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Differential effects of coenzyme Q10 and α-lipoic acid on two models of in vitro oxidative damage to the rabbit urinary bladder

  • Urology – Original Paper
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Abstract

Purpose

Partial bladder outlet obstruction (PBOO) in rabbits causes free radical production through ischemia and reperfusion within the bladder smooth muscle and mucosa. We had previously shown that pretreatment of rabbits with a combination of α-lipoic acid (αLA) and coenzyme Q10 (CoQ) protected the bladder from contractile and metabolic dysfunctions mediated by PBOO. In this study, we examined the ability of pretreatment with αLA and CoQ combination in rabbits to protect the bladder from contractile damage mediated by either hydrogen peroxide (H2O2) or in vitro ischemia–reperfusion (I/R) which represents two in vitro models of oxidative damage.

Methods and materials

Eight adult male New Zealand white rabbits were pretreated with CoQ and αLA orally for four weeks. Eight adult male control rabbits were given vehicle. Eight full-thickness bladder strips were isolated from each of 4 treated and 4 control rabbit bladders, and a dose–response curve to H2O2 (0.1–0.8%) was generated. Similarly, isolated strips of bladder from the remaining 4 control and 4 treated rabbits were subjected to 1 h of ischemia (no oxygen without glucose) followed by 2 h of incubation in oxygenated buffer with glucose. The effects on the contractile responses to field stimulation (FS) at 2, 8, and 32 Hz, carbachol, and potassium chloride (KCl) were determined.

Results

H2O2 reduced the contractile responses to KCl and carbachol to a significantly greater degree than to FS, whereas I/R reduced the contractile responses to FS to a significantly greater degree than to KCl and carbachol. Pretreatment of the rabbits with the combination of CoQ and αLA significantly protected the bladder from the damaging effects of I/R, but had virtually no effect on the damaging effects of H2O2.

Conclusion

Although both H2O2 and I/R are in vitro models of oxidative free radical damage to bladder smooth muscle, they have significantly different methods of action and different sensitivities to antioxidants.

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References

  1. Gosling JA et al (2000) Correlation between the structure and function of the rabbit urinary bladder following partial outlet obstruction. J Urol 163(4):1349–1356

    Article  PubMed  CAS  Google Scholar 

  2. Azadzoi KM et al (2010) Oxidative modification of mitochondrial integrity and nerve fiber density in the ischemic overactive bladder. J Urol 183(1):362–369

    Article  PubMed  Google Scholar 

  3. Lin WY et al (2009) Correlation of in vivo bladder blood flow measurements with tissue hypoxia. World J Urol. doi:10.1007/s00345-008-0369-6

    Google Scholar 

  4. Zhao Y et al (1997) Correlation of ischemia/reperfusion or partial outlet obstruction-induced spectrin proteolysis by calpain with contractile dysfunction in rabbit bladder. Urology 49(2):293–300

    Article  PubMed  CAS  Google Scholar 

  5. Yildirim A et al (2008) The role of free radicals and nitric oxide in the ischemia-reperfusion injury mediated by acute bladder outlet obstruction. Int Urol Nephrol 40(1):71–77

    Article  PubMed  CAS  Google Scholar 

  6. Emberton M et al (2008) Benign prostatic hyperplasia as a progressive disease: a guide to the risk factors and options for medical management. Int J Clin Pract 62(7):1076–1086

    Article  PubMed  CAS  Google Scholar 

  7. Tang J, Yang J (2009) Etiopathogenesis of benign prostatic hypeprlasia. Indian J Urol 25(3):312–317

    Article  PubMed  Google Scholar 

  8. Greenland JE, Brading AF (2001) The effect of bladder outflow obstruction on detrusor blood flow changes during the voiding cycle in conscious pigs. J Urol 165(1):245–248

    Article  PubMed  CAS  Google Scholar 

  9. Greenland JE et al (2000) The effect of bladder outlet obstruction on tissue oxygen tension and blood flow in the pig bladder. BJU Int 85(9):1109–1114

