Ratlarda Akrilamid İle İndüklenen Testiküler Toksikasyonda Melatoninin FSH/LH/Testosteron ve StAR/P450scc/17β-HSD3 Yolakları Üzerine Etkileri

Year 2025, Volume: 5 Issue: 2, 119 - 125, 19.09.2025

Samet Tekin , Yusuf Dağ , Furkan Aykurt , Merve Bolat , İsmail Bolat , Burak Batuhan Laçin , Burak Çınar , Mohamad Warda

https://doi.org/10.62425/jlasp.1678282

Abstract

Akrilamid (ACR), oksidatif stres ve üreme toksisitesine neden olduğu bilinen yüksek sıcaklıkta gıda işleme sırasında oluşan toksik bir bileşiktir. Bu çalışmada, hormonal düzenleme ve steroidojenik yollara odaklanılarak melatoninin (MEL) ACR kaynaklı testis toksisitesi üzerindeki koruyucu etkileri araştırılmıştır. 40 yetişkin erkek Wistar sıçanı beş gruba ayrılmıştır: kontrol, ACR (50 mg/kg), ACR+MEL10 (ACR + 10 mg/kg MEL), ACR+MEL20 (ACR + 20 mg/kg MEL) ve MEL20 (sadece 20 mg/kg MEL). Tedaviler 14 gün boyunca intragastrik gavaj yoluyla uygulanmıştır. Serum folikül uyarıcı hormon (FSH), luteinize edici hormon (LH) ve testosteron seviyeleri, testis steroidojenik enzim seviyeleri (StAR, P450scc, 17β-HSD3) ile birlikte ELISA yoluyla ölçülmüştür. Histopatolojik analiz, Johnsen puanlaması yoluyla spermatogenik bütünlüğü değerlendirmek için kullanıldı. ACR maruziyeti serum FSH, LH ve testosteron seviyelerini önemli ölçüde düşürdü (p< .001), StAR, P450scc ve 17β-HSD3 ekspresyonunda eş zamanlı bir azalma oldu. Histolojik değerlendirme şiddetli spermatosit dejenerasyonu, nekroz ve bozulmuş spermatogenez olduğunu ortaya koydu. MEL uygulaması bu etkileri doza bağlı bir şekilde iyileştirdi. ACR+MEL10 hormonal ve enzimatik seviyelerin kısmi restorasyonuyla sonuçlandı (p< .05), oysa ACR+MEL20 bu parametreleri kontrol seviyelerine yakın seviyelere geri getirdi (p> .05). MEL ayrıca histopatolojik hasarı hafifletti, seminifer tübül bütünlüğünü ve spermatogenik işlevi korudu. Bu bulgular, MEL'in antioksidan ve antiapoptotik etkileriyle ACR kaynaklı testis toksisitesine karşı koruyucu etkiler gösterdiğini, steroidojenik enzim aktivitesini ve hormonal dengeyi geri kazandırdığını göstermektedir. MEL takviyesi, erkek üreme sağlığını etkileyen çevresel toksik maddelere karşı potansiyel bir tedavi stratejisi olabilir. Tam koruyucu kapsamını açıklamak için daha fazla mekanik çalışma yapılması gerekmektedir.

Keywords

Akrilamid toksisitesi , Melatonin koruması , Oksidatif stres , Testiküler steroidogenez , Üreme toksisitesi.

Effects of Melatonin on FSH/LH/Testosterone and StAR/P450scc/17β-HSD3 Pathways in Acrylamide-Induced Testicular Toxication in Rats

