 1976. 260:153–155.
Article
40. Beatty S, Koh H, Phil M, Henson D, Boulton M. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol. 2000. 45:115–134.
Article
Full Text Links
  • NRP
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr