1. bookVolume 28 (2015): Issue 3 (September 2015)
Journal Details
License
Format
Journal
eISSN
2300-6676
First Published
30 May 2014
Publication timeframe
4 times per year
Languages
English
access type Open Access

The influence of montelukast on the autonomic nervous system activity in rats with cyclophosphamide-induced hemorrhagic cystitis

Published Online: 26 Nov 2015
Volume & Issue: Volume 28 (2015) - Issue 3 (September 2015)
Page range: 170 - 175
Received: 06 Jul 2015
Accepted: 21 Aug 2015
Journal Details
License
Format
Journal
eISSN
2300-6676
First Published
30 May 2014
Publication timeframe
4 times per year
Languages
English
Abstract

The complex pathogenesis of cyclophosphamide-induced hemorrhagic cystitis involves arachidonic acid-derived inflammatory mediators, among them leukotrienes. Montelukast, a leukotriene receptor antagonist, is reported to exert an alleviatory effect in the course of cystitis associated with overactive bladder symptoms. The aim of this study was to verify whether the effect of montelukast is also associated with its influence on autonomic activity. The experiment included 20 rats with cyclophosphamide-induced hemorrhagic cystitis (75 mg/kg, four doses every second day), among them, 10 treated with oral montelukast (10 mg/kg for 8 days) and 10 controls. Time and frequency domain analyses of heart rate variability (HRV) were conducted in all the rats as an indirect measure of their autonomic activity. The montelukast-treated animals showed an increase in root mean square of successive differences (rMSSD), as well as an increase in HRV spectrum total power (TP) and power of very low (VLF) spectral component. This suggests that due to its anti-inflammatory and its anti-leukotriene effect, montelukast improves overall autonomic activity, with no preferential influence on either the sympathetic or parasympathetic part. Furthermore, the increase in VLF corresponds to attenuation of inflammatory response. In conclusion, this study showed that aside from its antagonistic effect on leukotriene receptors, montelukast can also modulate autonomic activity.

Keywords

1. Altayli E. et al.: Prevention and treatment of cyclophosphamide and ifosfamide-induced hemorrhagic cystitis. J. Mol. Pathophysiol., 1, 53, 2012.10.5455/jmp.20120321060902Search in Google Scholar

2. Benarroch E.E.: Autonomic-mediated immunomodulation and potential clinical relevance. Neurology, 73, 236, 2009.10.1212/WNL.0b013e3181aebd43Search in Google Scholar

3. Bouchelouche K. et al.: Increased urinary leukotriene E4 and eosinophil protein X excretion in patients with interstitial cystitis. J. Urol., 166, 2121, 2001.10.1016/S0022-5347(05)65518-8Search in Google Scholar

4. Bouchelouche K. et al.: The action of cysteinyl-leukotrienes on intracelluar calcium mobilization in human detrusor myocytes. BJU Int., 87, 690, 2001.10.1046/j.1464-410x.2001.02135.xSearch in Google Scholar

5. Bouchelouche K. et al.: The cysteinyl leukotriene D4 receptor antagonist montelukast fort the treatment of interstitial cystitis. J. Urol., 166, 1734, 2001.10.1016/S0022-5347(05)65663-7Search in Google Scholar

6. Chuang Y.C. et al.: Intravesical botulinum toxin A administration inhibits COX-2 and EP4 expression and supresses bladder hyperactivity in cyclophosphamide-induced cystitis in rats. Eur. Urol., 56, 159, 2009.10.1016/j.eururo.2008.05.00718514386Search in Google Scholar

7. Dobrek Ł., Baranowska A., Thor P.J.: The inf luence of oxazaphosphorines alkylating agents on autonomic nervous system activity in rat experimental cystitis model. Acta Pol. Pharm., 70, 1097, 2013.Search in Google Scholar

8. Dobrek Ł., Thor P.: Heart rate variability in overactive bladder experimental model. Arch. Med. Sci., 9, 930, 2013.Search in Google Scholar

9. Dobrek Ł., Thor P.J.: Bladder urotoxicity pathophysiology induced by the oxazaphosphorine alkylating agents and ist chemoprevention. Postepy Hig. Med. Dosw. (online), 66, 592, 2012.Search in Google Scholar

