Histomorphological Effects of Oral Nicotine Administration on the Testes of Adult Wistar Rats

Subject Areas : Journal of Chemical Health Risks

Efe Ahama ¹ , Igho Odokuma ²

1 - Delta State University, Abraka, Nigeria
2 - Delta State University, Abraka, Nigeria

Received: 2022-01-05 Accepted : 2022-06-14 Published : 2023-06-01

Keywords: histomorphology, alkaloid, nicotine, Testes,

Abstract :

Nicotine is a potent para-sympathomimetic alkaloid, which belongs to the Nightshade family of plants and is abundant in the roots and leaves of these plants. Here, we investigated the histomorphological effects of oral nicotine exposure on the testes of adult Wistar rats. Sixteen adult male Wistar rats were divided into 4 groups (I, II, III, and IV), with each group containing 4 rats per group. Control group (I) received growers mash with water, group II received 2mg kg-1 day-1 of nicotine, group III received 4 mg kg-1 day-1 of nicotine and group IV received 6 mg kg-1 day-1 of nicotine via the oral route of administration, in addition to food and water for six weeks. At the end of the 7th, 21st, and 42nd days of the administration, animals were euthanized by cervical dislocation, and testes were harvested and processed with standard histological techniques. Euthanizing on these various days was done to assess the time and dose-dependent effect of nicotine on the testes. Findings from histological observation of the testes showed similar histoarchitectural changes on different days between the treated groups and the control group. These changes may be attributed to the drug metabolism of nicotine, administration route of nicotine, and drug dosage adopted in the current study. However experimental animals administered with nicotine for 42 days, showed normal histology of the testes with the presence of vascular congestion in the lumen of the seminiferous tubules. Within the limitation and design of this study, oral nicotine exposure at a low dose showed no features of testicular toxicity as there were no histoarchitectural distortions in the treated animals. However, our findings suggest that nicotine exposure at a low dose may possess a therapeutic effect in the management of testicular pathologies.

References:

1. Rodgman A.P., Thomas A., 2009. The chemical components of tobacco and tobacco smoke. Boca Raton; FL: CRC Presshttp://lccn.loc.gov/2008018913. Retrieved 2013-02-02.


2. Metcalf R.L., 2007. Insect Control Ullmann's Encyclopedia of Industrial Chemistry(7th ed.), Wiley. pp. 9


3. Beckman J., Lips K.S., 2013. The Non-Neuronal Cholinergic System in Health and Disease. Pharmacology. 92, 286 - 302


4. Kishioka S., Kiguchi N., Kobayashi Y., Saika F., 2014. Nicotine effects and the endogenous opioid system". Journal of Pharmacological Sciences. 125(2), 117 - 24.


5. Connolly G.N., Alpert H.R., Wayne G.F., Koh H., 2007. Trends in nicotine yield in smoke and its relationship with design characteristics among popular US cigarette brands; 1997-2005". Tobacco Control 16:e5.


6. Hollway A.C., 2014. Encyclopedia of Toxicology, Nicotine, 3^rd edition, Elsevier Inc. pp, 514-516.


7. Bonde J.P., Giwercman A., Ernest E., 1996. Identifying environmental risk to male reproductive function by occupational sperm studies: logistics and design problems. Occup Environ Med. 53, 511-9


8. Kunzle R., Muller M.D., Hanggi W., Birkhauser M.H., Drescher H., Bersinge N.A., 2003. Semen quality of male smokers and nonsmokers in fertile couples. Ferile. Steril. 79, 287-91


9. Bray C., Son J.H., Meizel S., 2005. Mice deficient in the α7 subunit of the nicotinic acetylcholine receptor produce sperm with impaired motility. Biol Reprod. 73, 807 - 814.


10. Haberberger R.V., 2002.Expression of the high-affinity choline transporter, CHT1, in the neuronal and non-neuronal cholinergic system of human neuronal cholinergic system in the endothelium: evidence and possiblepatho-biological significance. 119, 943-948.


