Protective Effects of Vasodilatory Î’eta-Blockers Carvedilol and Nebivolol against Glycerol Model of Rhabdomyolysis-Induced Acute Renal Failure in Rats

Authors

  • Ahmed Atwa Egyptian Russian University, Badr City
  • Rehab Hegazy Pharmacology Department, Medical Division, National Research Center, Giza
  • Nermeen Shaffie Pathology Department, Medical Division, National Research Center, Giza
  • Neamat Yassin Pharmacology Department, Medical Division, National Research Center, Giza
  • Sanaa Kenawy Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo

DOI:

https://doi.org/10.3889/oamjms.2016.082

Keywords:

Rhabdomyolysis, Acute renal failure, Carvedilol, Nebivolol, Glycerol, NO, Rat

Abstract

BACKGROUND: Rhabdomyolysis (RM)-induced acute renal failure (ARF) accounts for about 10–40% of all cases of ARF.

AIM: The present study investigated the possible protective effect of two nitric oxides (NO)-releasing third generation β-blockers, carvedilol (Carv) and nebivolol (Nebi), against RM-mimicking glycerol (Gly)-induced ARF in rats.

MATERIAL AND METHODS: After 24 h dehydration, rats received a single dose of 50% Gly (8 ml/kg, im). They were treated with vehicle, Carv (2.5 mg/kg/day, po) or Nebi (10 mg/kg, po) for 3 successive days starting from an hour prior to Gly injection. Evaluation of blood pressure and locomotor activity was performed during the experiment. 72 h following Gly administration, total protein in the urine, serum levels of creatinine, blood urea nitrogen, sodium and potassium as well as the renal contents of malondialdehyde, reduced glutathione and NO were assessed, together with a histopathological examination of renal tissues.

RESULTS: Carv and Nebi attenuated Gly-induced renal dysfunction and histopathological alterations. They decreased the Gly-induced oxidative stress and increased renal NO concentration. Restoration of normal blood pressure and improvement of locomotor activity were also observed.

CONCLUSION: The results clearly demonstrate protective effects of Carv and Nebi against renal damage involved in RM-induced ARF and suggest a role of their antioxidant and NO-releasing properties.

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References

Khan FY. Rhabdomyolysis: a review of the literature. Neth J Med. 2009;67(9): 272-83. PMid:19841484

Sani MA, Campana-Salort E, Begu-LeCorroller A, et al., Non-traumatic rhabdomyolysis and diabetes. Diabetes Metab. 2011;37(3): 262-4. http://dx.doi.org/10.1016/j.diabet.2011.03.003 PMid:21550832

Tseytlin D, Maynard S. Severe rhabdomyolysis secondary to adenovirus infection: case report and literature review. Clin Nephrol. 2016;85(4): 245-50. http://dx.doi.org/10.5414/CN108649 PMid:26857631

Holt SG, Moore KP. Pathogenesis and treatment of renal dysfunction in rhabdomyolysis. Intensive Care Med. 2001;27(5): 803-11. http://dx.doi.org/10.1007/s001340100878

Malinoski DJ, Slater MS, Mullins RJ. Crush injury and rhabdomyolysis. Crit Care Clin. 2004;20(1): 171-92. http://dx.doi.org/10.1016/S0749-0704(03)00091-5

Gonzalez D. Crush syndrome. Crit Care Med. 2005;33(1 Suppl):S34-41. http://dx.doi.org/10.1097/01.CCM.0000151065.13564.6F PMid:15640677

Devarajan P. Cellular and molecular derangements in acute tubular necrosis. Curr Opin Pediatr. 2005;17(2):193-9. http://dx.doi.org/10.1097/01.mop.0000152620.59425.eb PMid:15800411

Chatzizisis YS, Misirli G, Hatzitolios AI, Giannoglou GD. The syndrome of rhabdomyolysis: complications and treatment. Eur J Intern Med. 2008;19(8):568-74. http://dx.doi.org/10.1016/j.ejim.2007.06.037 PMid:19046720

Nath KA, Norby SM. Reactive oxygen species and acute renal failure. Am J Med. 2000;109(8):665-78. http://dx.doi.org/10.1016/S0002-9343(00)00612-4

