Simin FAZELIPOUR, Zahra TOOTIAN, Zahra GHAHRI SAREMI, Minoo SHAFII, Mohammad Taghi SHEIBANI, Seyed Babak KIAEI, Mehrnush KIUMARSI, Fardin ASSADI

Evaluation of histopathologic and histomorphometric changes of testicular tissue and gonadotropin levels following consumption of methylphenidate in male mice

One of the most common psychiatric disorders in children is attention-deficit/hyperactivity disorder, which is treated extensively by methylphenidate. This study investigates the assessment of the effects of methylphenidate on histopathologic and histomorphometric changes of the testes and serum levels of gonadotropin in mice. Materials and methods: In this study, 36 adult male mice were used. After determining their body weights, the animals were divided randomly into 2 experimental groups and 1 control group. The experimental groups received methylphenidate (2 and 10 mg kg-1 day-1) via gavage for a period of 40 days. After evaluation of body weight, general anesthesia was used for taking blood samples from the heart in order to measure testosterone and levels of gonadotropin in serum. For the purpose of weighing the bodies and measuring the thickness of the germinal epithelium, the testes were removed and the possibility of any pathological changes was considered. Results: The results showed that methylphenidate could decrease the thickness of the germinal epithelium and body weight significantly, and could increase the levels of spermatogonia and serum gonadotropins and testosterone. Histopathological changes were also seen for vascular dilatation and congestion in interstitial tissue. Conclusion: Our findings demonstrated that administration of methylphenidate in adulthood may have an effect on spermatogenesis due to the influence of gonadotropin hormones on testis function.

Anahtar Kelimeler:

Key words: Methylphenidate, testis, morphometric, gonadotropin, histopathology

Evaluation of histopathologic and histomorphometric changes of testicular tissue and gonadotropin levels following consumption of methylphenidate in male mice

Keywords:

Key words: Methylphenidate, testis, morphometric, gonadotropin, histopathology,

PDF

___

Kirby K, Rutman LE, Bernstein H. Attention-deficit/ hyperactivity disorder: a therapeutic update. Curr Opin Pediatr 2002; 14: 236–246.
Miller KJ, Castellanos FX. Attention deficit/hyperactivity disorders. Pediatr Rev 1998; 19: 373–384.
Brown RT, Freeman WS, Perrin JM, Stein MT, Amler RW, Feldman HM, Pierce K, Wolraich ML. Prevalence and assessment of attention-deficit/hyperactivity disorder in primary care settings. Pediatrics 2001; 107: E43.
Spencer T, Biederman J, Wilens T, Harding M, O’Donnell D, Griffin S. Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle. J Am Acad Child Adolesc Psychiatry 1996; 35: 409–432.
Findling RL, Dogin JW. Psychopharmacology of ADHD: children and adolescents. J Clin Psychiatry 1997; 9 (Suppl. 7): 42–
Zito JM, Safer DJ, dos Reis S, Gardner JF, Boles M, Lynch F. Trends in the prescribing of psychotropic medications to preschoolers. JAMA 2000; 283: 1025–1030.
Greenhill LL, Pliszka S, Dulcan MK, Bernet W, Arnold V, Beitchman J, Benson RS, Bukstein O, Kinlan J, McClellan J et al. Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults. J Am Acad Child Adolesc Psychiatry 2002; 41: 26S–49S.
Silver LB. Attention-deficit/hyperactivity disorder in adult life. Child Adolesc Psychiatr Clin North Am 2000; 9: 511–523.
Taylor FB, Russo J. Comparing guanfacine and dextroamphetamine for the treatment of adult attentiondeficit/hyperactivity disorder. J Clin Psychopharmacol 2001; 21: 223–228.
Adriani W, Leo D, Guarino M, Natoli A, Di Consiglio E, De Angelis G, Traina E, Testai E, Perrone-Capano C, Laviola G. Short-term effects of adolescent methylphenidate exposure on brain striatal gene expression and sexual/endocrine parameters in male rats. Ann N Y Acad Sci 2006; 1074: 52–73.
Manjanatha MG, Shelton SD, Dobrovolsky VN, Shaddock JG, McGarrity LG, Doerge DR, Twaddle NW, Lin CJ, Chen JJ, Mattison DR et al. Pharmacokinetics, dose-range, and mutagenicity studies of methylphenidate hydrochloride in B6C3F1 mice. Environ Mol Mutagen 2008; 49: 585–593.
Markowitz JS, DeVane CL, Pestreich LK, Patrick KS, Muniz R. A comprehensive in vitro screening of d-, l-, and dl-threomethylphenidate: an exploratory study. J Child Adolesc Psychopharmacol 2006; 16: 687–698.
Chapin R. Methylphenidate hydrochloride. Environ Health Perspect 1997; 105: 319–320.
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. J Urol 1996; 155: 327–331.
Teo SK, Stirling DI, Thomas SD, Hoberman AM, Christian MS, Khetani VD. The perinatal and postnatal toxicity of D-methylphenidate and D,L-methylphenidate in rats. Reproduct Toxicol 2002; 16: 353–366.
Fazelipour S, Hadipour Jahromy M, Tootian Z, Kiaei SB, Sheibani MT, Talaee N. The effect of chronic administration of methylphenidate on morphometric parameters of testes and fertility in male mice. J Reprod Infertil 2012; 13: 232–236.
Kallman WM, Isaac W. The effects of age and illumination on the dose-response curves for three stimulants. Psychopharmacologia 1975; 40: 313–318.
Patrick KS, Markowitz JS. Pharmacology of methylphenidate, amphetamine enantiomers and pemoline in attention-deficit hyperactivity disorder. Hum Psychopharmacol Clin Exp 1998; 12: 527–546.
Teo SK, Stirling DI, Thomas SD, Khetani VD. Neurobehavioral effects of racemic threo-methylphenidate and its D and L enantiomers in rats. Pharmacol Biochem Behav 2003; 74: 747– 7
Volkow ND, Wang GJ, Fowler JS, Fischman M, Foltin R, Abumrad NN, Gatley SJ, Logan J, Wong C, Gifford A et al. Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain. Life Sci 1999; 65: PL7–12.
Dafny N, Yang PB. The role of age, genotype, sex, and route of acute and chronic administration of methylphenidate: a review of its locomotor effects. Brain Res Bull 2006; 68: 393–405.
Wax PM. Analeptic use in clinical toxicology: a historical appraisal. J Toxicol Clin Toxicol 1997; 35: 203–209.
Chatterjee-Chakrabarty S, Miller BT, Collins TJ, Nagamani M. Adverse effects of methylphenidate on the reproductive axis of adolescent female rats. Fertil Steril 2005; 84: 1131–1138.
Meyers CA, Weitzner MA, Valentine AD, Levin VA. (1998)
Methylphenidate therapy improves cognition, mood, and function of brain tumor patients. J Clin Oncol 1998; 16: 2522– 25
Parran TV Jr, Jasinski DR. Intravenous methylphenidate abuse. Prototype for prescription drug abuse. Arch Intern Med 1991; 151: 781–783.
Crutchley A, Temlett JA. Methylphenidate (Ritalin) use and abuse. S Afr Med J 1999; 89: 1076–1079.
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. Hum Exp Toxicol 2011; 30: 1592–1600.
Yang GS, Wang W, Wang YM, Chen ZD, Wang S, Fang JJ. Effect of cocaine on germ cell apoptosis in rats at different ages. Asian J Androl 2006; 8: 569–575.
Homafar MA, Soleimanirad J, Ghanbari AA. A morphologic and morphometric study of adult mouse testis following different doses of busulfan administration. J Reproduct Infertil 2006; 7: 25–36.
James RW, Heywood R, Crook D. (1980) Effects of morphine sulphate on pituitary-testicular morphology of rats. Toxicol Lett 1980; 7: 61–70.
Saraiva KL, Silva VA Jr, Torres Dde O, Donato MA, Peres NG, Souza JR, Peixoto CA. Changes in mouse Leydig cells ultrastructure and testosterone secretion after diethylcarbamazine administration. Micron 2008; 39: 580– 5