ArchiveAdvanced Search

Similar Papers

Not found any similar paper or editorial letter. To find exact search features please click here.
Print this page Create this page as PDF Introduce this page to your friend Blind help
Volume 6, 2017, Issue 10, Pages 204-210; Paper doi: 10.15412/J.JBTW.01061004; Paper ID: 16505.
CrossMark
Previous PaperPrevious Paper      Next PaperNext Paper


Redox Imbalance and Reproductive Side Effects of Long and Short Term Nitroglycerin Treatment in Rat Uterus
(Research Paper)
  • 1 Recombinant Protein Laboratory, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
  • 2 Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  • 3 Department of Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • 4 Infertility Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  • 5 Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Correspondence should be addressed to Fatemeh Zal, Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Tel: ; Fax: ; Email: Fatemehzal@yahoo.com.

Abstract

Bioactivation of Nitroglycerin (NTG) results in reactive oxygen species and reactive nitrogen species formation. The aim of this study was to investigate the effects of NTG treatment on the redox homeostasis in rat uterus around the time of implantation and the number of pups. The rats in long-term test groups were treated subcutaneously with NTG (15mg kg-1 BW) and normal saline (1ml kg-1 B) in control groups for 4 weeks. Afterwards, they were mated and divided into four groups. Two groups were treated until 5 days after mating. Thereafter, they were sacrificed and the activities of glutathione peroxidase (GPx), catalase (CAT), and glutathione reductase as well as the levels of reduced glutathione (GSH) and malondialdehyde (MDA) in the uterus homogenates were measured. In other groups, treatments were continued until their pups were counted. In the short-term groups, treatments were started after mating, and all considered parameters were measured as similar as long term groups. Long-term NTG treatment significantly increased the MDA level and decreased the GPx activity and pups number compared to the controls (P<0.05), whereas no marked alteration in the activities of GR and CAT and the levels GSH were observed. However, short-term NTG treated groups showed no significant changes in all the parameters mentioned above as compared with the controls. Long-term NTG treatment, unlike short-term treatment, may cause impaired implantation and infertility, but there is also possibility for further improvement.

Keywords

Redox imbalance, Implantation, Infertility, Pups, Uterus homogenates

1. INTRODUCTION
I

nfertility is one of the most challenging problems in public health, affecting 15%–20% of couples of reproductive age (1). Forty to fifty percent of infertility cases are related to a gynecological problem (2). It is believed that oxidative stress has an important role in the pathophysiology of gynecological diseases, which are related to infertility (3, 8). High levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in uterine tissue may lead to oxidative stress-induced infertility. It is reported that in the western world 0.2-4% of all pregnancies are influenced by cardiovascular diseases (CVD).  During pregnancy, the most frequent cardiovascular events are related to hypertension (6–8%). On the other hand, the most common CVD present during pregnancy is congenital heart disease-CHD (75%), and most of the patients depend on nitroglycerin (NTG) to relieve their chest pain and hypertension (8). Bioactivation of NTG produces high levels of ROS and RNS, such as hydroxyl (OH), super oxide (O2.-), and nitric oxide (NO) radicals, and these species trigger oxidative stress-induced damage to key cellular targets (9, 10). Oxidative stress degrade polyunsaturated lipids, forming malondialdehyde (MDA), as a marker of oxidative stress (11). Gori et al, showed that NTG triggers ROS production by direct uncoupling of the mitochondrial respiratory chain (12). One study of 9 fertile women with regular cycles and 30 infertile women with endometriosis revealed that high endometrial levels of NO, as observed in patients with endometriosis, may produce an unfavorable environment for implantation (13). In another study, Barroso RP et al, showed that higher concentrations of NO inhibit both embryo development in vitro and implantation in vivo in mice (14). The human body has several mechanisms to counteract oxidative stress. One of these mechanisms is antioxidant enzymes, such as glutathione peroxidase (GPx), glutathione reductase (15, 16), and catalase (CAT) as well as reduced glutathione (GSH) to overcome oxidative stress (17). Based on the observations described above, we aimed to assess the long- and short-term effects of NTG treatment on oxidative features of rat uterine tissue around the time of implantation.

