SULPHATED POLYSACCHARIDES (SPS) FROM THE GREEN ALGA ULVA FASCIATA EXTRACT MODULATES LIVER AND KIDNEY FUNCTION IN HIGH FAT DIET-INDUCED HYPERCHOLESTEROLEMIC RATS
Abstract
Objective: Hypercholesterolemia (HC) was frequently associated with oxidative stress, and release of inflammatory cytokines is to determine the hypolipidemic effects of sulphated polysaccharides from seaweed Ulva fasciata algal extracts through measuring the activities of some parameters related to liver and kidney functions in the serum of hypercholesterolemic rats as compared to normal one.
Methods: Different groups of rats were administered a high cholesterol diet
. Liver and kidney functions, inflammatory cytokines (TNF-α, CRP, MPO and IL-10), oxidative stress (GSH, MDA and NO), in addition to cell adhesion molecules (ICAM-1 and VCAM-1) were assessed before and after treatment with the algal polysaccharides. In addition, histological examination of liver and kidney were performed to confirm the biochemical findings.
Results: The obtained results showed that oxidative stress and inflammatory markers associated with hypercholesterolemia were significantly increased in HC-rats. The histopathological examination of liver and kidney demonstrated severe degeneration with diffuse vacuolar degeneration, necrosis and the presence of fatty droplets. In addition; nephron-histological examination revealed, mild glomerular injury with mild vascular and inflammatory changes. Treatment with the algal sulphated polysaccharides effectively improved these disorders and diminished the formation of fatty liver, as well as renal dysfunction more than the reference drug; fluvastatin.
Conclusion: It could be concluded that the consumption of UFP (Ulva fasciata polysaccharides), may be associated with attenuation of inflammatory markers, amelioration of fatty liver and improvement of renal dysfunction, that in turn lead to counteract hypercholesterolemia and its related disorders; such as obesity, and heart disease.
Keywords: Non-alcoholic fatty liver disease, Seaweed, Ulva fasciata, Hypercholesterolemia, Hypolipidemic activity, Sulphated polysaccharides (SPs)
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Xin P, Han H, Gao D. Alleviative effects of resveratrol on nonalcoholic fatty liver disease are associated with up regulation of hepatic low-density lipoprotein receptor and scavenger receptor class B type I gene expressions in rats. Food Chem Toxicol 2013;52:12-8.
Yang L, Chen JH, Xu T. Hypocholesterolemic effect of rice protein is due to regulating hepatic cholesterol metabolism in adult rats. Gene 2013;512:470-6.
Buzand SY, Mashek DG. Hepatic long-chain acyl-CoA synthetase 5 mediates fatty acid channeling between anabolic and catabolic pathways. J Lipid Res 2010;51:3270-80.
Hylemon PB, Pandak WM, Vlahcecic ZR. Regulation of hepatic cholesterol homeostasis, the liver: Biology and pathobiology. Lippincott Williams and Wilkins, Philadelphia; 2001. p. 231-47.
Jelinek DA, Maghsoodi B, Borbon IA. Genetic variation in the mouse model of Niemann-Pick C1 affects female, as well as male, adiposity and hepatic bile transporters but has indeterminate effects on caveolae. Gene 2012;491:128-34.
Brunt EM, Tiniakos DG. Histopathology of nonalcoholic fatty liver disease. World J Gastroenterol 2010;16:5286-96.
Falck-Ytter Y, Younossi ZM, Marchesini G. linical features and natural history of nonalcoholic steatosis syndromes. Semin Liver Dis 2001;21:17-26.
Sahebkar A. Citrus auraptene: a potential multifunctional therapeutic agent for the nonalcoholic fatty liver disease. Ann Hepatol 2011;10:575-7.
Hajiaghamohammadi A, Ziaee A, Samimi R. The efficacy of licorice root extract in decreasing transaminase activities in non-alcoholic fatty liver disease: a randomized controlled clinical trial. Phytother Res 2012;26:1381-4.
Kohjima M, Enjoji M, Higuchi N. Reevaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease. Int J Mol Med 2007;20:351-8.
Lee MS, Kim D, Jo K. Nordihydroguaiaretic acid protects against high-fat-diet-induced fatty liver by activating AMP-activated protein kinase in obese mice. Biochem Biophys Res Commun 2010;401:92-7.
Rolo AP, Teodoro JS, Palmeira CM. The role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radical Biol Med 2012;52:59-69.
Ye P, Cheah IK, Halliwell B. High-fat diets and pathology in the guinea pig. Atherosclerosis or liver damage? Biochim Biophys Acta 2013;1832:355-64.
Loria P, Lonardo A, Targher G. Is liver fat detrimental to vessels? Intersections in the pathogenesis of NAFLD and atherosclerosis. Clin Sci 2008;115:1-12.
Scorletti E, Calder PC, Byrne CD. Non-alcoholic fatty liver disease and cardiovascular risk: metabolic aspects and novel treatments. Endocrine 2011;40:332-43.
Bhatia LS, Curzen NP, Calder PC. Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor? Eur Heart J 2012;33:1190-200.
Schaffer JE. Lipotoxicity: when tissues overeat. Curr Opin Lipidol 2003;14:281-7.
Crook ED, Thallapureddy A, Migdal S. Lipid abnormalities and renal disease: is dyslipidemia a predictor of progression of renal disease? Am J Med Sci 2003;325:340-8.
Muntner P, Coresh J, Smith JC. Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study. Kidney Int 2000;58:293-301.
Wilson SH, Chade AR, Feldstein A. Lipid-lowering-independent effects of simvastatin on the kidney in experimental hypercholesterolaemia. Nephrol Dial Transplant 2003;18:703-9.
Kim HJ, Moradi H, Vaziri ND. Renal mass reduction results in accumulation of lipids and dysregulation of lipid regulatory proteins in the remnant kidney. Am J Physiol 2009;296:F1297-306.
Vaziri ND, Bai Y, Yuan J. ApoA-1 mimetic peptide reverses uremia-induced upregulation of pro-atherogenic pathways in the aorta. Am J Nephrol 2010;32:201-11.
Pengzhan Y, Quanbin Z, Ning L. Polysaccharides from Ulva pertusa (Chlorophyta) and preliminary studies on their anti-hyperlipidemia activity. J Appl Phycol 2003;15:21-7.
Adaramoye O, Akinatyo O, Achen J. Lipid-lowering effects of methanolic extracts of Vernonia anygdalina leaves in rats fed on high cholesterol diet. Vasc Health Risk Manage 2008;4:235-41.
Allain CC, Poon LS, Chan CS. Enzymatic determination of total serum cholesterol. Clin Chem 1974;20:470-5.
Fassati P, Prencipe L. Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem 1982;28:2077-80.
Lopez-Virella MF, Stone P, Ellis S. Cholesterol determination in HDL separated by three different methods. Clin Chem 1977;23:882-4.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without the use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
Norbert WT. Clinical guide to laboratory tests. 3rd edition. Saunders WB. Company, Philadelphia; 1995.
Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminase. Am J Clin Pathol 1957;28:56-63.
Belfield A, Goldberg DM. Colorimetric determination of alkaline phosphatase activity. Enzymes 1971;12:561-8.
Walters M, Gerade H. Ultramicromethod for the determination of conjugated and total bilirubin in serum or plasma. Microchem J 1970;15:231.
Bradford M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-54.
Doumas BT, Watson WA, Biggs HG. Albumin standards and the measurement of serum albumin with Brom cresol green. Clin Chim Acta 1971;31:87-96.
Trinder P. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem 1969;6:24-5.
Fawcett JK, Scott JE. A rapid and precise method for the determination of urea. J Clin Pathol 1960;13:156-9.
Schirmeister J. Determination of creatinine level. Dtsch Med Wochenschr 1964;89:1940-7.
Satoh K. Serum lipid peroxide in cerebrovascular disorders which was determined by a new colorimetric method. Clin Chem Acta 1978;90:37-43.
Beutler E, Duron O, Kelly BM. An improved method for the determination of blood glutathione. J Lab Clin Med 1963;61:882-8.
Montgomery HAC, Dymock JF. The determination of nitrate in water. Analyst 1961;86:414-6.
