The Histomorphometric Alterations in Male Sprague-Dawley Rats Following Exposure to Dextromethorphan and Antioxidants Administration

Adebajo, Oluwaseye Adesina; Gbotolorun, Chinwe Stella; Oremosu, Ayodele; Adebajo, Perpetual Kuburat; Ojo, Joshua Honor; Udom Akpan, Utom-Obong; Sogbesan, Zainab Adebusola; Akpan, Bassey Helen; Okegbemi, Gloria Inioluwa; Oladipo, Jesulayomi Oluwayemisi; Akinwola, Oyindamola Dorcas

doi:10.61882/rabms.11.3.271

Volume 11, Issue 3 (8-2025) Journal of Research in Applied and Basic Medical Sciences 2025, 11(3): 271-279 | Back to browse issues page

‎ 10.61882/rabms.11.3.271

Mendeley

Zotero

RefWorks

Adebajo O A, Gbotolorun C S, Oremosu A, Adebajo P K, Ojo J H, Udom Akpan U, et al . The Histomorphometric Alterations in Male Sprague-Dawley Rats Following Exposure to Dextromethorphan and Antioxidants Administration. Journal of Research in Applied and Basic Medical Sciences 2025; 11 (3) :271-279
URL: http://ijrabms.umsu.ac.ir/article-1-429-en.html

The Histomorphometric Alterations in Male Sprague-Dawley Rats Following Exposure to Dextromethorphan and Antioxidants Administration

Oluwaseye Adesina Adebajo ^*

, Chinwe Stella Gbotolorun

, Ayodele Oremosu

, Perpetual Kuburat Adebajo

, Joshua Honor Ojo

, Utom-Obong Udom Akpan

, Zainab Adebusola Sogbesan

, Bassey Helen Akpan

, Gloria Inioluwa Okegbemi

, Jesulayomi Oluwayemisi Oladipo

, Oyindamola Dorcas Akinwola

Anatomy Department, Faculty of Basic Medical Sciences, College of Medicine of the University of Lagos, Lagos, Nigeria & Anatomy Programme, College of Health Sciences, Bowen University, Iwo campus, Osun State, Nigeria , oluwaseye.adebajo@bowen.edu.ng

Abstract: (124 Views)

Background Morphometric evaluation of seminiferous tubules and epididymis is a common parameter used to assess male fertility. This study aimed to evaluate the morphological changes in male rats following exposure to dextromethorphan.
Methods A total of 80 male rats (150 ± 30 g) were divided into four groups (N = 20; A-D) for the study. Group A received distilled water; group B received 20 mg/kg, group C received 40 mg/kg, and group D received 80 mg/kg of DM for a duration of four weeks. At the end of the treatment period, five rats were selected from each group and the following histomorphometric parameters were analyzed: diameter and height of the seminiferous tubule and epididymes, volume of testes, and the number of spermatogonia, spermatocytes, and spermatids within the seminiferous tubules. The remaining 15 rats were divided into three groups (N = 5; E-G). They received Rutin (25 mg/kg), Quercetin (50 mg/kg), and DW, respectively, for four weeks to ascertain the recovery rate.
Results All histomorphometric parameters decreased compared to the control group; however, when comparing the recovery-alone group to the treatment groups, a slight increase was observed. The morphometric measurements showed an increase when Rutin and Quercetin were compared to both the treatment and recovery-alone groups. The comparison between Rutin and Quercetin showed no substantial difference in their effects.
Conclusion Dextromethorphan has showed to have deleterious effect on the epididymal and testicular morphometry and this could culminate into infertility in males, however, these damages were significantly improved upon the administration of Rutin and Quercetin as antioxidants.