Moore KP, Holt SG, Patel RP, et al. A causative role for redox cycling of myoglobin and its inhibition by alkalinization in the pathogenesis and treatment of rhabdomyolysis-induced renal failure. J Biol Chem. 1998;273(48):31731-7. http://dx.doi.org/10.1074/jbc.273.48.31731 PMid:9822635

Boutaud O, Roberts LJ. 2nd, Mechanism-based therapeutic approaches to rhabdomyolysis-induced renal failure. Free Radic Biol Med. 2011;51(5):1062-7. http://dx.doi.org/10.1016/j.freeradbiomed.2010.10.704 PMid:21034813 PMCid:PMC3116013

Bristow MR, Larrabee P, Muller-Beckmann B, et al. Effects of carvedilol on adrenergic receptor pharmacology in human ventricular myocardium and lymphocytes. Clin Investig. 1992;70 (Suppl 1):S105-13. http://dx.doi.org/10.1007/BF00207620 PMid:1350478

Li T, Ke W, Sun P, et al. Carvedilol for portal hypertension in cirrhosis: systematic review with meta-analysis. BMJ Open. 2016;6(5):e010902. http://dx.doi.org/10.1136/bmjopen-2015-010902 PMid:27147389 PMCid:PMC4861122

Nichols AJ, Gellai M, Ruffolo RR. Studies on the mechanism of arterial vasodilation produced by the novel antihypertensive agent, carvedilol. Fundam Clin Pharmacol. 1991;5(1):25-38. http://dx.doi.org/10.1111/j.1472-8206.1991.tb00698.x PMid:1712335

Beattie K, Phadke G, Novakovic J. Carvedilol. Profiles Drug Subst Excip Relat Methodol. 2013;38:113-57. http://dx.doi.org/10.1016/B978-0-12-407691-4.00004-6 PMid:23668404

Ruffolo RR, Feuerstein GZ. Pharmacology of carvedilol: rationale for use in hypertension, coronary artery disease and congestive heart failure. Cardiovasc Drugs Ther. 1997;11 (Suppl 1):247-56. http://dx.doi.org/10.1023/A:1007735729121 PMid:9211017

Messerli FH, Grossman E. Beta-blockers in hypertension: is carvedilol different? Am J Cardiol. 2004;93(9) :7-12. http://dx.doi.org/10.1016/j.amjcard.2004.01.020 PMid:15144930

Kett MM, Denton KM, Boesen EI, Anderson WP. Effects of early carvedilol treatment and withdrawal on the development of hypertension and renal vascular narrowing. Am J Hypertens. 2004;17(2):161-6. http://dx.doi.org/10.1016/j.amjhyper.2003.09.013 PMid:14751659

Munzel T, Gori T. Nebivolol: the somewhat-different beta-adrenergic receptor blocker. J Am Coll Cardiol. 2009;54(16):1491-9. http://dx.doi.org/10.1016/j.jacc.2009.05.066 PMid:19815121

Garbin U, Fratta Pasini A, Stranieri C, et al. Effects of nebivolol on endothelial gene expression during oxidative stress in human umbilical vein endothelial cells. Mediators Inflamm. 2008;2008:367590. http://dx.doi.org/10.1155/2008/367590 PMid:18437228 PMCid:PMC2323596

Pires MJ, Rodriguez-Pena AB, Arevalo M, et al. Long-term nebivolol administration reduces renal fibrosis and prevents endothelial dysfunction in rats with hypertension induced by renal mass reduction. J Hypertens. 2007;25(12):2486-96. http://dx.doi.org/10.1097/HJH.0b013e3282efeecb PMid:17984671

Kumar A, Dogra S. Neuroprotective effect of carvedilol, an adrenergic antagonist against colchicine induced cognitive impairment and oxidative damage in rat. Pharmacol Biochem Behav 2009;92(1):25-31. http://dx.doi.org/10.1016/j.pbb.2008.10.005 PMid:18992766