Drury RA, Wallington EA. Careleton’s histological technique. 4th ed. Oxford. Oxford University Press; 1980.
Enjoji M, Nakamuta M. Is the control of dietary cholesterol intake sufficiently effective to ameliorate nonalcoholic fatty liver disease? World J Gastroenterol 2010;16:800-3.
Anstee QM, Daly AK, Day CP. Genetic modifiers of non-alcoholic fatty liver disease progression. Biochim Biophys Acta 2011;1812:1557-66.
Penga CH, Chang HC, Yang MY. Oat attenuates non-alcoholic fatty liver and obesity via inhibiting lipogenesis in the high fat-fed rat. J Funct Foods 2013;5:53-61.
Makni M, Fetoui H, Gargouri N. Hypolipidemic and hepatoprotective effects of flaxseed and pumpkin seed mixture in ω-3 and ω-6 fatty acids in hypercholesterolemic rats. Food Chem Toxicol 2008;46:3714-20.
Jang A, Srinivasan P, Lee NY. Comparison of hypolipidemic activity of synthetic gallic acid, linoleic acid ester with a mixture of gallic acid and linoleic acid, gallic acid, and linoleic acid on high-fat diet induced obesity in C57BL/6 Cr Slc mice. Chem Biol Interact 2008;174:109-17.
Mustad VA, Etherton TD, Cooper AD. Reducing saturated fat intake is associated with increased levels of LDL receptors on mononuclear cells in healthy men and women. J Lipid Res 1997;38:459-68.
Flock MR, Green MH, Kris-Etherton PM. Effects of adiposity on plasma lipid response to reductions in dietary saturated fatty acids and cholesterol. Adv Nutr 2011;2:261-74.
Godard M, De'corde K, Ventura E. Polysaccharides from the green alga Ulva rigida improve the antioxidant status and prevent fatty streak lesions in the high cholesterol fed hamster, an animal model of nutritionally induced atherosclerosis. Food Chem 2009;115:176-80.
Venkateson N, Devaraj S, Devaraj H. Increased binding of LDL and VLDL to apo-B, E-receptors of hepatic plasma membrane of rats treated with fibernat. Eur J Nutr 2003;42:262-71.
Qi HM, Zhang QB, Zhao TT. Antioxidant activity of different sulphate content derivatives of polsaccharides derived from Ulva pertusa (Cholorophyta) in vitro. Int J Biol Macromol 2010;37:195-9.
Dikkers A Tietge UJ. Biliary cholesterol secretion: more than a simple ABC. World J Gastroenterol 2010;16:5936-45.
Rosenson RS, Baker AL, Chow MJ. Hyperviscosity syndrome in a hypercholesterolemic patient with primary biliary cirrhosis. Gastroenterology 1990;98:1351-7.
Shivaraj G, Praksh D, Vinayak H. A review on liver function test. Pan Afr Med J 2009;3:17.
Noori S, Zafar H, Mahboob T. Biochemical effectiveness of cocoa powder on electrolytes homeostasis, liver and cardiac-specific enzymes and renal function. Pakistan J Nutr 2009;8:882-6.
Sudhahar V, Kumar SA, Sudharsan PT. Protective effect of lupeol and its ester on cardiac abnormalities in experimental hypercholesterolemia, Vascular Pharmacology 2007;46:412-8.
Kim AR, Lee JJ, Lee YM. Cholesterol-lowering and anti-obesity effects of Polymnia sonchifolia Poepp and Endl powder in rats fed a high fat-high cholesterol diet. J Korean Soc Food Sci Nutr 2010;39:210-8.
Mhamed M, Naoufel AZ, Jean-Baptiste M. Antihypertensive effect of Lepidium sativum L. in spontaneously hypertensive rats. J Ethnopharmacol 2005;100:193-7.
Yadav YC, Srivastav DN, Seth AK. Nephroprotective and curative activity of Lepidium Sativum L. seeds in albino rats using cisplatin induced nephrotoxicity. Pharmacol Line 2009;3:640-6.
Arhoghro EM, Ekpo KE, Ibeh GO. Effect of aqueous extract of scent leaf (Ocimum gratissimum) on carbon tetrachloride (CCl4) induced liver damage in albino Wister rats. Afr J Pharm Pharmacol 2009;3:562-7.
