Comparison of the Effect of Morphine Alone and with Naloxone on Testicular Morphology in Rats

Document Type : Original Article (s)

Authors

1 Associate Professor, Department of Histology, School of Medicine AND Maternal and Childhood Obesity Research Center, Urmia University of Medical Sciences, Urmia, Iran

2 General Practitioner, Department of Histology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran

3 Assistant Professor, Department of Pharmaceutics, School of Pharmacy AND Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, Iran

4 MSc Student, Department of Histology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran

5 Professor, Department of Anatomy, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran

6 PhD Student, Department of Reproductive Health, School of Midwifery, Tehran University of Medical Science, Tehran AND Instructor, Department of Midwifery, School of Midwifery, Urmia University of Medical Sciences, Urmia, Iran

Abstract

Background: Morphine is an analgesic drug from the opium family that directly affects central nervous system (CNS) to reduce pain. Naloxone is a pure opioid antagonist that eliminates their respiratory suppressive effects in CNS. The aim of present study was to compare the effect of morphine on testes, and serum level of cholesterol and testosterone in male rats.Methods: In this experimental study, 18 mature male Wistar rats were selected, and randomly divided in 3 equal groups. The groups received normal saline, morphine alone (5 mg/kg), or combination of morphine (5 mg/kg) and naloxone (0.4 mg/kg) subcutaneously 4 days in week for 7 weeks. After one week, the histological structure of testes was studied microscopically, and serum levels of cholesterol and testosterone were determined and compared between the groups.Findings: In histology, degeneration of some seminipherous tubules and increase of distance between them was seen in morphine group; these changes were not seen in morphine-naloxone and control groups. There was not any significant difference between the groups in terms of serum level of cholesterol and testosterone.Conclusion: Our study suggests that morphine can result in changes in the structure of the testes but the effect of morphine-naloxone on rats was only changes in body weight.

Keywords


  1. Katzung B, Trevor A. Basic and clinical pharmacology. 13th ed. New York, NY: McGraw-Hill Education; 2014.
  2. Sweetman SC. Martindale: The complete drug reference. London, UK: Pharmaceutical Press; 2007.
  3. Peyrovi T, Solaeymanirad J. Effect of long term addiction with morphine on fetal rat development. Med J Tabriz Univ Med Sci 2002; 35(52): 21-5. [In Persian].
  4. Lacy C. Drug information handbook international: A comprehensive resource for all clinicians and healthcare professionals. Hudson, OH: Lexi-Comp; 2006.
  5. Sobhani A, Sepehri G. Pharmacology. Tehran, Iran: Andisheh Avar Publications; 1998. p. 239-46. [In Persian].
  6. Mkhitarov VA, Lun'kova LK. Morphological characteristics of the testicles of male Wistar rats intoxicated with morphine. Arkh Patol 2008; 70(6): 41-4. [In Russian].
  7. Abdellatief RB, Elgamal DA, Mohamed EE. Effects of chronic tramadol administration on testicular tissue in rats: an experimental study. Andrologia 2015; 47(6): 674-9.
  8. Azari O, Emadi L, Kheirandish R, Shafiei Bafti H, Esmaili Nejad MR, Faroghi F. The effects of long-term administration of tramadol on epididymal sperm quality and testicular tissue in mice. Iranian Journal of Veterinary Surgery 2014; 09(1): 23-30.
  9. Yilmaz B, Konar V, Kutlu S, Sandal S, Canpolat S, Gezen MR, et al. Influence of chronic morphine exposure on serum LH, FSH, testosterone levels, and body and testicular weights in the developing male rat. Arch Androl 1999; 43(3): 189-96.
  10. Lamfon HA. Effect of morphine on testicular activity in albino rats. Oxford Research Forum Journal 2007; 2(4): 27-31.
  11. Rose JE, Levin ED, Behm FM, Westman EC, Stein RM, Lane JD, et al. Combined agonist-antagonist treatment for nicotine and other drug dependencies. Neuropsychopharmacology 1994; 11(4): 281
  12. Lee J, Choi J. Effects of epidural co-administration of morphine and naloxone on intestinal motility after total hysterectomy. Korean J Anesthesiol 2000; 38(2): 283.
  13. Koch J, Manworren R, Clark L, Quinn CT, Buchanan GR, Rogers ZR. Pilot study of continuous co-infusion of morphine and naloxone in children with sickle cell pain crisis. Am J Hematol 2008; 83(9): 728-31.
  14. Rozen D, Ling C, Schade C. Coadministration of an opioid agonist and antagonist for pain control. Pain Pract 2005; 5(1): 11-7.
  15. Payabvash S, Beheshtian A, Salmasi AH, Kiumehr S, Ghahremani MH, Tavangar SM, et al. Chronic morphine treatment induces oxidant and apoptotic damage in the mice liver. Life Sci 2006; 79(10): 972-80.
  16. Khadivi B, Peirouvi T, JavanmardI MZ, Rasmi Y. Short-term buserelin administration induces apoptosis and morphological changes in adult rat testes. Acta Cir Bras 2017; 32(2): 140-7.
  17. Cicero TJ, Davis LA, LaRegina MC, Meyer ER, Schlegel MS. Chronic opiate exposure in the male rat adversely affects fertility. Pharmacol Biochem Behav 2002; 72(1-2): 157-63.
  18. Cicero TJ, Meyer ER, Wiest WG, Olney JW, Bell RD. Effects of chronic morphine administration on the reproductive system of the male rat. J Pharmacol Exp Ther 1975; 192(3): 542-8.
  19. Hatami H, Mohseni S, Shaikhzadeh F, Nejati F. Comparative study of intraperitoneal injection. J Ilam Univ Med Sci 2013; 21(2): 60-7. [In Persian].
  20. Redmond DE, Krystal JH. Multiple mechanisms of withdrawal from opioid drugs. Annu Rev Neurosci 1984; 7: 443-78.
  21. Bablok L, Fracki S, Wielgos M, Czaplicki M, Marianowski L. The naloxone test in the degenerative changes of seminiferous tubules. Ginekol Pol 1998; 69(6): 374-9. [In Polish].
  22. Bhanot R, Wilkinson M. Opiatergic control of LH secretion is eliminated by gonadectomy. Endocrinology 1983; 112(1): 399-401.
  23. Fazelipour S, Kiaei SB, Tootian Z. Adverse effect of heroin hydrochloride on selected male reproductive parameters in mice. Comp Clin Path 2009; 19(6): 565-9.
  24. Budziszewska B, Leskiewicz M, Jaworska-Feil L, Lason W. The effect of N-nitro-L-arginine methyl ester on morphine-induced changes in the plasma corticosterone and testosterone levels in mice. Exp Clin Endocrinol Diabetes 1999; 107(1): 75-9.
  25. Asgary S, Naderi G, Shahrezaei J, Ahmad P. Comparison of plasma level of lipid peroxidation, lipids and blood sugar in opium addicted and control groups. J Qazvin Univ Med Sci 2003; 7(2): 115-9. [In Persian].
  26. Amini H, Ahmadiani A. Increase in testosterone metabolism in the rat central nervous system by formalin-induced tonic pain. Pharmacol Biochem Behav 2002; 74(1): 199-204.