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Modulatory Effects of Plant-Derived Stem Cell on Olanzapine-Induced Testicular Dysfunction in Male Wistar Rats
Abstract
Olanzapine-induced testicular dysfunction contributes to male infertility by disrupting steroidogenesis, energy metabolism, and oxidative balance. Plant-derived stem cells (PDSC), with antioxidant and regenerative properties, may offer protection against such drug-induced reproductive toxicity. To evaluate the modulatory effects of PDSC on testicular reproductive parameters in olanzapine-induced spermatotoxicity in male Wistar rats. Fifty adult male Wistar rats were randomly assigned to five groups (n = 10) and treated orally for 28 days. Group I received distilled water, Group II OLZ (10 mg/kg), and Groups III–V OLZ plus PDSC (100, 200, or 400 mg/kg). Sperm parameters, reproductive hormones (FSH, LH, testosterone), oxidative stress biomarkers, DNA damage marker (8-OHdG), testicular biochemical indices, and steroidogenic enzyme activities were evaluated. OLZ significantly reduced testosterone, testicular glycogen and cholesterol, normal sperm morphology, and 17betha-HSD activity, while increasing FSH, LH, MDA, and sperm motility. PDSC produced dose-dependent improvements, increasing testosterone, glycogen levels, and 17betha-HSD activity while reducing gonadotropins, oxidative stress, and DNA damage, particularly at 200 mg/kg. However, PDSC did not restore testicular cholesterol or zinc levels and was associated with reduced 3betha-HSD activity. PDSC mitigates olanzapine-induced reproductive toxicity through antioxidant, DNA-protective, and steroidogenic mechanisms, highlighting its potential for managing male reproductive dysfunction.
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Abd, M. E., Aziz, M. T., Atta, H. M., Fouad, H., Ahmed, H. H., Roshdy, N. K., et al. (2020). Therapeutic potential of mesenchymal stem cells in the regeneration of testicular tissue in a rat model of testicular degeneration. Journal of Advanced Research, 23, 101–112.
Agarwal, A., Virk, G., Ong, C., & du Plessis, S. S. (2014). Effect of oxidative stress on male reproduction. World Journal of Men's Health, 32(1), 1–17. https://doi.org/10.5534/wjmh.2014.32.1.1
Al-Enezi, M. A. (2015). Effect of Agnus castus extract on some reproductive parameters of female mice (Mus musculus L.). International Journal of Pharmaceutical and Biological Sciences, 5(2), 142–148.
Al-Saeed, M. H., Al-Saeed, A. H., & Al-Saeed, A. A. (2019). Olanzapine-induced reproductive toxicity in male rats: The potential role of oxidative stress. International Journal of Pharmacy and Pharmaceutical Sciences, 11(8), 54–59.
Ante, I. A., Togun, V. A., & Olanrewaju, O. J. (2025). Ethanolic fruit extract of Phoenix dactylifera improves male reproductive parameters and increases glycogen levels in male Wistar rats. Journal of Pharmacognosy and Phytochemistry, 24(2), 2291–2302.
Ard?ç, C. M., Ilg?n, S., Baysal, M., Karaduman, A. B., K?l?ç, V., Aydo?an-K?l?ç, G., Uçarcan, ?., & Atl?-Eklio?lu, Ö. (2021). Olanzapine induced reproductive toxicity in male rats. Scientific Reports, 11(1), 4739.
Devaraj, S., Wright, J., & Mottillo, E. P. (2024). Olanzapine-induced molecular alterations in skeletal muscle: A proteomics study [Thesis, Wayne State University].
Ebaid, H., Bashandy, S. A., Hassan, I., Al-Tamimi, J., Haredy, S. A., Imbabi, T., Omara, E. A., Bashandy, Y. S., & Awad, E. M. (2025). The preventive effect of zinc sulfate against olanzapine-induced testicular toxicity in male rats. Biological Trace Element Research, 203(7), 3764–3778.
Edah, M., Oritsemuelebi, B., Prosper, A. E., Asiwe, J. N., Parisi, C., Pane, C., Guerriero, G., & Orisakwe, O. E. (2026). Preclinical evidence on plant-derived aphrodisiacs and male reproductive function: Mechanisms, hormonal modulation, and translational implications. Current Pharmacology Reports, 12(1), 7.
El_Roghy, E. S., & Mahmoud, R. A. (2024). Effects of chronic administration of antipsychotic drug (olanzapine) on the anterior pituitary gland of adult male albino rats and the potential protective role of Hypericum Perforatum. Egyptian Journal of Histology, 47(1), 522–538.
