Evaluation of The Toxic Effects of Some Male Sexual Enhancement Drugs in the Testes of Male Wistar Rats
DOI:
https://doi.org/10.51459/jostir.2025.1.Special-Issue.0233Keywords:
oxidative damage, aphrodisiac, testicular toxicity, herbal drugsAbstract
Testicular damage is one of the most commonly reported adverse effect associated with many herbal drugs in Nigeria. This study evaluated the toxic effects of some male sexual enhancement drugs (ST and DB) in the testis of male Wistar rats. 18 male Wistar rats were randomized into three groups of 6 each. Group I received distilled water only, while others were administered 10 mL/Kg of ST and DB for 14 days respectively. Thereafter, the rats were sacrificed, the testes were harvested and testicular antioxidant concentration was evaluated. Rats treated with ST and DB had significantly (p<0.05) high malondialdehyde (MDA) activity compared to the control; catalase activity was significantly (p<0.05) low in rats administered ST while those administered DB had significant elevation in catalase concentration; superoxide dismutase (SOD) activity and reduced glutathione concentration (GSH) were was significantly (p<0.05) low in rats administered ST and DB; ST significantly increased, while DB significantly decreased the activity of glutathione-S-transferase. Testicular histology showed degenerative and necrotic changes in the seminiferous tubules. The GCMS results identified chemical compounds such as: 2,5-Furandione, 3-(dodecenyl) dihydro and 5-hydroxymethyfurfural which further raises concerns on the safety of DB and ST for oral consumption. These aphrodisiacs caused elevations in activities that are associated with cellular oxidative pathways as well as testicular damage. Thus, providing evidence that the aphrodisiacs may be unsafe for consumption and not strictly medicinal. Therefore, a more extensive chronic toxicity testing is recommended.
References
Aaseth, J.; Gerhardsson, L.; Skaug M.A.; & Alexander J. (2016). General Chemistry of Metal Toxicity and Basis for Metal Complexation. Chapter in: Chelation therapy in the treatment of metal intoxication. Pages 1-33. Academic Press. ISBN 9780128030721. https://doi.org/10.1016/B978-0-12-803072-1.00001-8
https://www.sciencedirect.com/science/article/pii/B9780128030721000018
Abdulmalik , O. , Safo , M.K. , Chen , Q. , et al. ( 2005 ). 5-hydroxymethyl-2-furfural modifies intracellular sickle haemoglobin and inhibits sickling of red blood cells† . British Journal of Haematology 128 ( 4 ): 552 – 561
Adams, R. P. (2001). Identification of essential oils by gas chromatography quadrupole mass spectrometry. Allured Publishing Corporation, Carol Stream, USA. 2001.
Akinola, A.O.; Oyeyemi, W.A.; Omotoso, D.R.; Daramola, O.O.; & Raji, Y. (2022). Protective role of methanol extract of Carpolobia lutea root against cadmium-induced changes in biochemical and antioxidant indices in liver of male Wistar rats. Ife Journal of Science vol. 24, no. 1. https://dx.doi.org/10.4314/ijs.v24i1.6
Alombong, A.G.; Bashige C.V.; Manya M.; Kamwimba M.A.; Bakari, A.S.; & Okusa, N.P. (2021). In vitro antioxidant activity and in vivo aphrodisiac activity in male Cavia porcellus of Albizia adianthifolia (Schum.) W. Wight and Pericopsis angolensis (Baker) Meeuwen. World Journal of Biology Pharmacy and Health Sciences. 5. 044-052. https://doi.org/10.30574/wjbphs.2021.5.3.0024
Ara, A.; Vishvkarma, R.; Mehta, P.; & Rajender, S. (2023). The profertility and aphrodisiac activities of Tribulus terrestris L.: evidence from meta-analyses", Andrologia, vol. 2023, Article ID 7118431, 21 pages, 2023. https://doi.org/10.1155/2023/7118431
Asmerom, D.; Kalay, T.H.; Araya, T.Y.; Desta, D.M.; Wondafrash, D.Z.; & Tafere, G.G. (2021). Medicinal Plants Used for the Treatment of Erectile Dysfunction in Ethiopia: A Systematic Review. BioMed research international, 2021, 6656406. https://doi.org/10.1155/2021/6656406.
