Document Type : Original Article
Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
Methylphenidate (MPH) and nicotine (NCT) have deleterious effects on testicular tissue, individually. Methylphenidate intake could increase the tendency to use NCT. In this study, the possible synergistic effects of MPH and NCTon the intensity of structural and functional changes of testicular tissue were evaluated using experimental animal study. Eighty male mature Wistar rats were used. MPH (5 and 10 mg/kg, IP) and NCT (2 and 4 mg/kg, IP) were administrated individually (MPH or NCT) or simultaneously (MPH + NCT) to eight treated groups of adult rats (n = 10/group) once a day for eight weeks. After the recording of body and testicular weight, the plasma level of pituitary gonadotropins, testosterone, and malondialdehyde (MDA) as lipid peroxidation index were measured. Also, testes samples were prepared for tissue lipid peroxidation assay, histomorphology, immunohistochemistry of p53 protein, and electron microscopy. Moreover, sperm analysis was performed on cauda epididymis. There was not any significant difference in initial and final body weight between groups. Testicular weight and testicular to body weight ratio were reduced in treated groups. LH, Testosterone, and plasma and tissue MDA were increased and FSH decreased dose-dependently in the most treated groups. Most of the histomorphometric, cell population, and sperm analysis parameters were decreased in treated groups in a dose-dependent manner. The light and electron micrographs showed various alterations in testicular tissue which were more obvious in higher doses of NCT or MPH and NCT + MPH groups. Immunostaining of testicular tissue revealed upregulation of p53 in treated groups, particularly in NCT + MPH groups. The results of this study showed that simultaneous administration of NCT and MPH could induce more alterations in the structure and function of testicular tissue compared to their individual administration.
- Guerriero G, Trocchia S, Abdel-Gawad FK, Ciarcia G. Roles of reactive oxygen species in the spermatogenesis regulation. Frontiers in Endocrinology, 2014; 5: 56.
- Zenzes MT. Smoking and reproduction: gene damage to human gametes and embryos. Human Reproduction Update, 2000; 6: 122-131.
- Aitken RJ, Roman SD. Antioxidant systems and oxidative stress in the testes. Oxidative Medicine and Cellular Longevity, 2008; 1: 15-24.
- Arabi M. Nicotinic infertility: assessing DNA and plasma membrane integrity of human spermatozoa. Andrologia, 2004; 36: 305-310.
- Cansu A. Ekinci Ö, Ekinci Ö, Serdaroglu A, Erdoğan D, Coşkun ZK, Gürgen SG. Methylphenidate has dose-dependent negative effects on rat spermatogenesis: decreased round spermatids and testicular weight and increased p53 expression and apoptosis. Human and Experimental Toxicology, 2011; 30: 1592-1600.
- Teo S. Stirling D, Thomas S, Hoberman A, Kiorpes A, Khetani V. A 90-day oral gavage toxicity study of d-methylphenidate and d, l-methylphenidate in Sprague–Dawley rats. Toxicology, 2002; 179: 183-196.
- Weyandt LL. Oster DR, Marraccini ME, Gudmundsdottir BG, Munro BA, Rathkey ES, McCallum A. Prescription stimulant medication misuse: Where are we and where do we go from here? Experimental and Clinical Psychopharmacology, 2016; 24: 400.
- Oyeyipo IP, Raji Y, Emikpe BO, Bolarinwa,A. . Effects of nicotine on sperm characteristics and fertility profile in adult male rats: a possible role of cessation. Journal of Reproduction and Infertility, 2011; 12: 201.
- Ghanbari M, Ahmadnia H, Moradi MR, Khajeh DM. Effect of cigarette smoke on spermatogenesis in rats 2007.
- Hassan A, Abo‐Azma SM, Fayed SM, Mostafa T. Seminal plasma cotinine and insulin‐like growth factor‐I in idiopathic oligoasthenoteratozoospermic smokers. BJU International, 2009: 103: 108-111.
- Nair AB, Jacob SA. Simple practice guide for dose conversion between animals and human. Journal of Basic and Clinical Pharmacy, 2016; 7: 27.
- Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 1979; 95: 351-358.
- Shetty G. Wilson G, Huhtaniemi I, Shuttlesworth GA, Reissmann T, Meistrich ML. Gonadotropin-releasing hormone analogs stimulate and testosterone inhibits the recovery of spermatogenesis in irradiated rats. Endocrinology, 2000; 141: 1735-1745.
- Pant N, Srivastava S. Testicular and spermatotoxic effects of quinalphos in rats. Journal of Applied Toxicology, 2003; 23: 271-274.
- Thakur M. Gupta H, Singh D, Mohanty IR, Maheswari U, Vanage G, Joshi DS. Histopathological and ultra structural effects of nanoparticles on rat testis following 90 days (chronic study) of repeated oral administration. Journal of Nanobiotechnology, 2014; 12: 42.
- Wooters TE, Neugebauer NM, Rush CR, Bardo MT. Methylphenidate enhances the abuse-related behavioral effects of nicotine in rats: intravenous self-administration, drug discrimination, and locomotor cross-sensitization. Neuropsychopharmacology, 2008; 33: 1137.
