Therapeutic effects of tender coconut water on oxidative stress in fructose fed insulin resistant hypertensive rats

Transcription

1 7 Asin Pcific Journl of Tropicl Medicine (1)7-76 Contents lists ville t ScienceDirect Asin Pcific Journl of Tropicl Medicine journl homepge: Document heding doi: Therpeutic effects of tender coconut wter on oxidtive stress in fructose fed insulin resistnt hypertensive rts D Bhgy 1, L Prem, T Rjmohn 1* 1 Deprtment of Biochemistry, University of Kerl, Krivttom Cmpus, Kerl, Trivndrum, , Indi Deprtment of Food Science nd Nutrition, Agriculturl College,Vellyni, Trivndrum, Kerl, Indi ARTICLE INFO Article history: Received 1 Novemer 11 Received in revised form 15 Decemer 11 Accepted 15 Jnury 1 Aville online Ferury 1 Keywords: Tender coconut wter Hypertension Oxidtive stress Hyperinsulinemi Lipid peroxidtion Histopthology ABSTRACT Ojective: To investigte whether tender coconut wter (TCW) mitigtes oxidtive stress in fructose fed hypertensive rts. Methods: Mle Sprgue Dwley rts were fed with fructose rich diet nd treted with TCW (4 ml/1 g of ody weight) for 3 susequent weeks. Systolic lood pressure ws mesured every three dys using the indirect til cuff method. At the end of the experimentl period, plsm glucose nd insulin, serum triglycerides nd free ftty cids, lipid peroxidtion mrkers (MDA, hydroperoxides nd conjugted dienes) nd the ctivities of ntioxidnt enzymes were nlyzed in ll the groups. Results: Tretment with TCW significntly lowered the systolic lood pressure nd reduced serum triglycerides nd free ftty cids. Plsm glucose nd insulin levels nd lipid peroxidtion mrkers such s MDA, hydroperoxides nd conjugted dienes were significntly reduced in fructose fed rts treted with TCW. Activities of ntioxidnt enzymes re up regulted significntly in TCW treted rts. Histopthologicl nlysis of liver showed tht TCW tretment reduced the lipid ccumultion nd inflmmtory infiltrtion without ny significnt heptocellulr dmge. Conclusions: The overll results suggest tht, TCW tretment could prevent nd reverse high lood pressure induced y high fructose diet proly y inhiition of lipid peroxidtion, upregultion of ntioxidnt sttus nd improved insulin sensitivity. 1. Introduction The metolic syndrome is ssocited with incresed risk for type dietes nd coronry hert disese[1]. This syndrome consists of cluster of clinicl normlities including dyslipidemi, specificlly elevted triglycerides, insulin resistnce nd hypertension[]. Severl lines suggest tht insulin resistnce plys key role in the development of metolic syndrome nd the hyperinsulinemi nd hyperlipidemi my e trget for the tretment of this disese cluster[3]. Fructose hs een implicted s contriutor to nerly ll of the clssic mnifesttions of the metolic syndrome. Rts fed with high fructose diet provide n niml model of insulin resistnce nd cquired form of systolic hypertension[4]. Studies hve shown tht high dosge of *Corresponding uthor: T Rjmohn, Deprtment of Biochemistry, University of Kerl, Krivttom Cmpus, Kerl, Trivndrum, , Indi. E-mil: t.rjmohn1@gmil.com fructose induces hyperinsulinemi, hypertriglyceridemi, impired glucose tolernce nd hypertension in rts[5]. In ddition, fructose consumption in rts hs pro-oxidnt effects[6] nd displys oxidtive stress, n imlnce etween free rdicl production nd ntioxidnt defense in severl tissues[7]. Oxygen rdicls re known to produce memrne peroxidtion nd mlondildehyde formtion[8]. Antioxidnts prevent the orgnism from the hrmful effects of free rdicls y scvenging or inhiiting their formtion[9]. A numer of studies hve reported tht the supplementtion of ntioxidnts improve insulin sensitivity in ptients with insulin resistnce[1], type dietes, hypertension nd crdiovsculr disese[11]. The recent trend worldwide hs een in fvor of phytochemicl therpeutics s they re economicl nd lrgely free from dverse side effects. Much ttention hs een focused on plnt foods tht my e eneficil in preventing metolic syndrome[1]. Dietry ptterns high in fruits, vegetles nd cerel content were generlly