Baffoe, M.; Koffuor, G.; Baffour-Awuah, A.; & Sallah, L. (2021). Assessment of Reproductive Toxicity of Hydroethanolic Root Extracts of Caesalpinia benthamiana, Sphenocentrum jollyanum, and Paullinia pinnata. Journal of Experimental Pharmacology, 13, 223–234. https://doi.org/10.2147/JEP.S283557
Beutler, E.; Duron, O.; & Kelly, B.M. (1963). Improved method for the determination of blood glutathione. J Lab Clin Med61: 882-8 (1963).
Brunetti, P.; Lo Faro, A. F.; Tini, A.; Busardò, F. P.; & Carlier, J. (2020). Pharmacology of herbal sexual enhancers: a review of psychiatric and neurological adverse effects. Pharmaceuticals (Basel, Switzerland), 13(10), 309. https://doi.org/10.3390/ph13100309
Calabrò, R.S.; Cacciola, A.; Bruschetta, D.; Milardi, D.; Quattrini, F.; Sciarrone, F.; la Rosa, G.; Bramanti, P.; & Anastasi, G. (2019). Neuroanatomy and function of human sexual behavior: A neglected or unknown issue? Brain and behavior, 9(12), e01389. https://doi.org/10.1002/brb3.1389.
Campbell, N.; Clark, J.P.; Stecher, V.J.; Thomas, J.W.; Callanan, A.C.; Donnelly, B.F.; Goldstein, I.; & Kaminetsky, J.C. (2013). Adulteration of purported herbal and natural sexual performance enhancement dietary supplements with synthetic phosphodiesterase type 5 inhibitors. The journal of sexual medicine 2013.
Chen, L.; Shi, G.; Huang, D.; Li, Y.; Ma, C.; Shi, M.; Su, B.; & Shi, G. (2019). Male sexual dysfunction: A review of literature on its pathological mechanisms, potential risk factors, and herbal drug intervention. Biomedicine & Pharmacotherapy, Volume 112, 2019, 108585. ISSN 0753-3322. https://doi.org/10.1016/j.biopha.2019.01.046. https://www.sciencedirect.com/science/article/pii/S0753332218353289).
Chukwudoruo, C. S., Osuji-Kalu-Ibe, N. C., Igwe, K. O., Iheme, C. I., Ujowundu, F. N., & Mba, B. A. (2021). Serum total protein concentration and liver enzymes activities in albino rats model administered with ethanolic leaf extract of Ficus capensis. Article Number - F29B1F266716. Vol.20(4), pp. 164-168. https://doi.org/10.5897/AJB2020.17107
Claiborne A. (1985). Catalase activity. In: Handbook of methods for oxygen radical research R. A. Greenwald, Ed. Boca Raton, 2018.
Czigle, S.; Nagy, M.; Mladěnka, P.; Tóth, J.; the OEMONOM (2023). Pharmacokinetic and pharmacodynamic herb-drug interactions-part I. Herbal medicines of the central nervous system. PeerJ, 11, e16149. https://doi.org/10.7717/peerj.16149.
Ekor, M. (2014). The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Frontiers in pharmacology, 4, 177. https://doi.org/10.3389/fphar.2013.00177.
Gornall, A.C.; Bardawill C.J;. & David M.M. Determination of serum protein by means of biuret reaction. J. Biol. Chem. 1949; 177: 751-756.
Giustarini, D., Milzani, A., Dalle-Donne, I., Rossi, R. (2023). How to Increase Cellular Glutathione. Antioxidants. 2023; 12(5):1094. https://doi.org/10.3390/antiox12051094
Habig, W.H.; Pabst, M.J.; & Jakoby, W.B. (1974). Glutathione S-transferases: the first enzymatic step in mercapturic acid formation.