Esan, D. T., Nnamani, K. Q., Olajide, A. O., Akingbade, O., Oluwade, D. B., Olawade, D. B., & Ramos, C. G. (2025). Women at the receiving end: Exploring couples' experiences of infertility challenges in Nigeria. bioRxiv.
Eze, E. D., Atiku, M. K., Alhassan, A. J., Ibrahim, A., Mohammed, A., Malgwi, I. S., et al. (2025). Sphenocentrum jollyanum (Pierre) aqueous leaf extract demonstrates anti-inflammatory, mitochondrial-protective and apoptotic-modulating influences while reversing hepatic and pancreatic damage in diabetic Wistar rats. Journal of Ethnopharmacology, 341, 118934.
Fallah, A., Mohammad-Hasani, A., & Colagar, A. H. (2018). Zinc is an essential element for male fertility: A review of Zn roles in men's health, germination, sperm quality, and fertilization. Journal of Reproduction & Infertility, 19(2), 69–81.
Gaikar, N. V., Raval, M. A., Patel, S. G., & Hingorani, L. L. (2021). Isolation and characterization of flavonoids from fraction of Blepharis persica (Burm. f.) O. Kuntze upregulated testosterone biosynthesis in vitro using TM3 Leydig cells. Pharmacognosy Magazine, 17(5 Suppl), S29–S37. https://doi.org/10.4103/pm.pm_406_20
Garcia-Alvarez, A., Mila-Villarroel, R., Ribas-Barba, L., Egan, B., Badea, M., Maggi, F. M., et al. (2016). Usage of plant food supplements across six European countries: Findings from the PlantLIBRA consumer survey. PLOS ONE, 11(3), e0150083. https://doi.org/10.1371/journal.pone.0150083
Görmü?, G., Ilg?n, S., Baysal, M., Karaduman, A. B., K?l?ç, V., Aydo?an-K?l?ç, G., Karagöz, O., & Atl?-Eklio?lu, Ö. (2021). Risperidone induced reproductive toxicity in male rats targeting Leydig cells and hypothalamic–pituitary–gonadal axis by inducing oxidative stress. Andrologia, 53(1), e13813.
Hermosaningtyas, A. A., Chanaj-Kaczmarek, J., Kikowska, M., Gornowicz-Porowska, J., Budzianowska, A., & Pawlaczyk, M. (2024). Potential of plant stem cells as helpful agents for skin disorders—a narrative review. Applied Sciences, 14(16), 7402.
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, 54(4), 287–293.
Kolli, P., Kelley, G., Rosales, M., Faden, J., & Serdenes, R. (2023). Olanzapine pharmacokinetics: A clinical review of current insights and remaining questions. Pharmacogenomics and Personalized Medicine, 1097–1108.
Lee, S., Kim, J., Kong, H., & Kim, Y. S. (2024). Ameliorative effects of elderberry (Sambucus nigra L.) extract and extract-derived monosaccharide-amino acid on H?O?-induced decrease in testosterone-deficiency syndrome in a TM3 Leydig cell. PLOS ONE, 19(4), e0302403.
Li, L., Zhong, D., Wang, S., & Zhou, M. (2025). Plant-derived materials for biomedical applications. Nanoscale, 17(2), 722–739.
Lima, L. A. R., Torres, S. M., Macêdo, S. R. B., Tenorio, F. C. A. M., Tenorio, B. M., & Silva Junior, V. A. (2023). Olanzapine treatment of lactating females causes testicular atrophy in prepuberal rat offspring. Biotechnic & Histochemistry, 98(3), 179–186. https://doi.org/10.1080/10520295.2022.2150314
Lobo, V., Patil, A., Phatak, A., & Chandra, N. (2017). Antioxidants: The role of dietary supplements. In S. Z. Kosti? (Ed.), Nutrition and health (1st ed., pp. 115–142). Nova Science Publishers.
Mlambo, R., Liu, J., Wang, Q., Tan, S., & Chen, C. (2023). Receptors involved in mental disorders and the use of clozapine, chlorpromazine, olanzapine, and aripiprazole to treat mental disorders. Pharmaceuticals, 16(4), 603.
Nimse, S. B., & Pal, D. (2015). Free radicals, natural antioxidants, and their role in restoration of cellular organelles. RSC Advances, 5(35), 27129–27153.