Abstract

Acrylamide (ACR) is a toxic compound formed during high-temperature food processing that is known to induce oxidative stress and reproductive toxicity. This study investigated the protective effects of melatonin (MEL) on ACR-induced testicular toxicity, with a focus on hormonal regulation and steroidogenic pathways. Forty adults male Wistar rats were divided into five groups: control, ACR (50 mg/kg), ACR+MEL10 (ACR + 10 mg/kg MEL), ACR+MEL20 (ACR + 20 mg/kg MEL), and MEL20 (20 mg/kg MEL alone). Treatments were administered via intragastric gavage for 14 days. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were measured via ELISA, alongside testicular steroidogenic enzyme levels (StAR, P450scc, 17β-HSD3). Histopathological analysis was used to assess spermatogenic integrity via Johnsen scoring. ACR exposure significantly reduced the serum FSH, LH, and testosterone levels (p< .001), with a concurrent decrease in StAR, P450scc, and 17β-HSD3 expression. Histological evaluation revealed severe spermatocyte degeneration, necrosis, and disrupted spermatogenesis. MEL administration ameliorated these effects in a dose-dependent manner. ACR+MEL10 resulted in partial restoration of hormonal and enzymatic levels (p< .05), whereas ACR+MEL20 restored these parameters to near-control levels (p> .05). MEL also mitigated histopathological damage, preserving seminiferous tubule integrity and spermatogenic function. These findings suggest that MEL exerts protective effects against ACR-induced testicular toxicity through its antioxidant and antiapoptotic effects, restoring steroidogenic enzyme activity and the hormonal balance. MEL supplementation may be a potential therapeutic strategy against environmental toxicants affecting male reproductive health. Further mechanistic studies are warranted to elucidate its full protective scope.

Keywords

Keywords: Acrylamide toxicity , Melatonin protection , Oxidative stress , Reproductive toxicity , Testicular steroidogenesis

Ethical Statement

Ethics committee approval was received for this study from the ‘’Local Ethics Committee of Atatürk University Animal Experiments’’ (Protocol Date:10/03/2025-Protocol Number: 59/2025)

