Advertisement

Comparative Clinical Pathology

, Volume 28, Issue 4, pp 1055–1060 | Cite as

The effect of tramadol and meloxicam, alone and in combination on oxidative stress status in dogs

  • Saeed NazifiEmail author
  • Aidin Shojaee Tabrizi
  • Saeedeh Mohammadi
  • Hoda Erjaee
  • Abdollah Mirzaie
Original Article
  • 53 Downloads

Abstract

Management of pain by different therapeutic agents has always been one of the most important components in clinical veterinary care. Concerns about various side effects of analgesics drugs have lead the pain relief to combination drug therapy. The present study was performed to evaluate the effect of combined tramadol and meloxicam on oxidative stress status in dogs. Twenty clinically healthy dogs were randomly divided into four groups and administered with placebo, tramadol, meloxicam, and combined meloxicam with tramadol for 10 days. The antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), total antioxidant capacity (TAC), and malondialdehyde (MDA) were assayed in blood samples which were collected in days 0, 5, 10, 15, and 20. In dogs administrated with tramadol, the antioxidant enzymes and TAC were significantly decreased and MDA level was significantly increased. However, meloxicam group showed no alteration in the levels of GPx, CAT, TAC, and MDA. Moreover, administration of meloxicam with tramadol improved oxidative stress status through inhibiting lipid peroxidation, increasing antioxidant enzymes, and TAC. These results indicate that meloxicam is effective in reducing oxidative stress induced by tramadol. Therefore, combination of tramadol and meloxicam is desired due to their potential analgesic result and ameliorating effect on oxidative stress status.

Keywords

Tramadol Meloxicam Oxidative stress Dog 

Notes

Funding information

This study is financially and technically supported by the Research Council of Shiraz University and School of Veterinary Medicine, Shiraz University (Grant No. 71-GR-VT-5).

