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Ghrelin and NUCB2/Nesfatin-1 expression in unilateral testicular torsion-induced rats with and without N-acetylcysteine
Corresponding Author(s) : S. Aydin
Cellular and Molecular Biology,
Vol. 63 No. 7: Issue 7
Abstract
Testicular torsion (TT) is a common urological problem in the field of pediatric surgery. The degree and duration of torsion determines the degree of testicular damage; however, its effects on the expression of octanoylated ghrelin and nucleobindin 2 (NUCB2) /nesfatin-1 synthetized from testicular tissue remain unclear. We explored the effects of experimentally induced unilateral TT on serum and contralateral testicular tissue ghrelin and NUCB2/nesfatin-1 levels, and determined whether N-acetyl cysteine (NAS) treatment had any effects on their expression. A total of 42 Wistar Albino strain rats were divided into 7 groups: Group (G) I control, GII sham, GIII 12-hour torsion, GIV 12-hour torsion + detorsion + 100 mg/kg NAS, GV 24-hour torsion, GVI 24-hour torsion + detorsion + 100 mg/kg NAS, and GVII 100 mg/kg NAS. Octanoylated ghrelin and NUCB2/nesfatin-1 concentrations were evaluated in serum using the ELISA method and in testicular tissue with immunohistochemical methods. Immunoreactivity of octanoylated ghrelin significantly increased in GI compared to GIII, GV, and GVI (p<0.05). NUCB2/nesfatin-1 immunoreactivity increased in GV and GVIII relative to GI (p<0.05). In the 12-hour torsion group, a significant decrease in octanoylated ghrelin levels with NAS treatment was observed; however, in the 24-hour torsion group, a significant decrease was not observed. In the 12-hour torsion + NAS treatment group, a significant change was not observed in NUCB2/nesfatin-1 expression. Following 24-hour torsion, an increase in NUCB2/nesfatin-1 levels was observed, and NAS treatment did not reverse this increase. It was determined that increases in the expression of octanoylated ghrelin and NUCB2/nesfatin-1, the latter of which was a result of TT, reflect damage in this tissue. Importantly, NAS treatment could prevent this damage. Thus, there may be a clinical application for the combined use of NAS and octanoylated ghrelin in preventing TT-related infertility.
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- Gökçe A, Oktar S, Koc A, Gonenci R, Yalcinkaya F, Yonden Z, et al. Protective effect of thymoquinone in experimental testicular torsion. Urol Int 2010; 85:461–5.
- Turner TT, Brown KJ. Spermatic cord torsion: loss of spermatogenesis despite return of blood flow. Biol Reprod 1993; 49:401–7.
- Bektaş H, í–zzeybek D, Günenç F, Akkuş M, Bağriyanik A, Küme T, et al. The effects of two different doses of dexmedetomidine in a testicular ischemia-reperfusion model in rats. Turkiye Klinikleri J Med Sci 2012; 32:766–74.
- García-Galiano D, Pineda R, Ilhan T, Castellano JM, Ruiz-Pino F, Sánchez-Garrido MA, et al. Cellular distribution, regulated expression, and functional role of the anorexigenic peptide, NUCB2/nesfatin-1, in the testis. Endocrinology 2012; 153:1959–71.
- Caminos JE, Nogueiras R, Gaytán F, Pineda R, González CR, Barreiro ML, et al. Novel expression and direct effects of adiponectin in the rat testis. Endocrinology 2008; 149:3390–402.
- Nogueiras R, Barreiro ML, Caminos JE, Gaytán F, Suominen JS, Navarro VM, et al. Novel expression of resistin in rat testis: Functional role and regulation by nutritional status and hormonal factors. J Cell Sci 2004; 117:3247–57.
- Tena-Sempere M, Barreiro ML, Gonzalez LC, Gaytan F, Zhang FP, Caminos JE, et al. Novel expression and functional role of ghrelin in rat testis. Endocrinology 2002; 143:717–725.
- Tena-Sempere M, Barreiro ML. Leptin in male reproduction: the testis paradigm. Mol Cell Endocrinol 2002; 188:9–13.
- Tena-Sempere M. Ghrelin as a pleotrophic modulator of gonadal function and reproduction. Nat Clin Pract Endocrinol Metab 2008; 4:666–74.
- Riley LG. Different forms of ghrelin exhibit distinct biological roles in tilapia. Front Endocrinol (Lausanne) 2013; 4:118.
- Aktaş BK, Bulut S, Bulut S, Baykam MM, Ozden C, Senes M, et al. The effects of N-acetylcysteine on testicular damage in experimental testicular ischemia/reperfusion injury. Pediatr Surg Int 2010; 26:293–8.
- Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 1981; 29:577–80.