2 D Bhgy et l./asin Pcific Journl of Tropicl Medicine (1) found to e ssocited with lower incidence of metolic syndrome[13]. Tender coconut wter (TCW), which is the liquid endosperm, is widely consumed in tropicl countries. TCW is the most nutritious wholesome everge tht the nture hs provided. TCW is nturl isotonic everge with lmost the sme level of electrolyte s we hve in our lood. The richness of mcro nd micro nutrients in TCW re reported to hve hypolipidemic, crdioprotective nd heptoprotective effects[14,15]. The therpeutic properties of tender coconut wter mde its usge s remedy for lot of ilments. Recent studies with TCW indicted tht it is rich source of crdioprotective fctors viz., L-rginine[16], mgnesium, potssium, clcium nd vitmin C which re known to reduce the risk for coronry hert disese[15, 17]. Current therpies for hypertension normlize lood pressure y vrious mens without removing the cuse. Mny of these tretments re prone to side effects which my result in poor complince. The idel tretment would e nturl compound tht would reduce the cuse of disese nd could control lood pressure without side effects. Epidemiologic studies hve suggested the ssocitions etween the consumption of ntioxidnts nd the prevention of mny humn diseses. Antioxidnts which occur nturlly in the diet my e tken s dietry supplements which re essentil to quench ROS[18]. Thus the present study ws done to investigte the effects of tender coconut wter (TCW) on oxidtive stress nd insulin resistnce in experimentlly induced hypertension in rts.. Mteril nd methods.1. Animls Mle Sprgue- Dwley rts weighing etween g were used for the study. The rts were kept in lortory niml unit with 1 hr light/drk cycle. Throughout the experiment, room temperture ws mintined t (5 依 ) 曟. The rts were mintined on stndrd chow diet (Si Feeds, Bnglore, Indi) nd wter d liitum prior to dietry mnipultion. They were trined for the first week to ecome cclimted to the procedure of indirect lood pressure mesurement. The lortory guidelines of the University Federtion of Animl Welfre for the use nd cre of nimls (1987) were followed throughout the experimentl period... Collection of tender coconut wter Young coconuts (Cocos nucifer) (West Cost Tll Vriety) 5-6 months of ge hrvested from the coconut trees grown on the University cmpus were used for the study. The coconuts were, roken crefully nd liquid endosperm ws collected nd used for the experiment..3. Experimentl design After cclimtiztion the rts were divided into 4 groups of 6 rts ech, nd treted with the following methods: Group I: Control Group II: Control + TCW Group III: Fructose fed rts Group IV: Fructose + TCW The first nd second group of rts received the control diet contining 71% corn strch, 8% ft nd 16% protein throughout the experiment. The third nd fourth group received diet contining 71% fructose, 8% ft nd 16% protein. From the third week onwrds the second nd fourth group of rts received TCW (4 ml/1 g of ody weight) y gstric intution. All other rts received sme volume of distilled wter. The diets were prepred fresh dily. The nimls were mintined in their respective groups for 4 dys..4. Blood pressure mesurement Systolic lood pressures (SBP) in conscious rts were mesured using the non-invsive til cuff method. The nimls were prewrmed t 3 曟. The equipment used included mgnetic niml holders connected with mnul scnner (model 65-1, IITC, Inc; woodlnd hills, Cliforni, USA), pulse mplifier (model 59, IITC, Inc.), nd dulchnnel flt ed recorder (model L-1-, IITC). During the mesurement seven individul redings were otined. The highest nd lowest redings were not considered nd the verge of the remining five redings ws retined. The systolic lood pressure (SBP) ws mesured every 3 dys..5. Biochemicl nlysis At the end of the experiment, the nimls were scrificed y decpittion