Hostname: page-component-586b7cd67f-l7hp2 Total loading time: 0 Render date: 2024-11-22T19:40:37.491Z Has data issue: false hasContentIssue false
  • English
  • Français

Resveratrol Ameliorates the Seminiferous Tubules Damages Induced by Finasteride in Adult Male Rats

Published online by Cambridge University Press:  05 October 2020

Amany Mohamed Shalaby Open the ORCID record for Amany Mohamed Shalaby [Opens in a new window] ,
Mohamed Ali Alabiad  and
Dina Fouad El Shaer
Amany Mohamed Shalaby*
Affiliation:
Histology and Cell Biology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
Mohamed Ali Alabiad
Affiliation:
Pathology Department, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt College of Medicine, Shaqra University, Shaqra, Kingdom of Saudi Arabia
Dina Fouad El Shaer
Affiliation:
Histology and Cell Biology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
*
*Author for correspondence: Amany Mohamed Shalaby, E-mail: [email protected]
Get access

Abstract

Finasteride is commonly used in the management of alopecia and nodular prostatic hyperplasia. It was reported to have a harmful effect on spermatogenesis with subsequent infertility. Thus, this research was to determine the ameliorative effect of resveratrol against testicular damage caused by finasteride. Forty adult male rats were randomly divided into four main groups: group I acted as the control, group II was administrated resveratrol 20 mg/kg/day, group III was administrated finasteride 5 mg/kg/day, and group IV was administrated finasteride and resveratrol as in the previous groups. Finasteride induced a significant decrement in the testosterone and dihydrotestosterone levels. The level of malondialdehyde significantly increased, while the levels of glutathione peroxidase, superoxide dismutase, and catalase significantly decreased in the finasteride-administrated rats. Variable histopathological alterations in the testes were revealed in the form of irregular seminiferous tubules. Some seminiferous tubules appeared with degenerated germinal epithelium. Others showed detachment of their germinal epithelium. Congested blood vessels and homogeneous acidophilic substance in-between tubules were also detected. A significant decrement in PCNA positive cells and a significant increment in Bax expression were demonstrated. Ultrastructural examination showed Sertoli cells with rarefied cytoplasm. Vacuolated cytoplasm, shrunken nuclei, and dilated perinuclear spaces were also revealed in the spermatogonia, primary spermatocytes, and early spermatids. On the contrary, few changes were noticed in rats received resveratrol concomitant with finasteride. This study indicated that resveratrol exerted a potent ameliorative effect against testicular injury caused by finasteride.

Keywords

5-α reductase inhibitorBaxelectron microscopyoxidative stressPCNAtestis
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 26 , Issue 6 , December 2020 , pp. 1176 - 1186
Copyright
Copyright © Microscopy Society of America 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adhikari, N, Sinha, N, Narayan, R & Saxena, KD (2001). Lead-induced cell death in testes of young rats. J Appl Toxicol 21, 275–277.CrossRefGoogle ScholarPubMed
Agarwal, A & Prabakaran, SA (2005). Mechanism, measurement, and prevention of oxidative stress in male reproductive physiology. Indian J Exp Biol 43(11), 963–974.Google ScholarPubMed
