Resveratrolün streptozotosin ile diyabet oluşturulan sıçanlarda vas deferens kontraktilitesi üzerindeki antioksidan etkileri

Amaç: Bu çalışmanın amacı, streptozotosin (STZ) ile diyabet oluşturulmuş sıçanlarda vas deferens kontraktilitesi üzerinde resveratrolün antioksidan etkilerini araştırmaktır. Gereç ve Yöntem: Erişkin erkek Wistar Albino sıçanlar kontrol, diyabetik ve resveratrol tedavisi uygulanan diyabetik olarak üç gruba ayrılmıştır. Diyabet, tek doz i.p. STZ enjeksiyonuyla (50mg/kg) oluşturulmuş ve STZ enjeksiyonundan 2 gün sonra hiperglisemi (>300 mg/dl) olan hayvanlar diyabetik olarak kabul edilmiştir. Tedavi grubundaki sıçanlara 4 hafta boyunca (20 mg/kg/gün, i.p.) resveratrol uygulanmıştır. 4 hafta sonunda sıçanların vas deferens dokuları izole edilmiş ve bu dokularda noradrenalin, ATP, elektriksel alan uyarısı (EAU) aracılı yanıtlar elde edilmiştir. Bulgular: Diyabetik sıçanlarda kontrol grubuna göre noradrenalin ve ATP aracılı yanıtlar anlamlı olarak artarken, EAU aracılı yanıtlar azalmıştır. EAU aracılı yanıtlar pirogallol varlığında diyabetik sıçanlarda kontrol sıçanlarına göre daha fazla inhibe olmuştur. Tempol varlığında ise EAU aracılı yanıtlardaki artış, diyabetik grupta kontrol grubuna göre anlamlı olarak fazla bulunmuştur. Resveratrol tedavisi, diyabetik sıçanlarda artan noradrenalin ve ATP aracılı yanıtları anlamlı olarak azaltmış, azalan EAU aracılı yanıtları ise artırmıştır. Sonuç: Bu çalışma resveratrol tedavisinin diyabetik sıçanlarda vas deferens kontraktilitesindeki bozukluğu antioksidan etkileri aracılığıyla düzelttiğini ortaya koymuştur. Sonuçlar, diyabet ile ilişkili ejakülasyon bozukluklarında oksidatif stresin rol oynayabileceğini ve antioksidan tedavinin bu bozukluklarda etkili olabileceğini düşündürmektedir.

Anahtar Kelimeler:

Diabetes mellitus, vas deferens, resveratrol

Antioxidant effects of resveratrol on vas deferens contractility in streptozotocin-induced diabetic rats

Purpose: The aim of the current study is to investigate the antioxidant effects of resveratrol on vas deferens contractility in streptozotocin-induced diabetic rats.Materials and Methods: Adult male Wistar Albino rats were separated into three groups: control, diabetic and resveratrol-treated diabetic. Diabetes was induced by a single i.p. injection of STZ (50 mg/kg), and 2 days after the STZ injection the rats having hyperglycemia (>300 mg/dl) were assigned to be diabetic. Rats in treatment group were administered resveratrol (20 mg/kg/day, i.p.) for 4 weeks. After 4 weeks, vas deferens tissues were isolated and, noradrenaline-, ATP- and electrical field stimulation (EFS)-induced responses were obtained from these tissues.Results: Noradrenaline- and ATP-induced responses significantly increased and EFS-induced responses significantly decreased in diabetic rats compared to control rats. EFS-induced responses in diabetic rats were inhibited more than control rats in the presence of pyrogallol. The increase in EFS-induced responses in the presence of tempol was found markedly enhanced in diabetic rats compared to control rats. Resveratrol treatment significantly ameliorated all the aforementioned responses. Conclusion: This study demonstrated that resveratrol restored impaired contractility of vas deferens in diabetic rats by its antioxidant effects, suggesting that oxidative stress may play a crucial role on the development of ejaculatory dysfunctions associated with diabetes and antioxidant treatment may be effective in these dysfunctions.

Keywords:

Diabetes mellitus, vas deferens, resveratrol,

PDF

___

1. Valensi P, Le Devehat C, Richard JL, Farez C, Khodabandehlou T, Rosenbloom RA et al. A multicenter, double-blind, safety study of QR-333 for the treatment of symptomatic diabetic peripheral neuropathy. A preliminary report. J Diabetes Complications. 2005;19:247-53.
2. Dunsmuir WD, Holmes SA. The aetiology and management of erectile, ejaculatory, and fertility problems in men with diabetes mellitus. Diabet Med. 1996;13:700-8.
3. Maresch CC, Stute DC, Alves MG, Oliveira PF, de Kretser DM, Linn T. Diabetes-induced hyperglycemia impairs male reproductive function: a systematic review. Hum Reprod Update. 2018;24:86-105.
4. Thorve VS, Kshirsagar AD, Vyawahare NS, Joshi VS, Ingale KG, Mohite RJ. Diabetes-induced erectile dysfunction: epidemiology, pathophysiology and management. J Diabetes Complications. 2011;25:129- 36.
5. Oztürk Y, Altan VM, Yildizoğlu-Ari N. Effects of experimental diabetes and insulin on smooth muscle functions. Pharmacol Rev. 1996;48:69-112.
6. Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care. 2003;26(5):1553-79.
7. Koslov DS, Andersson KE. Physiological and pharmacological aspects of the vas deferens-an update. Front Pharmacol. 2013;4:101.
8. Tomlinson DR, Gillon KR, Smith MG. Axonal transport of noradrenaline and noradrenergic transmission in rats with streptozotocin-induced diabetes. Diabetologia. 1982;22:199-204.
9. Peredo H, Agostini MD, Gimeno MF, Borda ES. Hypersensitivity to norepinephrine in vasa deferentia from diabetic rats. Possible participation of metabolic products of arachidonic acid. Prostaglandins Leukot Med. 1984;15:229-39.
10. Longhurst PA. The effects of testosterone or insulin treatment on contractile responses of the rat vas deferens following castration or streptozotocininduced diabetes mellitus. Gen Pharmacol. 1990;21:427-34.
11. Güneş A, Ceylan A, Sarioglu Y, Stefek M, Bauer V, Karasu C. Reactive oxygen species mediate abnormal contractile response to sympathetic nerve stimulation and noradrenaline in the vas deferens of chronically diabetic rats: effects of in vivo treatment with antioxidants. Fundam Clin Pharmacol. 2005;19:73-9.
12. Oztürk Y, Yildizoğlu-Ari N, Altan VM. Altered alphaadrenergic responses of vas deferens to noradrenaline and tyramine from rats with short- and long-term alloxan diabetes. Gen Pharmacol. 1994;25:1519-24.
13. Karasu C, Dewhurst M, Stevens EJ, Tomlinson DR. Effects of anti-oxidant treatment on sciatic nerve dysfunction in streptozotocin-diabetic rats; comparison with essential fatty acids. Diabetologia. 1995;38:129-34.
14. Kaur G, Padiya R, Adela R, Putcha UK, Reddy GS, Reddy BR et al. Garlic and resveratrol attenuate diabetic complications, loss of β-cells, pancreatic and hepatic oxidative stress in streptozotocin-induced diabetic rats. Front Pharmacol. 2016;7:360.
15. Oyenihi OR, Oyenihi AB, Adeyanju AA, Oguntibeju OO. Antidiabetic effects of resveratrol: the way forward in its clinical utility. J Diabetes Res. 2016;2016:9737483.
16. Longhurst PA. The effects of testosterone or insulin treatment on contractile responses of the rat vas deferens following castration or streptozotocininduced diabetes mellitus. Gen Pharmacol. 1990;21:427-34.
17. Longhurst PA. In vitro contractile responses of vasa deferentia from spontaneously diabetic BB rats. J Auton Pharmacol. 1991;11:63-71.
18. Tsounapi P, Honda M, Dimitriadis F, Shimizu S, Shiomi T, Hikita K et al. Antioxidant treatment ameliorates diabetes-induced dysfunction of the vas deferens in a rat model. Andrologia. 2018;50(1).
19. Kamata K, Kirisawa H. Changes in electrophysiological properties and noradrenaline response in vas deferens of diabetic rats. Eur J Pharmacol. 1998;350:237-41.
20. Obrosova IG. How does glucose generate oxidative stress in peripheral nerve? Int Rev Neurobiol. 2002;50:3-35.
21. Fahim AT, Abd El-Fattah AA, Sadik NAH, Ali BM. Resveratrol and dimethyl fumarate ameliorate testicular dysfunction caused by chronic unpredictable mild stress-induced depression in rats. Arch Biochem Biophys. 2019;665:152-65.
22. Yazir Y, Demirtaş Şahin T, Furat Rençber S, Gacar G, Halbutoğulları ZS, Utkan T et al. Restorative effect of resveratrol on expression of endothelial and neuronal nitric oxide synthase in cavernous tissues of chronic unpredictable mild stress-exposed rats: an impact of inflammation. Int J Impot Res. 2018;30:318-26.
23. Kumar A, Kaundal RK, Iyer S, Sharma SS. Effects of resveratrol on nerve functions, oxidative stress and DNA fragmentation in experimental diabetic neuropathy. Life Sci, 2007;80:1236-44.
24. Gocmez SS, Şahin TD, Yazir Y, Duruksu G, Eraldemir FC, Polat S et al. Resveratrol prevents cognitive deficits by attenuating oxidative damage and inflammation in rat model of streptozotocin diabetes induced vascular dementia. Physiol Behav. 2019;201:198-207.
25. Yu W, Wan Z, Qiu XF, Chen Y, Dai YT. Resveratrol, an activator of SIRT1, restores erectile function in streptozotocin-induced diabetic rats. Asian J Androl. 2013;15:646-51.