Protective effects of melatonin solid lipid nanoparticles on testis histology after testicular trauma in rats

Mehri Mirhoseini , Zahra Rezanejad Gatabi, Majid Saeedi , Katayoun Morteza-Semnani, Fereshteh Talebpour Amiri, Hamid Reza Kelidari, Abbas Ali Karimpour Malekshah


Testicular traumatic injuries occur frequently, which can result in an alteration in spermatogenesis.These injuries can also cause oxidative stress and male infertility. Antioxidant efficiency of melatonin (MLT), known as a potent antioxidant, will be improved if used in a form of solid lipid nanoparticles  (MLT-SLN). The aim of the current study is to evaluate the effect of MLT-loaded SLN on traumatic testis in rats. In this study 32 adult male Wistar rats were divided into 4 groups. Group 1 (sham group), right testicle was drawn out from the scrotum and returned without manipulation. Group 2, right testicle was dropped by 25 g sinker for 4 times. Group 3, animals were received a single dose (25 mg/kg) of MLT intraperitoneally after trauma. Group 4, animals were received a single dose of MLT-SLN intraperitoneally after trauma. Under anaesthesia, rats were sacrificed, and their testicles were removed three days after the surgery. After tissue processing, the sample sections were H&E stained. MLT and MLT-SLN could partially repair spermatogenesis by Johnson's criteria but the repairs were significant only in MLT-SLN group (P = 0.02). Trauma decreased seminiferous tubule diameter and its epithelium height. MLT could restore epithelium height (P ≤ 0.05) but its NPs improved both epithelium diameter (P ≤ 0.05) and thickness (P ≤ 0.001).  The Malondialdehyde increased significantly in trauma group (P = 0.002), but decreased in MLT and NPs groups compared to trauma group (P = 0.098 and P = 0.002 respectively). This decrease was significant only in NPs group. Testicular trauma disturbed spermatogenesis, morphometric, and oxidative parameters. MLT and specially MLT-SLN improved traumatic damages. 


Melatonin; Nanoparticles; Rats; Testis.

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Wang Z, Yang JR, Huang YM, Wang L, Liu LF, Wei YB, et al. Diagnosis and management of testicular rupture after blunt scrotal trauma: a literature review. Int Urol Nephrol. 2016;48(12):1967-1976.

Deurdulian C, Mittelstaedt CA, Chong WK, Fielding JR. US of acute scrotal trauma: optimal technique, imaging findings, and management. Radiographics. 2007;27(2):357-369.

Buckley JC, McAninch JW. Use of ultrasonography for the diagnosis of testicular injuries in blunt scrotal trauma. J Urol. 2006;175(1):175-178.

Lin WW, Kim ED, Quesada ET, Lipshultz LI, Coburn M. Unilateral testicular injury from external trauma: evaluation of semen quality and endocrine parameters. J Urol. 1998;159(3):841-843.

Srinivas M, Chandrasekharam VV, Degaonkar M, Gupta DK, Jha P, Jagannathan NR, et al. Effects of unilateral grade I testicular injury in rat. Urology. 2002;60(3):548-551.

Turner TT, Lysiak JJ. Oxidative stress: a common factor in testicular dysfunction. J Androl. 2008;29(5):488-498.

Bai Y, Zhang Y, Zhang J, Mu Q, Zhang W, Butch ER, et al. Repeated administrations of carbon nanotubes in male mice cause reversible testis damage without affecting fertility. Nat Nanotechnol. 2010;5(9):683-689.

Romeo C, Antonuccio P, Esposito M, Marini H, Impellizzeri P, Turiaco N, et al. Raxofelast, a hydrophilic vitamin E-like antioxidant, reduces testicular ischemia-reperfusion injury. Urol Res. 2004;32(5):367-371.

Hoffmeister CR, Durli TL, Schaffazick SR, Raffin RP, Bender EA, Beck RC, et al. Hydrogels containing redispersible spray-dried melatonin-loaded nanocapsules: a formulation for transdermal-controlled delivery. Nanoscale Res Lett. 2012;7(1):251-263.

Öner-Iyidogan Y, Gürdöl F, Öner P. The effects of acute melatonin and ethanol treatment on antioxidant enzyme activities in rat testes. Pharmacol Res. 2001;44(2):89-93.

Yurtcu M, Abasiyanik A, Bicer S, Avunduk MC. Efficacy of antioxidant treatment in the prevention of testicular atrophy in experimental testicular torsion. J Pediatr Surg. 2009;44(9):1754-1758.

Rezzani R, Rodella LF, Fraschini F, Gasco MR, Demartini G, Musicanti C, et al. Melatonin delivery in solid lipid nanoparticles: prevention of cyclosporine A induced cardiac damage. J Pineal Res. 2009;46(3):255-261.

Hafner A, Lovric J, Voinovich D, Filipovic-Grcic J. Melatonin-loaded lecithin/chitosan nanoparticles: physicochemical characterisation and permeability through Caco-2 cell monolayers. Int J Pharm. 2009;381(2):205-213.

Schwarz C, Mehnert W. Solid lipid nanoparticles (SLN) for controlled drug delivery. II. Drug incorporation and physicochemical characterization. J Microencapsul. 1999;16(2):205-213.

Ghasemiyeh P, Mohammadi-Samani S. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages. Res Pharm Sci. 2018;13(4):288-303.

Abbaspour M, Makhmalzadeh BS, Arastoo Z, Jahangiri A, Shiralipour R. Effect of anionic polymers on drug loading and release from clindamycin phosphate solid lipid nanoparticles. Trop J Pharm Res. 2013;12(4):477-482.

Kelidari HR, Saeedi M, Akbari J, Morteza-Semnani K, Gill P, Valizadeh H, et al. Formulation optimization and in vitro skin penetration of spironolactone loaded solid lipid nanoparticles. Colloids Surf B Biointerfaces. 2015;128:473-479.

Mohamad Ghasemi F, Faghani M, Khajehjahromi S, Bahadori M, Nasiri EE, Hemadi M. Effect of melatonin on proliferative activity and apoptosis in spermatogenic cells in mouse under chemotherapy. Journal of Reproduction and Contraception. 2010;21(2):79-94.

Eze J, Anene B, Chukwu C. Determination of serum and organ malondialdehyde (MDA) concentration, a lipid peroxidation index, in Trypanosoma brucei-infected rats. Comp Clin Path. 2008;17(2):67-72.

Moazeni M, Kelidari HR, Saeedi M, Morteza-Semnani K, Nabili M, Abdollahi Gohar A, et al. Time to overcome fluconazole resistant Candida isolates: solid lipid nanoparticles as a novel antifungal drug delivery system. Colloids Surf B Biointerfaces. 2016;142:400-407.

Mirhoseini M, Mohamadpour M, Khorsandi L. Toxic effects of Carthamus tinctorius L.(Safflower) extract on mouse spermatogenesis. Journal of assisted reproduction and genetics. 2012;29(5):457-461.

Mohamadghasemi F, Faghani M, Khajehjahromi S. The protective effects of melatonin on the histological changes of testis in busulfan-treated adult mice. J Reprod Infertil. 2010;11(2):67-76.

Shaul DB, Xie HW, Diaz JF, Mahnovski V, Hardy BE. Surgical treatment of testicular trauma: effects on fertility and testicular histology. J Pediatr Surg. 1997;32(1):84-87.

Mirhoseini M, Saki G, Hemadi M, Khodadadi A, Mohammadi Asl J. Melatonin and testicular damage in busulfan treated Mice. Iran Red Crescent Med J. 2014;16(2):e14463.

Priano L, Esposti D, Esposti R, Castagna G, De Medici C, Fraschini F, et al. Solid lipid nanoparticles incorporating melatonin as new model for sustained oral and transdermal delivery systems. J Nanosci Nanotechnol. 2007;7(10):3596-3601.

Aitken RJ, Roman SD. Antioxidant systems and oxidative stress in the testes. Oxid Med Cell Longev. 2008;1(1):15-24.

Koksal M, Oguz E, Baba F, Eren MA, Ciftci H, Demir ME, et al. Effects of melatonin on testis histology, oxidative stress and spermatogenesis after experimental testis ischemia-reperfusion in rats. Eur Rev Med Pharmacol Sci. 2012;16(5):582-588.

Ozkan KU, Boran C, Kilinc M, Garipardic M, Kurutas EB. The effect of zinc aspartate pretreatment on ischemia-reperfusion injury and early changes of blood and tissue antioxidant enzyme activities after unilateral testicular torsion-detorsion. J Pediatr Surg. 2004;39(1):91-95.

Yurtçu M, Abasiyanik A, Avunduk MC, Muhtaroğlu S. Effects of melatonin on spermatogenesis and testicular ischemia-reperfusion injury after unilateral testicular torsion-detorsion. J Pediatr Surg. 2008;43(10):1873-1878.

Johnsen SG. Testicular biopsy score count--a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones. 1970;1(1):2-25.


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