Amory, JK, Wang, C, Swerdloff, RS, Anawalt, BD, Matsumoto, AM, Bremner, WJ, Walker, SE, Haberer, LJ & Clark, RV (2007). The effect of 5a-reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men. J Clin Endocrinol Metab 92, 1659–1665.CrossRefGoogle Scholar
Archana, D, Supriya, C, Girish, BP, Kishori, B & Reddy, PS (2018). Alleviative effect of resveratrol on polyvinyl chloride-induced reproductive toxicity in male Wistar rats. Food Chem Toxicol 116, 173–181.CrossRefGoogle ScholarPubMed
Avdatek, F, Birdane, YO, Türkmen, R & Demirel, HH (2018). Ameliorative effect of resveratrol on testicular oxidative stress, spermatological parameters and DNA damage in glyphosate-based herbicide-exposed rats. Andrologia 50(7), 13036.CrossRefGoogle ScholarPubMed
Banerjee, B, Chakraborty, S, Chakraborty, P, Ghosh, D & Jana, K (2019). Protective effect of Resveratrol on benzo (a) pyrene induced dysfunctions of steroidogenesis and steroidogenic acute regulatory gene expression in Leydig cells. Front Endocrinol 10, 272.CrossRefGoogle ScholarPubMed
Bradbury, P & Rae, K (1996). Connective tissues and stains. In Theory and Practice of Histological Techniques, 4th ed., Bancroft, JD & Stevens, A (Eds.), pp. 113–137. New York: Churchill Livingstone.Google Scholar
Caruso, F, Tanski, J, Villegas-Estrada, A & Rossi, M (2004). Structural basis for antioxidant activity of trans-resveratrol: Ab initio calculations and crystal and molecular structure. J Agric Food Chem 52(24), 7279–7285.CrossRefGoogle ScholarPubMed
Chandler, DE & Roberson, RW (2009). Bioimaging: Current Concepts in Light and Electron Microscopy, p. 29. Burlington, Massachus: Jones & Bartlett Publishers.Google Scholar
Chiba, K, Yamaguchi, K, Li, F, Ando, M & Fujisawa, M (2011). Finasteride-associated male infertility. Fertil Steril 95, 1786.e9–1786.e11.CrossRefGoogle ScholarPubMed
Claiborn, A (1986). Catalase activity. In CRC Handbook of Methods for Oxygen Radical Research, 2nd ed., Greenwald, RA (Ed.), pp. 283–284. Boca Raton: CRC Press.Google Scholar
Clark, RV, Hermann, DJ, Cunningham, GR, Wilson, TH, Morrill, BB & Hobbs, S (2004). Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J Clin Endocrinol Metab 89, 2179–2184.CrossRefGoogle ScholarPubMed
D'andrea, MR, Alicknavitch, M, Nagele, RG & Damiano, BP (2010). Simultaneous PCNA and TUNEL labeling for testicular toxicity evaluation suggests that detection of apoptosis may be more sensitive than proliferation. Biotech Histochem 85(3), 195–204.CrossRefGoogle ScholarPubMed
Dawson-Saunders, B & Trapp, RG (2001). Section 5.6: Proportions when the same group is measured twice. In Basic & Clinical Biostatistics: Lange Medical Book, 3rd ed., Dawson, B, Trapp, RG & Trapp, R (Eds.), pp. 115–118. New York, Montreal: McGraw-Hill Book Co.Google Scholar
Eleawa, SM, Alkhateeb, MA, Alhashem, FH, Bin-Jaliah, I, Sakr, HF, Elrefaey, HM, Elkarib, AO, Alessa, RM, Haidara, MA, Shatoor, AS & Khalil, MA (2014). Resveratrol reverses cadmium chloride-induced testicular damage and subfertility by downregulating p53 and Bax and upregulating gonadotropins and Bcl-2 gene expression. J Reprod Dev 60(2), 115–127.CrossRefGoogle ScholarPubMed
Emanuel, R (2001). Essential Pathology, 3rd ed., p. 1. Philadelphia: Lippincott Williams & Wilkins.Google Scholar