Georgescu A, Popov D, Dragan E, Dragomir E, Badila E. Protective effects of nebivolol and reversal of endothelial dysfunction in diabetes associated with hypertension. Eur J Pharmacol. 2007;570(1-3):149-58. http://dx.doi.org/10.1016/j.ejphar.2007.05.031 PMid:17612521

Singh D, Chander V, Chopra K. Protective effect of naringin, a bioflavonoid on glycerol-induced acute renal failure in rat kidney. Toxicology. 2004;201(1-3):143-51. http://dx.doi.org/10.1016/j.tox.2004.04.018 PMid:15297029

Kauppila T, Tanila H, Carlson S, Taira T. Effects of atipamezole, a novel alpha 2-adrenoceptor antagonist, in open-field, plus-maze, two compartment exploratory and forced swimming tests in the rat. Eur J Pharmacol. 1991;205(2):177-82. http://dx.doi.org/10.1016/0014-2999(91)90817-A

Kelly MA, Rubinstein M, Phillips TJ, et al., Locomotor activity in D2 dopamine receptor-deficient mice is determined by gene dosage, genetic background and developmental adaptations. J Neurosci. 1998;18(9):3470-9. PMid:9547254

Ruiz-Larrea MB, Leal AM, Liza M, Lacort M, De Groot H. Antioxidant effects of estradiol and 2-hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes. Steroids. 1994;59(6):383-8. http://dx.doi.org/10.1016/0039-128X(94)90006-X

Drury R, Wallington E. Carleton's Histology Technique. Oxford University Press: New York, Toronto, 1967:p. 432.

Dunn OJ. Multiple comparisons using rank sums. Technometrics. 1964;6(3):241-252. http://dx.doi.org/10.1080/00401706.1964.10490181

Jones M, Onslow M, Packman A, Gebski V. Guidelines for statistical analysis of percentage of syllables stuttered data. J Speech Lang Hear Res. 2006;49(4):867-78. http://dx.doi.org/10.1044/1092-4388(2006/062)

Singh AP, Singh AJ, Singh N. Pharmacological investigations of Punica granatum in glycerol-induced acute renal failure in rats. Indian J Pharmacol. 2011;43(5):551-6. http://dx.doi.org/10.4103/0253-7613.84971 PMid:22021999 PMCid:PMC3195126

Lopez-Farre A, Gomez-Garre D, Bernabeu F, et al. Platelet-activating factor mediates glycerol-induced acute renal failure in rats. Clin Sci (Lond). 1990;79(6):551-8. http://dx.doi.org/10.1042/cs0790551

Ayvaz S, Aksu B, Kanter M, et al. Preventive effects of hyperbaric oxygen treatment on glycerol-induced myoglobinuric acute renal failure in rats. J Mol Histol. 2012;43(2):161-70. http://dx.doi.org/10.1007/s10735-012-9391-5 PMid:22311626

Ahmed OG, El-Mottaleb NA. Renal function and arterial blood pressure alterations after exposure to acetaminophen with a potential role of Nigella sativa oil in adult male rats. J Physiol Biochem. 2013;69(1):1-13. http://dx.doi.org/10.1007/s13105-012-0182-y PMid:22730078

Said MM. The protective effect of eugenol against gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. Fundam Clin Pharmacol. 2011;25(6):708-16. http://dx.doi.org/10.1111/j.1472-8206.2010.00900.x PMid:21105912

Ahmed OG, El-Mottaleb NA. Renal function and arterial blood pressure alterations after exposure to acetaminophen with a potential role of Nigella sativa oil in adult male rats. J Physiol Biochem. 2013;69(1):1-13. http://dx.doi.org/10.1007/s13105-012-0182-y PMid:22730078

Giannoglou GD, Chatzizisis YS, Misirli G. The syndrome of rhabdomyolysis: pathophysiology and diagnosis. Eur J Intern Med. 2007;18(2):90-100. http://dx.doi.org/10.1016/j.ejim.2006.09.020 PMid:17338959