2. MATERIALS AND METHODS
2.1. Materials

Glutathione reductase (GR), 0.033M oxidized glutathione (GSSG), 1mM reduced glutathione (GSH), 0.4 mM tert-butyl hydroperoxide (t-BuOOH), 1.01 nM bovine serum albumin (BSA), 0.5% 2-thiobarbituric acid (TBA), 20% trichloroacetic acid (TCA), Tris-HCL buffer (50mM Tris base, pH 7.6), 2 mM nicotinamide adenine dinucleotide phosphate (NADPH), tetraethoxypropane stock solution (5mM) and 1mM DTNB were purchased from Sigma Chemical Co (Poole, Dorset, UK); Na2-NADPH, di-sodium hydrogen phosphate (anhydrous) were obtained from Fluka Chemical Co (Buchs, Switzerland). Sodium azide, sodium chloride, Ethylenediaminetetraacetic acid (EDTA), and 120 mM hydrogen peroxide (H2O2) were purchased from Merck (Darmstadt, Germany). Nitroglycerin was purchased from Caspian company, Rasht, Iran.

2.2. Apparatus

All parameters were measured using the spectrophotometric method by shimadzu UV160 spectrophotometer. Tissue homogenizations were performed using Heidolph homogenizer DIAX 900. Centrifugation was performed by eppendorf® microcentrifuge 5417R. Memert water bath 37°C was used to control sample temperature.

2.3. Animals

All animal experiments were approved by the Ethics Committee of Shiraz University of Medical Sciences. Adult female Sprague-Dawley rats (175±15g), bred and raised at the university animal quarters, were housed and fed a rat chow diet (Pars Dam, Tehran, Iran). Eight groups of rats, each containing 10 animals, were used in the present study. All animals were kept under controlled conditions with a regular light cycle (12; 12 h light; dark cycle). During the experiments, rats had free access to food and water.

2.4. Experimental protocol and groups

To study the long-term effects of NTG, 40 female rats were divided into four groups of 10 animals (test and control). We used a commercial formulation of NTG in the form of 5 mg mL-1 ampules and 450 µL of NTG was administered each morning at a specific time (10 a.m.) to each rat. NTG [15 mg kg-1, subcutaneously (s.c.)] was administered to test group (a) and normal saline vehicle (1 ml kg-1, s.c.) was administered to control group (b) daily for 4 weeks (21). After 4 weeks, the rats were mated and mating was confirmed by the presence of spermatozoa in the vaginal smear the next morning (day 1 of pregnancy) (22). The rats were sacrificed on day 5 of pregnancy (implantation time) and the uteri were removed, washed in saline to remove blood, and kept at −70 °C until further analysis. Another test and control groups (c and d) were treated continuously until the pups were born, and finally, their pups were counted. To study the short-term effects of NTG, 40 female rats were mated, and after confirmation of mating, divided into four groups of 10 animals (22). NTG (15 mg kg-1, s.c.) was administered to test groups (e and f) and normal saline vehicle (1 ml kg-1, s.c.) was administered to controls (g and h) daily until implantation time (21). Then, all rats were sacrificed and the uteri were removed, washed in saline, and kept at −70 °C until further analysis. According to long term treated groups, groups f and h were treated with NTG until their pups were born and counted.

2.5. Homogenization of uterine tissues

The frozen uterine tissue samples were cut into small pieces and homogenized in ice-cold saline to produce 10% (w/v) homogenates which were centrifuged at 10000 × g for 20 min at 4 °C. The supernatants were used for the measurement of GPx, GR, CAT activities as well as MDA and GSH levels. The protein in the uterine supernatants was measured by the Bradford method, using bovine serum albumin as a standard (23).

2.6. Measurement of MDA concentration

Uterine MDA was assayed by a colorimetric method as described by Mostafavi-Pour et al. The MDA concentration was calculated using 1, 1, 3, 3-tetraethoxy propane (TEP) as a standard. The results were expressed as nmol mg-1 protein of the uterine supernatant (24).

2.7. Measurement of GSH concentration

The assay of GSH with DTNB [5, 5′-dithiobis-(2-nitrobenzoate)] dye was performed followed by a standard Ellman's method (25). Standard curve were made from 1mM solutions of GSH. Clear uterus supernatant was analyzed for GSH level. 2.3 ml of potassium phosphate buffer (0.2 M, pH 7.6) was added to 0.2 ml of supernatant and then 0.5 ml DTNB (0.001 M) was added to the solution. An absorbance of the products was observed after 5 min at 412 nm and the concentrations of GSH were expressed as µmol mg-1 protein.

2.8. Determination of GPx activity

The GPx activity of the uterus supernatant was measured by the method of Fecondo and Augusteyn , which monitor the regeneration of reduced glutathione (GSH) from oxidized glutathione (GSSG) upon the action of GR (Sigma Chemical Company, USA) and NADPH (Fluka Chemical Company, Switzerland) as described previously (26). The enzyme activity in the uterus supernatants was expressed as mU mg-1 of the protein using a molar extinction coefficient of 6.22 × 106/M/cm for NADPH.

2.9. Determination of CAT activity

CAT activity was estimated by monitoring H2O2 decomposition using the procedure of Aebi , as previously described (27). CAT activity was expressed as the mmol of H2O2 consumed per min/mg of the uterus supernatant protein using a molar extinction coefficient of 43.6/ M/cm for H2O2.

2.10. Determination of GR activity

GR activity was determined by the method of Carlberg and Mannervik , as previously described (28). GR, catalyzes the reduction of GSSG to GSH, using NADPH as a reductant for reducing GSSG molecule. Therefore, the measurement of NADPH consumption will result in the determination of GR activity. Results were based on a molar extinction coefficient for NADPH of 6.22×106M-1cm-1. One unit of GR is defined as mU mg-1 cell protein.

2.11. Statistical analysis

The data were analyzed using SPSS version 19 software (SPSS, Chicago, IL, USA). All data were analyzed by Mann-Whitney tests for group comparison and are expressed as mean ± standard error of the mean. The 0.05 level was used for statistical significance.

3. RESULTS AND DISCUSSION
3.1. Long and short term effects of NTG on MDA and GSH levels

Figure 1 a shows the uterus MDA level in long and short-term NTG treated test and control groups. The MDA levels in the long-term test group were increased significantly by 51.3% compared to the control group (P<0.05). According to our results, there was no difference between MDA levels of short-term NTG treated test and control groups (Figure 1 a). As depicted in Figure 1 b, there was no remarkable difference between the long term test and control groups in GSH levels. Short-term NTG treated test group had a mildly elevated GSH levels compared with the control group, but the difference is not significant.

3.2. Long- and short- term effects of NTG on GPx, GR and CAT activity

According to the Figure 2 a, long-term NTG treatment of the test group resulted in a significant decrease in GPx activity by %48.7 as compared to the controls (P<0.05). Compared with the control group, the Long-term administration of NTG to test group had no significant effect both on the GR and CAT activity. However, no significant differences were found between the activities of these three enzymes in short-term NTG treated group compared with the controls (Figure 2 b).

3.3. Long and short term effects of NTG treatment on the number of pups

As shown in Figure 3 , long-term NTG treatment significantly decreased the number of pups by 49.9% compared to control (P<0.05). However, in the short-term NTG treated group, there were no marked differences in the number of pups between the test and the control groups.

Figure 3. Effects of long and short-term NTG treatment on the number of pups (mean±SEM) compared to the control groups (normal saline); * P< 0.05

Our observations indicated that GPx activity in the long-term NTG treated group was significantly decreased compared with the controls (P < 0.05). these data are consistent with results of previous study, which showed that the red cell activity of the antioxidant enzymes, catalase, and GPx, were significantly decreased after intravenous NTG treatment (29). In addition, some investigations have shown that NTG treatment and RNS formation could lead to the inactivation of glutathione S-transferase (GST), a glutathione-mediated enzyme, by nitration or oxidation of some amino acid residues in the enzyme structure (30, 31). Accordingly, it appears that the mechanism of the reduction in GPx activity is similar to that of GST-inactivation. GPx is one of the first lines of defense against free-radical damage to tissues, thus inactivation of this enzyme in the uterus at implantation window may be detrimental to this process. In addition, the levels of MDA, as a marker of lipid peroxidation, were significantly increased in the long-term NTG treated group compared to control (P < 0.05). This observation is consistent with other investigations of effects of NTG treatment on MDA levels. Dudek et al., 2010 and Knorr et al., 2011 showed that NTG treated rats have significantly increased MDA levels as compared with the corresponding values in the control group (32, 33). In our study, long-term administration of NTG in test group showed no significant differences in the levels of GSH or in the activities of GR and CAT compared to the controls. GPx and GR are involved in oxidizing and reducing GSH respectively. According to our results, GPx activity decreased, but GR activity and GSH levels remained unchanged. A possible explanation for these data is that, according to the mechanism of reaction, the inactivated GPx and unchanged GR could result in intact GSH. This indicates that there was an imbalance in the redox homeostasis of uterine tissue. These findings are consistent with previous observations. Husain showed that long-term administration of NTG had no significant effects on activity of some antioxidant enzymes or GSH levels in rat heart tissue (34). However, one study reported that NTG treatment increased formation of superoxide and peroxynitrite leading to the significant decrease in plasma levels of lipophilic antioxidants , alpha and beta carotene, and superoxide dismutase activity (35). As shown in Figure 3 , long-term NTG treatment of test group significantly decreased the number of pups compared with the control group (P < 0.05). Although, some studies have found that nitric oxide may be needed in the process of implantation and improving pregnancy rate (36, 37), overly nitric oxide containing environment may exert an inhibitory effect on the expression of adhesion molecules and lead to impaired implantation (38). Accordingly, it appears that decreased number of pups in long term treatment of NTG in our study may be due to the implantation failure. However, as shown in Figure 1 a, Figure 1 b, Figure 2 b, and Figure 3 , no significant differences were observed in the activities of GPx, CAT, and GR or in the levels of MDA and GSH and number of pups in the short-term treated NTG groups as compared with the controls.

