Thymoquinone improves testicular damage and sperm quality in experimentally varicocele-induced adolescent rats.
Bax/Bcl-2
cytochrome c
testis
thymoquinone
varicocele
Journal
Andrologia
ISSN: 1439-0272
Titre abrégé: Andrologia
Pays: Germany
ID NLM: 0423506
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
revised:
15
02
2021
received:
19
01
2021
accepted:
17
02
2021
pubmed:
5
3
2021
medline:
22
6
2021
entrez:
4
3
2021
Statut:
ppublish
Résumé
The aim of this study was to investigate the protective and therapeutic effects of thymoquinone against the negative effects of varicocele on testicular tissue and sperm morphology. Five groups were formed by random selection from a total of 40 adult male Wistar rats (n = 8). Thymoquinone (5 mg/kg/day) was administered intraperitoneally to the varicocele-dimethyl sulfoxide-olive oil-thymoquinone (VT) group and the sham-thymoquinone group. At the end of the 60th day, all groups were anaesthetised and the left testis was removed from the body quickly. One half of the testis tissue, which was divided into two, was separated for biochemical and Western blot analysis, while the other half were fixed in Bouin's fixative. As a result of biochemical, molecular and histopathological analyses, a statistically significant increase was found in the varicocele group testicular tissues in the malondialdehyde level, apoptotic index, Bax expression, cytochrome c expression and Bax/Bcl-2 ratio compared with the sham group. In addition, histopathological changes characterised by partial or complete degeneration of the germinal epithelium were observed in the seminiferous tubules in the same group. Total oxidant status level and sperm count with abnormal morphology increased in varicocele group, whereas total antioxidant status level decreased. In the VT group, all of the biochemical, molecular and histopathological changes detected in the varicocele group were statistically significantly reduced. When the findings obtained in this study are evaluated, it can be said that thymoquinone has the potential to be used as a preventive and therapeutic pharmacological agent in the medical treatment of varicocele. Although the exact mechanism of action of thymoquinone has not been fully elucidated, the findings obtained in this study support the view that thymoquinone showed a cytoprotective effect by reducing apoptosis, oxidative stress and lipid peroxidation.
Substances chimiques
Benzoquinones
0
thymoquinone
O60IE26NUF
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14033Subventions
Organisme : This work was supported by Scientific Research Projects Unit of Nigde Omer Halisdemir Universityr
ID : SSB 2018/02-BAGEP
Organisme : This work was supported by Scientific Research Projects Unit of Nigde Omer Halisdemir University
ID : SSB 2018/02-BAGEP
Informations de copyright
© 2021 Wiley-VCH GmbH.
Références
Abbasi, M., Alizadeh, R., Abolhassani, F., Amidi, F., Hassanzadeh, G., Ejtemaei Mehr, S., & Dehpour, A. R. (2011). Aminoguanidine improves epididymal sperm parameters in varicocelized rats. Urologia Internationalis, 86(3), 302-306. https://doi.org/10.1159/000322154
Adams, J. M., & Cory, S. (1998). The Bcl-2 protein family: Arbiters of cell survival. Science, 281(5381), 1322-1326. https://doi.org/10.1126/science.281.5381.1322
