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Clofibric acid or diethylmaleate supplemented diet decrease blood pressure in DOCA-salt treated male Sprague-Dawley rats - relation with liver antioxidant status

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Abstract

The effects of 8-week diethylmaleate (DEM) and clofibric acid (CFA) supplemented diet on blood pressure, body and liver weights, liver antioxidant status and nitric oxide synthase (NOS) activity were investigated in 8-week DOCA-salt treated and untreated Sprague-Dawley male rats. It appeared that DEM and particularly CFA treatments were associated with a significant decrease in blood pressure in DOCA-salt treated rats, and an accentuation of the decreases in body weights in both diet supplemented groups. This was not associated with increases in NO production in the liver. In contrast, hepatic lipid peroxidation was significantly decreased in both DOCA-salt treated and untreated groups on DEM and particularly on CFA supplemented diet. The protective effects of CFA and DEM against hepatic cellular damage could be involved in the decreases in blood pressure in DOCA-salt treated rats, where CFA was more efficient than DEM. In CFA supplemented groups, there was a strong increase in hepatic superoxide dismutase (SOD), glutathione-peroxidase (GSH-Px), and catalase (CAT) activities and in DEM supplemented groups, increases in SOD and CAT activities and in GSH levels were observed. Our data suggest that normalization of blood pressure in DOCA-salt treated rats by CFA was due to an enhancement of the half-life of NO while DEM increased its availability.

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References

  1. Nakazono K, Watanabe N, Matsuno K, Sasaki J, Sato T, Inoue M: Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci USA 88: 10045-10048, 1991

    Google Scholar 

  2. Kumar KV, Das UN: Are free radicals involved in the pathobiology of human essential hypertension? Free Radic Res Commun 19: 59-66, 1993

    Google Scholar 

  3. Swei A, Lacy F, DeLano FA, Schmid-Schonbein GW: Oxidative stress in the Dahl hypertensive rat. Hypertension 30: 1628-1633, 1997

    Google Scholar 

  4. Ito H, Torii M, Suzuki T: A comparative study on defense systems for lipid peroxidation by free radicals in spontaneously hypertensive and normotensive rat myocardium. Comp Biochem Physiol 103B: 37-40, 1992

    Google Scholar 

  5. Halliwell B: Antioxidants in human health and disease. Annu Rev Nutr 16: 33-50, 1996

    Google Scholar 

  6. Russo C, Olivieri O, Girelli D, Faccini G, Zenari ML, Lombardi S, Corrocher R: Antioxidant status and lipid peroxidation in patients with essential hypertension. J Hypertens 16: 1267-1271, 1998

    Google Scholar 

  7. Yuan YV, Kitts DD, Godin DV: Variations in dietary fat and cholesterol intakes modify antioxidant status of SHR and WKY rats. J Nutr 128: 1620-1630, 1998

    Google Scholar 

  8. Vericel E, Narce M, Ulmann L, Poisson JP, Lagarde M: Age related changes in antioxidant defense mechanisms and peroxidation in isolated hepatocytes from spontaneously hypertensive and normotensive rats. Mol Cell Biochem 132: 25-29, 1994

    Google Scholar 

  9. Bui LM, Keen CL, Dubick MA: Comparative effects of 6-week nicotine treatment on blood pressure and components of the antioxidant system in male spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. Toxicology 98: 57-65, 1995

    Google Scholar 

  10. Hong H, Johnson P: Antioxidant enzyme activities and lipid peroxidation levels in exercised and hypertensive rat tissues. Int J Biochem Cell Biol 27: 923-931, 1995

    Google Scholar 

  11. Binda D, Nicod L, Viollon-Abadie C, Berthelot A, Coassolo P, Richert L: Hepatic antioxidant status in vitro in genetic (SHR) and mineralocorticoid-induced (DOCA) hypertensive rats–Comparison with ex vivo data. Mol Cell Biochem (submitted)

  12. Nicod L, Rodriguez S, Letang JM, Viollon-Abadie C, Jacqueson A, Berthelot A, Richert L: Antioxidant status and lipid peroxidation in control and DOCA-salt hypertensive male Sprague-Dawley rats. Mol Cell Biochem 203: 33-39, 2000

    Google Scholar 

  13. Romero-Alvira D, Roche E: High blood pressure, oxygen radicals and antioxidants: Ethiological relationships. Med Hypoth 46: 414-420, 1996

    Google Scholar 

  14. Gryglewski RJ, Palmer RMJ, Moncada S: Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxation factor. Nature 320: 454-456, 1986

    Google Scholar 

  15. Moncada S, Palmer RMJ, Higgs EA: Nitric oxide: Physiology, pathophysiology and pharmacology. Pharm Rev 43: 109-142, 1991

    Google Scholar 

  16. Hogg N, Singh RJ, Kalyanaraman SB: The role of glutathione in the transport and catabolism of nitric oxide. FEBS Lett 382: 223-228, 1996