Keywords: Dextromethorphan, Histomorphometry, Rutin, Quercetin

Full-Text [PDF 379 kb] (75 Downloads)

Type of Study: orginal article | Subject: Other

References

1. Colborn T, vom Saal FS, Soto AM. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect. 1993;101(5):378-84. [DOI:10.1289/ehp.93101378] [PMID]

2. Guillette LJ, Jr., Gross TS, Masson GR, Matter JM, Percival HF, Woodward AR. Developmental abnormalities of the gonad and abnormal sex hormone concentrations in juvenile alligators from contaminated and control lakes in Florida. Environ Health Perspect. 1994;102(8):680-8. [DOI:10.1289/ehp.94102680] [PMID]

3. Takeuchi S, Nakashima S, Tomiya A, Shinohara H. Experimental constraints on the low gas permeability of vesicular magma during decompression. Geophysical Research Letters. 2005;32(10). [DOI:10.1029/2005GL022491]

4. Moustafa MN SR, Zayed AE, El-Hafeez AH. Morphological and morphometric study of the development of seminiferous epithelium of donkey (Equus asinus) from birth to maturity. Journal of Cytology & Histology. 2015 [Google Scholar]

5. Zhou W, De Iuliis GN, Dun MD, Nixon B. Characteristics of the Epididymal Luminal Environment Responsible for Sperm Maturation and Storage. Front Endocrinol (Lausanne). 2018;9:59. [DOI:10.3389/fendo.2018.00059]

6. Aleksandrovych V, Walocha JA, Gil K. Telocytes in female reproductive system (human and animal). J Cell Mol Med. 2016;20(6):994-1000. [DOI:10.1111/jcmm.12843]

7. McDonough CE, Whittington E, Pitnick S, Dorus S. Proteomics of reproductive systems: Towards a molecular understanding of postmating, prezygotic reproductive barriers. J Proteomics. 2016;135:26-37. [DOI:10.1016/j.jprot.2015.10.015]

8. Brohi RD, Wang L, Talpur HS, Wu D, Khan FA, Bhattarai D, et al. Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review. Front Pharmacol. 2017;8:606. [DOI:10.3389/fphar.2017.00606] [PMID]

9. Brazel AJ, Ó'Maoiléidigh DS. Photosynthetic activity of reproductive organs. J Exp Bot. 2019;70(6):1737-54. [DOI:10.1093/jxb/erz033] [PMID]

10. WHO expert committee on drug dependence. World Health Organ Tech Rep Ser. 2012(973):1-26. [PMID]

11. Weinbroum AA. Dextromethorphan reduces immediate and late postoperative analgesic requirements and improves patients' subjective scorings after epidural lidocaine and general anesthesia. Anesth Analg. 2002;94(6):1547-52. https://doi.org/10.1213/00000539-200206000-00032 [DOI:10.1097/00000539-200206000-00032]

12. Weinbroum AA. A single small dose of postoperative ketamine provides rapid and sustained improvement in morphine analgesia in the presence of morphine-resistant pain. Anesth Analg. 2003;96(3):789-95. [DOI:10.1213/01.ANE.0000048088.17761.B4] [PMID]

13. Weinbroum AA. Pathophysiological and clinical aspects of combat anticholinesterase poisoning. Br Med Bull. 2004;72:119-33. [DOI:10.1093/bmb/ldh038] [PMID]

14. Gao HM, Liu B, Hong JS. Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. J Neurosci. 2003;23(15):6181-7. [DOI:10.1523/JNEUROSCI.23-15-06181.2003] [PMID]

15. Pioro EP, Brooks BR, Cummings J, Schiffer R, Thisted RA, Wynn D, et al. Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect. Ann Neurol. 2010;68(5):693-702. [DOI:10.1002/ana.22093]

16. Choi DK, Koppula S, Choi M, Suk K. Recent developments in the inhibitors of neuroinflammation and neurodegeneration: inflammatory oxidative enzymes as a drug target. Expert Opin Ther Pat. 2010;20(11):1531-46. [DOI:10.1517/13543776.2010.525220]

17. Kaur M, Sanches M. Experimental Therapeutics in Treatment-Resistant Major Depressive Disorder. J Exp Pharmacol. 2021;13:181-96. [DOI:10.2147/JEP.S259302] [PMCID]

18. Organisation WH. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. Cambridge university press. 1999. [Google Scholar]

19. Adebajo OA, Gbotolorun CS, Oremosu AA, Adebajo PK, Ojo JH. Ameliorative potential of quercetin and rutin on dextromethorphan-induced toxicity in Sprague-Dawley rats. Anatomy Journal of Africa. 2022;11(2):2218-23. [DOI:10.4314/aja.v11i2.10]