Agarwal, A., Sharma, R., Harlev, A., & Esteves, S. C. (2016). Effect of varicocele on semen characteristics according to the new 2010 World Health Organization criteria: A systematic review and meta-analysis. Asian Journal of Andrology, 18(2), 163-170. https://doi.org/10.4103/1008-682X.172638
Ahlberg, N. E., Bartley, O., & Chidekel, N. (1966). Right and left gonadal veins. An anatomical and statistical study. Acta Radiologica Diagnosis (Stockh), 4(6), 593-601. https://doi.org/10.1177/028418516600400601
Akdemir, S., Gurocak, S., Konac, E., Ure, I., Onen, H. I., Gonul, I. I., Sozen, S., & Menevse, A. (2014). Different surgical techniques and L-carnitine supplementation in an experimental varicocele model. Andrologia, 46(8), 910-916. https://doi.org/10.1111/and.12172
Aksoy, H., Aksoy, Y., Ozbey, I., Altuntas, I., & Akcay, F. (2000). The relationship between varicocele and semen nitric oxide concentrations. Urological Research, 28(6), 357-359. https://doi.org/10.1007/s002400000132
Ashraf, S. S., Rao, M. V., Kaneez, F. S., Qadri, S., Al-Marzouqi, A. H., Chandranath, I. S., & Adem, A. (2011). Nigella sativa extract as a potent antioxidant for petrochemical-induced oxidative stress. Journal of Chromatographic Science, 49(4), 321-326. https://doi.org/10.1093/chrsci/49.4.321
Ayan, M., Tas, U., Sogut, E., Caylı, S., Kaya, H., Esen, M., Erdemir, F., & Uysal, M. (2016). Protective effect of thymoquinone against testicular torsion induced oxidative injury. Andrologia, 48(2), 143-151. https://doi.org/10.1111/and.12424
Badary, O. A., Taha, R. A., Gamal El-Din, A. M., & Abdel-Wahab, M. H. (2003). Thymoquinone is a potent superoxide anion scavenger. Drug and Chemical Toxicology, 26(2), 87-98. https://doi.org/10.1081/dct-120020404
Barqawi, A., Caruso, A., & Meacham, R. B. (2004). Experimental varicocele induces testicular germ cell apoptosis in the rat. Journal of Urology, 171(1), 501-503. https://doi.org/10.1097/01.ju.0000088775.69010.61
Bitkin, A., Basak Ozbalci, A., Aydin, M., Keles, M., Akgunes, E., Atilla, M. K., & Irkilata, L. (2019). Effects of varicocele on testicles: Value of strain elastography: A prospective controlled study. Andrologia, 51(1), e13161. https://doi.org/10.1111/and.13161
Chen, B., Guo, J.-H., Lu, Y.-N., Ying, X.-L., Hu, K., Xiang, Z.-Q., Wang, Y.-X., Chen, P., & Huang, Y.-R. (2009). Leptin and varicocele-related spermatogenesis dysfunction: Animal experiment and clinical study. International Journal of Andrology, 32(5), 532-541. https://doi.org/10.1111/j.1365-2605.2008.00892.x
Choi, H., Kim, K. S., & Kim, K. M. (1990). The effect of experimental varicocele on the testis of adolescent rats. Journal of Urology, 144(2 Pt 2), 499-501; discussion 512-493. https://doi.org/10.1016/s0022-5347(17)39502-2
Curtin, J. F., Donovan, M., & Cotter, T. G. (2002). Regulation and measurement of oxidative stress in apoptosis. Journal of Immunological Methods, 265(1-2), 49-72. https://doi.org/10.1016/s0022-1759(02)00070-4
Dana, H., Bayramov, K. K., Delibasi, N., Tahtasakal, R., Bayramov, R., Hamurcu, Z., & Sener, E. F. (2020). Disregulation of autophagy in the transgenerational Cc2d1a mouse model of autism. NeuroMolecular Medicine, 22(2), 239-249. https://doi.org/10.1007/s12017-019-08579-x
Darakhshan, S., Bidmeshki Pour, A., Hosseinzadeh Colagar, A., & Sisakhtnezhad, S. (2015). Thymoquinone and its therapeutic potentials. Pharmacological Research, 95-96, 138-158. https://doi.org/10.1016/j.phrs.2015.03.011
