Neuroprotective effects of melatonin on erectile dysfunction in streptozotocin-induced diabetic rats
- 121 Downloads
To explore the neuroprotective effects and its possible mechanisms of melatonin (MT) on erectile dysfunction in streptozotocin-induced diabetic rats.
Twenty-eight Sprague–Dawley rats received intraperitoneal injection of streptozotocin and 8 weeks later, the determined diabetic rats randomly got intraperitoneal injection of phosphate buffer solution (PBS) or MT. Another 12 normal rats received PBS treatment. Four weeks later, intracavernous pressure, mean arterial pressure, pathological changes in penis, and major pelvic ganglion (MPG) were measured. Malondialdehyde, superoxide dismutase, p38 and p-p38 levels in penis were detected.
Diabetic rats showed significant decreases of erectile function accompanied with serious neuropathy in dorsal penile nerve (DPN) and MPG, meanwhile collagen deposition, oxidative stress, and p-p38 levels in penis were elevated. Melatonin treatment partially but significantly improved the erectile function, ameliorated neuropathy in DPN and MPG, and decreased collagen deposition, oxidative stress, and p-p38 levels in diabetic rats.
Melatonin treatment helps improve erectile function and ameliorate neuropathy and fibrosis in diabetic rats. These may be associated with reductions in oxidative stress, p38MAPK signaling pathway, and neuropathy.
KeywordsErectile dysfunction Diabetes mellitus Melatonin Neuroprotective Anti-oxidation p-P38
This study was funded by the National Natural Science Foundation of China (No. 81641165), Jiangsu Provincial Medical Youth Talent Foundation (QNRC2016720), China Postdoctoral Science Foundation (2015M580466), and Postdoctoral Science Foundation of Jiangsu Province (2016T90497).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed; all procedures performed in studies involving animals were in accordance with the ethical standards of the Committee for Animal Care and Use of Soochow University.
- 5.He SH, Wei AY, Ye TY, Yang Y, Luo XG, Liu Y, Zhang T (2011) Calcitonin gene-related peptide induces phenotypic transformation of corpus cavernosum smooth muscle cells in diabetic rats with erectile dysfunction. Natl J Androl 17(10):913–917Google Scholar
- 8.Jenwitheesuk A, Nopparat C, Mukda S, Wongchitrat P, Govitrapong P (2014) Melatonin regulates aging and neurodegeneration through energy metabolism, epigenetics, autophagy and circadian rhythm pathways. Int J Mol Sci 15(9):16848–16884. https://doi.org/10.3390/ijms150916848 CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Qiu XF, Li XX, Chen Y, Lin HC, Yu W, Wang R, Dai YT (2012) Mobilisation of endothelial progenitor cells: one of the possible mechanisms involved in the chronic administration of melatonin preventing erectile dysfunction in diabetic rats. Asian J Androl 14(3):481–486. https://doi.org/10.1038/aja.2011.161 CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Kahya MC, Naziroglu M, Ovey IS (2017) Modulation of diabetes-induced oxidative stress, apoptosis, and Ca(2+) entry through TRPM2 and TRPV1 channels in dorsal root ganglion and hippocampus of diabetic rats by melatonin and selenium. Mol Neurobiol 54(3):2345–2360. https://doi.org/10.1007/s12035-016-9727-3 CrossRefPubMedGoogle Scholar
- 20.Tavukcu HH, Sener TE, Tinay I, Akbal C, Ersahin M, Cevik O, Cadirci S, Reiter RJ, Sener G (2014) Melatonin and tadalafil treatment improves erectile dysfunction after spinal cord injury in rats. Clin Exp Pharmacol Physiol 41(4):309–316. https://doi.org/10.1111/1440-1681.12216 CrossRefPubMedGoogle Scholar
- 21.Kimball SR, Abbas A, Jefferson LS (2008) Melatonin represses oxidative stress-induced activation of the MAP kinase and mTOR signaling pathways in H4IIE hepatoma cells through inhibition of Ras. J Pineal Res 44(4):379–386. https://doi.org/10.1111/j.1600-079X.2007.00539.x CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Ma J, Shi M, Zhang X, Liu X, Chen J, Zhang R, Wang X, Zhang H (2018) GLP1R agonists ameliorate peripheral nerve dysfunction and inflammation via p38 MAPK/NFkappaB signaling pathways in streptozotocininduced diabetic rats. Int J Mol Med 41(5):2977–2985. https://doi.org/10.3892/ijmm.2018.3509 CrossRefPubMedGoogle Scholar