Ighodaro OM, Omole JO, Adejuwon AO. Effects of parinari polyandra seed extract on blood glucose level and biochemical indices in wistar rats. Int J Exp Diabesity Res 2012;1:68-72.
Kopec KL, Burns D. Nonalcoholic fatty liver disease: a review of the spectrum of disease, diagnosis, and therapy. Nutr Clin Pract 2011;26:565-76.
Musso G, Gambino R, Cassader M. Need for a three-focused approach to nonalcoholic fatty liver disease. J Hepatol 2011;53:1773-4.
Dröge W. Free radicals in the physiological control of cell function. Physiol Rev 2002;82:47-95.
Meister A. Glutathione. Ann Rev Biochem 1983;52:711-60.
Antoniades C, Shirodaria C, Crabtree M. Altered plasma versus vascular biopterins in human atherosclerosis reveal relationships between endothelial nitric oxide synthase coupling, endothelial function, and inflammation. Circulation 2007;116:2851-9.
Tall AR, Yvan-Charvet L, Terasaka N. HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis. Cell Metab 2008;7:365-75.
Bell LN, Molleston JP, Morton MJ. Hepatic lipid peroxidation and cytochrome P-450 2E1 in pediatric nonalcoholic fatty liver disease and its subtypes. J Clin Gastroenterol 2011;45:800-7.
Ueda S, Miyake I, Takata K. Ezetimibe, an inhibitor of intestinal cholesterol absorption, decreases serum level of malondialdehyde-modified low-density lipoprotein in patients with hypercholesterolemia. Int J Cardiol 2011;146:420-1.
Sathivel A, Raghavendran HR, Srinivasan P, Devaki T. Anti-peroxidative and anti-hyperlipidemic nature of Ulva lactuca crude polysaccharide on D-galactosamine-induced hepatitis in rats. Food Chem Toxicol 2008;46:3262-7.
Ridker PM. High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 2001;103:1813-8.
Sudano I, Spieker LE, Hermann F, Flammer A, Corti R, Noll G, et al. Protection of endothelial function: targets for nutritional and pharmacological interventions. J Cardiovasc Pharmacol Ther 2006;47:S136-50.
Han X, Kitamoto S, Wang H. Interleukin-10 overexpression in macrophages suppresses atherosclerosis in hyperlipidemic mice. FASEB J 2010;24:2869-80.
Hao MX, Jiang LS, Fang NY. The cannabinoid WIN55 212–2 protects against oxidized LDL-induced inflammatory response in murine macrophages. J Lipid Res 2010;51:2181-90.
Stuglin C, Prasad K. Effect of flaxseed consumption on blood pressure, serum lipids, hemopoietic system and liver and kidney enzymes in healthy humans. J Cardiovasc Pharmacol Ther 2005;10:23-7.
Wurochekke A, Anthony A, Obidah W. Biochemical effects on the liver and kidney of rats administered aqueous stem bark extract of Xemenia Americana. Afr J Biotechnol 2008;7:2777-80.
Montilla P, Espejo I, Munnoz MC, Bujalancea I, Munnoz-Castanneda JR, Tunez I. Protective effect of red wine on oxidative stress and antioxidant enzyme activities in the brain and kidney induced by feeding high cholesterol in rats. Clin Nutr 2006;25:146-53.
Herreo M, Cifuentes A, Ibanez E. Sub-and supercritical fluid extraction of functional ingredients from different natural sources: plants, food-by-products, algae and microalgae. Food Chem 2006;98:136-48.
Suanarunsawat T, Ayutthaya WDN, Songsak T, Thirawarapan S, Poungshompoo S. Lipid-lowering and antioxidative activities of aqueous extracts of Ocimum sanctum L. Leaves in Rats Fed with a High-Cholesterol Diet; Oxidative Medicine and Cellular Longevity; 2011. p. 9.
Alam N, Yoon KN, Lee TS, Lee UY. Hypolipidemic activities of dietary Pleurotus ostreatus in hypercholesterolemic rats. Mycobiology 2011;39:45-51.