Dehkordi, F. R., & Kamkhah, A. F. (2008). Antihypertensive effect of Nigella sativa seed extract in patients with mild hypertension. Fundamental & Clinical Pharmacology, 22(4), 447-452. https://doi.org/10.1111/j.1472-8206.2008.00607.x
Erboga, M., Aktas, C., Kurt, O., Uygur, R., Caglar, V., Turan, B. C., Topcu, B., Fidanol Erboga, Z., Gurel, A., & Ozen, O. A. (2016). Protective effects of thymoquinone on experimental testicular ischaemia-reperfusion injury: An apoptotic, proliferative and biochemical study. Andrologia, 48(2), 222-230. https://doi.org/10.1111/and.12436
Fretz, P. C., & Sandlow, J. I. (2002). Varicocele: Current concepts in pathophysiology, diagnosis, and treatment. Urologic Clinics of North America, 29(4), 921-937. https://doi.org/10.1016/s0094-0143(02)00075-7
Gokce, A., Oktar, S., Koc, A., Gonenci, R., Yalcinkaya, F., Yonden, Z., & Duru, M. (2010). Protective effect of thymoquinone in experimental testicular torsion. Urologia Internationalis, 85(4), 461-465. https://doi.org/10.1159/000318890
Gokce, A., Oktar, S., Koc, A., & Yonden, Z. (2011). Protective effects of thymoquinone against methotrexate-induced testicular injury. Human and Experimental Toxicology, 30(8), 897-903. https://doi.org/10.1177/0960327110382564
Grillo-Lopez, A. J. (1971). Primary right varicocele. Journal of Urology, 105(4), 540-541. https://doi.org/10.1016/s0022-5347(17)61569-6
Guo, W.-B., Yang, C., Bian, J., Xia, H., Yang, J.-K., Zhou, Q.-Z., Chen, M.-K., Xue, K.-Y., Zhang, W.-S., Wang, P., Li, X., & Liu, C.-D. (2018). With a new clip technique surgically inducing varicocele in Sprague-Dawley rats. BMC Urology, 18(1), 58. https://doi.org/10.1186/s12894-018-0350-7
Gur, F. M., Ikinci Keles, A., Erol, H. S., Guven, C., Taskin, E., Kaya, H., Gur, H. E., Odaci, E., Halici, M. B., & Timurkaan, S. (2021). The effect of 900-MHz radiofrequency electromagnetic fields during the adolescence on the histological structure of rat testis and its androgen and estrogen receptors localization. International Journal of Radiation Research, 19(1), 135-144. https://doi.org/10.29252/ijrr.19.1.135
Hendin, B. N., Kolettis, P. N., Sharma, R. K., Thomas, A. J. Jr, & Agarwal, A. (1999). Varicocele is associated with elevated spermatozoal reactive oxygen species production and diminished seminal plasma antioxidant capacity. Journal of Urology, 161(6), 1831-1834. https://doi.org/10.1016/S0022-5347(05)68818-0
Hendry, W. F., Sommerville, I. F., Hall, R. R., & Pugh, R. C. (1973). Investigation and treatment of the subfertile male. British Journal of Urology, 45(6), 684-692. https://doi.org/10.1111/j.1464-410x.1973.tb12240.x
Hosseini, M., Tavalaee, M., Rahmani, M., Eskandari, A., Shaygannia, E., Kiani-Esfahani, A., Zohrabi, D., & Nasr-Esfahani, M. H. (2020). Capsaicin improves sperm quality in rats with experimental varicocele. Andrologia, e13762. https://doi.org/10.1111/and.13762
Ikeda, M., Kodama, H., Fukuda, J., Shimizu, Y., Murata, M., Kumagai, J., & Tanaka, T. (1999). Role of radical oxygen species in rat testicular germ cell apoptosis induced by heat stress. Biology of Reproduction, 61(2), 393-399. https://doi.org/10.1095/biolreprod61.2.393
Jefferson, K. P., Persad, R. A., & Holly, J. M. (2000). Apoptosis and its relevance to urologists. BJU International, 86(5), 598-606. https://doi.org/10.1046/j.1464-410x.2000.00857.x
Johnsen, S. G. (1970). Testicular biopsy score count-a method for registration of spermatogenesis in human testes: Normal values and results in 335 hypogonadal males. Hormones, 1(1), 2-25. https://doi.org/10.1159/000178170