Compliance with ethical standards

The experiment was performed under the approval of the state committee on animal ethics, Shiraz University, Shiraz, Iran (IACUC no: 4687/63). Also, the recommendations of European Council Directive (86/609/EC) of November 24, 1986, regarding the protection of animals used for experimental purposes were considered.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Ahmed MA, Kurkar A (2014) Effects of opioid (tramadol) treatment on testicular functions in adult male rats: the role of nitric oxide and oxidative stress. Clin Exp Pharmacol Physiol 41:317–323CrossRefGoogle Scholar
  2. Bannwarth B (1999) Risk-benefit assessment of opioids in chronic noncancer pain. Drug Saf 21:283–296CrossRefGoogle Scholar
  3. Bilir A, Erkasap N, Koken T, Gulec S, Kaygisiz Z, Tanriverdi B, Kurt I (2007) Effects of tramadol on myocardial ischemia-reperfusion injury. Scand Cardiovasc J 41:242–247CrossRefGoogle Scholar
  4. Burak Cimen M, Bolgen Cimen Ö, Eskandari G, Sahin G, Erdogan C, Atik U (2003) In vivo effects of meloxicam, celecoxib, and ibuprofen on free radical metabolism in human erythrocytes. Drug Chem Toxicol 26:169–176CrossRefGoogle Scholar
  5. Collett BJ (2001) Chronic opioid therapy for non-cancer pain. Br J Anaesth 87:133–143CrossRefGoogle Scholar
  6. Craven M, Chandler ML, Steiner JM, Farhadi A, Welsh E, Pratschke K, Shaw DJ, Williams DA (2007) Acute effects of carprofen and meloxicam on canine gastrointestinal permeability and mucosal absorptive capacity. J Vet Intern Med 21:917–923CrossRefGoogle Scholar
  7. Engelhardt G (1996) Pharmacology of meloxicam, a new non-steroidal anti-inflammatory drug with an improved safety profile through preferential inhibition of COX-2. Br J Rheumatol 35:4–12CrossRefGoogle Scholar
  8. Erjaee H, Rajaian H, Nazifi S, Chahardahcherik M (2015) The effect of caraway (Carum carvi L.) on the blood antioxidant enzymes and lipid peroxidation in streptozotocin-induced diabetic rats. Comp Clin Pathol 24:1197–1203CrossRefGoogle Scholar
  9. Fang YZ, Yang S, Wu G (2002) Free radicals, antioxidants, and nutrition. Nutrition 18:872–879CrossRefGoogle Scholar
  10. Flecknell PA, Waterman-Pearson A (2000) Pain management in animals. WB SaundersGoogle Scholar
  11. Goverdhan P, Sravanthi A, Mamatha T (2012) Neuroprotective effects of meloxicam and selegiline in scopolamine-induced cognitive impairment and oxidative stress. Int J Alzheimers Dis 2012:1–8CrossRefGoogle Scholar
  12. Han HK, Choi HK (2007) Improved absorption of meloxicam via salt formation with ethanolamines. Eur J Pharm Biopharm 65:99–103CrossRefGoogle Scholar
  13. Hassan MH, El-Beshbishy HA, Aly H, Attia SM, Bahashwan SA, Ghobara MM (2014) Modulatory effects of meloxicam on cardiotoxicity and antitumor activity of doxorubicin in mice. Cancer Chemother Pharmacol 74:559–569CrossRefGoogle Scholar
  14. Ivanov I (1999) Low pH-induced hemolysis of erythrocytes is related to the entry of the acid into cytosole and oxidative stress on cellular membranes. Biochim Biophys Acta Biomembr 1415:349–360CrossRefGoogle Scholar
  15. Khan AM, Rampal S (2014) Effects of repeated oral administration of pazufloxacin mesylate and meloxicam on the antioxidant status in rabbits. J Am Assoc Lab Anim Sci 53:399–403Google Scholar
  16. Lin CS, Liu CY, Sun YL, Chang LC, Chiu YT, Huang SY, Lin JH, Yang PC, Chu R, Huang M (1997) Alteration of endogenous antioxidant enzymes in naturally occurring hypertrophic cardiomyopathy. Biochem Mol Biol Int 43:1253–1263Google Scholar
  17. Mathews KA (1996) Nonsteroidal anti-inflammatory analgesics in pain management in dogs and cats. Can Vet J 37:539–545Google Scholar
  18. McCord JM (2000) The evolution of free radicals and oxidative stress. Am J Med 108:652–659CrossRefGoogle Scholar
  19. McMichael MA (2007) Oxidative stress, antioxidants, and assessment of oxidative stress in dogs and cats. J Am Vet Med Assoc 231:714–720CrossRefGoogle Scholar
  20. Nikvsarkar M, Banerjee A, Shah D, Trivedi J, Patel M, Cherian B, Padh H (2006) Reduction in aluminum induced oxidative stress by meloxicam in rat brain. Iran Biomed J 10:151–155Google Scholar
  21. Ortiz MI, MolIna MAR, Arai Y, Romano CL (2012) Analgesic drugs combinations in the treatment of different types of pain. Pain Res Treat 2012:612519Google Scholar
  22. Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL (1992) Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an ‘atypical’ opioid analgesic. J Pharmacol Exp Ther 260:275–285Google Scholar
  23. Ramsey I (2008) BSAVA Small Animal Formulary, 7th Revised edn. British Small Animal Veterinary Association Publication, GloucesterGoogle Scholar
  24. Tallarida RJ (2001) Drug synergism: its detection and applications. J Pharmacol Exp Ther 298:865–872Google Scholar
  25. Taylor P (2003) Pain management in dogs and cats–more causes and locations to contemplate. WB SaundersGoogle Scholar
  26. Teixeira RC, Monteiro ER, Campagnol D, Coelho K, Bressan TF, Monteiro BS (2013) Effects of tramadol alone, in combination with meloxicam or dipyrone, on postoperative pain and the analgesic requirement in dogs undergoing unilateral mastectomy with or without ovariohysterectomy. Vet Anaesth Analg 40:641–649CrossRefGoogle Scholar
  27. Villegas I, Martin M, La Casa C, Motilva V, Alarcon de La Lastra C (2000) Effects of meloxicam on oxygen radical generation in rat gastric mucosa. Inflamm Res 49:361–366CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Clinical Studies, School of Veterinary MedicineShiraz UniversityShirazIran
  2. 2.Department of Basic Sciences, School of Veterinary MedicineShiraz UniversityShirazIran

Personalised recommendations