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Syringic acid ameliorates l-NAME-induced hypertension by reducing oxidative stress

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Abstract

The objective of the present study was to investigate the effects of syringic acid (SA), a phenolic acid, on Nω-nitro-l-arginine methyl ester (l-NAME)-induced hypertensive rats. Hypertension was induced in adult male albino rats by oral administration of l-NAME (40 mg/kg/day) dissolved in drinking water daily for 4 weeks. Rats were treated with different doses of SA (25, 50, and 100 mg/kg body weight (b.w.)). Systolic blood pressure of control and experimental rats was recorded. Plasma nitric oxide metabolites (NOx), lipid peroxidative products such as thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes, and antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, vitamin C, vitamin E, and reduced glutathione were estimated in erythrocytes, plasma, and tissues of experimental rats. Hepatic marker enzymes such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase and renal functional markers such as urea, uric acid, and creatinine were also estimated in serum. The increased levels of blood pressure, lipid peroxidation products, hepatic and renal function markers, and the decreased level of NOx and antioxidants in l-NAME-induced hypertensive rats were reversed upon SA treatment. The protective effect at the dose of the three tested doses (25, 50, and 100 mg/kg) of SA at a dose of 50 mg/kg b.w. exerts optimum protection. Biochemical findings are substantiated by the histological observation. The protective effects of SA are mediated by reducing oxidative stress and retaining the bioavailability of NO in the cardiovascular system.

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Abbreviations

ALP:

Alkaline phosphatase

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

CAT:

Catalase

CD:

Conjugated dienes

CVD:

Cardiovascular diseases

GPx:

Glutathione peroxidase

GSH:

Reduced glutathione

l-NAME:

Nω-nitro-l-arginine methyl ester

LOOH:

Lipid hydroperoxides

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NOx:

Nitric oxide metabolites

ROS:

Reactive oxygen species

SA:

Syringic acid

SBP:

Systolic blood pressure

SOD:

Superoxide dismutase

TBARS:

Thiobarbituric acid reactive substances

References

  • Abidi P, Afaq F, Arif JM, Lohani M, Rahman Q (1999) Chrysotile-mediated imbalance in the glutathione redox system in the development of pulmonary injury. Toxicol Lett 106:31–39

    Article  PubMed  CAS  Google Scholar 

  • Baylis C, Mitruka B, Deng A (1992) Chronic blockade of nitric oxide synthesis in the rat produces systemic hypertension and glumerular damage. J Clin Invest 90:278–281

    Article  PubMed  CAS  Google Scholar 

  • Bech JN, Nielsen CB, Ivarsen P, Jensen KT, Pedersen EB (1998) Dietary sodium affects systemic and renal hemodynamic response to NO inhibition in healthy humans. Am J Physiol 274:914–923

    Google Scholar 

  • Burtis CA, Ashwood ER (1996) Tietz fundamentals of clinical chemistry. Saunders Company, London, p 881

    Google Scholar 

  • Cayatte AJ, Palacino JJ, Horten K, Cohen RA (1994) Chronic inhibition of nitric oxide production accelerates neointima formation and impairs endothelial function in hypercholesterolemic rabbits. Arterioscler Thromb 14:753–759

    Article  PubMed  CAS  Google Scholar 

  • Dryden GW Jr, Deaciuc I, Arteel G, McClain CJ (2005) Clinical implications of oxidative stress and antioxidant therapy. Curr Gastroenterol Rep 7:308–316

    Article  PubMed  Google Scholar 

  • Gu D, Reynolds K, Wu X, Chen J, Duan X, Muntner P, Huang G, Reynolds RF, Su S, Whelton PK, He J, InterASIA Collaborative Group, The International Collaborative Study of Cardiovascular Disease in ASIA (2002) Prevalence, awareness, treatment, and control of hypertension in China. Hypertension 40:920–927

    Article  PubMed  CAS  Google Scholar 

  • Guimaraes CM, Giao MS, Martinez SS, Pintado AI, Pintado ME, Bento Malcata FX (2007) Antioxidant activity of sugar molasses, including protective effect against DNA oxidative damage. J Food Sci 72:39–43

    Article  Google Scholar 

  • Hamberg M, Svensson J, Wakabayashi T, Samuelsson B (1974) Isolation and structure of two prostaglandins endoperoxides that cause platelet aggregation. Proc Nat Acad Sci 71:345–359

    Article  PubMed  CAS  Google Scholar 

  • Harrison DG (1997) Cellular and molecular mechanisms of endothelial cell dysfunction. J Clin Invest 100:2153–2157

    Article  PubMed  CAS  Google Scholar 

  • Hirota A, Taki S, Kawaii S, Yano M, Abe N (2000) 1,1-Diphenyl-2-picrylhydrazyl radical-scavenging compounds from soybean miso and antiproliferative activity of isoflavones from soybean miso toward the cancer cell lines. Biosci Biotechnol Biochem 64:1038–1040

    Article  PubMed  CAS  Google Scholar 

  • Hoetzel A, Welle A, Schmidt R, Loop T, Humar M, Ryter SW, Geiger KK, Choi AM, Pannen BH (2008) Nitric oxide-deficiency regulates hepatic heme oxygenase-1. Nitric Oxide 18:61–69

    Article  PubMed  CAS  Google Scholar 

  • Huang PL, Huang Z, Mashimo H, Bloch KD, Moskowitz MA, Bevan JA, Fishman MC (1995) Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 377:239–242

    Article  PubMed  CAS  Google Scholar 

  • Ignarro LJ, Napoli C, Loscalzo J (2002) Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide: an overview. Circ Res 90:21–28

    Article  PubMed  CAS  Google Scholar 

  • Itoh A, Isoda K, Kondoh M, Kawase M, Kobayashi M, Tamesada M, Yagi K (2009) Hepatoprotective effect of syringic acid and vanillic acid on concanavalin A-induced liver injury. Biol Pharm Bull 32:1215–1219

    Article  PubMed  CAS  Google Scholar 

  • Itoh A, Isoda K, Kondoh M, Kawase M, Watari A, Kobayashi M, Tamesada M, Yagi K (2010) Hepatoprotective effect of syringic acid and vanillic acid on CCl4-induced liver injury. Biol Pharm Bull 33:983–987

    Article  PubMed  CAS  Google Scholar 

  • Jalili T, Carlstrom J, Kim S, Freeman D, Jin H, Wu TC, Litwin SE, David Symons J (2006) Quercetin-supplemented diets lower blood pressure and attenuate cardiac hypertrophy in rats with aortic constriction. J Cardiovasc Pharmacol 47:531–541

    Article  PubMed  CAS  Google Scholar 

  • Jiang ZY, Hunt JV, Wolff SP (1992) Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low density lipoprotein. Anal Biochem 202:384–389

    Article  PubMed  CAS  Google Scholar 

  • Kampa M, Alexaki VI, Notas G, Nifli AP, Nistikaki A, Hatzoglou A, Bakogeorgou E, Kouimtzoglou E, Blekas G, Boskou D, Gravanis A, Castanas E (2004) Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action. Breast Cancer Res 6:63–74

    Article  Google Scholar 

  • Khokhar S, Apenten RKO (2003) Iron binding characteristics of phenolic compounds: some tentative structure–activity relations. Food Chem 81:133–140

    Article  CAS  Google Scholar 

  • Kumar S, Prahalathan P, Raja B (2011) Antihypertensive and antioxidant potential of vanillic acid, a phenolic compound in L-NAME induced hypertensive rats: a dose-dependence study. Redox Rep 16:208–215

    Article  PubMed  CAS  Google Scholar 

  • Kumar S, Saravanakumar M, Raja B (2010) Efficacy of piperine, an alkaloidal constituent of pepper on nitric oxide, antioxidants and lipid peroxidation markers in L-NAME induced hypertensive rats. Int J Res Pharm Sci 3:300–307

    Google Scholar 

  • Loria P, Lonardo A, Carulli L, Verrone AM, Ricchi M, Lombardini S, Rudilosso A, Ballestri S, Carulli N (2005) The metabolic syndrome and non-alcoholic fatty liver disease. Aliment Pharmacol Ther 22:31–36

    Article  PubMed  Google Scholar 

  • Mahdi AA (2002) Free radicals and other antioxidants. A textbook of biochemistry by S.P. Singh, thirdth edn. CBS, New Delhi, pp 545–555

