Effect of γ-oryzanol on hyperlipidemia and thrombus formation in mice treated with poloxamer-407
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Department of Pharmacology, Institute of Pharmacy, Nirma University, Gujarat, India
Submission date: 2016-09-05
Acceptance date: 2017-02-16
Online publication date: 2018-03-26
Publication date: 2019-11-18
Corresponding author
Shital S Panchal   

Department of Pharmacology, Institute of Pharmacy, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad-382 481, Gujarat, India. Tel.: +91 9687626589. Fax: +9179 2717241917.
Pol. Ann. Med. 2018;25(2):184-189
Hyperlipidemic and thrombotic events are the most common risk factors for death related to cardiovascular diseases. γ-Oryzanol (OZ) is the active chemical constituent of Oryza sativa bran oil. It is reported for its antihyperlipidemic activity.

Our study was aimed to evaluate effect of OZ on atherothrombotic events, i.e. hyperlipidemia and thrombosis in animal model.

Material and methods:
Swiss albino male mice were divided into four groups. Animals were treated with atorvastatin (2 mg/kg, p.o., as the standard drug) and OZ (100 mg/kg, p.o.) up to 3 days. On the 3rd day poloxamer-407 (500 mg/kg, i.p.) was administered to induce hyperlipidemia. Thrombotic plaque was induced using FeCl3 (50%). Animals were sacrificed after 24 h from induction of hyperlipidemia. Blood was collected for estimation of lipid profile, coronary disease risk factors, blood coagulation parameters i.e. APTT and PT. Liver was isolated for estimation of oxidative stress parameters. Further, the effect of therapy on thrombus formation was observed by histopathology of carotid artery.

Results and discussion:
Treatment with OZ was found to improve the serum lipid profile, reduce coronary risk factors, and to decrease oxidative stress. Thrombus formation was found to be reduced on histopathological examination. OZ prolonged APTT and PT.

OZ found to be therapeutically efficient in hyperlipidemic and atherosclerotic risk management in the animals which may be due to its anti-oxidative stress activity.