4. CONCLUSION

According to our data, long-term NTG treatment may result in redox imbalance, impaired implantation and can lead to the infertility. However, it appears that the short-term NTG treatment may not have reproductive side effects.

ACKNOWLEDGMENT

This paper has been extracted from the MSc. thesis of Sadegh Rajabi and was supported by Grant Number 92-6643 from Vice-chancellor for Research Affairs of Shiraz University of Medical Sciences.

This paper has been extracted from the MSc. thesis of Sadegh Rajabi and was supported by Grant Number 92-6643 from Vice-chancellor for Research Affairs of Shiraz University of Medical Sciences, Shiraz, Iran.

AUTHORS CONTRIBUTION

All authors contributed equally in the preparation of the manuscript.

CONFLICT OF INTEREST

The authors declared no potential conflicts of interests with respect to the authorship and/or publication of this paper.

REFERENCES

1. Randolph Jr JF. Unexplained infertility. Clinical obstetrics and gynecology. 2000;43(4):897-901. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

2. Gurunath S, Pandian Z, Anderson RA, Bhattacharya S. Defining infertility--a systematic review of prevalence studies. Human reproduction update. 2011;17(5):575-88. [View at Google Scholar].

3. Güney M, Nasir S, Oral B, Karahan N, Mungan T. Effect of caffeic acid phenethyl ester on the regression of endometrial explants in an experimental rat model. Reproductive Sciences. 2007;14(3):270-9. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

4. Harma M, Harma M, Kocyigit A. Comparison of protein carbonyl and total plasma thiol concentrations in patients with complete hydatidiform mole with those in healthy pregnant women. Acta obstetricia et gynecologica Scandinavica. 2004;83(9):857-60. [View at Publisher]; [View at Google Scholar].

5. Palacio J, Iborra A, Ulcova‐Gallova Z, Badia R, Martinez P. The presence of antibodies to oxidative modified proteins in serum from polycystic ovary syndrome patients. Clinical & Experimental Immunology. 2006;144(2):217-22. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

6. Opuwari CS, Henkel RR. An Update on Oxidative Damage to Spermatozoa and Oocytes. BioMed research international. 2016;2016:9540142. [View at Google Scholar]; [View at PubMed].

7. Ismiyati A, Wiyasa IW, Hidayati DY. Protective Effect of Vitamins C and E on Depot-Medroxyprogesterone Acetate-Induced Ovarian Oxidative Stress In Vivo. Journal of toxicology. 2016;2016:3134105. [View at Google Scholar].

8. Manolis AS, Manolis TA, Metaxa S. Pregnancy and Cardiovascular Disease. Rhythmos. 2013;8(4):45-56. [View at Publisher]; [View at Google Scholar].

9. sweetman. SC. Martindale, the complete drug reference. 2. Thirty-fifth edition ed2007. p. 1163-6. [View at Google Scholar].

10. Hanafy KA, Krumenacker JS, Murad F. NO, nitrotyrosine, and cyclic GMP in signal transduction. Medical science monitor: international medical journal of experimental and clinical research. 2000;7(4):801-19. [View at Google Scholar].

11. Lykkesfeldt J. Malondialdehyde as biomarker of oxidative damage to lipids caused by smoking. Clinica chimica acta. 2007;380(1):50-8. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

12. Gori T, Daiber A, Di Stolfo G, Sicuro S, Dragoni S, Lisi M, et al. Nitroglycerine causes mitochondrial reactive oxygen species production: in vitro mechanistic insights. Canadian Journal of Cardiology. 2007;23(12):990-2. [View at Publisher]; [View at Google Scholar].

13. Khorram O, Lessey BA. Alterations in expression of endometrial endothelial nitric oxide synthase and α v β 3 integrin in women with endometriosis. Fertility and sterility. 2002;78(4):860-4. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

14. Barroso RP, Osuamkpe C, Nagamani M, Yallampalli C. Nitric oxide inhibits development of embryos and implantation in mice. Molecular human reproduction. 1998;4(5):503-7. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

15. Del Rio D, Stewart AJ, Pellegrini N. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutrition, Metabolism and Cardiovascular Diseases. 2005;15(4):316-28. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

16. Zal F, Mahdian Z, Zare R, Soghra B, Mostafavi-Pour Z. Combination of vitamin E and folic acid ameliorate oxidative stress and apoptosis in diabetic rat uterus. International journal for vitamin and nutrition research Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung Journal international de vitaminologie et de nutrition. 2014;84(1-2):55-64. [View at Publisher]; [View at Google Scholar]; [View at PubMed]; [View at Scopus].

17. Lu SC. Regulation of glutathione synthesis. Molecular aspects of medicine. 2009;30(1):42-59. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

18. Perkins AV. Endogenous anti‐oxidants in pregnancy and preeclampsia. Australian and New Zealand journal of obstetrics and gynaecology. 2006;46(2):77-83. [View at Publisher]; [View at Google Scholar]; [View at PubMed]; [View at Scopus].

19. Yan J, Meng X, Wancket LM, Lintner K, Nelin LD, Chen B, et al. Glutathione reductase facilitates host defense by sustaining phagocytic oxidative burst and promoting the development of neutrophil extracellular traps. The Journal of Immunology. 2012;188(5):2316-27. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

20. Fujii J, Iuchi Y, Okada F. Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system. Reproductive biology and endocrinology. 2005;3(1):43. [View at Google Scholar]; [View at PubMed].

21. Husain K. Interaction of regular exercise and chronic nitroglycerin treatment on blood pressure and rat aortic antioxidants. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2004;1688(1):18-25. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

22. Sookvanichsilp N, Pulbutr P. Anti-implantation effects of indomethacin and celecoxib in rats. Contraception. 2002;65(5):373-8. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

23. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical biochemistry. 1976;72(1):248-54. [View at Publisher]; [View at Google Scholar]; [View at PubMed].

24. Hajizadeh MR, Eftekhar E, Zal F, Jafarian A, Mostafavi-Pour Z. Mulberry leaf extract attenuates oxidative stress-mediated testosterone depletion in streptozotocin-induced diabetic rats. Iranian journal of medical sciences. 2014;39(2):123-9. [View at Google Scholar]; [View at PubMed].

25. Ellman GL. Tissue sulfhydryl groups. Archives of biochemistry and biophysics. 1959;82(1):70-7. [View at Publisher]; [View at Google Scholar].

26. Zal F, Mostafavi‐Pour Z, Vessal M. Comparison of the effects of vitamin and/or quercetin in attenuating chronic cyclosporine A-induced nephrotoxicity in male rats. Clinical and experimental pharmacology and physiology. 2007;34(8):720-4. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

27. Zal F, Taheri R, Khademi F, Keshavarz E, Rajabi S, Mostafavi-Pour Z. The combined effect of furosemide and propranolol on GSH homeostasis in ACHN renal cells. Toxicology mechanisms and methods. 2014:1-5. [View at Google Scholar].

28. Zal F, Mostafavi-Pour Z, Amini F, Heidari A. Effect of vitamin E and C supplements on lipid peroxidation and GSH-dependent antioxidant enzyme status in the blood of women consuming oral contraceptives. Contraception. 2012;86(1):62-6. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

29. AlIcIgüzel Y, Aktas S, Bozan H, Aslan M. Effect of intravenous nitroglycerin therapy on erythrocyte antioxidant enzymes. Journal of enzyme inhibition and medicinal chemistry. 2005;20(3):293-6. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

30. Wong PS-Y, Eiserich JP, Reddy S, Lopez CL, Cross CE, van der Vliet A. Inactivation of Glutathione S-Transferases by Nitric Oxide-Derived Oxidants: Exploring a Role for Tyrosine Nitration. Archives of biochemistry and biophysics. 2001;394(2):216-28. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

31. Lee W-I, Fung H-L. Mechanism-based partial inactivation of glutathione S-transferases by nitroglycerin: tyrosine nitration vs sulfhydryl oxidation. Nitric Oxide. 2003;8(2):103-10. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

32. Dudek M, Bilska A, Bednarski M, Iciek M, Kwiecień I, Sokołowska‐Jeżewicz M, et al. The effect of nitroglycerin tolerance on oxidative stress and anaerobic sulfur metabolism in rat tissues. Fundamental & clinical pharmacology. 2010;24(1):47-53. [View at Publisher]; [View at Google Scholar]; [View at PubMed]; [View at Scopus].

33. Knorr M, Hausding M, Kröller-Schuhmacher S, Steven S, Oelze M, Heeren T, et al. Nitroglycerin-Induced Endothelial Dysfunction and Tolerance Involve Adverse Phosphorylation and S-Glutathionylation of Endothelial Nitric Oxide Synthase Beneficial Effects of Therapy With the AT1 Receptor Blocker Telmisartan. Arteriosclerosis, thrombosis, and vascular biology. 2011;31(10):2223-31. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

34. Husain K. Interaction of physical training and chronic nitroglycerin treatment on blood pressure, nitric oxide, and oxidants/antioxidants in the rat heart. Pharmacological research. 2003;48(3):253-61. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

35. Warnholtz A, Mollnau H, Heitzer T, Kontush A, Möller-Bertram T, Lavall D, et al. Adverse effects of nitroglycerin treatment on endothelial function, vascular nitrotyrosine levels and cGMP-dependent protein kinase activity in hyperlipidemic Watanabe rabbits. Journal of the American College of Cardiology. 2002;40(7):1356-63. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

36. Tsui K-H, Li H-Y, Cheng J-T, Sung Y-J, Yen M-S, Hsieh S-LE, et al. The role of nitric oxide in the outgrowth of trophoblast cells on human umbilical vein endothelial cells. Taiwanese Journal of Obstetrics and Gynecology. 2015;54(3):227-31. [View at Google Scholar].

37. El-Berry S, Razik MA. Nitric oxide donors increases pregnancy rate in clomiphene citrate treated polycystic ovary infertile patients. Middle East Fertility Society Journal. 2010;15(2):106-9. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

38. Zhou J, Chen Y, Lang J-Y, Lu J-J, Ding J. Salvicine inactivates β1 integrin and inhibits adhesion of MDA-MB-435 cells to fibronectin via reactive oxygen species signaling. Molecular Cancer Research. 2008;6(2):194-204. [View at Publisher]; [View at Google Scholar]; [View at PubMed]; [View at Scopus].

39. Spiecker M, Darius H, Kaboth K, Hübner F, Liao JK. Differential regulation of endothelial cell adhesion molecule expression by nitric oxide donors and antioxidants. Journal of leukocyte biology. 1998;63(6):732-9. [View at Google Scholar].

40. Eguchi H, Ikeda Y, Ookawara T, Koyota S, Fujiwara N, Honke K, et al. Modification of oligosaccharides by reactive oxygen species decreases sialyl lewis x-mediated cell adhesion. Glycobiology. 2005;15(11):1094-101. [View at Publisher]; [View at Google Scholar]; [View at Scopus].

41. Sardarian A, Andisheh Tadbir A, Zal F, Amini F, Jafarian A, Khademi F, et al. Altered oxidative status and integrin expression in cyclosporine A-treated oral epithelial cells. Toxicol Mech Methods. 2015;25(2):98-104. [View at Publisher]; [View at Google Scholar]; [View at PubMed]; [View at Scopus].

42. Zal F, Mostafavi-Pour Z, Moattari A, Sardarian A, Vessal M. Altered expression of alpha 2 beta 1 integrin in kidney fibroblasts: a potential mechanism for CsA-induced nephrotoxicity. Arch Iran Med. 2014;17(8):556-62. [View at Google Scholar].

Paper Title: Redox Imbalance and Reproductive Side Effects of Long and Short Term Nitroglycerin Treatment in Rat Uterus
Paper Details: Volume 6, Issue 10, Pages: 204-210
Paper doi:10.15412/J.JBTW.01061004
Journal of Biology and Today's World
Journal home page: http://journals.lexispublisher.com/jbtw
Copyright © 2017 Zohreh Mostafavi-Pour et al. This is an open access paper distributed under the Creative Commons Attribution License.
Click here to have/see Comments & Letters to Editor about this paper