Han, J.; Xian, Z.; Zhang, Y.; Liu, J.; & Liang, A. (2019). Systematic Overview of Aristolochic Acids: Nephrotoxicity, Carcinogenicity, and Underlying Mechanisms. Frontiers in pharmacology, 10, 648. https://doi.org/10.3389/fphar.2019.00648
Harirugsakul, K, Wainipitapong, S.; Phannajit, J.; Paitoonpong, L.; & Tantiwongse, K. (2022) Erectile dysfunction after COVID-19 recovery: A follow-up study. PLoS ONE 17(10): e0276429. https://doi.org/10.1371/journal.pone.0276429.
Hazardous Substances Data Bank (HSDB). National Library of Medicine. Accessed January 2015 at http://toxnet.nlm.nih.gov.
Howie, A.F.; Forrester, L.M.; Glancey, M.J.; Schlager, J.J.; Powis, G.; Beckett, G.J.; Hayes, J.D.; & Wolf, C.R. (2019). Glutathione S-transferase and glutathione peroxidase expression in normal and tumour human tissues. Carcinogenesis 2019.
Hu, C., Liu, J.Y., Wang, W., Mota-Sanchez, D., He, S., Shi, Y. and Yang, X.Q. (2022). Glutathione S-transferase genes are involved in lambda-cyhalothrin resistance in Cydia pomonella via sequestration. Journal of Agricultural and Food Chemistry.
Ighodaro, O.M.; & Akinloye, O.A. (2018). First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria Journal of Medicine 2018.
Igweze, Z.N.; Amadi, C.N.; & Orisakwe, O.E. (2019). Unsafe herbal sex enhancement supplements in Nigerian markets: a human risk assessment. Environmental science and pollution research international, 26(22), 22522–22528. https://doi.org/10.1007/s11356-019-05511-5
Jairoun, A. A., Al-Hemyari, S. S., Shahwan, M., Zyoud, S. H., Ibrahim, B., & Zyoud, S. H. (2022). Screening and Determination of Synthetic PDE-5 Inhibitors in Adulterated Sexual Enhancement Supplements. Molecules (Basel, Switzerland), 27(19), 6737. https://doi.org/10.3390/molecules27196737
Kale, O.E.; & Awodele, O. (2016). Safety evaluation of Bon-santé cleanser® polyherbal in male Wistar rats. BMC Complementary and Alternative Medicine (2016) 16:188. https://doi.org/10.1186/s12906-016-1188-8
Karimi, A.; Majlesi, M.; & Rafieian-Kopaei, M. (2015). Herbal versus synthetic drugs; beliefs and facts. Journal of nephropharmacology, 4(1), 27–30.
Krause, W. J. (2001). The art of examinig and interpreting histologic preparations. A laboratory manual and guide for histology, 2nd edition. Partheton Publishing Group, UK. 9-10
Misra, H.P.; & Fridovich, I. (1972). The role of superoxide anion in the auto-oxidation of epinephrine and a simple assay for superoxide dismutase.
Msomi, Z.; & Simelane, M.B.C. (2019). Herbal Medicine. http://dx.doi.org/10.5772/intechopen.72816. Available from: https://www.researchgate.net/publication/330748906_Herbal_Medicine#fullTextFileContent
Nabi, S. and Nabi, S. (2014). Promotion of peroxidation and hydroperoxidation of lipids. Toxic effects of mercury.
Neychev, V.; & Mitev, V. (2016). Pro-sexual and androgen enhancing effects of Tribulus terrestris L.: fact or fiction. Journal of ethnopharmacology, 179, 345–355. https://doi.org/10.1016/j.jep.2015.12.055
Okaiyeto, K.; & Oguntibeju, O. O. (2021). African Herbal Medicines: Adverse Effects and Cytotoxic Potentials with Different Therapeutic Applications. International journal of environmental research and public health, 18(11), 5988. https://doi.org/10.3390/ijerph18115988
Petre, G. C.; Francini-Pesenti, F.; Vitagliano, A.; Grande, G.; Ferlin, A.; Garolla, A.; (2023). Dietary supplements for erectile dysfunction: analysis of marketed products, systematic review, meta-analysis and rational use. Nutrients. 2023 Aug 22;15(17):3677. https://doi.org/10.3390/nu15173677
Prabhakaran, D.K.; A. Nisha, P.; & Varghese. (2015). Prevalence and correlates of sexual dysfunction in male patients with alcohol dependence syndrome: a cross-sectional study. Indian J. Psychiatry, 60 (1) (2018), p. 71.
