Skip to main content
Log in

Antioxidant status, lipid peroxidation, mixed function oxidase and UDP-glucuronyl transferase activities in livers from control and DOCA salt-hypertensive male Sprague Dawley rats

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The effects of DOCA-salt hypertensive treatment on hepatic glutathione-dependent defense system, antioxidant enzymes, lipid peroxidation, mixed function oxidase and UDP-glucuronyl transferase activities were investigated in male Sprague Dawley rats.

Compared with controls, DOCA-salt hypertensive rats had lower body weights (linked to liver hypertrophy). Mixed function oxidase and p-nitrophenol-UGT activities were not affected by the treatment but a significant lower rate of the glucuronoconjugation rate of bilirubin (p < 0.001) was observed in DOCA-salt hypertensive rats. While cytosolic glutathione contents and glutathione reductase activity were not affected, glutathione peroxidase (p < 0.001), glutathione transferase (p < 0.001) and catalase (p < 0.01) activities were decreased and associated with higher malondialdehyde contents (p < 0.001) in treated rats. The imbalance in liver antioxidant status (increasing generation of cellular radical species), associated with increases in lipid peroxidation, suggests that oxidative stress might be directly related to arterial hypertension in DOCA-salt treated male Sprague Dawley rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. DiPette DJ: Experimental models of hypertension. In: J.L. Izzo, H.R. Black (eds). Hypertension Primer. American Heart Association, Dallas, 1993, pp 95-97

    Google Scholar 

  2. Schenk J, McNeill XX: The pathogenesis of DOCA-salt hypertension. J Pharm Toxicol Meth 27: 161-170, 1992

    Google Scholar 

  3. Don BR, Schambelan M: Adrenal cortical hypertension: Pathophysiology. In: J.L. Izzo, H.R. Black (eds). Hypertension Primer. American Heart Association, Dallas, 1993, pp 104-106

    Google Scholar 

  4. 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 

  5. Papies B, Schimke I, Moritz V: Enhanced formation of lipid peroxides might contribute to the high sensitivity of spontaneously hypertensive rats towards isoproterenol-induced myocardial damage. Biomed Biochim Acta 48: 681-687, 1989

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  10. Kitts DD, Yuan YV, Godin DV: Plasma and lipoprotein lipid composition and hepatic antioxidant status in spontaneously hypertensive (SHR) and normotensive (WKY) rats. Can J Physiol Pharmacol 76: 202-209, 1998

    Google Scholar 

  11. Kaplowitz N, Yee Aw T, Ookhtens M: The regulation of hepatic glutathione. Ann Rev Pharmacol Toxicol 25: 715-744, 1985

    Google Scholar 

  12. 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 

  13. 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 

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

    Google Scholar 

  15. DeSandro V, Chevrier M, Boddaert A, Melcion C, Cordier A, Richert L: Comparison of the effects of propylthiouracil, diphenyl hydantoin, 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 

  16. 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 

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

    Google Scholar 

  18. 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 

  19. Burke MD, Thompson S, Elcombe CR, Halpert J, Haaparanta T, Mayer RT: Ethoxy-, pentoxy-and benzyloxy-phenoxazones and homologues: A series of substrates to distinguish between different induced cytochromes P-450. Biochem Pharmacol 34: 3337-3345, 1985

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  22. 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 

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

    Google Scholar 

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

    Google Scholar 

  25. Bock KW, Fröhling W, Remmer H, Rexer B: Effects of phenobarbital and 3-methylcholantrene on substrate specificity of rat liver microsomal UDP-glucuronyltransferase. Biochim Biophys Acta 327: 46-56, 1973

    Google Scholar 

  26. Viollon-Abadie C, Lassere D, Morel C, Debruyne E, Nicod L, Carmichael N, Richert L: Phenobarbital, β-naphthoflavone, clofibrate and pregnenolone-16α-carbonitrile do not affect hepatic thyroid hormone UDP-glucuronosyl transferase activity and thyroid gland function in mice. Toxicol Appl Pharmacol 155: 1-12, 1999

    Google Scholar 

  27. Heirwegh KPM, Van Der Vijver M, Fevery J: Assay and properties of digitonin-activated bilirubin uridine diphosphate glucuronyltransferase from rat liver. Biochem J 129: 605-618, 1972

    Google Scholar 

  28. Yagi K: A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med 15: 212-216, 1976

    Google Scholar 

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

    Google Scholar 

  30. Rodriguez S, Bidet A, Berthelot A, Richert L: Arginase activity and manganese content in various tissues from control and DOCA salthypertensive male Sprague Dawley rats. Trace Elements and Electrolytes 15: 181-184, 1998

    Google Scholar 

  31. Cross CE, Halliwell B, Borish ET, Pryor WA, Ames BN, Saul RL: Oxygen radicals and human disease. Ann Intern Med 107: 526-545, 1987

    Google Scholar 

  32. Hoida G, Lindt S, Eichenberger E: The course of blood pressure and organ changes in rats with DOCA-hypertension. Arzneim Forsch 26: 2003-2008, 1976

    Google Scholar 

  33. 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-salt-hypertensive rats. Hypertension 23: 752-756, 1994

    Google Scholar 

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

    Google Scholar 

  35. Meister A, Anderson ME: Glutathione. Ann Rev Biochem 52: 711-760, 1983

    Google Scholar 

  36. Uhlig S, Wendel A: The physiological consequences of glutathione variations. Life Sci 51: 1083-1094, 1992

    Google Scholar 

  37. 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 

  38. 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 

  39. Grant MH, Duthie SJ, Gray AG, Burke MD: Mixed function oxidase and UDP-glucuronyltransferase activities in the human Hep G2 hepatoma cell line. Biochem Pharmacol 37: 4111-4116, 1988

    Google Scholar 

  40. Totis M, Batt AM, Siest G: Human liver cytochromes P450. J Pharm Clin 10: 93-98, 1991

    Google Scholar 

  41. DeMorais SMF, Chow SYM, Wells PG: Biotransformation and toxicity of acetaminophen in congenic RHA rats with or without a hereditary deficiency in bilirubin UDP-glucuronosyltransferase. Toxicol Appl Pharmacol 117: 81-87, 1992

    Google Scholar 

  42. Farber JL, Gerson RJ: Mechanisms of cell injury with hepatotoxic chemicals. Pharmacol Rev 36: 71S-75S, 1984

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nicod, L., Ridriguez, S., Letang, JM. et al. Antioxidant status, lipid peroxidation, mixed function oxidase and UDP-glucuronyl transferase activities in livers from control and DOCA salt-hypertensive male Sprague Dawley rats. Mol Cell Biochem 203, 33–39 (2000). https://doi.org/10.1023/A:1007041532523

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007041532523

Navigation