References

• Adiguzel, C., Karaboduk, H., & Uzunhisarcikli, M. (2024). Protective Role of Melatonin Against Abamectin-Induced Biochemical, Immunohistochemical, and Ultrastructural Alterations in the Testicular Tissues of Rats. Microscopy and Microanalysis, 30(5), 962-977. https://doi.org/10.1093/mam/ozae080
• Afzal, A., Zhang, Y., Afzal, H., Saddozai, U. A. K., Zhang, L., Ji, X. Y., & Khawar, M. B. (2024). Functional role of autophagy in testicular and ovarian steroidogenesis. Frontiers in Cell and Developmental Biology, 12. https://doi.org/10.3389/fcell.2024.1384047
• Batuwita, B. K. H. H., Jayasinghe, J. M. J. K., Marapana, R. A. U. J., Jayasinghe, C. V. L., & Jinadasa, B. K. K. K. (2025). Reduction of Asparagine and Reducing Sugar Content, and Utilization of Alternative Food Processing Strategies in Mitigating Acrylamide Formation-A Review. Food and Bioprocess Technology, 18(3), 2101-2144. https://doi.org/10.1007/s11947-024-03565-z
• Bolat, I., Bolat, M., Kiliçlioglu, M., Okur, S., Gölgeli, A., Gözegir, B.,…Warda, M. (2024). Investigation of the Effects of Boric Acid against Post Operative Testicular Adhesion Caused by Experimental Laporotomy in Rats. Biological Trace Element Research. 203, 3181-3194. https://doi.org/10.1007/s12011-024-04400-4
• Chen, H., Ge, R. S., & Zirkin, B. R. (2009). Leydig cells: From stem cells to aging. Molecular and Cellular Endocrinology, 306(1-2), 9-16. https://doi.org/10.1016/j.mce.2009.01.023
• Erdem, E., Sapmaz, T., Aras, S., Sevgin, K., Baki, K. B., Topkaraoglu, S.,…Irkorucu, O. (2024). Melatonin administration in testicular damage caused by low and high-dose rate radiotherapy: An experimental study. Radiation Physics and Chemistry, 220. https://doi.org/10.1016/j.radphyschem.2024.111692
• Esteves, S. C., & Humaidan, P. (2025). The role of luteinizing hormone activity in spermatogenesis: from physiology to clinical practice. Reproductive Biology and Endocrinology, 23(Suppl1). https://doi.org/10.1186/s12958-024-01333-4
• Farag, O. M., Abd-Elsalam, R. M., El Badawy, S. A., Ogaly, H. A., Alsherbiny, M. A., & Ahmed, K. A. (2021). Portulaca oleracea seeds’ extract alleviates acrylamide-induced testicular dysfunction by promoting oxidative status and steroidogenic pathway in rats. BMC Complementary Medicine and Therapies, 21(1), 1-15. https://doi.org/10.1186/s12906-021-03286-2
• Farouk, S. M., Gad, F. A., Almeer, R., Abdel-Daim, M. M., & Emam, M. A. (2021). Exploring the possible neuroprotective and antioxidant potency of lycopene against acrylamide-induced neurotoxicity in rats’ brain. Biomedicine and Pharmacotherapy, 138, 111458. https://doi.org/10.1016/j.biopha.2021.111458
• Frungieri, M. B., Calandra, R. S., & Rossi, S. P. (2017). Local Actions of Melatonin in Somatic Cells of the Testis. International Journal of Molecular Sciences, 18(6), 1170. https://doi.org/10.3390/ijms18061170
• Gao, J. G., Jiang, Y., Zheng, J. T., & Nie, L. W. (2022). Pubertal exposure to acrylamide disrupts spermatogenesis by interfering with meiotic progression in male mice. Toxicology Letters, 358, 80-87. https://doi.org/10.1016/j.toxlet.2022.01.014
• Gul, M., Kayhan Kustepe, E., Erdemli, M. E., Altinoz, E., Gozukara Bag, H. G., Gul, S., & Gokturk, N. (2021). Protective effects of crocin on acrylamide-induced testis damage. Andrologia, 53(9), e14176. https://doi.org/10.1111/and.14176
• Halford, N. G., Curtis, T. Y., Muttucumaru, N., Postles, J., Elmore, J. S., & Mottram, D. S. (2012). The acrylamide problem: a plant and agronomic science issue. Journal of Experimental Botany, 63(8), 2841-2851. https://doi.org/10.1093/jxb/ers011
• Jimenez-Jorge, S., Guerrero, J. M., Jimenez-Caliani, A. J., Naranjo, M. C., Lardone, P. J., Carrillo-Vico, A.,…Molinero, P. (2007). Evidence for melatonin synthesis in the rat brain during development. Journal of Pineal Research, 42(3), 240-246. https://doi.org/10.1111/j.1600-079X.2006.00411.x
• Kumar, V., Chakraborty, A., Kural, M. R., & Roy, P. (2009). Alteration of testicular steroidogenesis and histopathology of reproductive system in male rats treated with triclosan. Reproductive Toxicology, 27(2), 177-185. https://doi.org/10.1016/j.reprotox.2008.12.002
