The Protective Effect of Melatonin Supplementation Against Taxol-induced Testicular Cytotoxicity in Adult Rats

Overview

Journal Braz J Med Biol Res

Specialties Biology
General Medicine

Date 2022 Feb 9

PMID 35137851

Authors

H R Aboelwafa

R A Ramadan

A F El-Kott

F M Abdelhamid

Affiliations

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Abstract

The aim of the present investigation was to study the toxic influences of taxol (TXL) on the testes of rats and the protective impact of melatonin (MLT) against such effects. Rats were classified into control, sham, TXL, MLT, and MLT+TXL-treated groups. Histological and ultrastructural changes were observed in testicular tissues of TXL-intoxicated rats including thickening of tunica albuginea and degenerative alterations in spermatogenic, Sertoli, and Leydig cells. A significant increase (P≤0.05) was found in the thickness of tunica albuginea and numbers of tubules without sperm, apoptotic germinal epithelia, and apoptotic Leydig cells, whereas the diameter of tubules and height of germinal epithelia displayed a significant decrease (P≤0.05) compared with the control, sham, and MLT-treated groups. Immunohistochemically, a marked decrease (P≤0.05) in Bcl-2 immunoreactivity and significant elevation (P≤0.05) in P53 and caspase-3 immunoreactivities were recorded. Co-treatment of MLT and TXL modulated such histological, histomorphometrical, and ultrastructural changes induced by TXL. Also, MLT had a protective effect against testicular apoptosis induced by TXL, as shown by the elevated expression of Bcl-2 and decreased expression of P53 and caspase-3. In conclusion, the current investigation proved that MLT had a protective role against TXL-induced testicular cytotoxicity, which may be a result of inhibition of testicular apoptosis.

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References

Alonso-Gonzalez C, Menendez-Menendez J, Gonzalez-Gonzalez A, Gonzalez A, Cos S, Martinez-Campa C . Melatonin enhances the apoptotic effects and modulates the changes in gene expression induced by docetaxel in MCF‑7 human breast cancer cells. Int J Oncol. 2017; 52(2):560-570. DOI: 10.3892/ijo.2017.4213. View

Luo C, Yang Q, Liu Y, Zhou S, Jiang J, Reiter R . The multiple protective roles and molecular mechanisms of melatonin and its precursor N-acetylserotonin in targeting brain injury and liver damage and in maintaining bone health. Free Radic Biol Med. 2018; 130:215-233. DOI: 10.1016/j.freeradbiomed.2018.10.402. View

Wang Y, Zhou L, Xiao M, Sun Z, Zhang C . Nanomedicine-based paclitaxel induced apoptotic signaling pathways in A562 leukemia cancer cells. Colloids Surf B Biointerfaces. 2016; 149:16-22. DOI: 10.1016/j.colsurfb.2016.08.022. View

Ohta H, Aizawa S, Nishimune Y . Functional analysis of the p53 gene in apoptosis induced by heat stress or loss of stem cell factor signaling in mouse male germ cells. Biol Reprod. 2003; 68(6):2249-54. DOI: 10.1095/biolreprod.102.014779. View

Haghi-Aminjan H, Asghari M, Farhood B, Rahimifard M, Goradel N, Abdollahi M . The role of melatonin on chemotherapy-induced reproductive toxicity. J Pharm Pharmacol. 2017; 70(3):291-306. DOI: 10.1111/jphp.12855. View

Tan D, Manchester L, Hardeland R, Lopez-Burillo S, Mayo J, Sainz R . Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. J Pineal Res. 2002; 34(1):75-8. DOI: 10.1034/j.1600-079x.2003.02111.x. View

Monsees T, Franz M, Gebhardt S, Winterstein U, Schill W, Hayatpour J . Sertoli cells as a target for reproductive hazards. Andrologia. 2000; 32(4-5):239-46. DOI: 10.1046/j.1439-0272.2000.00391.x. View

Dobashi M, Fujisawa M, Naito I, Yamazaki T, Okada H, Kamidono S . Distribution of type IV collagen subtypes in human testes and their association with spermatogenesis. Fertil Steril. 2003; 80 Suppl 2:755-60. DOI: 10.1016/s0015-0282(03)00775-1. View

Agarwal M, Agarwal A, Taylor W, Stark G . p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts. Proc Natl Acad Sci U S A. 1995; 92(18):8493-7. PMC: 41183. DOI: 10.1073/pnas.92.18.8493. View

10.

Yano C, Dolder H . Rat testicular structure and ultrastructure after paracetamol treatment. Contraception. 2002; 66(6):463-7. DOI: 10.1016/s0010-7824(02)00407-9. View

11.

Eren H, Mercantepe T, Tumkaya L, Mercantepe F, Dil E, Horsanali M . Evaluation of the protective effects of amifostine and melatonin against cisplatin induced testis injury via oxidative stress and apoptosis in rats. Exp Mol Pathol. 2019; 112:104324. DOI: 10.1016/j.yexmp.2019.104324. View

12.

Manivannan B, Mittal R, Goyal S, Ansari A, Lohiya N . Sperm characteristics and ultrastructure of testes of rats after long-term treatment with the methanol subfraction of Carica papaya seeds. Asian J Androl. 2009; 11(5):583-99. PMC: 3735006. DOI: 10.1038/aja.2009.25. View

13.

Martinez-Campa C, Menendez-Menendez J, Alonso-Gonzalez C, Gonzalez A, Alvarez-Garcia V, Cos S . What is known about melatonin, chemotherapy and altered gene expression in breast cancer. Oncol Lett. 2017; 13(4):2003-2014. PMC: 5403278. DOI: 10.3892/ol.2017.5712. View

14.

Hu W, Ma Z, Jiang S, Fan C, Deng C, Yan X . Melatonin: the dawning of a treatment for fibrosis?. J Pineal Res. 2015; 60(2):121-31. DOI: 10.1111/jpi.12302. View

15.

Nirupama M, Devaki M, Nirupama R, Yajurvedi H . Chronic intermittent stress-induced alterations in the spermatogenesis and antioxidant status of the testis are irreversible in albino rat. J Physiol Biochem. 2012; 69(1):59-68. DOI: 10.1007/s13105-012-0187-6. View

16.

Kamsrijai U, Wongchitrat P, Nopparat C, Satayavivad J, Govitrapong P . Melatonin attenuates streptozotocin-induced Alzheimer-like features in hyperglycemic rats. Neurochem Int. 2019; 132:104601. DOI: 10.1016/j.neuint.2019.104601. View

17.

Luo L, Li Y, Yang Y, He Y, Wang Y, Xu Z . Multinucleated cells are involved in normal development and apoptosis in mouse testes. Mol Med Rep. 2013; 8(3):865-70. DOI: 10.3892/mmr.2013.1568. View

18.

Bonnefont-Rousselot D, Collin F . Melatonin: action as antioxidant and potential applications in human disease and aging. Toxicology. 2010; 278(1):55-67. DOI: 10.1016/j.tox.2010.04.008. View

19.

Dykstra M, Mann P, Elwell M, Ching S . Suggested Standard Operating Procedures (SOPs) for the preparation of electron microscopy samples for toxicology/pathology studies in a GLP environment. Toxicol Pathol. 2003; 30(6):735-43. DOI: 10.1080/01926230290166823. View

20.

Huisman C, Ferreira C, Broker L, Rodriguez J, Smit E, Postmus P . Paclitaxel triggers cell death primarily via caspase-independent routes in the non-small cell lung cancer cell line NCI-H460. Clin Cancer Res. 2002; 8(2):596-606. View