nd lood smples were collected for iochemicl determintions. Blood glucose nd Serum triglyceride ws estimted using regent kit purchsed from Agppe dignostics Pvt Ltd. (Thne, Mhrshtr, Indi). Serum free ftty cids were estimted y the method of Flholt et l (1973). Plsm insulin ws ssyed y enzyme linked immunosorent ssy (ELISA) kit (BARC, Bomy, Indi). Activities of ntioxidnt enzymes superoxide dismutse (SOD), ctlse (CAT), glutthione peroxidse (GPx), glutthione reductse (GRd) nd glutthione content (GC) were ssyed in liver, hert, kidney nd ort. Protein content ws estimted y the method of Lowry et l[19]. Mlondildehyde (MDA), hydroperoxides (HP) nd conjugted dienes (CD) ws ssyed in different tissues. An HPLC method ws used for the determintion of plsm

3 mmhg 7 D Bhgy et l./asin Pcific Journl of Tropicl Medicine (1)7-76 vitmin E. concentrtion of plsm vitmin C ws estimted spectrophotometriclly..6. Histopthologicl nlysis The liver tissues were rpidly dissected out nd fixed y immersion t room temperture in 1% formlin solution. For the histologicl exmintions, prffin emedded tissue sections of liver were stined with hemtoxylin eosin (H&E). The tissue smples were then exmined nd photogrphed under light microscope for oservtion of structurl normlity..7. Sttisticl nlysis The SPSS sttisticl progrm ws employed. The results were evluted using nlysis of vrince (ANOVA) utilizing the F test. The results re presented s the men vlue 依 SD for the control nd experimentl rts. Differences mong the mens for the groups were ssessed using the Duncns Multiple Rnge Test to determine which men vlues were significntly different t P< Results Figure 1 shows weekly systolic lood pressure in control nd experimentl rts. All the groups of rts presented similr systolic lood pressure reding t the eginning of the experiment. The fructose- treted rts displyed continuous increse in systolic lood pressure during the first three weeks from (119 依 ) mmhg to (145 依 ) mmhg (P<.5). Administrtion of TCW during the susequent weeks mrkedly reduced the lood pressure from (145 依 ) mmhg to (16 依 3) mmhg. Thus there ws progressive decrese in lood pressure from third week onwrds Group 1 Group Group 3 Group 4 Weeks Figure 1. Effect of TCW on systolic lood pressure in control nd fructose fed hypertensive rts. Vlues re men 依 SD for six rts in ech group. P<.5, significntly different from control group, significntly different from fructose group. Tle 1 indictes the effect of TCW on plsm insulin nd glucose, serum triglyceride nd free ftty cids in control nd experimentl groups. Plsm glucose nd insulin, serum triglyceride nd free ftty cids were significntly higher in fructose-fed rts wheres TCW dministrtion decresed the plsm insulin nd glucose, serum triglyceride nd free ftty cids rised y high fructose diet. Figure, 3 & 4 shows the levels of mlondildehyde (MDA), hydroperoxides (HP) nd conjugted dienes (CD) in tissues (liver, hert, kidney nd ort) in control nd experimentl nimls. Fructose fed rts showed significntly (P<.5) higher levels of lipid peroxidtion products when compred to control rts. Tretment with TCW decresed the levels of MDA, HP nd CD ner to norml nd ws significntly lower s compred with untreted fructose fed rts. mmol/1 g tissue 栺 栻 栿 桇 Hert Aort Figure. Concentrtion of mlondildehyde (MDA) in tissues of control nd experimentl nimls. mmol/1 g 栺 栻 栿 桇 Hert Aort Figure 3. Levels of hydroperoxides (HP) in tissues of control nd experimentl nimls. Figure 5, 6, 7, 8 & 9 summrizes the ctivities of enzymtic ntioxidnts viz superoxide dismutse (SOD), ctlse (CAT), glutthione peroxidse (GPx), glutthione reductse (GRd) nd glutthione content (GC) in the tissues (liver, hert kidney nd ort) of control nd experimentl nimls. The ctivities of ntioxidnt enzymes were significntly decresed (P<.5) in fructose-fed rts thn control rts. Tretment with TCW in fructose fed rts showed elevted levels of ntioxidnt enzymes in tissues.

