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Tadalafil attenuates spinal cord injury induced oxidative organ damage in rats

Year 2014, Volume: 18 Issue: 2, 49 - 55, 16.05.2014

Abstract

Spinal cord injury (SCI) has been shown to cause systemic
inflammatory response syndrome (SIRS) which damages
multiple organs due to an influx of inflammatory cells from the
circulation. In this study, we evaluated the effect of tadalafil, a
phoshodiesterase inhibitor, against spinal cord, kidney and
bladder damage in experimental animal model of spinal cord
injury. Male Wistar albino rats were divided into sham-operated
control, and either vehicle or tadalafil-treated SCI groups. In
order to induce SCI, a standard weight-drop method that
induced a moderately severe injury (100 g/cm force) at T10,
was used. Injured animals were given either 10 mg/kg tadalafil
or vehicle 15 minutes post injury and repeated daily for seven
days. After decapitation spinal cord, kidney and bladder tissue
samples were obtained to examine oxidative tissue injury;
malondialdehyde (MDA) and glutathione (GSH) levels, and
superoxide dismutase (SOD), myeloperoxidase (MPO) and
caspase-3 activities. Tissues were also examined histologically.
In the injured animals, MDA levels MPO and caspase-3
activities in tissues were found significantly increased while
tadalafil treatment reversed these increases. On the other hand
SCI-induced decreases in GSH levels and SOD activities were
also reversed with tadalafil treatment. According to the results,
tadalafil exerts beneficial effects against SCI-induced
oxidative damage in spinal cord and also in remote organs
such as kidney and bladder tissues through its antiinflammatory
and antioxidant effects.
Key words: tadalafil; spinal cord