Gambini, J, Inglés, M, Olaso, G, Lopez-Grueso, R, Bonet-Costa, V, Gimeno-Mallench, L, Mas-Bargues, C, Abdelaziz, KM, Gomez-Cabrera, MC, Vina, J & Borras, C (2015). Properties of resveratrol: In vitro and in vivo studies about metabolism, bioavailability, and biological effects in animal models and humans. Oxid Med Cell Longev 2015, reference id number 837042.CrossRefGoogle ScholarPubMed
Gamble, M (2008). The hematoxylins and eosin. In Theory and Practice of Histological Techniques, 6th ed., Bancroft, JD & Gamble, M (Eds.), pp. 121–135. London: Churchill Livingstone.CrossRefGoogle Scholar
Giuliano, F (2006). Impact of medical treatments for benign prostatic hyperplasia on sexual function. BJU Int. 97, 34–38.CrossRefGoogle ScholarPubMed
Guyton, AC & Hall, JE (2000. Reproductive and hormonal function of male (and the pineal gland). In Text Book of Medical Physiology, Guyton, AC & Hall, JE (Eds.), , 9th ed.. pp. 916–928. London, Toronto, Philadelphia: A.S. and Saunders CompanyGoogle Scholar
Irwig, MS (2012). Depressive symptoms and suicidal thoughts among former users of finasteride with persistent sexual side effects. J Clin Psychiatry 73, 1220–1223.CrossRefGoogle ScholarPubMed
Irwig, MS & Kolukula, S (2011). Persistent sexual side effects of finasteride for male pattern hair loss. J Sex Med 8, 1747–1753.CrossRefGoogle ScholarPubMed
Jiang, YG, Tao, PE, Yong, LU, Li, MC & Lin, YH (2008). Resveratrol reestablishes spermatogenesis after testicular injury in rats caused by 2,5-hexanedione. Chin Med J 121(13), 1204–1209.CrossRefGoogle ScholarPubMed
Juan, ME, Gonzalez-Pons, E, Munuera, T, Ballester, J, Rodríguez-Gil, JE & Planas, JM (2005). trans-Resveratrol, a natural antioxidant from grapes, increases sperm output in healthy rats. J Nutr 135(4), 757–760.CrossRefGoogle ScholarPubMed
Koksal, IT, Usta, M, Orhan, I, Abbasoglu, S & Kadıoglu, A (2003). Potential role of reactive oxygen species on testicular pathology associated with infertility. Asian J Androl 5, 95–99.Google ScholarPubMed
Kolasa, A, Marchlewicz, M, Wenda-Rozewicka, L & Wiszniewska, B (2004). Morphology of the testis and the epididymis in rats with dihydrotestosterone (DHT) deficiency. Rocz Akad Med Bialymst 49, 117–119.Google ScholarPubMed
Kolasa, A, Marchlewicz, M, Wenda-Różewicka, L & Wiszniewska, B (2011). DHT deficiency perturbs the integrity of the rat seminiferous epithelium by disrupting tight and adherens junctions. Folia Histochem Cytobiol 49(1), 62–71.CrossRefGoogle ScholarPubMed
Kondo, T, Goto, S, Ihara, Y, Urata, Y, Ikedas, S, Hishikawa, Y, Izumi, S, Shin, M & Koji, T (2002). Diethylstilbestrol attenuates antioxidant activities in testis from male mice. Free Radic Res 36, 957–966.CrossRefGoogle ScholarPubMed
Kumar, V, Abbas, AK, Fasuto, N & Aster, JC (2015). Robbins & Cotran Pathologic Basis of Disease, 9th ed., p. 42. Philadelphia, USA: Elsevier Saunders.Google Scholar
Layton, C & Bancroft, J (2013). Carbohydrates. In Bancroft's Theory and Practice of Histological Techniques, 7th ed., Bancroft, J, Layton, Ch & Suvarana, S (Eds.), , pp. 215. London: Churchill Livingstone/Elsevier.CrossRefGoogle Scholar
Li, E, Guo, Y, Wang, G, Chen, F & Li, Q (2015). Effect of resveratrol on restoring spermatogenesis in experimental cryptorchid mice and analysis of related differentially expressed proteins. Cell Biol Int 39, 733–740.CrossRefGoogle ScholarPubMed