- Karaguzel E, Sivrikaya A, Mentese A, Yulug E, Turkmen S, Kutlu O, et al. Investigation of tyrphostin AG 556 for testicular torsion-induced ischemia reperfusion injury in rat. J Pediatr Urol 2014; 10:223–9.
- Cuzzocrea S, Zingarelli B, Gilad E, Hake P, Salzman AL, Szabó C. Protective effect of melatonin in carrageenan-induced models of local inflammation: Relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity. J Pineal Res 1997; 23:106–16.
- Sukhotnik I, Voskoboinik K, Lurie M, Coran AG, Greenblatt R, Shiloni E, et al. Effect of testicular ischemia-reperfusion on recruitment of neutrophils, E-selectin expression and germ cell apoptosis in the contralateral testis in a rat. Pediatr Surg Int 2007; 23:479–85.
- Barreiro ML, Gaytan F, Caminos JE, Pinilla L, Casanueva FF, Aguilar E, et al. Cellular location and hormonal regulation of ghrelin expression in rat testis. Biol Reprod 2002; 67:1768–76.
- Rifaioglu MM, Motor S, Davarci I, Tuzcu K, Sefil F, Davarci M, et al. Protective effect of ebselen on experimental testicular torsion and detorsion injury. Andrologia 2014; 46:1134–40.
- Turner TT. Acute experimental testicular torsion: No effect on the contralateral testis. J Androl 1985; 6:65–72.
- Wei SM, Yan ZZ, Zhou J. Protective effect of rutin on testicular ischemia-reperfusion injury. J Pediatr Surg 2011; 46:1419–24.
- Taati M, Moghadasi M, Dezfoulian O, Asadian P, Zendehdel M. Effects of ghrelin on germ cell apoptosis and proinflammatory cytokines production in ischemia-reperfusion of the rat testis. Iran J Reprod Med 2015; 13:85–92.
- Aydin S, Ogeturk M, Kuloglu T, Kavakli A, Aydin S. Effect of carnosine supplementation on apoptosis and irisin, total oxidant and antioxidants levels in the serum, liver and lung tissues in rats exposed to formaldehyde inhalation. Peptides 2015; 64:14–23.
- Kheradmand A, Dezfoulian O, Alirezaei M, Rasoulian B. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats. Biochem Biophys Res Commun 2012; 419:299–304.
- Somuncu S, Cakmak M, Erdoğan S, Caglayan O, Caglayan F, Akman H, et al. Protective effects of trapidil in lung after abdominal aorta induced ischemia-reperfusion injury: An experimental study. Pediatr Surg Int 200; 21:983–8.
- Delhanty PJ, van der Lely AJ. Ghrelin and glucose homeostasis. Peptides 2011; 32:2309–18.
- Wang T, Yuan D, Zhou C, Lin F, Wei R, Chen H, et al. Molecular characterization of melanin-concentrating hormone (MCH) in Schizothorax prenanti: Cloning, tissue distribution and role in food intake regulation. Fish Physiol Biochem 2016; 42:883–93.
- Yosten GL, Redlinger L, Samson WK. Evidence for a role of endogenous nesfatin-1 in the control of water drinking. J Neuroendocrinol 2012; 24:1078–84.
- Stengel A. Nesfatin-1: More than a food intake regulatory peptide. Peptides 2015; 72:175–83.
- Ahmadizad S, Avansar AS, Ebrahim K, Avandi M, Ghasemikaram M. The effects of short-term high-intensity interval training vs. moderate-intensity continuous training on plasma levels of nesfatin-1 and inflammatory markers. Horm Mol Biol Clin Investig 2015; 21:165–73
References
Gökçe A, Oktar S, Koc A, Gonenci R, Yalcinkaya F, Yonden Z, et al. Protective effect of thymoquinone in experimental testicular torsion. Urol Int 2010; 85:461–5.
Turner TT, Brown KJ. Spermatic cord torsion: loss of spermatogenesis despite return of blood flow. Biol Reprod 1993; 49:401–7.
Bektaş H, í–zzeybek D, Günenç F, Akkuş M, Bağriyanik A, Küme T, et al. The effects of two different doses of dexmedetomidine in a testicular ischemia-reperfusion model in rats. Turkiye Klinikleri J Med Sci 2012; 32:766–74.
García-Galiano D, Pineda R, Ilhan T, Castellano JM, Ruiz-Pino F, Sánchez-Garrido MA, et al. Cellular distribution, regulated expression, and functional role of the anorexigenic peptide, NUCB2/nesfatin-1, in the testis. Endocrinology 2012; 153:1959–71.
Caminos JE, Nogueiras R, Gaytán F, Pineda R, González CR, Barreiro ML, et al. Novel expression and direct effects of adiponectin in the rat testis. Endocrinology 2008; 149:3390–402.