Kadioglu, A., Tefekli, A., Cayan, S., Kandirali, E., Erdemir, F., & Tellaloglu, S. (2001). Microsurgical inguinal varicocele repair in azoospermic men. Urology, 57(2), 328-333. https://doi.org/10.1016/s0090-4295(00)00908-0
Karna, K. K., Choi, B. R., Kim, M. J., Kim, H. K., & Park, J. K. (2019). The effect of Schisandra chinensis Baillon on cross-talk between oxidative stress, endoplasmic reticulum stress, and mitochondrial signaling pathway in testes of varicocele-induced SD rat. International Journal of Molecular Sciences, 20(22), 5785. https://doi.org/10.3390/ijms20225785
Köksal, I. T., Tefekli, A., Usta, M., Erol, H., Abbasoglu, S., & Kadioglu, A. (2000). The role of reactive oxygen species in testicular dysfunction associated with varicocele. BJU International, 86(4), 549-552. https://doi.org/10.1046/j.1464-410x.2000.00755.x
Koksal, T., Erdogru, T., Toptas, B., Gulkesen, K. H., Usta, M., Baykal, A., & Baykara, M. (2002). Effect of experimental varicocele in rats on testicular oxidative stress status. Andrologia, 34(4), 242-247. https://doi.org/10.1046/j.1439-0272.2002.00500.x
Kruger, T. F., Menkveld, R., Stander, F. S., Lombard, C. J., Van der Merwe, J. P., van Zyl, J. A., & Smith, K. (1986). Sperm morphologic features as a prognostic factor in in vitro fertilization. Fertility and Sterility, 46(6), 1118-1123. https://doi.org/10.1016/s0015-0282(16)49891-2
Lipshultz, L. I., & Corriere, J. N. Jr (1977). Progressive testicular atrophy in the varicocele patient. Journal of Urology, 117(2), 175-176. https://doi.org/10.1016/s0022-5347(17)58387-1
Mahdavi, R., Heshmati, J., & Namazia, N. (2015). Effects of black seeds (Nigella sativa) on male infertility: A systematic review. Journal of Herbal Medicine, 5(3), 133-139. https://doi.org/10.1016/j.hermed.2015.03.002
Mansour, M. A., Nagi, M. N., El-Khatib, A. S., & Al-Bekairi, A. M. (2002). Effects of thymoquinone on antioxidant enzyme activities, lipid peroxidation and DT-diaphorase in different tissues of mice: A possible mechanism of action. Cell Biochemistry and Function, 20(2), 143-151. https://doi.org/10.1002/cbf.968
Moreno, R. D., Lizama, C., Urzua, N., Vergara, S. P., & Reyes, J. G. (2006). Caspase activation throughout the first wave of spermatogenesis in the rat. Cell and Tissue Research, 325(3), 533-540. https://doi.org/10.1007/s00441-006-0186-4
Ning, J.-Z., Rao, T., Cheng, F., Yu, W.-M., Ruan, Y., Yuan, R., Zhu, S.-M., Du, Y., & Xiao, C.-C. (2017). Effect of varicocelectomy treatment on spermatogenesis and apoptosis via the induction of heat shock protein 70 in varicoceleinduced rats. Molecular Medicine Reports, 16(4), 5406-5412. https://doi.org/10.3892/mmr.2017.7239
Noske, H. D., & Weidner, W. (1999). Varicocele - A historical perspective. World Journal of Urology, 17(3), 151-157. https://doi.org/10.1007/s003450050123
Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95(2), 351-358. https://doi.org/10.1016/0003-2697(79)90738-3
Onur, R., Semercioz, A., Orhan, I., & Yekeler, H. (2004). The effects of melatonin and the antioxidant defence system on apoptosis regulator proteins (Bax and Bcl-2) in experimentally induced varicocele. Urological Research, 32(3), 204-208. https://doi.org/10.1007/s00240-004-0403-0
Raifer, J. (1998). Varicocele. Congenital anomalies of the scrotum and testis. In P. C. Walsh, A. B. Retik, E. D. Vaughan, & A. J. Wein (Eds.), Campbell's urology (pp. 2186-2195). W.B. Saunders Company.