4 D Bhgy et l./asin Pcific Journl of Tropicl Medicine (1) mmol/1 g Hert Aort 伊 1-3 Units/mg protein Hert Aort Figure 4. Levels of conjugted dienes (CD) in tissues of control nd experimentl nimls. Figure 8. Activities of glutthione reductse (GRd) of control nd experimentl nimls. One unit is defined s the 毺 mole of NADPH oxidized per minute. Units/mg protein Hert Aort Figure 5. Activities of superoxide dismutse (SOD) in the tissues of control nd experimentl nimls. One unit is defined s the enzyme concentrtion required to inhiit the opticl density t 56 nm of chromogen produced y 5% in one minute Hert Aort 3 1 栺 栻 栿 桇 Figure 6. Activities of ctlse (CAT) in the tissues of control nd experimentl nimls. One unit is defined s the velocity constnt per second. 伊 1-3 Units/mg protein Hert 6 5 Aort Figure 7. Activities of glutthione peroxidse (GPx) in the tissues of control nd experimentl nimls. One unit is defined s the 毺 mole of NADPH oxidized per minute. 伊 1-3 Units/mg protein mmol/1 g Hert Aort Figure 9. Concentrtion of reduced glutthione in the tissues of control nd experimentl nimls. Figure 1 represents the concentrtion of non-enzymtic ntioxidnts viz Vitmin C nd Vitmin E in plsm of control nd experimentl nimls. Significnt (P<.5) decrese in the concentrtion of ntioxidnt vitmins were oserved in fructose-fed rts where s tretment with fructose fed rts with TCW rought the levels to ner control vlues. mg/dl Group 1 Group Group 3 Group 4 Vitmin C Vitmin E Figure 1. Concentrtion of vitmin C nd vitmin E in plsm of control nd experimentl nimls. Histopthologicl nlysis of the liver showed tht (Figure 11) fructose feeding cused lipid ccumultion, heptocellulr dmge nd inflmmtory infiltrtion when compred to control rts. TCW tretment in fructose fed rts showed reduced lipid ccumultion nd with out ny heptocellulr dmge nd inflmmtory infiltrtion.

5 74 D Bhgy et l./asin Pcific Journl of Tropicl Medicine (1)7-76 Tle 1 Effect of TCW on plsm insulin, plsm glucose, serum triglycerides nd serum free ftty cids in control nd fructose-fed hypertensive rts. Prmeters Plsm insulin ( 毺 IU/mL) Plsm glucose (mg/dl) Serum triglycerides (mg/dl) Serum free ftty cids (mg/dl) Control 1. 依 依 依 依.63 Control+ TCW. 依 依 依 依 3.5 Fructose 46. 依 依 依 依 4.61 Fructose+ TCW 7. 依 依 依 依 3.9 Vlues re men 依 SD for six rts in ech group. P<.5, significntly different from control group, significntly different from fructose group. A C Figure 11. Histopthologicl nlysis of the liver. A. Control group:the liver rchitecture is norml with cords of heptocytes with norml cytoplsm nd centrl nuclei. No norml fetures; B. Control + TCW treted group: No heptic dmge nd ftty infiltrtion. The liver rchitecture sme s norml. C. Fructose fed group: of fructose fed rts showed degenertive chnges, heptocellulr dmge, inflmmtory infiltrtion nd cytoplsmic vcuoliztion (sphericl vcuoles) ccumulted with lipids (LA); D. Fructose fed + TCW treted group: TCW tretment in fructose fed rts showed no heptocellulr dmge nd inflmmtory infiltrtion with lower lipid ccumultion (LA). 4. Discussion In the present study high fructose feeding resulted in hyperglycemi, hypertriglyceridemi nd hyperinsulinemi which correltes with the results supported y other studies[]. Susequent findings suggest tht the defects in glucose metolism my ply role in the development of hypertension, dyslipidemi nd coronry disese[1]. Hyperglycemi is well known to generte rective oxygen species (ROS) nd susequent lipid peroxidtion. Accumulting evidence indictes tht hyperglycemi cn cuse the production of free rdicls[]. Enhnced lipid peroxidtion in fructose-fed rts could e ssocited with high circulting glucose, which enhnces free rdicl production from glucose utoxidtion nd protein glyction[3]. Hyperglycemi is generlly ccepted to cuse vsculr complictions nd the involvement of oxidtive dmge induced y glucose hs een proposed in its pthogenesis[4]. Increse in