Oladipupo, A. R., Alaribe, S. C. A., Ogunlaja, A. S., Beniddir, M. A., Gordon, A. T., Ogah, C. O., Okpuzor, J., & Coker, H. A. B. (2025). Oleanolic acid purified from the stem bark of Olax subscorpioidea Oliv inhibits the function and catalysis of human 17?-hydroxysteroid dehydrogenase 1. Journal of Biomolecular Structure and Dynamics, 43(14), 7949–7962. https://doi.org/10.1080/07391102.2024.2423173
Oruch, R., Rajab, H. A., Elderbi, M. A., Pryme, I. F., Fasmer, O. B., & Lund, A. (2025). Drawbacks of olanzapine therapy: An emphasis on its metabolic effects and discontinuation. Journal of Clinical Medicine, 14(22), 8125.
Qiao, Y., Sun, J., Xia, S., Tang, X., Shi, Y., & Le, G. (2019). Effects of resveratrol on gut microbiota and fat storage in a mouse model with high-fat diet-induced obesity. Food & Function, 10(5), 2777–2788. https://doi.org/10.1039/c9fo00091j
Razdan, S., Greer, A. B., Patel, A., Alameddine, M., Jue, J. S., & Ramasamy, R. (2018). Effect of prescription medications on erectile dysfunction. Postgraduate Medical Journal, 94(1109), 171–178.
Remita, F., Abdennour, C., Talbi, A., & Khelili, K. (2023). Protective role of Crataegus monogyna on sperm quality and testis oxidative stress against copper-induced toxicity. Acta Biologica Turcica, 36(4), 1–10.
Rotimi, D. E., Iyobhebhe, M., Oluwayemi, E. T., Olajide, O. P., Akinsanola, B. A., Evbuomwan, I. O., Asaleye, R. M., & Ojo, O. A. (2024). Energy metabolism and spermatogenesis. Heliyon, 10(19).
Saad, S., Abdennour, C., Remita, F., & Khelili, K. (2024). Therapeutic potential of adipose-derived mesenchymal stem cells and their exosomes in restoring spermatogenesis and mitigating oxidative stress in a busulfan-induced azoospermia model. Acta Biologica Turcica, 37(1), 1–15.
Salehi, B., Azzini, E., Zucca, P., Varoni, E. M., Anil Kumar, N. V., Dini, L., Panzarini, E., Rajkovic, J., Valere Tsouh Fokou, P., Peluso, I., & Mishra, A. P. (2020). Plant-derived bioactives and oxidative stress-related disorders: A key trend towards healthy aging and longevity promotion. Applied Sciences, 10(3), 947.
Sharma, A., Minhas, S., Dhillo, W. S., & Jayasena, C. N. (2021). Male infertility due to testicular disorders. The Journal of Clinical Endocrinology & Metabolism, 106(2), e442–e459.
Sharma, A., Shrivastava, D., & Sharma, I. V. A. (2022). Psychological problems related to infertility. Cureus, 14(10).
Siddiqa, A., Qureshi, R., Yasmin, G., Rafique, S., Zafar, N. U., Hussain, C. S., Rehman, S. U., & Naheed, N. (2025). Unlocking the dual healing powers of plant-based metallic nanoparticles: Managing diabetes and tackling male infertility challenges. Frontiers in Endocrinology, 16, 1482127.
Turcu, A. F., Rege, J., Auchus, R. J., & Rainey, W. E. (2020). 11-Oxygenated androgens in health and disease. Nature Reviews Endocrinology, 16(5), 284–296.
Vander Borght, M., & Wyns, C. (2018). Fertility and infertility: Definition and epidemiology. Clinical Biochemistry, 62, 2–10.
Widhiantara, I. G., Wiradana, P. A., Permatasari, A. A., Sari, N. K., Rosiana, I. W., & Astuti, N. P. (2023). Blumea balsamifera leaf extract maintains testosterone levels in hypercholesterolemic rats through antioxidant mechanism and upregulation of StAR gene expression. Biomedical and Pharmacology Journal, 16(3), 1463–1472.
World Health Organization. (2023). Infertility prevalence estimates, 1990–2021. World Health Organization.
Zakrzewski, W., Dobrzy?ski, M., Szymonowicz, M., & Rybak, Z. (2019). Stem cells: Past, present, and future. Stem Cell Research & Therapy, 10(1), 68.
DOI: https://doi.org/10.14421/biomedich.2026.151.1431-1438
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