    Article  PubMed  CAS  Google Scholar 

  10. Levin RM et al (1995) Genetic and cellular characteristics of bladder outlet obstruction. Urol Clin North Am 22(2):263–283

    PubMed  CAS  Google Scholar 

  11. Lieb J et al (2001) The effect of urine volume and nitric oxide on basal bladder blood flow: response to catheterization and drainage. Neurourol Urodyn 20(1):115–124

    Article  PubMed  CAS  Google Scholar 

  12. Okuda M et al (1992) Oxygen radical generation during ischemia-reperfusion in the isolated perfused rat liver monitored by enhanced chemiluminescence. Circ Shock 38(4):228–237

    PubMed  CAS  Google Scholar 

  13. Schroder A et al (2001) Increased blood flow after catheterization and drainage in the chronically obstructed rabbit urinary bladder. Urology 58(2):295–300

    Article  PubMed  CAS  Google Scholar 

  14. Schumer M et al (1992) Morphologic, biochemical, and molecular evidence of apoptosis during the reperfusion phase after brief periods of renal ischemia. Am J Pathol 140(4):831–838

    PubMed  CAS  Google Scholar 

  15. Bertelli A, Ronca G (1990) Carnitine and coenzyme Q10: biochemical properties and functions synergism and complementary action. Int J Tissue React 12(3):183–186

    PubMed  CAS  Google Scholar 

  16. Crane FL (2001) Biochemical functions of coenzyme Q10. J Am Coll Nutr 20(6):591–598

    PubMed  CAS  Google Scholar 

  17. Levin RM et al (2000) Obstructive response of human bladder to BPH vs. rabbit bladder response to partial outlet obstruction: a direct comparison. Neurourol Urodyn 19(5):609–629

    Article  PubMed  CAS  Google Scholar 

  18. Juan YS et al (2009) Coenzyme Q10 diminishes ischemia-reperfusion induced apoptosis and nerve injury in rabbit urinary bladder. Neurourol Urodyn 28(4):339–342

    Article  PubMed  CAS  Google Scholar 

  19. Juan YS et al (2008) Coenzyme Q10 protect against ischemia/reperfusion induced biochemical and functional changes in rabbit urinary bladder. Mol Cell Biochem 311(1–2):73–80

    Article  PubMed  CAS  Google Scholar 

  20. Juan YS et al (2008) The beneficial effect of coenzyme Q10 and lipoic acid on obstructive bladder dysfunction in the rabbit. J Urol 180(5):2234–2240

    Article  PubMed  CAS  Google Scholar 

  21. Dlugosz A et al (2004) Oxidative stress and coenzyme Q10 supplementation in renal transplant recipients. Int Urol Nephrol 36(2):253–258

    Article  PubMed  CAS  Google Scholar 

  22. Moini H, Packer L, Saris NE (2002) Antioxidant and prooxidant activities of alpha-lipoic acid and dihydrolipoic acid. Toxicol Appl Pharmacol 182(1):84–90

    Article  PubMed  CAS  Google Scholar 

  23. Shay KP et al (2009) Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta 1790(10):1149–1160

    PubMed  CAS  Google Scholar 

  24. Biewenga GP, Haenen GR, Bast A (1997) The pharmacology of the antioxidant lipoic acid. Gen Pharmacol 29(3):315–331

    PubMed  CAS  Google Scholar 

  25. Matsumoto S, Leggett RE, Levin RM (2003) The effect of vitamin E on the response of rabbit bladder smooth muscle to hydrogen peroxide. Mol Cell Biochem 254(1–2):347–351

    Article  PubMed  CAS  Google Scholar 

  26. Ohnishi N et al (1998) Effect of repetitive stimulation on the contractile response of rabbit urinary bladder subjected to in vitro hypoxia or in vitro ischemia followed by reoxygenation. Pharmacology 57(3):139–147