plsm glucose level ssocited with hyperinsulinemi suggests impired insulin ction in fructose fed rts. Insulin resistnce my occur due to defect in insulin inding cused y decresed receptor numer B D or ffinity or defects t the level of effecter molecules such s glucose trnsporters nd enzymes involved in glucose metolism[5]. Studies hve demonstrted tht low levels of insulin stimulted glucose oxidtion in the liver, skeletl muscle nd dipose tissue in fructose-fed rts. Previous reports suggest tht fructose feeding decreses the efficcy of insulin extrction y the liver, which retrds insulin clernce from the circultion[6]. Heptic metolism of fructose leds to ltertions in the ctivities of key enzymes of glucose metolism nd ctivtion of stress sensitive pthwys tht my desensitize insulin signling[7]. Free ftty cids (FFA) concentrtion ws found to e elevted in the plsm of fructose-induced hypertensive rts. Lower levels of free ftty cids in serum suggest tht the sustrte vilility for lipid peroxidtion is less which correltes with the decresed levels of lipid peroxides. The lower level of lipid peroxides oserved in TCW fed rts not only due to the reduction of FFA ut lso due to incresed levels of free rdicl scvenging enzymes. Hypertriglyceridemi is nother fctor tht could enhnce the formtion of lipid peroxides. It hs een reported tht lipid peroxide levels directly correlte with hypertriglyceridemi in dietic ptients[8]. In ddition to this, fructose itself enhnces the formtion of ROS[9]. The lower levels of free ftty cids nd triglycerides in TCW treted rts my e due to its hypolipidemic effects. Our previous studies hve lso found tht TCW exhiits significnt hypolipidemic nd ntihypertensive effects in fructose fed hypertensive rts[3]. Insulin hs regultory effect on FFA metolism[31]. A defect in the ility of insulin to regulte the free ftty cid metolism could contriute to the incresed free ftty cid levels. Plsm FFA levels remin higher in hypertensive thn in control rts during hyperglycemiinduced hyperinsulinemi[3]. Increse in plsm FFA hve demonstrted tht the increse in plsm FFA concentrtion resulting from infusion of triglyceride emulsions hs een shown to ccelerte endogenous glucose production nd cuse fsting hyperglycemi in norml humns. Elevted levels of plsm FFA my ply key role in the pthogenesis of NIDDM y inhiiting peripherl glucose utiliztion nd y promoting heptic glucose overproduction[33]. FFA is n importnt sustrtes for heptic triglyceride synthesis nd diminished suppression of plsm FFA y insulin leds to higher plsm triglyceride levels. The cute inhiitory effect of insulin on heptic VLDL-lipoprotein secretion is modified y the mient plsm FFA concentrtion[34]. In this study high fructose diet led to incresed tissue lipid peroxidtion in rts. Lipid peroxidtion is fundmentl process in therogenesis nd hypertension. Lipid peroxidtion products my contriute to tissue dmge through direct cytotoxic ctions on endothelil cells. In our study tretment with tender coconut wter ws le to decrese tissue lipid peroxides indicting tht coconut wter possess ntioxidnt property. Administrtion of TCW mrkedly lowered lipid peroxides viz MDA, HP nd CD in the

6 D Bhgy et l./asin Pcific Journl of Tropicl Medicine (1) liver, hert, kidney nd ort. TCW tretment incresed the ctivity of SOD nd Ctlse nd it scvenges superoxide rdicls nd reduces oxidtive stress. SOD scvenges superoxide rdicls nd reduces oxidtive stress. SOD is n importnt ntioxidnt metllo enzyme tht ctlyzes very efficiently the dismuttion of superoxide ions into oxygen nd H O. SOD elimintes superoxide rdicl nd thus protects the cells from dmge induced y free rdicls. Ctlse ctivity incresed in tissues with TCW tretment, indicting tht dministrtion of TCW help to lower hydrogen peroxide concentrtion nd its decomposition nd susequently reduce oxidtive stress. Fructose fed rts showed decrese in GC, GPx nd GRd ctivities