References

  • Hulsebosch CE. Recent advances in pathophysiology and treatment of spinal cord injury. Adv Physiol Educ 2002; 26:238-55.
  • Jia Z, Zhu H, Li J, Wang X, Misra H, Li Y. Oxidative stress in spinal cord injury and antioxidant-based intervention. Spinal Cord 2012;50:264-74.
  • Scott GS, Cuzzocrea S, Genovese T, Koprowski H, Hooper DC. Uric acid protects against secondary damage after spinal cord injury. Proc Natl Acad Sci U S A 2005; 102:3483-8.
  • Genovese T, Mazzon E, Muia C, Bramanti P, De Sarro A, Cuzzocrea S. Attenuation in the evolution of experimental spinal cord trauma by treatment with melatonin. J Pineal Res 2005;38:198-208.
  • Erşahin M, Çevik Ö, Akakın D, Şener A, Özbay L, Yegen BC, Şener G. Montelukast inhibits caspase-3 activity and ameliorates oxidative damage in the spinal cord and urinary bladder of rats with spinal cord injury. Prostaglandins Other Lipid Mediat 2012;99:131-9.
  • Uckert S, Hedlund P, Andersson KE, Truss MC, Jonas U, Stief CG. Update on phosphodiesterase (PDE) isoenzymes as pharmacologic targets in urology: present and future. Eur Urol 2006;50:1194-207; discussion 120
  • Katz SD, Balidemaj K, Homma S, Wu H, Wang J, Maybaum S. Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure. J Am Coll Cardiol 2000;36:845-51.
  • Sebkhi A, Strange JW, Phillips SC, Wharton J, Wilkins MR. Phosphodiesterase type 5 as a target for the treatment of hypoxia-induced pulmonary hypertension. Circulation 2003;107:3230-5.
  • Reffelmann T, Kloner RA. Therapeutic potential of phosphodiesterase 5 inhibition for cardiovascular disease. Circulation 2003;108:239-44.
  • Das A, Xi L, Kukreja RC. Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling. J Biol Chem 2005;280:12944-55.
  • Yigitaslan S, Ozatik O, Ozatik FY, Erol K, Sirmagul B, Baseskioglu AB. Effects of Tadalafil on Hemorrhagic Cystitis and Testicular Dysfunction Induced by Cyclophosphamide in Rats. Urol Int. 2013 Sep 18.
  • [Epub ahead of print]. Guzeloglu M, Yalcinkaya F, Atmaca S, Bagriyanik A, Oktar S, Yuksel O, Fansa I, Hazan E. The beneficial effects of tadalafil on renal ischemia-reperfusion injury in rats. Urol Int 2011; 86: 197-203.
  • Allen AR. Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture dislocation of spinal column. A preliminary report. JAMA 1911;57: 878.
  • Hillegas LM, Griswold DE, Brickson B, Albrightson-Winslow C. Assesment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods 1990;24:285-95.
  • Beuge JA, Aust SD. Microsomal lipid peroxidation, Methods Enzymol 1978;52:302.
  • Beutler E. Glutathione in Red Blood Cell Metabolism. A Manuel of Biochemical Methods. Grune&Stratton, NewYork. 1975, p. 112.
  • Mylroie AA, Collins H, Umbles C, Kyle J. Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol 1986;82:512-20.
  • La Rosa G, Cardali S, Genovese T, Conti A, Di Paola R, La Torre D, Cacciola F, Cuzzocrea S. Inhibition of the nuclear factorkappaB activation with pyrrolidine dithiocarbamate attenuating inflammation and oxidative stress after experimental spinal cord trauma in rats. J Neurosurg Spine 2004;1:311-21.
  • Genovese T, Mazzon E, Di Paola R, Crisafulli C, Muia C, Bramanti P, Cuzzocrea S. Increased oxidative-related mechanisms in the spinal cord injury in old rats. Neurosci Lett 2006; 393:141-46.
  • Fleming JC, Bailey CS, Hundt H, Gurr KR, Bailey SI, Cepinskas G, Lawendy AR, Badhwar A. Remote inflammatory response in liver is dependent on the segmental level of spinal cord injury. J Trauma Acute Care Surg 2012;72:1194-201;discussion 1202.
  • Liu J, Tang T, Yang H. Protective effect of deferoxamine on experimental spinal cord injury in rat. Injury 2011;42:742-5.
  • Kettle AJ, Winterbourn CC. Myeloperoxidase: a key regulator of neutrophil oxidant production. Redox Report 1997;3:3–15.
  • Cevik O, Erşahin M, Sener TE, Tinay I, Tarcan T, Cetinel S, Sener A, Toklu HZ, Sener G. Beneficial effects of quercetin on rat urinary bladder after spinal cord injury. J Surg Res 2013;183:695-703.
  • Tavukçu HH, Sener TE, Tinay I, Akbal C, Erşahin M, Cevik O, Cadırcı S, Reiter RJ, Sener G. Melatonin and tadalafil treatment improves erectile dysfunction after spinal cord injury in rats. Clin Exp Pharma col Physiol 2014;41:309-16.
  • Wang Y, Su R, Lv G, Cao Y, Fan Z, Wang Y, Zhang L, Yu D, Mei X. Supplement zinc as an effective treatment for spinal cord ischemia/ reperfusion injury in rats. Brain Res 2014;1545:45-53.
  • Küçük A, Yucel M, Erkasap N, Tosun M, Koken T, Ozkurt M, Erkasap S. The effects of PDE5 inhibitory drugs on renal ischemia/reperfusion injury in rats. Mol Biol Rep 2012;39:9775-82.
  • Kayiran O, Cuzdan SS, Uysal A, Kocer U. Tadalafil significantly reduces ischemia reperfusion injury in skin island flaps. Indian J Plast Surg 2013;46:75-81.
  • Circu ML, Aw TY. Glutathione and modulation of cell apoptosis. Biochim Biophys Acta 2012;1823:1767-77.
  • Ross D. Glutathione, free radicals and chemotherapeutic agents. Pharmacol Ther 1988;37:231–49.
  • Acuna-Castroviejo D, Martin M, Macias M, Escames G, Leon J, Khaldy A, Reiter RJ. Melatonin, mitochondria, and cellular bioenergetics. J Pineal Res 2001;30:65–74.
  • Kannan K, Jain SK. Oxidative stress and apoptosis. Pathophysiology 2000;7:153–63.
  • Grunenfelder J, Miniati DN , Murata S , Falk V , Hoyt EG , Kown M , Koransky ML, Robbins RC. Upregulation of Bcl-2 through caspase-3 inhibition ameliorates ischemia/reperfusion injury in rat cardiac allografts. Circulation 2001; 104: 1202– I206.