11. McGehee D.S., Role L.W., 1995.Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons. Annu Rev Physiol. 57, 521-46.


12. Animal research ethics, 2005. A handbook of USP researchers. 1st ed. Research office publisher, South Pacific. 2, 3-4.


13. Oyem J.C., Odokuma E.I., 2018. Histomorphological Effects of Nicotine on Selected Parts of the Brain of Adult Wistar Rats. Galician Medical Journal. 25(2), 4


14. Festing M.F.W., 2020. How to Reduce the Number of Animals Used in Research by Improving Experimental Design and Statistics, ANZCCART Human Science Fact Sheet T10.


15. Jatinder S., 2012 National centre for replacement, refinement, and reduction animals in research. Experimental design/statistics. J Pharmacol Pharmacother. 3(1), 8789.


16. Obernier J.A., Baldwin R.L., 2008. Establishing an appropriate period of acclimatization following transportation of laboratory animals. ILAR J. 47(4), 364-369


17. Reilley J.S., 2000. Euthanasia of animals used for scientific purposes. 1^st ed. ANZCCART, Australia. 1, 11


18. Burnett D., Crocker J., 2005. Specimen handling and preparation for routine diagnostic histopathology. In: The science of laboratory diagnosis. 2nd ed. John Wiley and sons, England. 1, 5-7.


19. Ross M.H., Pawlina W., 2016. Histology: a text and atlas: with correlated cell and molecular biology (7^th Edition). WoltersKluwer. pp. 984.


20. Rieger J., Pelckmann L.M., Drewes B., 2021. Preservation and processing of intestinal tissue for assessment of histopathology. Methods in Molecularbiology. (Clifton, N.J.) 2223, 267 - 280.


21. Jamshidian H., Amini E., 2019. Effects of Opium Dependency on Testicular Tissue in a Rat Model: An Experimental Study. Urol J. 16, 375-79.


22. Bolat S.M., Akdeniz E., 2015. Smoking and Lower Urinary Tract Symptoms. Urol J. 12, 2447-51.


23. Dalila R., Aicha J., 2018. Semen Parameter Alteration, Histological Changes and Role of Oxidative Stress in Adult Rat Epididymis on Exposure to Electronic Cigarette Refill Liquid. Chinese Journal of Physiology. 61(2), 75-84.


24. Abeer R.H.M., Nashwa M.M.S., 2019. Ameliorative Effect of Zinc Oxide Nanoparticles on Nicotine Induced Testicular Dysfunction; Biochemical and Histological Study. Toxicol Environ Health Sci. 11(2), 104-113.


25. Davoud K., Seyyed M.M.S., Ahmed A., Leila K., Farhad R., 2021. Administration of Nicotine Exacerbates the Quinine-induced Structural and Functional Alterations of Testicular Tissue in Adult Rats: An Experimental Study. Urology Journal. 18(1), 103-110.


26. Oyeyipo I.P., Adeyemi D.H., Abe T.R., 2018. Testosterone and testicular changes in F1 offspring of Wistar rats maternally exposed to nicotine during gestation. JBRA Assisted Reproduction. 22(3),162-166.


27. Ibraheem M.G., Nanyak Z.G., Adamu G., Ayaka L., Ali A.H., Mohammed M.B., Najimuddeen B., Ahmed M.R., Samuel O.O., 2013. The effect of aqueous leave extract of nicotianatabacum (tobacco) on some reproductive parameters and micro-anatomical architecture of the testis in male albino wistar rats. Journal of Natural Sciences Research. 3(5), 2224-3186


28. Bisong S.A., Ukoh I.E., Nna V.U., Ebong P.E., 2018. Vitamin E attenuates nicotine and noise- induced reproductive impairment in male albino Wistar rats, Andrologiae13050. https://doi.org/10.1111/and.13050


29. U.S. Enviromental Protection Agency Guidelines for Reproductive Toxicity Risk Assessment Proposed Guidelines: Proposed Guidelines for Female Reproductive Risk and Proposed Guidelines for Male Reproductive Risk. Report No:EPA/630/R-96/009 [accessed: 10 March 2019] Available from, https://www.epa.gov/sites/production/files/201411/documents/guidelines_repro-toxicity.pdf. (1996).