McLachlan, RI, O'Donnell, L, Meachem, SJ, Stanton, PG, de Kretser, DM, Pratis, K & Robertson, DM (2002). Identification of specific sites of hormonal regulation in spermatogenesis in rats, monkeys, and man. Recent Prog Horm Res 57, 149–179.CrossRefGoogle ScholarPubMed
Moffit, JS, Bryant, BH, Hall, SJ & Boekelheide, K (2007). Dose-dependent effects of Sertoli cell toxicants 2,5-hexanedione, carbendazim, and mono-(2-ethylhexyl) phthalate in adult rat testis. Toxicol Pathol 35(5), 719–727.CrossRefGoogle ScholarPubMed
Mokhtari, M, Shariati, M & Amiri, J (2007). Effects of tamsolusin on serum testosterone and gonadotropins concentration in adult male rats. JRUMS 6(1), 1–6.Google Scholar
Mokni, M, Limam, F, Elkahoui, S, Amri, M & Aouani, E (2007). Strong cardioprotective effect of resveratrol, a red wine polyphenol, on isolated rat hearts after ischemia/reperfusion injury. Arch Biochem Biophys 457, 1–6.CrossRefGoogle ScholarPubMed
Obaid, FN & Jaffat, HS (2018). Physiological and histological study of the effect of finasteride drug (Prostacare-5 mg) on the fertility of Albino male rats. Plant Arch 18(1), 863–866.Google Scholar
Omur, AD, Yildirim, B, Saglam, YS, Comakli, S & Ozkaraca, M (2019). Activity of resveratrol on the influence of aflatoxin B1 on the testes of Sprague Dawley rats. Pol J Vet Sci 22(2), 313–320.Google ScholarPubMed
Paglia, DE & Valentine, WN (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70(1), 158–169.Google ScholarPubMed
Pandya, C, Pillai, P, Nampoothiri, LP, Bhatt, N & Gupta, S (2012). Effect of lead and cadmium co-exposure on testicular steroid metabolism and antioxidant system of adult male rats. Andrologia 44, 813–822.CrossRefGoogle ScholarPubMed
Rhoden, EL, Gobbi, D, Menti, E, Rhoden, C & Telöken, C (2002). Effects of the chronic use of finasteride on testicular weight and spermatogenesis in Wistar rats. BJU Int 89(9), 961–963.CrossRefGoogle ScholarPubMed
Rolf, C, Von Eckardstein, S, Koken, U & Nieschlag, E (2002). Testosterone substitution of hypogonadal men prevents the age-dependent increases in body mass index, body fat and leptin seen in healthy ageing men: Results of a cross-sectional study. Eur J Endocrinol 146(4), 505–511.CrossRefGoogle ScholarPubMed
Serga, CN (2009). The Effect of different doses of finasteride on epididymis and testosterone and DHT concentrations in rats. J Cairo Univ 77(1), 429–437.Google Scholar
Shalaby, AM, Aboregela, AM, Alabiad, MA & El Shaer, DF (2020). Tramadol promotes oxidative stress, fibrosis, apoptosis, ultrastructural and biochemical alterations in the adrenal cortex of adult male rat with possible reversibility after withdrawal. Microsc Microanal 26(3), 509–523.CrossRefGoogle ScholarPubMed
Shati, AA (2019). Resveratrol improves sperm parameter and testicular apoptosis in cisplatin-treated rats: Effects on ERK1/2, JNK, and Akt pathways. Syst Biol Reprod Med 65(3), 236–249.CrossRefGoogle ScholarPubMed
Shibata, Y, Ono, Y, Kashiwagi, B, Suzuki, K, Fukabori, Y, Honma, S & Yamanaka, H (2003). Hormonal and morphologic evaluation of the effects of anti-androgens on the blood supply of the rat prostate. Urology 62, 942–946.CrossRefGoogle ScholarPubMed
Shin, S, Jeon, JH, Park, D, Jang, MJ, Choi, JH, Choi, BH, Joo, SS, Nahm, SS, Kim, JC & Kim, YB (2008). trans-Resveratrol relaxes the corpus cavernosum ex vivo and enhances testosterone levels and sperm quality in vivo. Arch Pharmacal Res 31(1), 83–87.CrossRefGoogle ScholarPubMed