Rajendar, B., Bharavi,K.; Rao, G.; Kishore, P.V.S.; Kumar P.; & Satish Kumar C.S.V. (2011). "Protective effect of an aphrodisiac herb Tribulus terrestris Linn on cadmium-induced testicular damage." Indian Journal of Pharmacology, vol. 43, no. 5, Sept.-Oct. 2011, p. 568. Gale OneFile: Health and Medicine, link.gale.com/apps/doc/A268031629/HRCA?u=anon~616d7da6&sid=googleScholar&xid=1d1a7da1
Registration, Evaluation and Authorisation of Chemicals (REACH) Dossier. Maleic Anhydride (CAS No. 108-31-6), accessed January 2015 at http://echa.europa.eu/information-on-chemicals/registered-substances
Roy, Z., Bansal, R., Siddiqui, L., & Chaudhary, N. (2023). Understanding the Role of Free Radicals and Antioxidant Enzymes in Human Diseases. Current pharmaceutical biotechnology, 24(10), 1265–1276. https://doi.org/10.2174/1389201024666221121160822
Sabatino, A.; Regolisti, G.; Karupaiah, T.; Sahathevan, S.; Singh, B.K.S.; Khor, B.H.; Salhab, N.; Karavetian, M.; Cupisti, A.; & Fiaccadori, E. (2017). Protein-energy wasting and nutritional supplementation in patients with end-stage renal disease on hemodialysis. Clin. Nutr. 2017;36:663–671. https://doi.org/10.1016/j.clnu.2016.06.007
Safe Work Australia (SWA). Hazardous Substances Information system (HSIS). Accessed January 2015 at http://hsis.safeworkaustralia.gov.au/HazardousSubstance.
Sasikumar, C.S.; & Devi, C.S. (2018). Protective effect of Abana®, a poly-herbal formulation, on isoproterenol-induced myocardial infarction in rats. Indian Journal of Pharmacology 2018.
Strange, R.C.; Spiteri, M.A.; Ramachandran, S.; and Fryer, A.A. (2022). Glutathione-S-transferase family of enzymes. Mutation research/fundamental and molecular mechanisms of mutagenesis.
Tralau, T.; & Luch, A. (2022). The evolution of our understanding of endo-xenobiotic crosstalk and cytochrome P450 regulation and the therapeutic implications. Expert opinion on drug metabolism & toxicology 2022.
Vashney, R.; & Kale, R.K. (1990). Effects of calmodulin antagonists. Int. J Rad.Biol.1990. 58:733-743.
Vyas, R.; Kesari, K.K.; Slama, P.; Roychoudhury, S.; & Sisodia, R. (2022). Differential activity of antioxidants in testicular tissues following administration of Chlorophytum borivilianum in gamma-irradiated swiss albino mice. Frontiers in pharmacology, 12, 774444. https://doi.org/10.3389/fphar.2021.774444
Wang, Y.; Branicky, R.; Noë, A.; & Hekimi, S. (2018). Superoxide dismutases: Dual roles in controlling ros damage and regulating ros signaling. Journal of Cell Biology. 217, 1915–1928.
Yakubu, M.T.; Abdulraheem, G.O.; & Nafiu, M.O. (2021). Toxicological effects of polyherbal formulations for malaria, yellow fever and haemorrhoids in Ilorin metropolis, Nigeria, on male Wistar rats: A comparative biochemical and histological study. Biokemistri Volume 33, Number 3. http://journals.niseb.org. http://www.bioline.org.br/bk
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Journal of Science, Technology and Innovation Research
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.