Stojiljkovic N, Stoiljkovic M, Randjelovic P, Veljkovic S, Mihailovic D. Cytoprotective effect of vitamin C against gentamicin-induced acute kidney injury in rats. Exp Toxicol Pathol. 2012;64(1-2):69-74. http://dx.doi.org/10.1016/j.etp.2010.06.008 PMid:20619622

Hegazy R, Salama A, Mansour D, Hassan A. Renoprotective Effect of Lactoferrin against Chromium-Induced Acute Kidney Injury in Rats: Involvement of IL-18 and IGF-1 Inhibition. PLoS One. 2016;11(3):e0151486. http://dx.doi.org/10.1371/journal.pone.0151486 PMid:26990190 PMCid:PMC4798745

Baud L, Ardaillou R. Involvement of reactive oxygen species in kidney damage. Br Med Bull. 1993;49(3):621-9. PMid:8221027

Helmy MM, El-Gowelli HM. Montelukast abrogates rhabdomyolysis-induced acute renal failure via rectifying detrimental changes in antioxidant profile and systemic cytokines and apoptotic factors production. Eur J Pharmacol. 2012;683(1-3):294-300. http://dx.doi.org/10.1016/j.ejphar.2012.03.018 PMid:22449377

Yousefipour Z, Oyekan A, Newaz M. Interaction of oxidative stress, nitric oxide and peroxisome proliferator activated receptor gamma in acute renal failure. Pharmacol Ther. 2010;125(3):436-45. http://dx.doi.org/10.1016/j.pharmthera.2009.12.004 PMid:20117134

Habibi J, Hayden MR, Sowers JR, et al. Nebivolol attenuates redox-sensitive glomerular and tubular mediated proteinuria in obese rats. Endocrinology. 2011;152(2):659-68. http://dx.doi.org/10.1210/en.2010-1038 PMid:21177830 PMCid:PMC3037162

Aydogdu N, Atmaca G, Yalcin O, Batcioglu K, Kaymak K. Effects of caffeic acid phenethyl ester on glycerol-induced acute renal failure in rats. Clin Exp Pharmacol Physiol. 2004;31(9):575-9. http://dx.doi.org/10.1111/j.1440-1681.2004.04050.x PMid:15479163

Aydogdu N, Atmaca G, Yalcin O, et al. Protective effects of L-carnitine on myoglobinuric acute renal failure in rats. Clin Exp Pharmacol Physiol. 2006;33(1-2):119-24. http://dx.doi.org/10.1111/j.1440-1681.2006.04336.x PMid:16445710

Seifter JL, Samuels MA. Uremic encephalopathy and other brain disorders associated with renal failure. Semin Neurol. 2011;31(2):139-43. http://dx.doi.org/10.1055/s-0031-1277984 PMid:21590619

Can C, Sen S, Boztok N, Tuglular I. Protective effect of oral L-arginine administration on gentamicin-induced renal failure in rats. Eur J Pharmacol. 2000;390(3):327-34. http://dx.doi.org/10.1016/S0014-2999(00)00025-X

Kumar P, Clark M. Renal disease in Textbook of Clinical Medicine. Saunders: London, 2005:p. 605-648. PMid:15826618

Morsy MA, Heeba GH. Nebivolol Ameliorates Cisplatin-Induced Nephrotoxicity in Rats. Basic Clin Pharmacol Toxicol. 2016;118(6):449-55. http://dx.doi.org/10.1111/bcpt.12538 PMid:26617394

Rodrigues MA, Rodrigues JL, Martins NM, et al. Carvedilol protects against cisplatin-induced oxidative stress, redox state unbalance and apoptosis in rat kidney mitochondria. Chem Biol Interact. 2011;189(1-2):45-51. http://dx.doi.org/10.1016/j.cbi.2010.10.014 PMid:21044617

Carvalho Rodrigues MA, dos Santos NA, da Silva Faria MC, et al. Carvedilol protects the kidneys of tumor-bearing mice without impairing the biodistribution or the genotoxicity of cisplatin. Chem Biol Interact. 2016;245:59-65. http://dx.doi.org/10.1016/j.cbi.2015.12.020 PMid:26751708

Dulin B, Abraham WT. Pharmacology of carvedilol. Am J Cardiol. 2004:93(9):3-6. http://dx.doi.org/10.1016/j.amjcard.2004.01.003 PMid:15144929

Lysko PG, Feuerstein GZ, Ruffolo RR. Carvedilol: a novel multiple action antihypertensive drug. Pharm News. 1995;2:12-16.