Nogueiras R, Barreiro ML, Caminos JE, Gaytán F, Suominen JS, Navarro VM, et al. Novel expression of resistin in rat testis: Functional role and regulation by nutritional status and hormonal factors. J Cell Sci 2004; 117:3247–57.
Tena-Sempere M, Barreiro ML, Gonzalez LC, Gaytan F, Zhang FP, Caminos JE, et al. Novel expression and functional role of ghrelin in rat testis. Endocrinology 2002; 143:717–725.
Tena-Sempere M, Barreiro ML. Leptin in male reproduction: the testis paradigm. Mol Cell Endocrinol 2002; 188:9–13.
Tena-Sempere M. Ghrelin as a pleotrophic modulator of gonadal function and reproduction. Nat Clin Pract Endocrinol Metab 2008; 4:666–74.
Riley LG. Different forms of ghrelin exhibit distinct biological roles in tilapia. Front Endocrinol (Lausanne) 2013; 4:118.
Aktaş BK, Bulut S, Bulut S, Baykam MM, Ozden C, Senes M, et al. The effects of N-acetylcysteine on testicular damage in experimental testicular ischemia/reperfusion injury. Pediatr Surg Int 2010; 26:293–8.
Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 1981; 29:577–80.
Karaguzel E, Sivrikaya A, Mentese A, Yulug E, Turkmen S, Kutlu O, et al. Investigation of tyrphostin AG 556 for testicular torsion-induced ischemia reperfusion injury in rat. J Pediatr Urol 2014; 10:223–9.
Cuzzocrea S, Zingarelli B, Gilad E, Hake P, Salzman AL, Szabó C. Protective effect of melatonin in carrageenan-induced models of local inflammation: Relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity. J Pineal Res 1997; 23:106–16.
Sukhotnik I, Voskoboinik K, Lurie M, Coran AG, Greenblatt R, Shiloni E, et al. Effect of testicular ischemia-reperfusion on recruitment of neutrophils, E-selectin expression and germ cell apoptosis in the contralateral testis in a rat. Pediatr Surg Int 2007; 23:479–85.
Barreiro ML, Gaytan F, Caminos JE, Pinilla L, Casanueva FF, Aguilar E, et al. Cellular location and hormonal regulation of ghrelin expression in rat testis. Biol Reprod 2002; 67:1768–76.
Rifaioglu MM, Motor S, Davarci I, Tuzcu K, Sefil F, Davarci M, et al. Protective effect of ebselen on experimental testicular torsion and detorsion injury. Andrologia 2014; 46:1134–40.
Turner TT. Acute experimental testicular torsion: No effect on the contralateral testis. J Androl 1985; 6:65–72.
Wei SM, Yan ZZ, Zhou J. Protective effect of rutin on testicular ischemia-reperfusion injury. J Pediatr Surg 2011; 46:1419–24.
Taati M, Moghadasi M, Dezfoulian O, Asadian P, Zendehdel M. Effects of ghrelin on germ cell apoptosis and proinflammatory cytokines production in ischemia-reperfusion of the rat testis. Iran J Reprod Med 2015; 13:85–92.
Aydin S, Ogeturk M, Kuloglu T, Kavakli A, Aydin S. Effect of carnosine supplementation on apoptosis and irisin, total oxidant and antioxidants levels in the serum, liver and lung tissues in rats exposed to formaldehyde inhalation. Peptides 2015; 64:14–23.
Kheradmand A, Dezfoulian O, Alirezaei M, Rasoulian B. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats. Biochem Biophys Res Commun 2012; 419:299–304.
Somuncu S, Cakmak M, Erdoğan S, Caglayan O, Caglayan F, Akman H, et al. Protective effects of trapidil in lung after abdominal aorta induced ischemia-reperfusion injury: An experimental study. Pediatr Surg Int 200; 21:983–8.
Delhanty PJ, van der Lely AJ. Ghrelin and glucose homeostasis. Peptides 2011; 32:2309–18.
Wang T, Yuan D, Zhou C, Lin F, Wei R, Chen H, et al. Molecular characterization of melanin-concentrating hormone (MCH) in Schizothorax prenanti: Cloning, tissue distribution and role in food intake regulation. Fish Physiol Biochem 2016; 42:883–93.
Yosten GL, Redlinger L, Samson WK. Evidence for a role of endogenous nesfatin-1 in the control of water drinking. J Neuroendocrinol 2012; 24:1078–84.
Stengel A. Nesfatin-1: More than a food intake regulatory peptide. Peptides 2015; 72:175–83.
Ahmadizad S, Avansar AS, Ebrahim K, Avandi M, Ghasemikaram M. The effects of short-term high-intensity interval training vs. moderate-intensity continuous training on plasma levels of nesfatin-1 and inflammatory markers. Horm Mol Biol Clin Investig 2015; 21:165–73