Saypol, D. C., Howards, S. S., Turner, T. T., & Miller, E. D. Jr (1981). Influence of surgically induced varicocele on testicular blood flow, temperature, and histology in adult rats and dogs. Journal of Clinical Investigation, 68(1), 39-45. https://doi.org/10.1172/jci110252
Schatte, E. C., Hirshberg, S. J., Fallick, M. L., Lipschultz, L. I., & Kim, E. D. (1998). Varicocelectomy improves sperm strict morphology and motility. Journal of Urology, 160(4), 1338-1340. https://doi.org/10.1016/S0022-5347(01)62531-X
Shoji, H., & Koletzko, B. (2007). Oxidative stress and antioxidant protection in the perinatal period. Current Opinion in Clinical Nutrition and Metabolic Care, 10(3), 324-328. https://doi.org/10.1097/MCO.0b013e3280a94f6d
Sinha Hikim, A. P., & Swerdloff, R. S. (1999). Hormonal and genetic control of germ cell apoptosis in the testis. Reviews of Reproduction, 4(1), 38-47. https://doi.org/10.1530/ror.0.0040038
Suzuki, N., & Sofikitis, N. (1999). Protective effects of antioxidants on testicular function of varicocelized rats. Yonago Acta Medica Journal, 42, 87-94.
Taghizadeh, L., Eidi, A., Mortazavi, P., & Rohani, A. H. (2017). Effect of selenium on testicular damage induced by varicocele in adult male Wistar rats. Journal of Trace Elements in Medicine and Biology, 44, 177-185. https://doi.org/10.1016/j.jtemb.2017.08.003
Tek, M., Cayan, S., Yilmaz, N., Oguz, I., Erdem, E., & Akbay, E. (2009). The effect of vascular endothelial growth factor on spermatogenesis and apoptosis in experimentally varicocele-induced adolescent rats. Fertility and Sterility, 91(5 Suppl), 2247-2252. https://doi.org/10.1016/j.fertnstert.2008.06.008
Tufek, N. H., Altunkaynak, M. E., Altunkaynak, B. Z., & Kaplan, S. (2015). Effects of thymoquinone on testicular structure and sperm production in male obese rats. Systems Biology in Reproductive Medicine, 61(4), 194-204. https://doi.org/10.3109/19396368.2015.1044135
WHO Manual for the Standardized Investigation and Diagnosis of the Infertile Couple (2000).
Youssef, T., Abd-Elaal, E., Gaballah, G., Elhanbly, S., & Eldosoky, E. (2009). Varicocelectomy in men with nonobstructive azoospermia: Is it beneficial? International Journal of Surgery, 7(4), 356-360. https://doi.org/10.1016/j.ijsu.2009.05.009
Zhang, J., Jin, P. P., Gong, M., Yi, Q. T., & Zhu, R. J. (2018). Role of leptin and the leptin receptor in the pathogenesis of varicocele-induced testicular dysfunction. Molecular Medicine Reports, 17(5), 7065-7072. https://doi.org/10.3892/mmr.2018.8753
Zheng, Y., Zhang, X., Zhou, J., Cheng, F., & Zhou, B. (2008). Effects on the ipsilateral testis during progression of experimental varicocele in rat. Medical Science Monitor, 14(6), BR122-126.
Zhou, S.-F., Li, J.-P., Yang, Y.-X., Liu, Q.-L., Pan, S., He, Z., Zhang, X., Yang, T., Chen, X.-W., Wang, D., & Qiu, J. (2015). The investigational Aurora kinase A inhibitor alisertib (MLN8237) induces cell cycle G2/M arrest, apoptosis, and autophagy via p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells. Drug Design, Development and Therapy, 9, 1627-1652. https://doi.org/10.2147/DDDT.S75378