    Google Scholar 

  17. Boyland E, Chasseaus LF: Enzyme-catalysed conjugations of glutathione with unsaturated compounds. Biochem J 104: 95-105, 1967

    Google Scholar 

  18. Nicod L, Viollon C, Regnier A, Jacqueson A, Richert L: Rifampicin and isoniazid increase acetaminophen and isoniazid cytotoxicity in human HepG2 hepatoma cells. Hum Exp Toxicol 16: 28-34, 1997

    Google Scholar 

  19. Mitchell DB, Acosta D, Bruckner JV: Role of glutathione depletion in the toxicity of acetaminophen in a primary culture system of rat hepatocytes. Toxicology 37: 127-146, 1985

    Google Scholar 

  20. Aniya Y, Teruya M: Activation of hepatic microsomal glutathione S-transferase of rats by a glutathione depletor, diethylmaleate. J Pharmacobiodyn 15: 473-479, 1992

    Google Scholar 

  21. Duthie SJ, Melvin WT, Burke MD: Bromobenzene detoxification in the human liver-derived HepG2 cell line. Xenobiotica 3: 265-279, 1994

    Google Scholar 

  22. Buchmuller-Rouiller Y, Corrrandin SB, Smith J, Schneider P, Ransijn A, Jongeneel CV, Mauel J: Role of glutathione in macrophage activation: Effect of cellular glutathione depletion on nitrite production and leishmanicidal activity. Cell Immunol 164: 73-80, 1995

    Google Scholar 

  23. Duval DL, Sieg DJ, Billings RE: Regulation of nitric oxide synthase by reactive oxygen intermediates and glutathione. Arch Biochem Biophys 316: 699-706, 1995

    Google Scholar 

  24. Witiak DT, Newman HAI, Fuller DR: In: Clofibrate and Related Analogs. Marcel Dekker Inc., New York, 1977, 131-134

    Google Scholar 

  25. Reddy JK, Rao MS: Oxidative DNA damage caused by persistent peroxisome proliferation: Its role in hepatocarcinogenesis. Mutat Res 214: 63-68, 1989

    Google Scholar 

  26. Austin EW, Okita JR, Okita RT, Larson JL, Bull RJ: Modification of lipoperoxidative effects of dichloroacetate and trichloroacetate is associated with peroxisome proliferation. Toxicology 97: 59-69, 1995

    Google Scholar 

  27. Manautou JE, Silva VM, Hennig GE, Whiteley HE: Repeat dosing with the peroxisome proliferator clofibrate decreases the toxicity of model hepatotoxic agents in male mice. Toxicology 127: 1-10, 1998

    Google Scholar 

  28. Roman RJ, Ma YH, Frohlich B, Markham B: Clofibrate prevents the development of hypertension in Dahl salt-sensitive rats. Hypertension 21: 985-988, 1993

    Google Scholar 

  29. De Sandro V, Chevrier M, Boddaert A, Melcion C, Cordier A, Richert L: Comparison of the effects of propylthiouracil, diphenylhydantoin, phenobarbital and 3-methylcholanthrene on hepatic and renal T4 metabolism and thyroid gland function in rats. Toxicol Appl Pharmacol 111: 263-278, 1991

    Google Scholar 

  30. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MI, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC: Measurement of protein using bicinchoninic acid. Anal Biochem 150: 76-85, 1985

    Google Scholar 

  31. Griffith OW: Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 106: 207-212, 1980

    Google Scholar 

  32. Allen KG, Arthur JR: Inhibition by 5-sulphosalicylic acid of the glutathione reductase recycling assay for glutathione analysis. Clin Chim Acta 162: 237-239, 1987

    Google Scholar 

  33. Lawrence RA, Burk RF: Glutathione peroxidase activity in seleniumdeficient rat liver. Biochem Biophys Res Commun 71: 952-958, 1976

    Google Scholar 

  34. Carlberg I, Mannervik B: Glutathione reductase. Meth Enzymol 113: 484-490, 1985

    Google Scholar 

  35. Bellomo G, Mirabelli F, Dimonte D, Richelmi P, Thor H, Orrenius C, Orrenius S: Formation and reduction of glutathione mixed disulfides during oxidative stress. Biochem Pharmacol 36: 1313-1320, 1987

    Google Scholar 

  36. Habig WH, Pabst JM, Jakobi WB: Glutathione-S-Transferases. J Biol Chem 249: 7130-7139, 1974

    Google Scholar 

  37. Aebi H: Catalase in vitro. Meth Enzymol 105: 121-126, 1984

    Google Scholar 

  38. McCord JM, Fridovich I: Superoxide dismutase, an enzymatic function for erythrocuprein (hemocuprein). J Biol Chem 244: 6049-6055, 1969

    Google Scholar 

  39. Flohé L, Otting F: Superoxide dismutase assays. Meth Enzymol 105: 93-104, 1984

    Google Scholar 

  40. Okhawa H, Ohishi N, Yagi K: Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95: 351-358, 1979

    Google Scholar 

  41. Knowles RG, Salter M: Measurement of NOS activity by conversion of radiolabeled arginine to citrulline using ion-exchange separation. In: M.A. Titheradge (ed). Methods in Molecular Biology–Nitric Oxide Protocols. Humana Press Inc., Totowa, NJ, 1992, 67-73