Singh, I, Goyal, Y & Ranawat, P (2017). Potential chemoprotective role of resveratrol against cisplatin induced testicular damage in mice. Chem Biol Interact 273, 200–211.CrossRefGoogle ScholarPubMed
Sun, Y, Oberley, LW & Li, Y (1988). A simple method for clinical assay of superoxide dismutase. Clin Chem 34, 497–500.CrossRefGoogle ScholarPubMed
Tam, NN, Gao, Y, Leung, YK & Ho, SM (2003). Androgenic regulation of oxidative stress in the rat prostate: Involvement of NAD (P) H oxidases and antioxidant defense machinery during prostatic involution and regrowth. Am J Pathol 163(6), 2513–2522.CrossRefGoogle ScholarPubMed
Thompson, IM, Goodman, PJ, Tangen, CM, Lucia, MS, Miller, GJ, Ford, LG, Lieber, MM, Cespedes, RD, Atkins, JN, Lippman, SM & Carlin, SM (2003). The influence of finasteride on the development of prostate cancer. N Engl J Med 349(3), 215–224.CrossRefGoogle ScholarPubMed
Türedi, S, Yuluğ, E, Alver, A, Kutlu, Ö & Kahraman, C (2014). Effects of resveratrol on doxorubicin induced testicular damage in rats. Exp Toxicol Pathol 67(3), 229–235.CrossRefGoogle ScholarPubMed
Turkmen, R, Birdane, YO, Demirel, HH, Kabu, M & Ince, S (2019). Protective effects of resveratrol on biomarkers of oxidative stress, biochemical and histopathological changes induced by sub-chronic oral glyphosate-based herbicide in rats. Toxicol Res 8(2), 238–245.CrossRefGoogle ScholarPubMed
Uchiyama, M & Mihara, M (1978). Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 86, 271–278.CrossRefGoogle Scholar
Vidigal, DJ, Silva, AL, Fonseca, LM, Vasconcelos, AC, Resende, DF & Vidigal, FE (2008). The effect of finasteride on spermatogenesis of Mesocricetus auratus. Acta Cir Bras 23(3), 282–286.CrossRefGoogle ScholarPubMed
Woods, A & Stirling, J (2008). Electron microscope. In Theory and Practice of Histological Techniques, Bancroft, J & Gamble, M (Eds.), p. 600. Philadelphia, PA: Churchill Livingstone/Elsevier.Google Scholar
Wu, C, Zhang, Y, Shen, Q, Zhou, Z, Liu, W & Hua, J (2016). Resveratrol changes spermatogonial stem cells (SSCs) activity and ameliorates their loss in busulfan-induced infertile mouse. Oncotarget 7, 82085–82096.CrossRefGoogle ScholarPubMed
Xue, LY, Zhang, XH, Xing, LX, Jie, LI & Wang, GX (2007). Serum hormone and cellular proliferation changes of testis in rats with experimental orchitis induced by lipopolysaccharide. J Reprod Contracept 18(3), 181–186.CrossRefGoogle Scholar
Yay, NÖ, Şener, G & Ercan, F (2019). Resveratrol treatment reduces apoptosis and morphological alterations in cisplatin induced testis damage. J Res Pharm 23(4), 621–631.Google Scholar
Youssef, S & Mohamed, SB (2017). Impact of finasteride administration on neuroactive steroid levels to induce persistent sexual side effects and anxious/depressive disorders and the possible protective effect of Vitamin E. Int Res J Appl Basic Sci 11(2), 200–220.Google Scholar
Yuluğ, E, Türedi, S, Karagüzel, E, Kutlu, Ö, Menteşe, A & Alver, A (2014). The short term effects of resveratrol on ischemia–reperfusion injury in rat testis. J Pediatr Surg 49(3), 484–489.CrossRefGoogle ScholarPubMed
Zarei, F, Yousofvand, N, Khazaei, M & Ghanbari, A (2013). Effect of exogenous testosterone, finasteride, and castration on serum level of thyroxin. Iran Biomed J 17(4), 221.Google ScholarPubMed