    Article  PubMed  CAS  Google Scholar 

  27. Whitbeck C et al (2006) Comparative effects of in vitro ischemia on contractile responses of mouse and rat bladders to various forms of stimulation. Urology 67(4):859–863

    Article  PubMed  Google Scholar 

  28. Mannikarottu A, Kogan B, Levin RM (2005) Ischemic etiology of obstructive bladder dysfunction: a review. Recent Res Devel Mol Cell Biochem 2:15–34

    CAS  Google Scholar 

  29. Levin RM et al (2005) Effect of ethanol on the response of the rat urinary bladder to in vitro ischemia: protective effect of alpha-lipoic acid. Mol Cell Biochem 271(1–2):133–138

    Article  PubMed  CAS  Google Scholar 

  30. Levin RM et al (2000) Normal detrusor is more sensitive than hypertrophied detrusor to in vitro ischemia followed by re-oxygenation. Neurourol Urodyn 19(6):701–712

    Article  PubMed  CAS  Google Scholar 

  31. Aikawa K, Leggett RE, Levin RM (2003) Effect of age on hydrogen peroxide mediated contraction damage in the male rat bladder. J Urol 170(5):2082–2085

    Article  PubMed  Google Scholar 

  32. Beck RP (1989) Neuropharmacology of the lower urinary tract in women. Obstet Gynecol Clin North Am 16(4):753–771

    PubMed  CAS  Google Scholar 

  33. Andersson KE, Sjogren C (1982) Aspects on the physiology and pharmacology of the bladder and urethra. Prog Neurobiol 19(1–2):71–89

    Article  PubMed  CAS  Google Scholar 

  34. Eglen RM (2006) Muscarinic receptor subtypes in neuronal and non-neuronal cholinergic function. Auton Autacoid Pharmacol 26(3):219–233

    Article  PubMed  CAS  Google Scholar 

  35. Juan YS et al (2007) The effect of partial bladder outlet obstruction on carbonyl and nitrotyrosine distribution in rabbit bladder. Urology 70(6):1249–1253

    Article  PubMed  Google Scholar 

  36. Juan YS et al (2009) Effect of ischemia/reperfusion on bladder nerve and detrusor cell damage. Int Urol Nephrol 41(3):513–521

    Article  PubMed  Google Scholar 

  37. Lin WY et al (2008) Effect of co-enzyme Q10 and alpha-lipoic acid on response of rabbit urinary bladder to repetitive stimulation and in vitro ischemia. Urology 72(1):214–219

    Article  PubMed  Google Scholar 

  38. Wang D et al (2009) Pygeum africanum: effect on oxidative stress in early diabetes-induced bladder. Int Urol Nephrol. doi:10.1007/s11255-009-9610-5

    Google Scholar 

  39. Oka M et al (2009) Suppression of bladder oxidative stress and inflammation by a phytotherapeutic agent in a rat model of partial bladder outlet obstruction. J Urol 182(1):382–390

    Article  PubMed  CAS  Google Scholar 

  40. Toklu H et al (2006) The beneficial effect of resveratrol on rat bladder contractility and oxidant damage following ischemia/reperfusion. Pharmacology 78(1):44–50

    Article  PubMed  CAS  Google Scholar 

  41. Sener G et al (2003) Melatonin treatment protects against ischemia/reperfusion-induced functional and biochemical changes in rat urinary bladder. J Pineal Res 34(3):226–230

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This material is based upon work supported in part by the Office of Research and Development Medical Research Service, Department of Veteran’s Affairs, and in part by the Capital Region Medical Research Foundation.

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Correspondence to Robert M. Levin.

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Li, H.T., Schuler, C., Leggett, R.E. et al. Differential effects of coenzyme Q10 and α-lipoic acid on two models of in vitro oxidative damage to the rabbit urinary bladder. Int Urol Nephrol 43, 91–97 (2011). https://doi.org/10.1007/s11255-010-9771-2

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  • DOI: https://doi.org/10.1007/s11255-010-9771-2

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