Feuerstein GZ, Yue TL, Cheng HY, Ruffolo RR. Myocardial protection by the novel vasodilating beta-blocker, carvedilol: potential relevance of anti-oxidant activity. J Hypertens Suppl. 1993;11(4):S41-8. http://dx.doi.org/10.1097/00004872-199306003-00010

Afzal MZ, Reiter M, Gastonguay C, et al. Nicorandil, a Nitric Oxide Donor and ATP-Sensitive Potassium Channel Opener, Protects Against Dystrophin-Deficient Cardiomyopathy. J Cardiovasc Pharmacol Ther. 2016. http://dx.doi.org/10.1177/1074248416636477 PMid:26940570

Sealey JE, Laragh JH. A proposed cybernetic system for sodium and potassium homeostasis: coordination of aldosterone and intrarenal physical factors. Kidney Int. 1974;6(5):281-90. http://dx.doi.org/10.1038/ki.1974.114

Sacco G, Evangelista S, Manzini S, Parlani M, Bigioni M. Combined antihypertensive and cardioprotective effects of nebivolol and hydrochlorothiazide in spontaneous hypertensive rats. Future Cardiol. 2011;7(6):757-63. http://dx.doi.org/10.2217/fca.11.70 PMid:22050062

Rodriguez-Perez JC, Losada A, Anabitarte A, et al. Effects of the novel multiple-action agent carvedilol on severe nephrosclerosis in renal ablated rats. J Pharmacol Exp Ther. 1997;283(1):336-44. PMid:9336341

Greven J, Gabriels G. Effect of nebivolol, a novel beta 1-selective adrenoceptor antagonist with vasodilating properties, on kidney function. Arzneimittelforschung. 2000;50(11):973-9. PMid:11148863

Halliwell B, Gutteridge JM. The importance of free radicals and catalytic metal ions in human diseases. Mol Aspects Med. 1985;8(2):89-193. http://dx.doi.org/10.1016/0098-2997(85)90001-9

Labrid C. Cellular disorders induced by ischemia. The effect of trimetazidine. Presse Med. 1986;15(35):1754-7. PMid:3024147

Clausen T, Flatman JA. Beta 2-adrenoceptors mediate the stimulating effect of adrenaline on active electrogenic Na-K-transport in rat soleus muscle. Br J Pharmacol. 1980;68(4):749-55. http://dx.doi.org/10.1111/j.1476-5381.1980.tb10868.x PMid:6247002 PMCid:PMC2044229

Shah KB, Rao K, Sawyer R, Gottlieb SS. The adequacy of laboratory monitoring in patients treated with spironolactone for congestive heart failure. J Am Coll Cardiol. 2005;46(5):845-9. http://dx.doi.org/10.1016/j.jacc.2005.06.010 PMid:16139135

Lysko PG, Lysko KA, Webb CL, Feuerstein G. Neuroprotective effects of carvedilol, a new antihypertensive, at the N-methyl-D-aspartate receptor. Neurosci Lett. 1992;148(1-2):34-8. http://dx.doi.org/10.1016/0304-3940(92)90798-C

Ilhan A, Yilmaz HR, Armutcu F, Gurel A, Akyol O. The protective effect of nebivolol on ischemia/reperfusion injury in rabbit spinal cord. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28(7):1153-60. http://dx.doi.org/10.1016/j.pnpbp.2004.06.023 PMid:15610928

Seren M, Budak B, Turan N, et al. Collaborative therapy with nebivalol and L-NAME for spinal cord ischemia/reperfusion injury. Ann Vasc Surg. 2008;22(3):425-31. http://dx.doi.org/10.1016/j.avsg.2007.12.024 PMid:18466820

Kumar P, Kumar A. Prolonged pretreatment with carvedilol prevents 3-nitropropionic acid-induced behavioral alterations and oxidative stress in rats. Pharmacol Rep. 2008;60(5):706-15. PMid:19066418