Tadalafil attenuates spinal cord injury induced oxidative organ damage in rats

Year 2014, Volume: 18 Issue: 2, 49 - 55, 16.05.2014

Abstract

References

  • Hulsebosch CE. Recent advances in pathophysiology and treatment of spinal cord injury. Adv Physiol Educ 2002; 26:238-55.
  • Jia Z, Zhu H, Li J, Wang X, Misra H, Li Y. Oxidative stress in spinal cord injury and antioxidant-based intervention. Spinal Cord 2012;50:264-74.
  • Scott GS, Cuzzocrea S, Genovese T, Koprowski H, Hooper DC. Uric acid protects against secondary damage after spinal cord injury. Proc Natl Acad Sci U S A 2005; 102:3483-8.
  • Genovese T, Mazzon E, Muia C, Bramanti P, De Sarro A, Cuzzocrea S. Attenuation in the evolution of experimental spinal cord trauma by treatment with melatonin. J Pineal Res 2005;38:198-208.
  • Erşahin M, Çevik Ö, Akakın D, Şener A, Özbay L, Yegen BC, Şener G. Montelukast inhibits caspase-3 activity and ameliorates oxidative damage in the spinal cord and urinary bladder of rats with spinal cord injury. Prostaglandins Other Lipid Mediat 2012;99:131-9.
  • Uckert S, Hedlund P, Andersson KE, Truss MC, Jonas U, Stief CG. Update on phosphodiesterase (PDE) isoenzymes as pharmacologic targets in urology: present and future. Eur Urol 2006;50:1194-207; discussion 120
  • Katz SD, Balidemaj K, Homma S, Wu H, Wang J, Maybaum S. Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure. J Am Coll Cardiol 2000;36:845-51.
  • Sebkhi A, Strange JW, Phillips SC, Wharton J, Wilkins MR. Phosphodiesterase type 5 as a target for the treatment of hypoxia-induced pulmonary hypertension. Circulation 2003;107:3230-5.
  • Reffelmann T, Kloner RA. Therapeutic potential of phosphodiesterase 5 inhibition for cardiovascular disease. Circulation 2003;108:239-44.
  • Das A, Xi L, Kukreja RC. Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling. J Biol Chem 2005;280:12944-55.
  • Yigitaslan S, Ozatik O, Ozatik FY, Erol K, Sirmagul B, Baseskioglu AB. Effects of Tadalafil on Hemorrhagic Cystitis and Testicular Dysfunction Induced by Cyclophosphamide in Rats. Urol Int. 2013 Sep 18.
  • [Epub ahead of print]. Guzeloglu M, Yalcinkaya F, Atmaca S, Bagriyanik A, Oktar S, Yuksel O, Fansa I, Hazan E. The beneficial effects of tadalafil on renal ischemia-reperfusion injury in rats. Urol Int 2011; 86: 197-203.
  • Allen AR. Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture dislocation of spinal column. A preliminary report. JAMA 1911;57: 878.
  • Hillegas LM, Griswold DE, Brickson B, Albrightson-Winslow C. Assesment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods 1990;24:285-95.
  • Beuge JA, Aust SD. Microsomal lipid peroxidation, Methods Enzymol 1978;52:302.
  • Beutler E. Glutathione in Red Blood Cell Metabolism. A Manuel of Biochemical Methods. Grune&Stratton, NewYork. 1975, p. 112.
  • Mylroie AA, Collins H, Umbles C, Kyle J. Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol 1986;82:512-20.
  • La Rosa G, Cardali S, Genovese T, Conti A, Di Paola R, La Torre D, Cacciola F, Cuzzocrea S. Inhibition of the nuclear factorkappaB activation with pyrrolidine dithiocarbamate attenuating inflammation and oxidative stress after experimental spinal cord trauma in rats. J Neurosurg Spine 2004;1:311-21.
  • Genovese T, Mazzon E, Di Paola R, Crisafulli C, Muia C, Bramanti P, Cuzzocrea S. Increased oxidative-related mechanisms in the spinal cord injury in old rats. Neurosci Lett 2006; 393:141-46.
  • Fleming JC, Bailey CS, Hundt H, Gurr KR, Bailey SI, Cepinskas G, Lawendy AR, Badhwar A. Remote inflammatory response in liver is dependent on the segmental level of spinal cord injury. J Trauma Acute Care Surg 2012;72:1194-201;discussion 1202.
  • Liu J, Tang T, Yang H. Protective effect of deferoxamine on experimental spinal cord injury in rat. Injury 2011;42:742-5.
  • Kettle AJ, Winterbourn CC. Myeloperoxidase: a key regulator of neutrophil oxidant production. Redox Report 1997;3:3–15.
  • Cevik O, Erşahin M, Sener TE, Tinay I, Tarcan T, Cetinel S, Sener A, Toklu HZ, Sener G. Beneficial effects of quercetin on rat urinary bladder after spinal cord injury. J Surg Res 2013;183:695-703.
  • Tavukçu HH, Sener TE, Tinay I, Akbal C, Erşahin M, Cevik O, Cadırcı S, Reiter RJ, Sener G. Melatonin and tadalafil treatment improves erectile dysfunction after spinal cord injury in rats. Clin Exp Pharma col Physiol 2014;41:309-16.
  • Wang Y, Su R, Lv G, Cao Y, Fan Z, Wang Y, Zhang L, Yu D, Mei X. Supplement zinc as an effective treatment for spinal cord ischemia/ reperfusion injury in rats. Brain Res 2014;1545:45-53.
  • Küçük A, Yucel M, Erkasap N, Tosun M, Koken T, Ozkurt M, Erkasap S. The effects of PDE5 inhibitory drugs on renal ischemia/reperfusion injury in rats. Mol Biol Rep 2012;39:9775-82.
  • Kayiran O, Cuzdan SS, Uysal A, Kocer U. Tadalafil significantly reduces ischemia reperfusion injury in skin island flaps. Indian J Plast Surg 2013;46:75-81.
  • Circu ML, Aw TY. Glutathione and modulation of cell apoptosis. Biochim Biophys Acta 2012;1823:1767-77.
  • Ross D. Glutathione, free radicals and chemotherapeutic agents. Pharmacol Ther 1988;37:231–49.
  • Acuna-Castroviejo D, Martin M, Macias M, Escames G, Leon J, Khaldy A, Reiter RJ. Melatonin, mitochondria, and cellular bioenergetics. J Pineal Res 2001;30:65–74.
  • Kannan K, Jain SK. Oxidative stress and apoptosis. Pathophysiology 2000;7:153–63.
  • Grunenfelder J, Miniati DN , Murata S , Falk V , Hoyt EG , Kown M , Koransky ML, Robbins RC. Upregulation of Bcl-2 through caspase-3 inhibition ameliorates ischemia/reperfusion injury in rat cardiac allografts. Circulation 2001; 104: 1202– I206.
There are 32 citations in total.