30. Wang X., Zheng M., Liu J., Huang Z., Bai Y., Ren Z., Wang Z., Tian Y., Qiao Z., Liu W., Feng F., 2017. Differences of first pass effect in the liver and intestine contribute to the stereoselective pharmacokinetics of rhynchophylline and isorhynchophylline epimers in rats. Journal of Ethnopharmacology. 209, 175 - 183.


31. Benowitz N.L., 2009. Pharmacology of nicotine: addiction, smoking-induced disease and therapeutics. Annual review of Pharmacology and Toxicology. 49, 57 - 71.


32. Rang H.P., Dale M.M., Ritter J.M., Flower R.J., 2007. Rang and Dale’s Pharmacology, 6^th edition, Churchill Livingstone Elsevier, 2007, edition, Section 1 Chapter 8. pp. 104-108


33. Jensen K.P., DeVito E.E., 2016. Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences.Neuro Psychopharmacology. 41(8), 2034 - 2040.


34. Jensen K.P., DeVito E.E., Sofuoglu M., 2016. How Intravenous Nicotine Administration in Smokers Can Inform Tobacco Regulatory Science. Tob Regul Sci. 2(4), 452 - 463.


35. Goodwin A.K., Hiranita T., Paule M.G., 2015. The Reinforcing Effects of Nicotine in Humans and Nonhuman Primates: A Review of Intravenous Self-Administration Evidence and Future Directions for Research. Nicotine Tob Res. 17(11),1297-1310


36. Benowitz N.L., Henningfield J.E., 1994. Establishing a nicotine threshold for addiction. The implications for tobacco regulation. N Engl J Med. 331(2), 123 - 125.


37. Hatsukami D.K., Benowitz N.L., 2013. Nicotine Reduction: Strategic Research Plan. Nicotine & Tobacco Research. 15(6), 1003 - 1013.


38. Ichipi-Ifukor P.C., Asagba S.O., Nwose C., 2022. Palm oil extracts protected against cadmium chloride poisoning via inhibition of oxidative stress in rats. Bull Natl Res Cent. 46(5), 1-11


39. Oyem J.C., Chris-Ozoko L.E., Enaohwo M.T., Otabor F.O., Okudayo V.A., Udi O.A., 2021. Antioxidative properties of Ocimum gratissimumalters Lead acetate induced oxidative damage in lymphoid tissues and hematological parameters of adult Wistar rats. Toxicol Rep. 10(8), 215-222.


40. Mujittapha S.U., Kauthar M., Azeez I.O., Oyem J.C., 2020. Ascorbic acid improves extrapyramidal syndromes and corpus striatal degeneration induced by dopamine-2 receptor inhibition in Wistar rats. Drug Metab Pers Ther. 2020 Nov 2:/j/dmdi.ahead-of-print/dmdi-2020-0137/dmdi-2020-0137.xml.


41. Chris-Ozoko L.E., Okpe O., Iju W.J., Oyem J.C., 2018. Histomorphological Effects of Cottonseed Oil on Testes in Adult Male Wistar Rats. Galician Medical Journal. 25(4), 1-5


42. Malczewska-Jaskóła K., Jasiewicz B., Mrówczyńska L., 2016. Nicotine alkaloids as antioxidant and potential protective agents against in vitro oxidative haemolysis. Chem Biol Interact. 5(243), 62-71.


43. Newman M.B., Arendash G.W., Shytle R.D., Bickford P.C., Tighe T., Sanberg P.R., 2002. Nicotine's oxidative and antioxidant properties in CNS. Life Sci. 71(24), 2807-20.