- Agarwal A, Makker K, Sharma R. Clinical relevance of oxidative stress in male factor infertility: an update. American Journal of Reproductive Immunology, 2008; 59: 2-11.
- Adeoya-Osiguwa SA, Gibbons R, Fraser LR. Identification of functional α2-and β-adrenergic receptors in mammalian spermatozoa. Human Reproduction, 2006; 21: 1555-1563.
- Otth C. Torres M, Ramírez A, Fernandez JC, Castro M, Rauch MC, Brito M, Yanez AJ, Rodríguez‐Gil JE, Slebe JC, Concha II. Novel identification of peripheral dopaminergic D2 receptor in male germ cells. Journal of Cellular Biochemistry 2007; 100: 141-150.
- Adriani W. Leo D, Guarino M, Natoli A, Di Consiglio E, De Angelis G, Traina E, Testai E, Perrone‐Capano CA, Laviola G. Short‐term effects of adolescent methylphenidate exposure on brain striatal gene expression and sexual/endocrine parameters in male rats. Annals of the New York Academy of Sciences, 2006; 1074: 52-73.
- Ciechanowska M, Łapot M, Mateusiak K, Przekop F. Neuroendocrine regulation of GnRH release and expression of GnRH and GnRH receptor genes in the hypothalamus-pituitary unit in different physiological states. Reproductive Biology, 2010; 10: 85-124.
- Abdollahzadeh A, Kianifard D, Saiah GV. Study of the long-term and dose dependent effects of methylphenidate and monosodium glutamate on the hormonal alterations of the pituitary-testicular axis and sperm analysis in adolescence rats. Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca. Veterinary Medicine, 2017; 74: 75-81.
- Mosadegh M, Hasanzadeh S, Razi M. Nicotine-induced damages in testicular tissue of rats; evidences for bcl-2, p53 and caspase-3 expression. Iranian Journal of Basic Medical Sciences, 2017; 20: 199.
- Crissman JW. Goodman DG, Hildebrandt PK, Maronpot RR, Prater DA, Riley JH, Seaman WJ, Thake DC. Best practices guideline: toxicologic histopathology. Toxicologic Pathology, 2004; 32: 126-131.
- Walker WH, Cheng J. FSH and testosterone signaling in Sertoli cells. Reproduction, 2005; 130: 15-28.
- George VK. Li H, Teloken C, Grignon DJ, Lawrence WD, Dhabuwala CB. Effects of long-term cocaine exposure on spermatogenesis and fertility in peripubertal male rats. The Journal of Urology, 1996; 155: 327-331.
- Katoh C. Kitajima S, Saga Y, Kanno J, Horii I, Inoue T. Assessment of quantitative dual-parameter flow cytometric analysis for the evaluation of testicular toxicity using cyclophosphamide-and ethinylestradiol-treated rats. The Journal of Toxicological Sciences, 2002; 27: 87-96.
- Azad F, Nejati V, Shalizar-Jalali A, Najafi G, Rahmani F. Royal jelly protects male mice against nicotine-induced reproductive failure. Veterinary Research Forum, 2018; 9: 231.
- Shen HM, Ong CN. Detection of oxidative DNA damage in human sperm and its association with sperm function and male infertility. Free Radical Biology and Medicine, 2000; 28: 529-536.
- Shukla KK, Mahdi AA, Rajender, S. Apoptosis, spermatogenesis and male infertility. Front Biosci (Elite Ed), 2012; 4: 746-754.
- Yin Y, Stahl BC, Dewolf WC, Morgentaler A. P53 and Fas are sequential mechanisms of testicular germ cell apoptosis. Journal of Andrology, 2002; 23: 64-70.
- Li M. He Y, Dubois W, Wu X, Shi J, Huang J. Distinct regulatory mechanisms and functions for p53-activated and p53-repressed DNA damage response genes in embryonic stem cells. Molecular Cell, 2012; 46: 30-42.
- Aydos K, Güven M, Can B, Ergün A. Nicotine toxicity to the ultrastructure of the testis in rats. BJU International, 2001; 88: 622-626.
- Bahcelioglu M. Gozil R, Take G, Elmas C, Oktem H, Kadioglu D, Calguner E, Erdogan D, Sargon MF, Yazici AC, Tas M. Dose-related immunohistochemical and ultrastructural changes after oral methylphenidate administration in cerebrum and cerebellum of the rat. The World Journal of Biological Psychiatry, 2009; 10: 531-543.
- Haider S, Talati J, Servos G. Ultrastructure of peritubular tissue in association with tubular hyalinization in human testis. Tissue and Cell, 1999; 31: 90-98.
- Cameron DF, Murray FT, Drylie DD. Interstitial compartment pathology and spermatogenic disruption in testes from impotent diabetic men. The Anatomical Record, 1985; 213: 53-62.
- Yoon YS. Yoon DS, Lim IK, Yoon SH, Chung HY, Rojo M, Malka F, Jou MJ, Martinou JC, Yoon G. Formation of elongated giant mitochondria in DFO‐induced cellular senescence: involvement of enhanced fusion process through modulation of Fis1. Journal of Cellular Physiology, 2006; 209: 468-480.