Abstract
In the present study, the role of pentacyclic triterpenes, lupeol and its ester lupeol linoleate, was studied in relation to hepatic oxidative abnormalities and lipoprotein peroxidation in hypercholesterolemic rats. Hypercholesterolemia was induced in male Wistar rats by feeding them with high cholesterol diet (4% cholesterol + 1% cholic acid; HCD) for 30 days. Pentacyclic triterpenes, lupeol and lupeol linoleate were supplemented (50 mg/kg body wt/day) during the last 15 days. After the experimental period, there was a significant depression in hepatic activities of antioxidant enzymes, SOD (38.39%), CAT (25.03%) and GPx (30.26%) along with a marked fall in the levels of non-enzymic antioxidant molecules GSH (31.39%), vitamin C (46.07%) and vitamin E (42.28%), with a concomitant increase (p<0.001) in lipid peroxidation and in the activities of serum alkaline phosphatase, lactate dehydrogenase and aminotransferases when compared to controls. Treatment with triterpenes decreased lipid peroxidation and reverted the activities of antioxidants (p<0.001 and p<0.01) and marker enzymes to near control. Histopathological findings further confirmed the hepatoprotective nature of triterpenes by showing the normal architecture in treated rats, as against the fatty cellular changes in HCD fed rats. Further, the susceptibility of apo-B containing lipoprotein to oxidation by copper and Fenton’s reagent was increased in in vitro condition in HCD fed rats, whereas the lipoproteins were less susceptible to oxidation in triterpenes treated animals. Therefore, it may be concluded that lupeol and its ester afford protection against the hepatic abnormalities and lipoprotein peroxidation in hypercholesterolemic rats.
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Gupta PP, Tandon HD, Ramalingaswami V (1976) Cirrhosis of the liver in rabbits induced by a high cholesterol diet – an experimental model. Indian J Med Res 64:1516–1526
Assy N, Kaita K, Mymin D, Levy C, Rosser B, Minuk G (2000) Fatty infiltration of liver in hyperlipidemic patients. Dig Dis Sci 45:1929–1934
Balkan J, Kanbagli O, Hatipoglu A, Kucuk M, Cevikbas U, Aykac-Toker G, Uysal M (2002) Improving effect of dietary taurine supplementation on the oxidative stress and lipid levels in the plasma, liver and aorta of rabbits fed on a high-cholesterol diet. Biosci Biotechnol Biochem 66:1755–1758
Young IS, McEneny J (2001) Lipoprotein oxidation and atherosclerosis. Biochem Soc Trans 29:358–362
Prasad K, Kalra J (1993) Oxygen free radicals and hypercholesterolemic atherosclerosis: effect of vitamin E. Am Heart J 125:958–973
Nadkarni KM: Indian Materia Medica, vol I, 3rd edn. Bombay: Popular Book Depot. pp. 371–372, 1976
Baskar R, Meenalakshmi Malini M, Varalakshmi P, B.K. Bhima Roa (1996) Effect of lupeol isolated from Crataeva nurvala stem bark against free radical-induced toxicity in experimental urolithiasis. Fitoterapia 67:121–126
Liu J, Liu Y, Mao Q, Klaassen CD (1994) The effects of 10 triterpenoid compounds on experimental liver injury in mice. Fundam Appl Toxicol 22: 34–40
Sassa H, Takaishi Y, Terada H (1990) The triterpene celastrol as a very potent inhibitor of lipid peroxidation in mitochondria. Biochem Biophys Res Commun 172:890–897
Andrikopoulos NK, Kaliora AC, Assimopoulou AN, Papapeorgiou VP (2003) Biological activity of some naturally occurring resins, gums and pigments against in vitro LDL oxidation. Phytother Res 17:501–507
Geetha T, Varalakshmi P (1998) Anti-inflammatory activity of lupeol and lupeol linoleate in adjuvant-induced arthritis. Fitoterapia 69:13–19
Sunitha S, Nagaraj M, Varalakshmi P (2001) Hepatoprotective effect of lupeol and lupeol linoleate on tissue antioxidant defence system in cadmium-induced hepatotoxicity in rats. Fitoterapia 72:516–523
Sudhahar V, Kumar SA, Varalakshmi P (2006) Role of lupeol and lupeol linoleate on lipemic-oxidative stress in experimental hypercholesterolemia. Life Sci 78:1329–1335
Lowry OH, Rosebrough NJ, Farr AI, Randall RJ (1951) Protein measurement with folin-phenol reagent. J Biol Chem 193:265–275
King J: The dehydrogenases or oxidoreductases – lactate dehydrogenase. In: Van D, (ed.) Practical clinical enzymology. Nostrand Company Limited, London, pp. 83–93, 1965
King J (1965) The hydrolases – acid and alkaline phosphatases. In: Van D (Eds.), Practical clinical enzymology, Nostrand Company Limited, London pp 191–208
King J (1965) The transferases-alanine and aspartate transaminases. In: Van D (eds.) Practical clinical enzymology, Nostrand Company Limited, London pp 121–138
Hogberg J, Larson RE, Kristoferson A, Orrenius S (1974) NADPH-dependent reductase solubilized from microsomes by peroxidation and its activity. Biochem Biophys Res Commun 56:836–842
Devasagayam TP (1986) Lipid peroxidation in rat uterus. Biochim Biophys Acta 876:507–514
Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474
Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590
Moron MS, Depierre JW, Mannervik B (1979) Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 582:67–78
Omaye ST, Turnbull JD, Sauberlich HE (1979) Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Meth Enzymol 62:3–11
Desai ID (1984) Vitamin E analysis methods for animal tissues. Meth Enzymol 105:138–147
Wilson DE, Spiger MJ (1973) A dual precipitation method for quantitative plasma lipoprotein measurement without ultracentrifugation. J Lab Clin Med 82: 473–482
Deepa PR, Varalakshmi P (2005) Atheroprotective effect of exogenous heparin-derivative treatment on the aortic disturbances and lipoprotein oxidation in hypercholesterolemic diet fed rats. Clin Chim Acta 355:119–130
Davi G, Alessandrini P, Mezzetti A, Minotti G, Bucciarelli T, Costantini F, Cipollone F, Bon GB, Ciabattoni G, Patrono C (1997) In vivo formation of 8-Epi-prostaglandin F2 alpha is increased in hypercholesterolemia. Arterioscler Thromb Vasc Biol 17:3230–3235
Napoli C, Postiglione A, Triggiani M, Corso G, Palumbo G, Carbone V, Ruocco A, Ambrosio G, Montefusco S, Malorni A, Condorelli M, Chiariello M (1995) Oxidative structural modifications of low density lipoprotein in homozygous familial hypercholesterolemia. Atherosclerosis 118:259–273
Keaney JF Jr, Guo Y, Cunningham D, Shwaery GT, Xu A, Vita JA (1996) Vascular incorporation of alpha-tocopherol prevents endothelial dysfunction due to oxidized LDL by inhibiting protein kinase C stimulation. J Clin Invest 98:386–394
Halliwell B, Gutteridge JMC (1990) Role of free radicals and catalytic metal ions in Human disease: an overview. Methods in enzymology, Academic Press, San Diego pp. 1–85
Geetha RK, Vasudevan DM (2004) Inhibition of lipid peroxidation by botanical extracts of Ocimum sanctum: in vivo and in vitro studies. Life Sci 76: 21–28
Wissler RW (1992) Theories and new horizons in the pathogenesis of atherosclerosis and the mechanisms of clinical effects. Arch Pathol Lab Med 116:1281–1291
Gokkusu C, Ademoglu E, Turkoglu UM, Oz H, Oz F (1996) Thymosin alpha 1 protects liver and aorta from oxidative damage in atherosclerotic rabbits. Life Sci 59:1059–1067
Sassa H, Takaishi Y, Terada H (1990) The triterpene celastrol as a very potent inhibitor of lipid peroxidation in mitochondria. Biochem Biophys Res Commun 172:890–897
Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL (1989) Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320:915–924
Yamashita K, Lu H, Lu J, Chen G, Yokoyama T, Sagara Y, Manabe M, Kodama H (2002) Effect of three triterpenoids, lupeol, betulin, and betulinic acid on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils. Clin Chim Acta 325:91–96
Klaassen CD, Bracken WM, Dudley RE, Goering PL, Hazelton GA, Hjelle JJ (1985) Role of sulfhydryls in the hepatotoxicity of organic and metallic compounds. Fundam Appl Toxicol 5:806–815
Bertoni-Freddari C, Fattoretti P, Caselli U, Paoloni R, Meier-Ruge W (1995) Vitamin E deficiency as a model of precocious brain aging: assessment by X-ray microanalysis and morphometry. Scanning Microsc 9:289–301
Freeman BA, Crapo JD (1982) Biology of disease: free radicals and tissue injury. Lab Invest 47:412–426
Deepa PR, Varalakshmi P (2004) Protective effects of certoparin sodium, a low molecular weight heparin derivative, in experimental atherosclerosis. Clin Chim Acta 339:105–115
Nikiema JB, Vanhaelen-Fastre R, Vanhaelen M, Fontaine J, De Graef C, Heenen M (2001) Effects of antiinflammatory triterpenes isolated from Leptadenia hastata latex on keratinocyte proliferation. Phytother Res 15:131–134
Goldstein JL, Brown MS (1977) The low-density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem 46:897–930
Rosenfeld ME (1991) Oxidized LDL affects multiple atherogenic cellular responses. Circulation 83:2137–2140
Ross R (1995) Cell biology of atherosclerosis. Annu Rev Physiol 57:791–804
Mahley RW (1988) Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240:622–630
Heinecke JW (1998) Oxidants and antioxidants in the pathogenesis of atherosclerosis: implications for the oxidized low density lipoprotein hypothesis. Atherosclerosis 141:1–15
Esterbauer H, Ramos P (1996) Chemistry and pathophysiology of oxidation of LDL. Rev Physiol Biochem Pharmacol 127:31–64
Gutteridge JM (1995) Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 41:1819–1828
Stohs SJ, Bagchi D (1995) Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med 18:321–336
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Sudhahar, V., Kumar, S.A., Varalakshmi, P. et al. Mitigating role of lupeol and lupeol linoleate on hepatic lipemic-oxidative injury and lipoprotein peroxidation in experimental hypercholesterolemia. Mol Cell Biochem 295, 189–198 (2007). https://doi.org/10.1007/s11010-006-9288-2
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DOI: https://doi.org/10.1007/s11010-006-9288-2