    Google Scholar 

  42. Kasiske BL, O'Donnell MP, Garvis WJ, Keane WF: Pharmacologic treatment of hyperlipidemia reduces glomerular injury in rat 5/6 nephrectomy model of chronic renal failure. Circ Res 62: 367-374, 1988

    Google Scholar 

  43. Hawakawa H, Hirata Y, Suzuki E, Kimura K, Kikichi K, Nagano T, Hirobe M, Omata M: Long term administration of L-arginine improves nitric-oxide release from kidney in deoxycorticosterone acetate-salthypertensive rats. Hypertension 23: 752-756, 1994

    Google Scholar 

  44. Van Den Munckhof RJM, Bosch KS, Fredericks WM: The different effects of peroxisome proliferators clofibric acid and bis(2-ethylhexyl) phtaleate on the activities of peroxisomal oxidases in rat liver. Histochem J 30: 339-349, 1998

    Google Scholar 

  45. Costa LG, Murphy SD: Effect of diethylmaleate and other glutathione depletors on protein synthesis. Biochem Pharmacol 35: 3383-3388, 1986

    Google Scholar 

  46. Tanaka K, Smith PF, Stromberg PC, Eydelloth RS, Herold EG, Grossman SJ, Frank JD, Hertzog PR, Soper KA, Keenan KP: Studies of early hepatocellular proliferation and peroxisomal proliferation in Sprague-Dawley rats treated with tumorigenic doses of clofibrate. Toxicol Appl Pharmacol 116: 71-77, 1992

    Google Scholar 

  47. Giugliano D, Ceriello A, Paolisso G: Diabetes mellitus, hypertension, and cardiovascular disease: Which role for oxidative stress? Metabolism 44: 363-368, 1995

    Google Scholar 

  48. Digiesi V, Oliviero C, Gianno V, Rossetti M, Fiorillo C, Oradei A, Lenuzza M, Nassi P: Reactive metabolites of oxygen, lipid peroxidation, total antioxidant capacity and vitamin E in essential arterial hypertension. Clin Ter 148: 515-519, 1997

    Google Scholar 

  49. Newaz MA, Nawal NN: Effect of alpha-tocopherol on lipid peroxidation and total antioxidant status in spontaneously hypertensive rats. Am J Hypertens 11: 1480-1485, 1998

    Google Scholar 

  50. Wen Y, Killalea S, McGettigan P, Feely J: Lipid peroxidation and antioxidant vitamins C an E in hypertensive patients. Ir J Med Sci 165: 210-212, 1996

    Google Scholar 

  51. Cabell KS, Johnson P: Effects of antihypertensive drugs on rat tissue antioxidant enzyme activities and lipid peroxidation levels. Biochem Pharmacol 54: 133-141, 1997

    Google Scholar 

  52. Prabha PN, Das UN, Koratkar R, Sagar P, Ramesh G: Free radical generation, lipid peroxidation and essential fatty acids in uncontrolled essential hypertension. Prostaglandins Leukot Essent Fatty Acids 41: 27-33, 1990

    Google Scholar 

  53. Tse WY, Maxwell SR, Thomason H, Blann A, Thorpe GH, Waite M, Holder R: Antioxidant status in controlled and uncontrolled hypertension and its relationship to endothelial damage. J Hum Hypertens 8: 843-849, 1994

    Google Scholar 

  54. Spolarics Z, Wu JX: Role of glutathione and catalase in H2O2 detoxification in LPS-activated hepatic endothelial and Kupffer cells. Am J Physiol (Gastro-intest Liver Physiol 36) 273: G1304-G1311, 1997

    Google Scholar 

  55. Sozmen B, Kazaz C, Taskiran D, Tuzun S, Sozmen EY: Effect of Ndicyclopropylmethyl-amino-2-oxazoline (S-3341) on antioxidant status and nitric oxide in hypertensive patients. Curr Med Res Opin 14: 89-96, 1998

    Google Scholar 

  56. Parik T, Allikmets K, Teesalu R, Zilmer M: Evidence for oxidative stress in essential hypertension: Perspective for antioxidant therapy. J Cardiovasc Risk 3: 49-54, 1996

    Google Scholar 

  57. Galley HF, Thornton J, Howdle PD, Walker BE, Webster NR: Combination oral antioxidant supplementation reduces blood pressure. Clin Sci 92: 361-365, 1997

    Google Scholar 

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Nicod, L., Rodriguez, S., Jacqueson, A. et al. Clofibric acid or diethylmaleate supplemented diet decrease blood pressure in DOCA-salt treated male Sprague-Dawley rats - relation with liver antioxidant status. Mol Cell Biochem 213, 65–73 (2000). https://doi.org/10.1023/A:1007112130769

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