    Google Scholar 

  • Mates JM, Sanchez-Jimenez F (1999) Antioxidant enzymes and their implications in pathophysiologic processes. Front Biosci 4:339–345

    Article  Google Scholar 

  • Mattila P, Kumpulainen J (2002) Determination of free and total phenolic acids in plant-derived foods by HPLC with diode-array detection. J Agric Food Chem 50:3660–3667

    Article  PubMed  CAS  Google Scholar 

  • Mittal BV, Singh AK (2010) Hypertension in the developing world: challenges and opportunities. Am J Kidney Dis 55:590–598

    Article  PubMed  Google Scholar 

  • Nakmareong S, Kukongviriyapan U, Pakdeechote P, Donpunha W, Kukongviriyapan V, Kongyingyoes B, Sompamit K, Phisalaphong C (2011) Antioxidant and vascular protective effects of curcumin and tetrahydrocurcumin in rats with L-NAME induced hypertension. Naunyn-Schmied Arch Pharmacol 383:519–529

    Article  CAS  Google Scholar 

  • Nguelefack-Mbuyoa PE, Nguelefackb TB, Dongmoc B, Afkird S, Azebazee AGB, Dimoa T, Legssyerd A, Kamanyi A, Ziyyat A (2008) Anti-hypertensive effects of the methanol/methylene chloride stem bark extract of mammea africana in L-NAME-induced hypertensive rats. J Ethnopharmacol 117:446–450

    Article  Google Scholar 

  • Niehaus WG, Samuelson B (1968) Formation of malondialdehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Pharmacol 6:126–130

    CAS  Google Scholar 

  • Pechanova O, Bernatova I, Babal P, Martinez MC, Kysela S, Stvrtina S, Andriantsitohaina R (2004) Red wine polyphenols prevent cardiovascular alterations in L-NAME-induced hypertension. J Hyperten 22:1551–1559

    Article  CAS  Google Scholar 

  • Pereira LM, Bezerra DG, Machado DL, Mandarim-de-lacerda CA (2004) Enalapril attenuates cardiorenal damage in nitric-oxide-deficient spontaneously hypertensive rats. Clin Sci 106:337–343

    Article  PubMed  CAS  Google Scholar 

  • Prahalathan P, Kumar S, Raja B (2012) Morin a bioflavonoid, rescues kidney and heart from DOCA-salt hypertensive rats: a biochemical and histopathological study. Metabolism 61:1087–1099

    Article  PubMed  CAS  Google Scholar 

  • Pushpavalli G, Veeramani C, Pugalendi KV (2010) Influence of chrysin on hepatic marker enzymes and lipid profile against d-galactosamine-induced hepatotoxicity rats. Food Chem Toxicol 48:1654–1659

    Article  PubMed  CAS  Google Scholar 

  • Quam L, Smith R, Yach D (2006) Rising to the global challenge of the chronic disease epidemic. Lancet 368:1221–1223

    Article  PubMed  Google Scholar 

  • Ramachandran V, Raja B (2010) Protective effects of syringic acid against acetaminophen induced hepatic damage in albino rats. J Basic Clin Physiol Pharmacol 21:369–385

    Article  PubMed  CAS  Google Scholar 

  • Ramachandran V, Saravanan R, Raja B (2011) Attenuation of oxidative stress by syringic acid on acetaminophen-induced nephrotoxic rats. Comp Clin Pathol. doi:10.1007/s00580-011-1327-z

  • Rao KS, Recknagel RO (1968) Early onset of lipid peroxidation in rat liver after carbon tetrachloride administration. Exp Mol Pathol 9:271–278

    Article  PubMed  CAS  Google Scholar 

  • Retelny VS, Neuendorf A, Roth JL (2008) Nutrition protocols for the prevention of cardiovascular disease. Nutr Clin Pract 23:468–476

    Article  PubMed  Google Scholar 

  • Rice-Evans CA, Miller NJ, Paganga G (1996) Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 20:933–956

    Article  PubMed  CAS  Google Scholar 

  • Rosselli M, Keller PJ, Dubey RK (1998) Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Hum Reprod Update 4:3–24

    Article  PubMed  CAS  Google Scholar 

  • Saravanakumar M, Kumar S, Raja B (2010) Antihypertensive and antioxidant potential of borneol - a natural terpene in L-NAME-induced hypertensive rats. Int J Pharma Biol Arch 1:271–279

    Google Scholar 

  • Saravanakumar M, Raja B (2011) Veratric acid, a phenolic acid attenuates blood pressure and oxidative stress in L-NAME induced hypertensive rats. Eur J Pharma 671:87–94

    Article  CAS  Google Scholar 

  • Senthil S, Chandramohan G, Pugalendi KV (2007) Isomers (oleanolic and ursolic acids) differ in their protective effect against isoproterenol-induced myocardial ischemia in rats. Int J Cardiol 119:131–133

    Article  PubMed  CAS  Google Scholar 

  • Sharifi AM, Akbarloo N, Darabi R (2005) Investigation of local ACE activity and structural alterations during development of L-NAME-induced hypertension. Pharmacol Res 52:438–444

    Article  PubMed  CAS  Google Scholar 

  • Silambarasan T, Raja B (2012) Diosmin, a bioflavonoid reverses alterations in blood pressure, nitric oxide, lipid peroxides and antioxidant status in DOCA-salt induced hypertensive rats. Eur J Pharm 679:81–89

    Article  CAS  Google Scholar 

  • Taniyama Y, Griendling KK (2003) Reactive oxygen species in the vasculature: molecular and cellular mechanism. Hypertension 42:1075–1081

    Article  PubMed  CAS  Google Scholar 

  • Toba H, Nakagawa Y, Miki S, Shimizu T, Yoshimura A, Inoue R, Asayama J, Kobara M, Nakata T (2005) Calcium channel blockades exhibit anti-inflammatory and antioxidative effects by augmentation of endothelial nitric oxide synthase and the inhibition of angiotensin converting enzyme in the NG-Nitro-L-arginine methyl ester-induced hypertensive eat aorta: vasoprotective effects beyond the blood pressure-lowering effects of amlodipine and manidipine. Hypertens Res 28:689–700

    Article  PubMed  CAS  Google Scholar 

  • Ulker S, McKeown PP, Bayraktutan U (2003) Vitamins reverse endothelial dysfunction through regulation of eNOS and NAD(P)H oxidase activities. Hypertension 41:534–539

    Article  PubMed  Google Scholar 

  • Veeramani C, Aristatle B, Pushpavalli G, Pugalendi KV (2011) Effects of Melothria maderaspatana leaf extract on antioxidant status in sham-operated and uninephrectomized DOCA-salt hypertensive rats. Saudi J Biolog Sci 18:99–105

    Article  Google Scholar 

  • Wenz G, Han BH, Muller A (2006) Experimental and theoretical studies on the inclusion complexation of syringic acid with α, β, γ and Heptakis (2, 6-di-O-methyl)-β-cyclodextrin. Chem Res 106:782–817

    Article  CAS  Google Scholar 

  • Wu XY, Liu YH, Sheng W, Sun J, Qin G (1997) Chemical constituents of Isatis indigotica. Planta Med 63:55–57

    Article  PubMed  CAS  Google Scholar 

  • Yu BP (1994) Cellular defenses against damage from reactive oxygen species. Physiol Rev 74:139–162

    PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Annamalai University for the financial assistance in the form of “University Research Fellowship” to Mr. S. Kumar. The authors wish to record their sincere thanks to Dr. P. Viswanathan, Professor, Department of Pathology, Rajah Muthiah Medical College and Hospital, Annamalai University, Tamilnadu, India for his assistance in histopathological studies.

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We declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamilnadu, 608 002, India

    Subramanian Kumar, Pichavaram Prahalathan & Boobalan Raja

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  1. Subramanian Kumar
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Correspondence to Boobalan Raja.

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Kumar, S., Prahalathan, P. & Raja, B. Syringic acid ameliorates l-NAME-induced hypertension by reducing oxidative stress. Naunyn-Schmiedeberg's Arch Pharmacol 385, 1175–1184 (2012). https://doi.org/10.1007/s00210-012-0802-7

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