• Lebda, M., Gad, S., & Gaafar, H. (2014). Effects of lipoic Acid on acrylamide induced testicular damage. Mater Sociomed, 26(3), 208-212. https://doi.org/10.5455/msm.2014.26.208-212
• Li, C., & Zhou, X. (2015). Melatonin and male reproduction. Clinica Chimica Acta, 446, 175-180. https://doi.org/10.1016/j.cca.2015.04.029
• Mogol, B. A., & Gökmen, V. (2016). Thermal process contaminants: acrylamide, chloropropanols and furan. Current Opinion in Food Science, 7, 86-92. https://doi.org/10.1016/j.cofs.2016.01.005
• Mokhlis, H. A., Rashed, M. H., Saleh, I. G., Eldeib, M. G., El-Husseiny, A. A., Khidr, E. G.,…Aglan, A. (2023). Hydrogen sulfide alleviates acrylamide-induced testicular toxicity in male rats. Toxicology and Environmental Health Sciences, 15(1), 41-51. https://doi.org/10.1007/s13530-022-00156-3
• Mukherjee, A., & Haldar, C. (2014). Photoperiodic regulation of melatonin membrane receptor (MT1R) expression and steroidogenesis in testis of adult golden hamster, Mesocricetus auratus. Journal of Photochemistry and Photobiology, 140, 374-380. https://doi.org/10.1016/j.jphotobiol.2014.08.022
• Murugesan, P., Muthusamy, T., Balasubramanian, K., & Arunakaran, J. (2007). Effects of vitamins C and E on steroidogenic enzymes mRNA expression in polychlorinated biphenyl (Aroclor 1254) exposed adult rat Leydig cells. Toxicology, 232(3), 170-182. https://doi.org/10.1016/j.tox.2007.01.008
• Owagboriaye, F. O., Dedeke, G. A., Ademolu, K. O., Olujimi, O. O., Ashidi, J. S., & Adeyinka, A. A. (2017). Reproductive toxicity of Roundup herbicide exposure in male albino rat. Experimental and Toxicologic Pathology, 69(7), 461-468. https://doi.org/10.1016/j.etp.2017.04.007
• Rovira, J., Diekmann, F., Ramirez-Bajo, M. J., Banon-Maneus, E., Moya-Rull, D., & Campistol, J. M. (2012). Sirolimus-associated testicular toxicity: detrimental but reversible. Transplantation, 93(9), 874-879. https://doi.org/10.1097/TP.0b013e31824bf1f0
• Tareke, E., Rydberg, P., Karlsson, P., Eriksson, S., & Tornqvist, M. (2002). Analysis of acrylamide, a carcinogen formed in heated foodstuffs. Journal of Agricultural and Food Chemistry, 50(17), 4998-5006. https://doi.org/10.1021/jf020302f
• Tijmes, M., Pedraza, R., & Valladares, L. (1996). Melatonin in the rat testis: evidence for local synthesis. Steroids, 61(2), 65-68. https://doi.org/10.1016/0039-128x(95)00197-x
• Tyl, R. W., Marr, M. C., Myers, C. B., Ross, W. P., & Friedman, M. A. (2000). Relationship between acrylamide reproductive and neurotoxicity in male rats. Reproductive Toxicology, 14(2), 147-157. https://doi.org/10.1016/s0890-6238(00)00066-6
• Walker, W. H., & Cheng, J. (2005). FSH and testosterone signaling in Sertoli cells. Reproduction, 130(1), 15-28. https://doi.org/10.1530/rep.1.00358
• Wang, H., Huang, P., Lie, T., Li, J., Hutz, R. J., Li, K., & Shi, F. (2010). Reproductive toxicity of acrylamide-treated male rats. Reproductive Toxicology, 29(2), 225-230. https://doi.org/10.1016/j.reprotox.2009.11.002
• Yan, F., Wang, L., Zhao, L., Wang, C., Lu, Q., & Liu, R. (2023). Acrylamide in food: Occurrence, metabolism, molecular toxicity mechanism and detoxification by phytochemicals. Food and Chemical Toxicology, 175, 113696. https://doi.org/10.1016/j.fct.2023.113696
• Yassa, H. A., George, S. M., Refaiy Ael, R., & Moneim, E. M. (2014). Camellia sinensis (green tea) extract attenuate acrylamide induced testicular damage in albino rats. Environmental Toxicology, 29(10), 1155-1161. https://doi.org/10.1002/tox.21846
• Yildizbayrak, N., & Erkan, M. (2018). Acrylamide disrupts the steroidogenic pathway in Leydig cells: possible mechanism of action. Toxicological and Environmental Chemistry, 100(2), 235-246. https://doi.org/10.1080/02772248.2018.1458231
• Yu, K., Deng, S. L., Sun, T. C., Li, Y. Y., & Liu, Y. X. (2018). Melatonin Regulates the Synthesis of Steroid Hormones on Male Reproduction: A Review. Molecules, 23(2), 447. https://doi.org/10.3390/molecules23020447
• Zamani, E., Shaki, F., AbedianKenari, S., & Shokrzadeh, M. (2017). Acrylamide induces immunotoxicity through reactive oxygen species production and caspase-dependent apoptosis in mice splenocytes via the mitochondria-dependent signaling pathways. Biomedicine and Pharmacotherapy, 94, 523-530. https://doi.org/10.1016/j.biopha.2017.07.033