10. Girard B.M. et al.: Increased expression of interleukin-6 family members and receptors in urinary bladder with cyclophosphamideinduced bladder inflammation in female rats. Front. Neurosci., 5, article 20, 2011.10.3389/fnins.2011.00020304455921373362Search in Google Scholar

11. Goncalves H. et al.: Analysis of heart rate variability in a rat model of induced pulmonary hypertension. Med. Eng. Phys., 32, 746, 2010.10.1016/j.medengphy.2010.04.01820547091Search in Google Scholar

12. Grover S. et al.: Role of inflammation in bladder function and interstitial cystitis. Ther. Adv. Urol., 3, 19, 2011.10.1177/1756287211398255312608821789096Search in Google Scholar

13. Haeggstrom J.Z., Funk C.D.: Lipooxygenase and leukotriene pathways: biochemistry, biology and roles in disease. Chem. Rev., 111, 5866, 2011.Search in Google Scholar

14. Huston J.M., Tracey K.J.: The pulse of inflammation: heart rate variability, the cholinergic anti-inf lammatory pathway and implications for therapy. J. Intern. Med., 269, 45, 2011.Search in Google Scholar

15. Karim N, Hasan JA, Ali SS. Heart rate variability - a review. J. Basic Appl. Sci., 7, 71, 2011.Search in Google Scholar

16. Lampert R. et al. : Decreased heart rate variability is associated with higher levels of inflammation in middle-aged men. Am. Heart J., 156, 759e1, 2008.10.1016/j.ahj.2008.07.009258793218926158Search in Google Scholar

17. Lanza,G.A. et al.: Relation of heart rate variability to serum levels of C reactive protein in patients with unstable angina pectoris. Am. J. Cardiol., 97,1702, 2006.Search in Google Scholar

18. Lee G., Romih R., Zupancic D.: Cystitis: from urothelial cell biology to clinical application. Biomed. Res. Int., article ID 473536, 2014.10.1155/2014/473536402211324877098Search in Google Scholar

19. Mohamadin A.M. et al.: Montelukast, a leukotriene receptor antagonist abrogates lipopolysaccharide-induced toxicity and oxidative stress in rat liver. Pathophysiology, 18, 235, 2011.Search in Google Scholar

20. Mukherjee N. et al.: Pre-treatment with amifostine protects against cyclophosphamide-induced disruption of taste in mice. PLoS ONE, 8, e61607, 2013.10.1371/journal.pone.0061607363401923626702Search in Google Scholar

21. Nicolini A. et al.: Malnutrition, anorexia and cachexia in cancer patients: a mini review on pathogenesis and treatment. Biomed. Pharmacother., 67, 807, 2013.Search in Google Scholar

22. No Authors listed. Heart rate variability. Standards of measurement, physiological interpretation and clinical use. Task Force of The European Society of Cardiology and The North American Society of Pacing and Electrophysiology. Eur. Heart J., 17, 354, 1996.Search in Google Scholar

23. Papaioannou V., Pneumatikos I., Maglaveras N.: Association of heart rate variability and inflammatory response in patients with cardiovascular diseases: current strengths and limitations. Front. Physiol., 4, 174, 2013.Search in Google Scholar

24. Rahnama’i M.S., van Koevringe G.A., van Kerrebroeck P.E.: Overactive bladder symptom and the potential role of prostaglandins and phosphodiesterases: an introduction. Nephro. Urol. Mon., 5, 933, 2013.Search in Google Scholar

25. Sztajzel J.: Heart rate variability: a noninvasive electrocardiographic method to measure the autonomic nervous system. Swiss. Med. Wkly. 134, 514, 2004.Search in Google Scholar

26. Tintinger G.R. et al.: Montelukast: more than a cysteinyl leukotriene receptor antagonist? ScientificWorldJournal, 10, 2403, 2010.10.1100/tsw.2010.229576394121170491Search in Google Scholar

27. Traut J.L. et al.: Montelukast for symptom control of interstitial cystitis. Ann. Pharmacother., 45, e49, 2011.10.1345/aph.1Q13021862713Search in Google Scholar

28. Zeng J. et al.: Cause of residual urine in bladder outlet obstruction: an experimental study in the rat. J. Urol., 188, 1027, 2012. 10.1016/j.juro.2012.04.10122819110Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo