Antioxidant and antiapoptotic effects of erdosteine in a rat model of ovarian ischemia-reperfusion injury

Document Type: Original Article

Authors

1 University of Trakya, Faculty of Medicine, Department of Obstetrics and Gynecology, 22030, Balkan Campus, Edirne, Turkey

2 University of Trakya, Faculty of Medicine, Department of Histology and Embryology, 22030, Balkan Campus, Edirne, Turkey

3 Yildiz Technical University, Biochemistry Division, Department of Bioengineering, Faculty of Chemical and Metallurgical Engineering, Istanbul, Turkey

Abstract

Objective(s): To evaluate the protective effect of erdosteine, an antiapoptotic and antioxidant agent, on torsion–detorsion evoked histopathological changes in experimental ovarian ischemia-reperfusion (IR) injury.
Materials and Methods: Eighteen female Wistar albino rats were used in control, IR, and IR+Edosteine (IR-E) groups, (n=6 in each). The IR-E group received the erdosteine for seven days before the induction of torsion/retorsion, (10 mg/kg/days). The IR and IR-E groups were exposed to right unilateral adnexal torsion for 3 hr. Three hours later, re-laparotomy was performed, and the right ovaries were surgically excised. Oxidant and antioxidants levels were determined in serum. The ovarian tissue samples were received and fixed with 10% neutral buffered formalin. The sections were stained with H&E, anti-PCNA, and TUNEL.
Results: The IR group were showed severe acute inflammation, polynuclear leukocytes and macrophages, stromal oedema and haemorrhage. Treatment with erdosteine in rats significantly retained degenerative changes in the ovaryPCNA (+) cell numbers were significantly decreased in the IR and IR-E groups unlike the control group. However, its numbers were significantly increased in the IR-E group unlike the IR group. TUNEL (+) cell numbers were significantly increased in the IR group unlike the control and the IR-E groups. In erdosteine treated group, TUNEL (+) cells were detected significantly less than the IR group (P<0.05).
Conclusion: In conclusion, erdosteine maybe a protective agent for ovarian damage and decreasing lipid peroxidation products and leukocytes aggregation after adnexal torsion in animals.

Keywords


1.Hibbard LT. Adnexal torsion. Am J Obstet Gynecol 1985; 152:456–461.

2.Cohen SB, Oelsner G, Seidman DS, Admon D, Mashiach S, Goldenberg M. Laparoscopic detorsion allows sparing of the twisted ischemic adnexa. J Am Assoc Gynecol Laparosc 1999; 6:139-143.

3.Ozkisacik S, Yazici M, Gursoy H, Culhaci N. Does gradual detorsion protect the ovary against ischemia-reperfusion injury in rats? Pediatr Surg Int 2014; 30:437-440.

4.Sirmali M, Uz E, Sirmali R, Kilbaş A, Yilmaz HR, Ağaçkiran Y, et al. The effects of erdosteine on lung injury induced by the ischemia-reperfusion of the hind-limbs in rats. J Surg Res 2008; 145:303-307.

5.Fardoun RZ. The use of vitamin E in type 2 diabetes mellitus. Clin Exp Hypertens 2007; 29:135-148.

6.Eppihimer MJ, Granger DN. Ischemia/ reperfusion-induced leukocyte-endothelial interactions in postcapillary venules. Shock 1997; 8:16–25.

7.Sirmali M, Uz E, Sirmali R, Kilbaş A, Yilmaz HR, Altuntaş I, et al. Protective effects of erdosteine and vitamins C and E combination on ischemia-reperfusion-induced lung oxidative stress and plasma copper and zinc levels in a rat hind limb model. Biol Trace Elem Res 2007; 118:43-52.

8.Gencer M, Karaca T, Güngör AN, Hacıvelioğlu SÖ, Demirtaş S, Turkon H, et al. The protective effect of quercetin on IMA levels and apoptosis in experimental ovarian ischemia-reperfusion injury. Eur J Obstet Gynecol Reprod Biol 2014; 177:135-140.

9.Jain SK, McVie R, Duett J, Herbst JJ. Erythrocyte membrane lipid peroxidation and glycocylated hemoglobin in diabetes. Diabetes 1989; 38:1539–1543.

10.Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med. 1963; 61: 882-888.

11.Griffith OW. Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 1980; 106:207–212.

12.Omaye ST, Turnbul JD, Savberlich HE. Ascorbic acid analysis II. Determination after derivatisation with 2.2. dinitrophenylhidrazine. Selected methods for determination of ascorbic acid in animal cells tissues and fluids. In: McCormick DB, Wright LD.editors. Methods in Enzymology. New York, USA: Academic Press; 1979.p.62:7–8.

13.Suzuki I, Katoh N. A simple and cheap method for measuring serum vitamin A in cattle using spectrophototmeter. Nihon Juigaku Zasshi 1990; 52:1281–1283.

14.Martinek R. Method for determination of vitamin E (total tocopherol) in serum. Clin Chem 1964; 10:1078–1086.

15.Aebi H. Catalase in vitro. Methods Enzymol 1984; 105:121–126.

16.Oguz S, Kanter M, Erboga M, Ibis C. Protective effect of Urtica dioica on liver damage induced by biliary obstruction in rats. Toxicol Ind Health 2013; 29:838-845.

17.Ayvaz S, Aksu B, Karaca T, Cemek M, Tarladacalisir Y-T, Ayaz A, et al. Effects of methylene blue in acute lung injury induced by blunt chest trauma. Hippokratia 2014; 18:50-56.

18.Dokuyucu R, Karateke A, Gokce H, Kurt RK, Ozcan O, Ozturk S, et al. Antioxidant effect of erdosteine and lipoic acid in ovarian ischemia-reperfusion injury. Eur J Obstet Gynecol Reprod Biol 2014; 183:23-27.

19.Yesilyurt A, Erden IA, Bilgic I, Erden G, Albayrak A. The protective effect of erdosteine on radiocontrast induced nephrotoxicity in rats. Environ Toxicol 2011; 26:395–402.

20.Ozerol E, Bilgic S, Iraz M, Cigli A, Ilhan A, Akyol O. The protective effect of erdosteine on short-term global brain ischemia/reperfusion injury in rats. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33:20-24.

21.Tunc T, Uysal B, Atabek C, Kesik V, Caliskan B, Oztas E, et al. A. Erdosteine and ebselen as useful agents in intestinal ischemia/reperfusion injury. J Surg Res 2009; 155:210-216.

22.Mallick IH, Yang W, Winslet MC, Seifalian AM. Ischemia-reperfusion injury of the intestine and protective strategies against injury. Dig Dis Sci 2004; 49:1359.

23.Caglayan EK, Caglayan K, Göcmen AY, Cinar H, Seckin L, Seckin S, et al. Protective effect of ethyl pyruvate on ischemia-reperfusion injury in rat ovary: biochemical and histopathological evaluation. Eur J Obstet Gynecol Reprod Biol 2014; 182:154-159.

24.Celik M, Aksoy AN, Aksoy H, Aksoy Y, Halici Z. Sildenafil reduces ischemia-reperfusion injury in rat ovary: biochemical and histopathological evaluation. Gynecol Obstet Invest 2014; 78:162-167.

25.Yurdakul T, Kulaksizoglu H, Pişkin MM, Avunduk MC, Ertemli E, Gokçe G, et al. Combination antioxidant effect of α-tocoferol and erdosteine in ischemia-reperfusion injury in rat model. Int Urol Nephrol 2010; 42:647-655.

26.Sirmali R, Armağan A, Öktem F, Uz E, Kirbas A, Dönmez S, et al. Protective effects of erdosteine, vitamin E, and vitamin C on renal injury induced by the ischemia-reperfusion of the hind limbs in rats. Turk J Med Sci 2015; 45:33-37.

27.Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol 2000; 190: 255–266.

28.Yesildağ A, Ozden A, Yilmaz HR, Uz E, Ağackiran Y, Yesildağ M, et al. Erdosteine modulates radiocontrast-induced hepatotoxicity in rat. Cell Biochem Funct 2009; 27:142–147.

29.Minutoli L, Irrera N, Squadrito F, Marini H, Nicotina PA, Arena S, et al. Effects of ischaemic post-conditioning on the early and late testicular damage after experi-mental testisischaemia-reperfusion. Andrology 2014; 2:76-82.

30.Sapmaz-Metin M, Topcu-Tarladacalisir Y, Uz YH, Inan M, Omurlu IK, Cerkezkayabekir A, et al. Vitamin E modulates apoptosis and c-jun N-terminal kinase activation in ovarian torsion–detorsion injury. Exp Mol Pathol 2013; 95:213–219.