Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced
Neuropathy in Rats

Balkaya, Muharrem; EKİCİ, Mehmet

doi:10.4103/nsn.nsn_113_21

Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats

Mehmet EKİCİ, (Sivas Cumhuriyet Üniversitesi, Veteriner Hekimliği Fakültesi, Fizyoloji Veterinerlik Bölümü, Sivas, Türkiye)

Muharrem BALKAYA (Aydın Adnan Menderes Üniversitesi, Veteriner Hekimliği Fakültesi, Fizyoloji Veterinerlik Bölümü, Işıklı, Aydın, Türkiye)

Neurological sciences and neurophysiology (Online)

8 1

Yıl: 2021 Cilt: 38 Sayı: 4 Sayfa Aralığı: 262 - 270 Metin Dili: İngilizce DOI: 10.4103/nsn.nsn_113_21 İndeks Tarihi: 31-05-2022

Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats

Öz:

Objective: Paclitaxel (Ptx), used to treat cancer, still causes neuropathic pain and peripheral neuropathy today. This study was conducted to evaluate the effects of progesterone (Pg) and oxytocin (Oxy) on peripheral neuropathy rat model induced by Ptx. Materials and Methods: A total of 38 male Sprague–Dawley rats were randomly divided into five groups, e.g., control (n = 6), Ptx (n = 8), Ptx + Oxy (n = 8), Ptx + Pg (n = 8), and Ptx + Oxy + Pg (n = 8). The rats were monitored daily for body weight change throughout the experiment. To evaluate peripheral neuropathy, electroneuromyography measurements (latency, amplitude, and motor nerve conduction velocity (MNCV)) were recorded from the sciatic nerve innervating the gastrocnemius muscle. Sciatic nerve tissue samples were collected for histopathological evaluation. Results: Ptx led to significant reductions in body weight from day 6 (P < 0.05). There was no difference between groups in the distal latency and amplitudes (P > 0.05). Proximal latency was prolonged in Ptx group rats than in other groups (P < 0.05). Importantly, it was found that MNCV was higher in the Ptx + Pg group than Ptx, Ptx + Oxy, and Ptx + Oxy + Pg groups (P < 0.05). Furthermore, Pg‑administered rats had the lowest nerve degeneration compared to rats administered Oxy and Oxy + Pg (P < 0.05). Conclusions: The present findings suggest that Pg has a protective effect on peripheral neuropathy induced by Ptx in rat.

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1. Schloss JM, Colosimo M, Airey C, Masci PP, Linnane AW, Vitetta L. Nutraceuticals and chemotherapy induced peripheral neuropathy (CIPN): A systematic review. Clin Nutr 2013;32:888‑93.
2. Abu Samaan TM, Samec M, Liskova A, Kubatka P, Büsselberg D. Paclitaxel’s mechanistic and clinical effects on breast cancer. Biomolecules 2019;9:789.
3. Zajączkowska R, Kocot‑Kępska M, Leppert W, Wrzosek A, Mika J, Wordliczek J. Mechanisms of chemotherapy‑induced peripheral neuropathy. Int J Mol Sci 2019;20:1451.
4. Argyriou AA, Chroni E, Koutras A, Iconomou G, Papapetropoulos S, Polychronopoulos P, et al. Preventing paclitaxel‑induced peripheral neuropathy: A phase II trial of vitamin E supplementation. J Pain Symptom Manage 2006;32:237‑44.
5. Freilich RJ, Balmaceda C, Seidman AD, Rubin M, DeAngelis LM. Motor neuropathy due to docetaxel and paclitaxel. Neurology 1996;47:115‑8.
6. Cavaletti G, Tredici G, Braga M, Tazzari S. Experimental peripheral neuropathy induced in adult rats by repeated intraperitoneal administration of taxol. Exp Neurol 1995;133:64‑72.
7. Cliffer KD, Siuciak JA, Carson SR, Radley HE, Park JS, Lewis DR, et al. Physiological characterization of Taxol‑induced large‑fiber sensory neuropathy in the rat. Ann Neurol 1998;43:46‑55.
8. Griffiths LA, Duggett NA, Pitcher AL, Flatters SJ. Evoked and ongoing pain‑like behaviours in a rat model of paclitaxel‑induced peripheral neuropathy. Pain Res Manag 2018;2018:8217613.
9. Persohn E, Canta A, Schoepfer S, Traebert M, Mueller L, Gilardini A, et al. Morphological and morphometric analysis of paclitaxel and docetaxel‑induced peripheral neuropathy in rats. Eur J Cancer 2005;41:1460‑6.
10. Wozniak KM, Wu Y, Farah MH, Littlefield BA, Nomoto K, Slusher BS. Neuropathy‑inducing effects of eribulin mesylate versus paclitaxel in mice with preexisting neuropathy. Neurotox Res 2013;24:338‑44.
11. Melli G, Jack C, Lambrinos GL, Ringkamp M, Höke A. Erythropoietin protects sensory axons against paclitaxel‑induced distal degeneration. Neurobiol Dis 2006;24:525‑30.
12. Jurek B, Neumann ID. The oxytocin receptor: From intracellular signaling to behavior. Physiol Rev 2018;98:1805‑908.
13. Faghihi M, Alizadeh AM, Khori V, Latifpour M, Khodayari S. The role of nitric oxide, reactive oxygen species, and protein kinase C in oxytocin‑induced cardioprotection in ischemic rat heart. Peptides 2012;37:314‑9.
14. Erkanli Senturk G, Erkanli K, Aydin U, Yucel D, Isiksacan N, Ercan F, et al. The protective effect of oxytocin on ischemia/ reperfusion injury in rat urinary bladder. Peptides 2013;40:82‑8.
15. Espinosa de Los Monteros‑Zúñiga A, Martínez‑Lorenzana G, Condés‑Lara M, González‑Hernández A. In vivo dissection of two intracellular pathways involved in the spinal oxytocin‑induced antinociception in the rat. ACS Chem Neurosci 2021;12:3140‑7.
16. Akman T, Akman L, Erbas O, Terek MC, Taskiran D, Ozsaran A. The preventive effect of oxytocin to Cisplatin‑induced neurotoxicity: An experimental rat model. Biomed Res Int 2015;2015:167235.
17. Giatti S, Romano S, Pesaresi M, Cermenati G, Mitro N, Caruso D, et al. Neuroactive steroids and the peripheral nervous system: An update. Steroids 2015;103:23‑30.
18. Falvo E, Diviccaro S, Melcangi RC, Giatti S. Physiopathological role of neuroactive steroids in the peripheral nervous system. Int J Mol Sci 2020;21:9000.
19. Roglio I, Bianchi R, Camozzi F, Carozzi V, Cervellini I, Crippa D, et al. Docetaxel‑induced peripheral neuropathy: Protective effects of dihydroprogesterone and progesterone in an experimental model. J Peripher Nerv Syst 2009;14:36‑44.
20. Erdoğan MA, Taşkıran E, Yiğittürk G, Erbaş O, Taşkıran D. The investigation of therapeutic potential of oxytocin and liraglutide on vincristine‑induced neuropathy in rats. J Biochem Mol Toxicol 2020;34:e22415.
21. Miguel CA, Raggio MC, Villar MJ, Gonzalez SL, Coronel MF. Anti‑allodynic and anti‑inflammatory effects of 17α‑hydroxyprogesterone caproate in oxaliplatin‑induced peripheral neuropathy. J Peripher Nerv Syst 2019;24:100‑10.
22. Erbas O, Taşkıran D, Oltulu F, Yavaşoğlu A, Bora S, Bilge O, et al. Oxytocin provides protection against diabetic polyneuropathy in rats. Neurol Res 2017;39:45‑53.
23. Meyer L, Patte‑Mensah C, Taleb O, Mensah‑Nyagan AG. Cellular and functional evidence for a protective action of neurosteroids against vincristine chemotherapy‑induced painful neuropathy. Cell Mol Life Sci 2010;67:3017‑34.
24. Sameni H, Panahi M. The effect of co‑administration of 4‑methylcatechol and progesterone on sciatic nerve function and neurohistological alterations in streptozotocin‑induced diabetic neuropathy in rats. Cell J 2011;13:31‑8.
25. Bader AM, Datta S, Moller RA, Covino BG. Acute progesterone treatment has no effect on bupivacaine‑induced conduction blockade in the isolated rabbit vagus nerve. Anesth Analg 1990;71:545‑8.
26. Coronel MF, Labombarda F, Roig P, Villar MJ, De Nicola AF, González SL. Progesterone prevents nerve injury‑induced allodynia and spinal NMDA receptor upregulation in rats. Pain Med 2011;12:1249‑61.
27. Jarahi M, Sheibani V, Safakhah HA, Torkmandi H, Rashidy‑Pour A. Effects of progesterone on neuropathic pain responses in an experimental animal model for peripheral neuropathy in the rat: A behavioral and electrophysiological study. Neuroscience 2014;256:403‑11.
28. Osako Y, Otsuka T, Taniguchi M, Oka T, Kaba H. Oxytocin enhances presynaptic and postsynaptic glutamatergic transmission between rat olfactory bulb neurones in culture. Neurosci Lett 2001;299:65‑8.
29. Breton JD, Veinante P, Uhl‑Bronner S, Vergnano AM, Freund‑Mercier MJ, Schlichter R, et al. Oxytocin‑induced antinociception in the spinal cord is mediated by a subpopulation of glutamatergic neurons in lamina I‑II which amplify GABAergic inhibition. Mol Pain 2008;4:19.
30. Dose F, Zanon P, Coslovich T, Taccola G. Nanomolar oxytocin synergizes with weak electrical afferent stimulation to activate the locomotor CpG of the rat spinal cord in vitro. PLoS One 2014;9:e92967.
31. Ahn SW, Yoon BN, Kim JE, Seok JM, Kim KK, Lim YM, et al. Nerve conduction studies: Basic principal and clinical usefulness. Ann Clin Neurophysiol 2018;20:71.
32. Carson FL, Hladik C. Histotechnology : A Self‑Instructional Text. 3rd ed. Hong Kong: American Society for Clinical Pathology Press; 2009.
33. Kızılay Z, Erken HA, Çetin NK, Aktaş S, Abas Bİ, Yılmaz A. Boric acid reduces axonal and myelin damage in experimental sciatic nerve injury. Neural Regen Res 2016;11:1660‑5.
34. McQuade RM, Stojanovska V, Abalo R, Bornstein JC, Nurgali K. Chemotherapy‑induced constipation and diarrhea: Pathophysiology, current and emerging treatments. Front Pharmacol 2016;7:414.
35. Duggett NA, Griffiths LA, Flatters SJ. Paclitaxel‑induced painful neuropathy is associated with changes in mitochondrial bioenergetics, glycolysis, and an energy deficit in dorsal root ganglia neurons. Pain 2017;158:1499‑508.
36. Abelenda M, Puerta M. Leptin release is decreased in white adipocytes isolated from progesterone‑treated rats. Endocr Res 2004;30:335‑42.
37. Boltong A, Keast R. The influence of chemotherapy on taste perception and food hedonics: A systematic review. Cancer Treat Rev 2012;38:152‑63.
38. de Vries YC, Helmich E, Karsten MD, Boesveldt S, Winkels RM, van Laarhoven HW. The impact of chemosensory and food‑related changes in patients with advanced oesophagogastric cancer treated with capecitabine and oxaliplatin: A qualitative study. Support Care Cancer 2016;24:3119‑26.
39. Morton GJ, Thatcher BS, Reidelberger RD, Ogimoto K, Wolden‑Hanson T, Baskin DG, et al. Peripheral oxytocin suppresses food intake and causes weight loss in diet‑induced obese rats. Am J Physiol Endocrinol Metab 2012;302:E134‑44.
40. Blevins JE, Graham JL, Morton GJ, Bales KL, Schwartz MW, Baskin DG, et al. Chronic oxytocin administration inhibits food intake, increases energy expenditure, and produces weight loss in fructose‑fed obese rhesus monkeys. Am J Physiol Regul Integr Comp Physiol 2015;308:R431‑8.