20. Hamzeh M, Robaire B. Effect of testosterone on epithelial cell proliferation in the regressed rat epididymis. Journal of andrology. 2009;30(2):200-12. [DOI:10.2164/jandrol.108.006171]

21. Vidal JD, Whitney KM. Morphologic manifestations of testicular and epididymal toxicity. Spermatogenesis. 2014;4(2):e979099. [DOI:10.4161/21565562.2014.979099] [PMCID]

22. Tvrdá E, Kňažická Z, Lukáčová J, Schneidgenová M, Goc Z, Greń A, et al. The impact of lead and cadmium on selected motility, prooxidant and antioxidant parameters of bovine seminal plasma and spermatozoa. Journal of environmental science and health Part A, Toxic/hazardous substances & environmental engineering. 2013;48(10):1292-300. [DOI:10.1080/10934529.2013.777243]

23. Afolabi OA, Anyogu DC, Hamed MA, Odetayo AF, Adeyemi DH, Akhigbe RE. Glutamine prevents upregulation of NF-kB signaling and caspase 3 activation in ischaemia/reperfusion-induced testicular damage: An animal model. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;150:113056. [DOI:10.1016/j.biopha.2022.113056]

24. Almeida FF, Leal MC, França LR. Testis morphometry, duration of spermatogenesis, and spermatogenic efficiency in the wild boar (Sus scrofa scrofa). Biology of reproduction. 2006;75(5):792-9. [DOI:10.1095/biolreprod.106.053835] [PMID]

25. Resende FC, Avelar GF. The sexual segment of the kidney of a tropical rattlesnake, Crotalus durissus (Reptilia, Squamata, Viperidae), and its relationship to seasonal testicular and androgen cycles. Journal of morphology. 2021;282(9):1402-14. [DOI:10.1002/jmor.21394]

26. 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. [DOI:10.1111/and.12316] [PMID]

27. Meydanli EG, Gumusel A, Ozkan S, Tanriverdi G, Balci MBC, Develi Is S, et al. Effects of resveratrol on high-fructose-induced testis injury in rats. Ultrastructural pathology. 2018;42(1):65-73. [DOI:10.1080/01913123.2017.1397075]

28. Shukla KK, Mahdi AA, Rajender S. Apoptosis, spermatogenesis and male infertility. Frontiers in bioscience (Elite edition). 2012;4(2):746-54. [DOI:10.2741/e415] [PMID]

29. Adetunji AO. Histopathological Degeneration of Spermatogenesis and Histomorphometric Alterations of the Testicular Microanatomy of Male Wistar Rats after Oral Lead Intoxication. Journal of Krishna Institute of Medical Sciences (JKIMSU). 2019;8(2). [Google Scholar]

30. Mruk DD, Cheng CY. Sertoli-Sertoli and Sertoli-germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis. Endocrine reviews. 2004;25(5):747-806. [DOI:10.1210/er.2003-0022] [PMID]

31. Wang X, Yin L, Wen Y, Yuan S. Mitochondrial regulation during male germ cell development. Cellular and molecular life sciences : CMLS. 2022;79(2):91. [DOI:10.1007/s00018-022-04134-3]

32. Boekelheide K, Kleymenova E, Liu K, Swanson C, Gaido KW. Dose-dependent effects on cell proliferation, seminiferous tubules, and male germ cells in the fetal rat testis following exposure to di(n-butyl) phthalate. Microscopy research and technique. 2009;72(8):629-38. [DOI:10.1002/jemt.20684] [PMCID]

33. Walczak-Jędrzejowska R, Marchlewska K, Oszukowska E, Filipiak E, Słowikowska-Hilczer J, Kula K. Estradiol and testosterone inhibit rat seminiferous tubule development in a hormone-specific way. Reproductive biology. 2013;13(3):243-50. [DOI:10.1016/j.repbio.2013.07.005] [PMID]