There is no conflict of interest for this paper.
Sharma K, Kumar K, Mishra N. Nanoparticulate carrier system: a novel treatment approach for hyperlipidemia. Drug Deliv. 2016;23(3):684–699.
Longo M, Crosignani A, Podda M. Hyperlipidemia in chronic cholestatic liver disease. Curr Treat Options Gastroenterol. 2001;4(2):111–114.
Chaudhary HR, Brocks DR. The single dose poloxamer 407 model of hyperlipidemia; systemic effects on lipids assessed using pharmacokinetic methods, and its effects on adipokines. J Pharm Pharm Sci. 2013;16(1):65–73.
Johnston TP, Li Y, Jamal AS, Stechschulte DJ, Dileepan KN. Poloxamer 407-induced atherosclerosis in mice appears to be due to lipid derangements and not due to its direct effects on endothelial cells and macrophages. Mediators Inflamm. 2003;12(3):147–155.
Eitzman DT, Westrick RJ, Xu Z, Tyson J, Ginsburg D. Hyperlipidemia promotes thrombosis after injury to atherosclerotic vessels in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2000;20(7):1831–1834.
Fuster V, Stein B, Ambrose JA, Badimon L, Badimon JJ, Chesebro JH. Atherosclerotic plaque rupture and thrombosis. Evolving concepts. Circulation. 1990;82(3 Suppl):II47–II59.
Rao SK, Prasad T, Mohanta GP, Manna PK. An overview of statins as hypolipidemic drugs. Int J Pharm Sci Drug Res. 2011;3(3):178–183.
Abbas A, Milles J, Ramachandran S. Rosuvastatin and atorvastatin: comparative effects on glucose metabolism in non-diabetic patients with dyslipidaemia. Clin Med Insights Endocrinol Diabetes. 2012;5:13.
Sultan S, Hynes N. The ugly side of statins. Systemic appraisal of the contemporary un-known unknowns. OJEMD. 2013;3(3):179–185.
Patel M, Naik SN. Gamma-oryzanol from rice bran oil – A review. J Sci Ind Res (India). 2004;63:569–578.
Khalil OA, Ramadan KS, Danial EN, Ayaz NO. Antidiabetic activity of Rosmarinus officinalis and its relationship with the antioxidant property. African J Pharm Pharmacol. 2012;6(14):1031–1036.
Ghatak SB, Panchal SJ. Anti-hyperlipidemic activity of oryzanol, isolated from crude rice bran oil, on triton WR-1339-induced acute hyperlipidemia in rats. Brazilian J Pharmacogn. 2012;22(3):642–648.
Ragland BD, Konrad RJ, Chaffin C, Robinson CA, Hardy RW. Evaluation of a homogeneous direct LDL-cholesterol assay in diabetic patients: effect of glycemic control. Clin Chem. 2000;46(11):1848–1851.
Kim HY, Jeong DM, Jung HJ, Jung YJ, Yokozawa T, Choi JS. Hypolipidemic effects of Sophora flavescens and its constituents in poloxamer 407-induced hyperlipidemic and cholesterol-fed rats. Biol Pharm Bull. 2008;31(1):73–78.
Millán J, Pintó X, Muñoz A, et al. Lipoprotein ratios: physiological significance and clinical usefulness in cardiovascular prevention. Vasc Health Risk Manag. 2009;5:757–765.
Łukaszewicz-Hussain A, Moniuszko-Jakoniuk J. Liver catalase, glutathione peroxidase and reductase activity, reduced glutathione and hydrogen peroxide levels in acute intoxication with chlorfenvinphos, an organophosphate insecticide. Polish J Environ Stud. 2004;13(3):303–309.
Otitoju O, Onwurah INE. Superoxide dismutase (SOD) activity and serum calcium level in rats exposed to a locally produced insecticide “Rambo Insect Powder.” Anim Res Int. 2005;2(1):261–266.
Moron MS, Depierre JW, Mannervik B. Levels of Glutathione, Glutathione reductase and Glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta. 1979;582(1):67–78.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351–358.
Ghatak SB, Dhamecha PS, Bhadada SV, Panchal SJ. Investigation of the potential effects of metformin on atherothrombotic risk factors in hyperlipidemic rats. Eur J Pharmacol. 2011;659(2–3):213–223.
Kurz KD, Main BW, Sandusky GE. Rat model of arterial thrombosis induced by ferric chloride. Thromb Res. 1990;60(4):269–280.
Singh RB, Mengi SA, Xu YJ, Arneja AS, Dhalla NS. Pathogenesis of atherosclerosis: A multifactorial process. Exp Clin Cardiol. 2002;7(1):40–53.
Ibrahim AY, Hendawy SF, Elsayed AAA, Omer EA. Evaluation of hypolipidemic Marrubium vulgare effect in Triton WR-1339-induced hyperlipidemia in mice. Asian Pac J Trop Med. 2016;9(5):453–459.
Ballantyne CM, Olsson AG, Cook TJ, Mercuri MF, Pedersen TR, Kjekshus J. Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S. Circulation. 2001;104(25):3046–3051.
Toth PP, Grabner M, Punekar RS, Quimbo RA, Cziraky MJ, Jacobson TA. Cardiovascular risk in patients achieving low-density lipoprotein cholesterol and particle targets. Atherosclerosis. 2014;235(2):585–591.
Korolenko TA, Johnston TP, Tuzikov FV, et al. Early-stage atherosclerosis in poloxamer 407-induced hyperlipidemic mice: pathological features and changes in the lipid composition of serum lipoprotein fractions and sub fractions. Lipids Health Dis. 2016;15(1):16.
Korolenko TA, Tuzikov F V, Johnston TP, et al. Influence of poloxamer 407 on fractional and subfractional composition of serum lipoproteins of mice. Health (Irvine Calif). 2010;2(7):722.
Sarker M, Mahmud ZA, Saha SK, Tithi NS, Ali MS, Bachar SC. Anti hyperlipidemic activity of flowers of Punica granatum in poloxamer-407 induced hyperlipidemic mice model. Pharmacogn J. 2012;4(27):66–70.
Holvoet P, Theilmeier G, Shivalkar B, Flameng W, Collen D. LDL hypercholesterolemia is associated with accumulation of oxidized LDL, atherosclerotic plaque growth, and compensatory vessel enlargement in coronary arteries of miniature pigs. Arterioscler Thromb Vasc Biol. 1998;18(3):415–422.
Park J, Yeom M, Hahm D-H. Fucoidan improves serum lipid levels and atherosclerosis through hepatic SREBP-2-mediated regulation. J Pharmacol Sci. 2016;131(2):84–92.
Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol. 2009;7(1):65–74.
Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014;2014:360438.
Johnston TP, Zhou X. Oxidation of low-density lipoprotein cholesterol following administration of poloxamer 407 to mice results from an indirect effect. J Cardiovasc Pharmacol. 2007;49(4):246–252.
Chen SJ, Yen CH, Huang YC, Lee BJ, Hsia S, Lin PT. Relationships between inflammation, adiponectin, and oxidative stress in metabolic syndrome. PLoS One. 2012;7(9):e45693.
Bojanini EU, Loaiza-Bonilla A, Pimentel A. Prekallikrein Deficiency Presenting as Recurrent Cerebrovascular Accident: Case Report and Review of the Literature. Case Rep Hematol. 2012;2012:1–3.
Eckly A, Hechler B, Freund M, et al. Mechanisms underlying FeCl3-induced arterial thrombosis. J Thromb Haemost. 2011;9(4):779–789.
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