41. Bromberg MB. An electrodiagnostic approach to the evaluation of peripheral neuropathies. Phys Med Rehabil Clin N Am 2013;24:153‑68.
42. Gao WQ, Dybdal N, Shinsky N, Murnane A, Schmelzer C, Siegel M, et al. Neurotrophin‑3 reverses experimental cisplatin‑induced peripheral sensory neuropathy. Ann Neurol 1995;38:30‑7.
43. Gilardini A, Avila RL, Oggioni N, Rodriguez‑Menendez V, Bossi M, Canta A, et al. Myelin structure is unaltered in chemotherapy‑induced peripheral neuropathy. Neurotoxicology 2012;33:1‑7.
44. Pourmohammadi N, Alimoradi H, Mehr SE, Hassanzadeh G, Hadian MR, Sharifzadeh M, et al. Lithium attenuates peripheral neuropathy induced by paclitaxel in rats. Basic Clin Pharmacol Toxicol 2012;110:231‑7.
45. Stecker MM, Baylor K, Chan YM. Acute nerve compression and the compound muscle action potential. J Brachial Plex Peripher Nerve Inj 2008;3:1.
46. Nodera H, Bostock H, Izumi Y, Nakamura K, Urushihara R, Sakamoto T, et al. Activity‑dependent conduction block in multifocal motor neuropathy: Magnetic fatigue test. Neurology 2006;67:280‑7.
47. Melcangi RC, Garcia‑Segura LM. Therapeutic approaches to peripheral neuropathy based on neuroactive steroids. Expert Rev Neurother 2006;6:1121‑5.
48. Giatti S, Diviccaro S, Serafini MM, Caruso D, Garcia‑Segura LM, Viviani B, et al. Sex differences in steroid levels and steroidogenesis in the nervous system: Physiopathological role. Front Neuroendocrinol 2020;56:100804.
49. Jure I, De Nicola AF, Labombarda F. Progesterone effects on the oligodendrocyte linage: All roads lead to the progesterone receptor. Neural Regen Res 2019;14:2029‑34.
50. Leonelli E, Bianchi R, Cavaletti G, Caruso D, Crippa D, Garcia‑Segura LM, et al. Progesterone and its derivatives are neuroprotective agents in experimental diabetic neuropathy: A multimodal analysis. Neuroscience 2007;144:1293‑304.
51. Azcoitia I, Leonelli E, Magnaghi V, Veiga S, Garcia‑Segura LM, Melcangi RC. Progesterone and its derivatives dihydroprogesterone and tetrahydroprogesterone reduce myelin fiber morphological abnormalities and myelin fiber loss in the sciatic nerve of aged rats. Neurobiol Aging 2003;24:853‑60.
52. Melcangi RC, Azcoitia I, Ballabio M, Cavarretta I, Gonzalez LC, Leonelli E, et al. Neuroactive steroids influence peripheral myelination: A promising opportunity for preventing or treating age‑dependent dysfunctions of peripheral nerves. Prog Neurobiol 2003;71:57‑66.
53. Erbaş O, Ergenoglu AM, Akdemir A, Yeniel AÖ, Taskiran D. Comparison of melatonin and oxytocin in the prevention of critical illness polyneuropathy in rats with experimentally induced sepsis. J Surg Res 2013;183:313‑20.
54. Gümüs B, Kuyucu E, Erbas O, Kazimoglu C, Oltulu F, Bora OA. Effect of oxytocin administration on nerve recovery in the rat sciatic nerve damage model. J Orthop Surg Res 2015;10:161.
55. Luppi P, Levi‑Montalcini R, Bracci‑Laudiero L, Bertolini A, Arletti R, Tavernari D, et al. NGF is released into plasma during human pregnancy: An oxytocin‑mediated response? Neuroreport 1993;4:1063‑5.
56. Petersson M, Lundeberg T, Sohlström A, Wiberg U, Uvnäs‑Moberg K. Oxytocin increases the survival of musculocutaneous flaps. Naunyn Schmiedebergs Arch Pharmacol 1998;357:701‑4.
57. Viero C, Dayanithi G. Neurosteroids are excitatory in supraoptic neurons but inhibitory in the peripheral nervous system: It is all about oxytocin and progesterone receptors. Prog Brain Res 2008;170:177‑92.
58. Schumacher M, Coirini H, Pfaff DW, McEwen BS. Behavioral effects of progesterone associated with rapid modulation of oxytocin receptors. Science 1990;250:691‑4.
59. Grazzini E, Guillon G, Mouillac B, Zingg HH. Inhibition of oxytocin receptor function by direct binding of progesterone. Nature 1998;392:509‑12.
60. Koksma JJ, van Kesteren RE, Rosahl TW, Zwart R, Smit AB, Lüddens H, et al. Oxytocin regulates neurosteroid modulation of GABA(A) receptors in supraoptic nucleus around parturition. J Neurosci 2003;23:788‑97.
61. Garofalo EG, Raymondo SG. Effect of oxytocin on estrogen and progesterone receptors in the rat uterus. Vet Res 1995;26:284‑91.