in tissues. Glutthione levels nd ctivities of glutthione dependent enzymes were incresed in rts treted with TCW. GPx nd GRd re essentil for mintining the constnt rtio of reduced glutthione to oxidized glutthione in cells. Decresed glutthione levels on fructose fed rts my e due to incresed utiliztion for protecting sulfhydryl group of proteins from lipid peroxides. TCW feeding restores the glutthione level nd incresed the ctivities of GPx nd GRd. The increse in plsm lipid peroxides could lso hve resulted from decline in cellulr, non-enzymtic nd enzymtic ntioxidnt potentil in fructose-fed rts. The ctlytic ctions of ntioxidnt enzymes re importnt for the effective removl of oxygen rdicls. Prolonged exposure of rts to hyperglycemic condition reduces the ctivities of ntioxidnt enzymes such s Ctlse, Superoxide dismutse, Glutthione reductse nd Glutthione peroxidse in fructose-fed rts s supported y studies. Free rdicl dmge decreses the ctivities of ntioxidnt enzymes such s ctlse, Glutthione Peroxidse nd Superoxide dismutse[35] which hve een reported to e reversed y vitmins in hypertension[36]. Modifiction of Cu-Zn Superoxide dismutse y glyction t specific lysine residue leds to inctivtion nd fermenttion of the enzyme in the dietic condition[37]. Reports re ville tht[38] ctlse gene expressions re reduced in liver nd hert of rts fed with fructose. Chemicl chrcteriztion of tender coconut wter reveled tht it contins reducing sugr (4%), proteins (15 mg/dl), Sodium (4 mg/dl), potssium( mg/dl), clcium (4 mg/dl), mgnesium (16 mg/dl), Selenium (.1 mg/dl), L-rginine (3 mg/dl), vitmin C (3 mg/dl) nd polyphenols (3.75 mg/dl). The superior effects of TCW in reducing oxidtive stress in fructose fed rts re due to the presence of these iologiclly ctive compounds. Phenolic compounds re excellent free rdicl scvengers, exert significnt ntioxidnt ctivities nd therey reduce oxidtive stress. Vitmin C cn directly scvenge singlet oxygen, superoxide nd hydroxyl rdicls. It reduces the risk of CVD y reducing lood pressure, lood cholesterol nd the formtion of oxidized LDL cholesterol[39]. Vitmin C is known to increse tissue glutthione, storge form of cysteine which is reported to prevent hypertension[4]. Potssium is reported to e ntihypertensive nd incresed dietry potssium cn lower lood pressure in nimls nd humns[41]. Mg hs een lso reported to reduce free rdicl genertion[4-49]. L- rginine hs een reported to inhiit the genertion of ROS nd lipid peroxidtion nd ct s n ntihypertensive gent. There were reports tht L-rginine hs significnt ntioxidnt, hypolipidemic, vsodiltor nd ntitherogenic effect[5]. Supplementtion with L-rginine locks the progression of plques vi restortion of NOS sustrte vilility nd reduction of vsculr oxidtive stress supported y recent studies[51]. Histopthologicl studies of liver tissue lso reveled the protective effect of tender coconut wter ginst fructose induced tissue dmge. In conclusion, results of the present study shows tht TCW tretment effectively reduced the oxidtive stress in fructose fed hypertensive rts nd improved the ntioxidnt sttus. The ility to ring fvorle metolic environment nd the ntioxidnt ctivity mkes tender coconut wter n idel cndidte for the tretment of clinicl conditions ssocited with hypertension. Conflict of interest The uthors declre tht there re no conflicts of interest. Acknowledgements First uthor thnk University of Kerl, Thiruvnnthpurm, Indi for finncil support. We thnk Dr. Snkr (Professor nd Hed, Dept of Pthology, Govt. Medicl College, Trivndrum, Kerl, Indi) for helping histopthologicl nlysis. References [1] Chilton RJ. Clinicl implictions of the metolic syndrome. JAOA 1; 11: e5. [] Frnco OH, Mssro JM, Civil J, Coin MR, O Mlley B, Agostino RB. Trjectories of entering the metolic syndrome: the frminghm hert study. Circultion 9; 1: [3] Bruce KD, Hnson MA. The developmentl origins, mechnisms, nd implictions of metolic