34. Orman D, Vardi N, Ates B, Taslidere E, Elbe H. Aminoguanidine mitigates apoptosis, testicular seminiferous tubules damage, and oxidative stress in streptozotocin-induced diabetic rats. Tissue & cell. 2015;47(3):284-90. [DOI:10.1016/j.tice.2015.03.006]

35. Takahashi M, Matsui H. Mechanisms of testicular toxicity. Journal of Toxicologic Pathology. 1993;6(2):161-74. [DOI:10.1293/tox.6.161]

36. Hussein YM, Mohamed RH, Shalaby SM, Abd El-Haleem MR, Abd El Motteleb DM. Anti-oxidative and anti-apoptotic roles of spermatogonial stem cells in reversing cisplatin-induced testicular toxicity. Cytotherapy. 2015;17(11):1646-54. [DOI:10.1016/j.jcyt.2015.07.001]

37. Monsefi M, Fereydouni B, Rohani L, Talaei T. Mesenchymal stem cells repair germinal cells of seminiferous tubules of sterile rats. Iranian journal of reproductive medicine. 2013;11(7):537-44. [Google Scholar]

38. Tripathi UK, Chhillar S, Kumaresan A, Aslam MK, Rajak SK, Nayak S, et al. Morphometric evaluation of seminiferous tubule and proportionate numerical analysis of Sertoli and spermatogenic cells indicate differences between crossbred and purebred bulls. Veterinary world. 2015;8(5):645-50. [DOI:10.14202/vetworld.2015.645-650] [PMCID]

39. Roshankhah S, Jalili C, Salahshoor MR. Effects of Crocin on Sperm Parameters and Seminiferous Tubules in Diabetic Rats. Advanced biomedical research. 2019;8:4. [DOI:10.4103/abr.abr_124_18]

40. Kaukab N, Saeed M. Effects of caffeine on rat testes. Prof Med J. 1999;6:1-5. [Google Scholar]

41. Luca VS, Miron A, Aprotosoaie AC. The antigenotoxic potential of dietary flavonoids. Phytochemistry Reviews. 2016;15(4):591-625. [DOI:10.1007/s11101-016-9457-1]

42. Shi GJ, Li Y, Cao QH, Wu HX, Tang XY, Gao XH, et al. In vitro and in vivo evidence that quercetin protects against diabetes and its complications: A systematic review of the literature. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2019;109:1085-99. [DOI:10.1016/j.biopha.2018.10.130] [PMID]

43. Azeem M, Hanif M, Mahmood K, Ameer N, Chughtai FRS, Abid U. An insight into anticancer, antioxidant, antimicrobial, antidiabetic and anti-inflammatory effects of quercetin: a review. Polymer bulletin (Berlin, Germany). 2023;80(1):241-62. [DOI:10.1007/s00289-022-04091-8] [PMID] [PMCID]

44. Chandra AK, Sengupta P, Goswami H, Sarkar M. Effects of dietary magnesium on testicular histology, steroidogenesis, spermatogenesis and oxidative stress markers in adult rats. Indian journal of experimental biology. 2013;51(1):37-47. [Google Scholar]

45. Wagner IV, Klöting N, Atanassova N, Savchuk I, Spröte C, Kiess W, et al. Prepubertal onset of obesity negatively impacts on testicular steroidogenesis in rats. Molecular and cellular endocrinology. 2016;437:154-62. [DOI:10.1016/j.mce.2016.08.027]

46. Lim TK. Edible medicinal and non-medicinal plants: Springer; 2012. [DOI:10.1007/978-94-007-4053-2]

47. Anchelin Flageul M. The zebrafish (Danio rerio): new model to study the role of telomerase in aging and regeneration= El pez cebra (Danio rerio): nuevo modelo para el estudio de la función de la telomersa en envejecimiento y regeneración. Proyecto de investigación:. 2016. [Google Scholar]

48. Wang L, Wei C, Jing J, Shao M, Wang Z, Wen B, et al. The Effects of Polyphenols on Doxorubicin-Induced Nephrotoxicity by Modulating Inflammatory Cytokines, Apoptosis, Oxidative Stress, and Oxidative DNA Damage. Phytotherapy research : PTR. 2025;39(5):2147-64. [DOI:10.1002/ptr.8470]