Details

Primary Language English
Journal Section Articles
Authors

Tarık Şener

İlker Tınay This is me

Cem Akbal This is me

Mehmet Erşahin This is me

Özge Çevik This is me

Selin Çadırcı This is me

Özlem Çilingir This is me

Şule Çetinel This is me

Göksel Şener This is me

Publication Date May 16, 2014
Published in Issue Year 2014 Volume: 18 Issue: 2

Cite

APA Şener, T., Tınay, İ., Akbal, C., Erşahin, M., et al. (2014). Tadalafil attenuates spinal cord injury induced oxidative organ damage in rats. Marmara Pharmaceutical Journal, 18(2), 49-55. https://doi.org/10.12991/mpj.2014186119
AMA Şener T, Tınay İ, Akbal C, Erşahin M, Çevik Ö, Çadırcı S, Çilingir Ö, Çetinel Ş, Şener G. Tadalafil attenuates spinal cord injury induced oxidative organ damage in rats. Marmara Pharm J. May 2014;18(2):49-55. doi:10.12991/mpj.2014186119
Chicago Şener, Tarık, İlker Tınay, Cem Akbal, Mehmet Erşahin, Özge Çevik, Selin Çadırcı, Özlem Çilingir, Şule Çetinel, and Göksel Şener. “Tadalafil Attenuates Spinal Cord Injury Induced Oxidative Organ Damage in Rats”. Marmara Pharmaceutical Journal 18, no. 2 (May 2014): 49-55. https://doi.org/10.12991/mpj.2014186119.
EndNote Şener T, Tınay İ, Akbal C, Erşahin M, Çevik Ö, Çadırcı S, Çilingir Ö, Çetinel Ş, Şener G (May 1, 2014) Tadalafil attenuates spinal cord injury induced oxidative organ damage in rats. Marmara Pharmaceutical Journal 18 2 49–55.
IEEE T. Şener, “Tadalafil attenuates spinal cord injury induced oxidative organ damage in rats”, Marmara Pharm J, vol. 18, no. 2, pp. 49–55, 2014, doi: 10.12991/mpj.2014186119.
ISNAD Şener, Tarık et al. “Tadalafil Attenuates Spinal Cord Injury Induced Oxidative Organ Damage in Rats”. Marmara Pharmaceutical Journal 18/2 (May 2014), 49-55. https://doi.org/10.12991/mpj.2014186119.
JAMA Şener T, Tınay İ, Akbal C, Erşahin M, Çevik Ö, Çadırcı S, Çilingir Ö, Çetinel Ş, Şener G. Tadalafil attenuates spinal cord injury induced oxidative organ damage in rats. Marmara Pharm J. 2014;18:49–55.
MLA Şener, Tarık et al. “Tadalafil Attenuates Spinal Cord Injury Induced Oxidative Organ Damage in Rats”. Marmara Pharmaceutical Journal, vol. 18, no. 2, 2014, pp. 49-55, doi:10.12991/mpj.2014186119.
Vancouver Şener T, Tınay İ, Akbal C, Erşahin M, Çevik Ö, Çadırcı S, Çilingir Ö, Çetinel Ş, Şener G. Tadalafil attenuates spinal cord injury induced oxidative organ damage in rats. Marmara Pharm J. 2014;18(2):49-55.