syndrome. J Nutr 1; 14: [4] Ryssiguier Y, Gueux E, Nowcki W, Rock E, Mzur A. High fructose consumption comined with low dietry mgnesium intke my increse the incidence of the metolic syndrome y inducing inflmmtion. Mgnesium Res 6; 19: [5] Rutlede AC, Adeli K. Fructose nd the metolic syndrome. Nutrition Rev 7; 65: S13-S3. [6] Chess DJ, Xu W, Khirllh R, O She KM, KopWJ, Azimzdeh AM, et l. The ntioxidnt tempol ttenutes pressure overlodinduced crdic hypertrophy nd contrctile dysfunction in mice fed high fructose diet. Am J Physiol Hert Circ Physiol 8; 95: H3-H3. [7] Sivkumr AS, Anurdh CV. Effect of glngin supplementtion on oxidtive chnges nd inflmmtory chnes in fructose-fed rt liver. Chemico- Biol Int 11; 193: [8] Sugndhi R, Rjmni S, Rvichndrn MK, Anurdh CV. Effect of food sesoning spices mixture on iomrkers of oxidtive stress in tissues of fructose- fed insulin resistnt rts. J Med Foods 7; 1: [9] Htzitolios A, Ilidis F, Ktsiki N, Bltzi M. Is the hypertensive effect of dietry supplements vi ldehydes reduction evidence sed? A systemtic review. Clin Exp Hypertension 8; 3: [1] Grssi D, Necozione S, Lippi C, Croce G, Vleri L, Psquletti P, et l. Coco reduces lood pressure nd insulin resistnce nd improves endothelium-dependent vsodiltion in hypertensives. Hypertension 5; 46: [11] Grssi D, Desideri G, Necozione S, Lippi C, Csle R, Properzi G, et l. Blood pressure is reduced nd insulin sensitivity incresed in glucose- intolernt hypertensive sujects fter 15 dys of consuming high polyphenol drk chocolte. J Nutr 8; 138:

7 76 D Bhgy et l./asin Pcific Journl of Tropicl Medicine (1) [1] Fujiok K, Greenwy F, Yin SJ. The effects of grpe fruit on weight nd insulin resistnce: reltionship to the metolic syndrome. J Med Food 7; 9: [13] Bxter A J, Coyne T, McClintock : Dietry ptterns nd metolic syndrome- review of epidemiologic evidence. Asi Pc J Clin Nutr 6; 15: [14] Sndhy VG, Rjmohn T. Comprtive evlution of the hypolipidemic effects of coconut wter nd lovsttin in rts fed ft-cholesterol enriched diet. Food ChemToxicol 8; 46: [15] Prthpn A, Rjmohn T. Antioxidnt nd ntithromotic ctivity of tender coconut wter in experimentl myocrdil infrction. J Food Biochem 11; 35(5): [16] Schulmn SP, Becker LC, Kss DA, Chmpion HC, Terrin ML, Formn S, et l. Arginine therpy in cute myocrdil infrction. AMA 6; 95: [17] Chiplonkr SA, Agte VV, Trwdi KV, Pknikr KM, Diwte UP. Micronutrient deficiencies s predisposing fctors for hypertension in lcto- Vegetrin Indin dults. Am J Coll Nutr 4; 3: [18] Seifried HE, Anderson DE, Fisher EI, Milner A. A review of the interction mong dietry interction mong dietry ntioxidnts nd rective oxygen species. The J Nutr Biochem 7; 18: [19 ]Lowry OH, Roserough NJ, Frr AL, Rndll RJ. Protein mesurement with the Folin phenol regent. J Biol Chem 1951; 193: [] Nndhini ATA, Thirunvukkrsu V, Rvichndrn MK, Anurdh CV. Effect of turine on iomrkers of oxidtive stress in tissues of fructose-fed insulin-resistnt rts. Singpore Med J 5; 46: [1] Americn Dietes Assocition. Stndrds of medicl cre in dietes. Dietes Cre 11; 34: S11-S61. [] Kngrlkr VA, Ptil SD, Bndivdekr RM. Oxidtive stress nd dietes: A Review. Int J Phrm Appl 1; 1: [3] Roussel AM, Hininger I, Benr R, Ziegenfuss TN, Anderson RA. Antioxidnt effects of cinnmon extrct in people with impired fsting glucose tht re overweight or oese. J Am Coll Nutr 9; 8: [4] Node K, Inoue T. Post prndil hyperglycemi s n etiologicl fctor in vsculr filure. Crdiovsc Dietol 9; 8: 3. [5] Biley CJ. Treting insulin resistnce: future prospects. Dietes Vsc Dis Res 7; 4:. [6] Ngi Y, Yonemitsu S, Erion D M, Iwski T, Strk R, Weismnn D, et l.: The role of peroxisome prolifertor- ctivted receptor gmm coctivtor 1 et in the pthogenesis of fructose- induced insulin resistnce. Cell Met 9; 9: [7] Muoio DM, Newgrd CB. Moleculr nd metolic mechnisms of insulin resistnce nd 毬 -cell filure in type dietes. Moleculr Cell Biology; 8; 9: [8] Al-Rwi