Jovanovic D, Jovovic D, Mihailovic-Stanojevic N, et al. Influence of carvedilol on chronic renal failure progression in spontaneously hypertensive rats with adriamycin nephropathy. Clin Nephrol. 2005;63(6):446-53. http://dx.doi.org/10.5414/CNP63446 PMid:15960146

Guerrero E, Voces F, Ardanaz N, et al. Long-term treatment with nebivolol improves arterial reactivity and reduces ventricular hypertrophy in spontaneously hypertensive rats. J Cardiovasc Pharmacol. 2003;42(3):348-55. http://dx.doi.org/10.1097/00005344-200309000-00005 PMid:12960679

Afonso RA, Patarrao RS, Macedo MP, Carmo MM. Carvedilol's actions are largely mediated by endogenous nitric oxide. Rev Port Cardiol. 2006;25(10):911-7. PMid:17190240

Afonso RA, Patarrao RS, Macedo MP, Carmo MM. Carvedilol action is dependent on endogenous production of nitric oxide. Am J Hypertens. 2006;19(4):419-25. http://dx.doi.org/10.1016/j.amjhyper.2005.11.011 PMid:16580580

Kalinowski L, Dobrucki LW, Szczepanska-Konkel M, et al. Third-generation beta-blockers stimulate nitric oxide release from endothelial cells through ATP efflux: a novel mechanism for antihypertensive action. Circulation. 2003;107(21):2747-52. http://dx.doi.org/10.1161/01.CIR.0000066912.58385.DE PMid:12742996

Gandhi C, Zalawadia R, Balaraman R. Nebivolol reduces experimentally induced warm renal ischemia reperfusion injury in rats. Ren Fail. 2008;30(9):921-30. http://dx.doi.org/10.1080/08860220802353900 PMid:18925533

Uzar E, Acar A, Evliyaoglu O, et al. The anti-oxidant and anti-apoptotic effects of nebivolol and zofenopril in a model of cerebral ischemia/reperfusion in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2012;36(1):22-8. http://dx.doi.org/10.1016/j.pnpbp.2011.08.011 PMid:21888941

Evangelista S, Garbin U, Pasini AF, et al. Effect of DL-nebivolol, its enantiomers and metabolites on the intracellular production of superoxide and nitric oxide in human endothelial cells. Pharmacol Res. 2007;55(4):303-9. http://dx.doi.org/10.1016/j.phrs.2006.12.008 PMid:17280840

Ignarro LJ. Different pharmacological properties of two enantiomers in a unique beta-blocker, nebivolol. Cardiovasc Ther. 2008;26(2):115-34. http://dx.doi.org/10.1111/j.1527-3466.2008.00044.x PMid:18485134

Varagic J, Ahmad S, Brosnihan KB, et al. Salt-induced renal injury in spontaneously hypertensive rats: effects of nebivolol. Am J Nephrol. 2010;32(6):557-66. http://dx.doi.org/10.1159/000321471 PMid:21042014 PMCid:PMC2992650

Ruilope LM, Lahera V, Rodicio JL, Romero JC. Participation of nitric oxide in the regulation of renal function: possible role in the genesis of arterial hypertension. J Hypertens. 1994;12(6):625-31. http://dx.doi.org/10.1097/00004872-199406000-00002 PMid:7963487

Maree A, Peer G, Schwartz D, et al. Role of nitric oxide in glycerol-induced acute renal failure in rats. Nephrol Dial Transplant. 1994;9 (Suppl 4):78-81. PMid:7528365

Published

2016-08-01

How to Cite

1.
Atwa A, Hegazy R, Shaffie N, Yassin N, Kenawy S. Protective Effects of Vasodilatory Î’eta-Blockers Carvedilol and Nebivolol against Glycerol Model of Rhabdomyolysis-Induced Acute Renal Failure in Rats. Open Access Maced J Med Sci [Internet]. 2016 Aug. 1 [cited 2024 Mar. 29];4(3):329-36. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2016.082

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A - Basic Science