AER  Vol.2 No.2 , June 2014
Aliskiren Augments the Activities of Anti-Oxidant Enzymes in Liver Homogenates of DOCA Salt-Induced Hypertensive Rats
Author(s) Sahar Kamal*
ABSTRACT
Hypertension is a serious problem that is recently thought to be associated with damaging effects on target organs partially via oxidative stress. On the other hand, there is accumulating literature describing some sort of therapeutic interaction between antioxidant enzymes in vital organs and hypertension. Therefore, the aim of this study is to investigate the possible effect of a direct renin inhibitor, aliskiren, used in treatment of hypertension via renin-angiotensin-aldosterone system (RAAS), on selected anti-oxidant enzymes in hepatic homogenates in DOCA salt-induced hypertesnive albino rats. Thirty male wister albino rats were assigned randomly into 3 groups (n = 10/ group). Group 1 received no treatement and serves as control. Group 2 received 0.5% carboxymethylcellulose sodium ip as a solvent of aliskiren, as a direct renin inhibitor (DRI). Group 3 received aliskiren 100 mg/kg/day ip for 4 weeks through gastric tube. Systolic blood pressure (SBP) was measured every week and its mean was recorded at the end of the study. Superoxide dismutase (SOD) enzyme in RBCs lysates, activities of catalase (CAT) and glutathione peroxidase enzymes and thiobarbituric acid reactive substance (TBARS), as a marker of lipid peroxidation, in hepatic homogenates were measured at the end of the study. DRI produced a marked reduction in mean SBP of hypertensive rats. It also significantly (p < 0.05) increased the activities of measured anti-oxidant enzymes while it significantly (p < 0.05) reduced TBARS in liver homogenates. These results indicated that renin possesses an oxidative effect in the liver in hypertensive rats. Aliskiren, in addition to its powerful anti-hypertensive effect, it could induce a great anti-oxidant effect in liver homogenates of DOCA salt-hypertensive rats.

Cite this paper
Kamal, S. (2014) Aliskiren Augments the Activities of Anti-Oxidant Enzymes in Liver Homogenates of DOCA Salt-Induced Hypertensive Rats. Advances in Enzyme Research, 2, 92-99. doi: 10.4236/aer.2014.22010.
References
[1]   Fisher, N.D. and Hollenberg, N.K. (2001) Is There a Future for Renin Inhibitors? Expert Opinion on Investigational Drugs, 10, 417-426.
http://dx.doi.org/10.1517/13543784.10.3.417

[2]   Harrison, D.G. and Gongora, M.C. (2009) Oxidative Stress and Hypertension. Medical Clinics of North America, 93, 621-635.
http://dx.doi.org/10.1016/j.mcna.2009.02.015

[3]   De Champlain, J., Wu, R., Girouard, H., Karas, M., EL Midaoui, A., Laplante, M.A. and Wu, L. (2004) Oxidative Stress in Hypertension. Clinical and Experimental Hyper-tension, 26, 593-601.
http://dx.doi.org/10.1081/CEH-200031904

[4]   Staessen, J.A., Li, Y. and Richart, T. (2006) Oral Renin Inhibitors. Lancet, 368, 1449-1456.
http://dx.doi.org/10.1016/S0140-6736(06)69442-7

[5]   Li, Y.C. (2007) Inhibition of Renin: An Updated Review of the Development of Renin Inhibitors. Current Opinion in Investigational Drugs, 8, 750-757.

[6]   Matsumura, Y., Hashimoto, N., Taira, S., Kuro, T., Kitano, R., Ohkita, M., Opgenorth, J. and Takaoka, M. (1999) Different Contributions of Endothelin-A and Endothelin-B Receptors in the Pathogenesis of Deoxycorticosterone Acetate-Salt-Induced Hypertension in Rats. Hypertension, 33, 759-765.
http://dx.doi.org/10.1161/01.HYP.33.2.759

[7]   Rashikh, A., Ahmad, S.J., Pillai, K.K., Kohli, K. and Najmi, A.K. (2012) Aliskiren Attenuates Myocardial Apoptosis and Oxidative Stress in Chronic Murine Model of Cardiomyopathy. Biomedicine & Pharmacotherapy, 66, 138-143.

[8]   Bunag, R. (1973) Validation in Awake Rats of a Tail-Cuff Method for Measuring Systolic Pressure. Journal of Applied Physiology, 34, 279-282.