NH. Oxidtive stress, ntioxidnt sttus nd lipid profile in the sliv of type dietes. Dietes Vsc Disese Res 11; 8:. [9] Mhfouz MH, El-Ghffr AA, Mohmed MA, Ghnem HM. Effects of L-crnitine nd cinnmon extrct tretment on lens crystllins of rts fed high fructose diet. Am J Biochem Biotechnol 11; 7: [3] Node K. Inoue: Postprndil hyperglycemi s n etiologicl fctor in vsculr filure. Crdiovsc Dietol 9; 8: 3. [31] Duez H, Lewis GF. Ft metolism in insulin resistnce nd type dietes. Contemp Endocrinol 8; 1: [3] Bscino H, Federico L, Adeli K. Fructose, insulin resistnce nd metolic dyslipidemi. Nutr Metol 5; : 5. [33] Cusi K. Role of insulin resistnce nd lipotoxicity in non-lcohol steto-heptitis. Clin Dis 9; 13: [34] Thirunvukkrsu V, Anith AT, Nndhini C, Anurdh V. Effect of lph lipoic cid on lipid profile in rts fed high-fructose diet. Exp Dietes Res 5; 5: [35] Zgrodzki P, Joniec A, Gwlik M, Krosnik M, Folt M, Brton H, et l. High fructose model of oxidtive stress nd metolic disturnces in rts. Prt I- Antioxidnt sttus of rt s tissues. Bull Vet Inst Pulwy 7; 51: [36] Girrd A. Fructose-enriched diet modifies ntioxidnt sttus nd lipid metolism in spontneously hypertensive rts. Nutrition 6; : [37] Chng T, Wu L. Methylglyoxl, oxidtive stress nd hypertension. Cn J Physiol Phrmcol 6; 84: [38] Ching RHH, Yeun LOY, Tse IMY, Hung Sit W, Li ETS. Supplementtion of ittermelon to rts fed high fructose diet during gesttion nd lcttion meliortes fructose induced dyslipidemi nd heptic oxidtive stress in mle offspring. The J Nutr 11; iii [39] Bsu A, Wilkinson M, Penugond K, Simmons B, Betts NM, Lyons TJ. Freeze-dried strwerry powder improves lipid profile nd lipid peroxidtion in women with metolic syndrome: seline nd post-intervention effects. Nutr J 9; 8: 43. [4] Vsdev S, Stuckless J. Role of methylglyoxl in essentil hypertension. Int J Angiol 1; 19: e58-e65. [41] Hddy FJ, Vnhoutte PM, Feletou M. Role of potssium in regulting lood flow nd lood pressure. Am J Regul Integr Comp Physiol 6; 9: R546-R55. [4] Jin YT, Hsee N, Mtsusk T, Ntori S, Oht T, Tsuji S, et l. Mgnesium ttenutes isoproterenol induced cute crdic dysfunction nd et drenergic desensitiztion. Am J Hert circul Physiol 7; 9: H1593-H1599. [43] Okfor OY, Erukinure OL, Ajioye JA, Adejoi RO, Owoli FO, Kosoko SB. Modultory effect of pinepple peel extrct on lipid peroxidtion, ctlse ctivity nd heptic iomrker levels in lood plsm of lcohol induced oxidtive stressed rts. Asin Pc J Trop Biomed 11; 1: [44] Sin EP, Indu H, Rsool M. Efficcy of oswellic cid on lysosoml cid hydrolses, lipid peroxidtion nd nti-oxidnt sttus in gouty rthritic mice. Asin Pc J Trop Biomed 11; : [45] Beher S, Mngrj M, Mohptr PC. Dignostic efficcy of ischemi modified lumin nd its correltion with lipid profile, oxidtive stress in cute myocrdil infrct ptients on dmission. Asin Pc J Trop Dis 11; : [46] Mukherjee M, Gywli P, Thkur RK, Shenoy RP, Ro A. Assessment of frequency of micronucleted exfolited uccl cells in reltion to oxidtive stress in orl lichen plnus in costl Krntk, Indi. Asin Pc J Trop Dis 11; 1: [47] Hemlth J, Wilm DSCR. Evlution of effect of smoking nd hypertension on serum lipid profile nd oxidtive stress. Asin Pc J Trop Dis 11; 1: [48] Erukinure OL, Ajioye JA, Adejoi RO, Okfor OY, Adenekn SO. Protective effect of pinepple (Anns cosmosus) peel extrct on lcohol induced oxidtive stress in rin tissues of mle lino rts. Asin Pc J Trop Dis 11; 1: 5-9. [49] Thirumli T, Viviyn Thers S, Elumli EK, Dvid E. Intense nd exhustive exercise induce oxidtive stress in skeletl muscle. Asin Pc J Trop Dis 11; 1: [5] El- Krish AAA, Ad El-Wh HMF, Ad-Ellh Syed H. The effect of L- rginine or L-citrulline supplementtion on iochemicl prmeters nd the vsculr ortic wll in high ft nd high- cholesterol fed rts. Cell Biochem Fun 11; 9: [51] Jeng Y, Lur L, Friedlich HAL, Shi Y, Rogers JT, Hung X. L-rginine nd Alzheimer s disese. Int J Clin Exp Pthol 9; 3:11-38.