APA	EKİCİ M, Balkaya M (2021). Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats. , 262 - 270. 10.4103/nsn.nsn_113_21
Chicago	EKİCİ Mehmet,Balkaya Muharrem Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats. (2021): 262 - 270. 10.4103/nsn.nsn_113_21
MLA	EKİCİ Mehmet,Balkaya Muharrem Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats. , 2021, ss.262 - 270. 10.4103/nsn.nsn_113_21
AMA	EKİCİ M,Balkaya M Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats. . 2021; 262 - 270. 10.4103/nsn.nsn_113_21
Vancouver	EKİCİ M,Balkaya M Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats. . 2021; 262 - 270. 10.4103/nsn.nsn_113_21
IEEE	EKİCİ M,Balkaya M "Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats." , ss.262 - 270, 2021. 10.4103/nsn.nsn_113_21
ISNAD	EKİCİ, Mehmet - Balkaya, Muharrem. "Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats". (2021), 262-270. https://doi.org/10.4103/nsn.nsn_113_21

APA	EKİCİ M, Balkaya M (2021). Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats. Neurological sciences and neurophysiology (Online), 38(4), 262 - 270. 10.4103/nsn.nsn_113_21
Chicago	EKİCİ Mehmet,Balkaya Muharrem Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats. Neurological sciences and neurophysiology (Online) 38, no.4 (2021): 262 - 270. 10.4103/nsn.nsn_113_21
MLA	EKİCİ Mehmet,Balkaya Muharrem Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats. Neurological sciences and neurophysiology (Online), vol.38, no.4, 2021, ss.262 - 270. 10.4103/nsn.nsn_113_21
AMA	EKİCİ M,Balkaya M Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats. Neurological sciences and neurophysiology (Online). 2021; 38(4): 262 - 270. 10.4103/nsn.nsn_113_21
Vancouver	EKİCİ M,Balkaya M Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats. Neurological sciences and neurophysiology (Online). 2021; 38(4): 262 - 270. 10.4103/nsn.nsn_113_21
IEEE	EKİCİ M,Balkaya M "Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats." Neurological sciences and neurophysiology (Online), 38, ss.262 - 270, 2021. 10.4103/nsn.nsn_113_21
ISNAD	EKİCİ, Mehmet - Balkaya, Muharrem. "Protective Effects of Oxytocin and Progesterone on Paclitaxel-induced Neuropathy in Rats". Neurological sciences and neurophysiology (Online) 38/4 (2021), 262-270. https://doi.org/10.4103/nsn.nsn_113_21