[9]   Sato, R., Goldstein, J. and Brown, M. (1993) Replacement of Serine-871 of Hamster 3-Hydroxy-3-Methylglutaryl-CoA Reductase Prevents Phosphorylation by AMP-Activated Kinase and Blocks Inhibition of Sterol Synthesis Induced by ATP Depletion. Proceedings of the National Academy of Sciences, 90, 9261-9265.
http://dx.doi.org/10.1073/pnas.90.20.9261

[10]   Sinha, K.A. (1972) Colorimetric Assay of Catalase. Analytical Biochemistry, 47, 389-394.
http://dx.doi.org/10.1016/0003-2697(72)90132-7

[11]   Rotruck, J., Pope, A., Ganther, H., Swanson, A., Hafeman, D. and Hoekstra, W. (1973) Biochemical Role as a Component of Glutathione Peroxidase. Science, 79, 588-590.
http://dx.doi.org/10.1126/science.179.4073.588

[12]   Fraga, C., Leibovitz, B. and Tappel, A. (1988) Lipid Peroxidation Measured as Thiobarbituric Acid Reactive Substances in Tissue Slices: Characterization and Comparison with Homogenates and Microsomes. Free Radical Biology & Medicine, 4, 155-161.
http://dx.doi.org/10.1016/0891-5849(88)90023-8

[13]   Bradford, M. (1976) A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Analytical Biochemistry, 72, 248-254.
http://dx.doi.org/10.1016/0003-2697(76)90527-3

[14]   Oliver, G., Rainer, G., Diana, R., Johanna, T., Stephanie, T. and Gerhard-Anton, M. (2011) Renal Protective Effects of Aliskiren Beyond Its Antihypertensive Property in a Mouse Model of Progressive Fibrosis. American Journal of Hypertension, 24, 355-361.
http://dx.doi.org/10.1038/ajh.2010.231

[15]   Aihara, Y., Yoshiji, H., Noguchi, R., Kaji, K., Namisaki, T., Shirai, Y., Douhara, A., Moriya, K., Kawaratani, H. and Fukui, H. (2013) Direct Renin Inhibitor, Aliskiren, Attenuates the Progression of Non-Alcoholic Steatohepatitis in the Rat Model. Hepatology Research, 43, 1241-1250.
http://dx.doi.org/10.1111/hepr.12081

[16]   Aso, Y. (2008) Cardiovascular Disease in Patients with Diabetic Nephropathy. Current Molecular Medicine, 8, 533- 543.
http://dx.doi.org/10.2174/156652408785747960

[17]   Rojas, A., Mercadal, E., Figueroa, H. and Morales, M.A. (2008) Advanced Glycation and ROS: A Link between Diabetes and Heart Failure. Current Vascular Pharmacology, 6, 44-51.
http://dx.doi.org/10.2174/157016108783331312

[18]   Al-Aubaidy, H., Sahib, H., Mohammad, B., Hadi, N. and Abas, S. (2013) Antiatherosclerotic Potential of Aliskiren: Its Antioxidant and Anti-Inflammatory Effects in Rabbits: A Randomized Controlled Trial. Journal of Pharmaceutical Technology and Drug Research.

[19]   Prasanna, G. and Purnima, A. (2011) Protective Effect of Leaf Extract of Trichilia Connaroides on Hypercholesterolemia Induced Oxidative Stress. International Journal of Pharmacology, 7, 106-112.
http://dx.doi.org/10.3923/ijp.2011.106.112

[20]   Prasad, K. and Kalra, J. (1993) Oxygen Free Radicals and Hypercholesterolemic Atherosclerosis: Effect of Vitamin E. American Heart Journal, 125, 958-973.
http://dx.doi.org/10.1016/0002-8703(93)90102-F

[21]   Panganamala, R.V., Sharma, H.M., Heikkila, R.E., Geer, J.C. and Cornwell, D.G. (1976) Role of Hydroxyl Radical Scavengers Dimethyl Sulfoxide, Alcohols and Methional in the Inhibition of Prostaglandin Biosynthesis. Prostaglandins, 11, 599-607.
http://dx.doi.org/10.1016/0090-6980(76)90063-0

[22]   Del Fiorentino, A., Cianchetti, S., Celi, A. and Pedrinelli, R. (2010) Aliskiren, a Renin Inhibitor, Downregulates TNF-Alpha-Induced Tissue Factor Expression in HUVECS. Journal of the Renin-Angiotensin-Aldosterone System, 11, 243- 247.
http://dx.doi.org/10.1177/1470320310379449

 
 
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