DOI QR코드

DOI QR Code

Protective Effects of the Nuclear Factor Kappa B Inhibitor Pyrrolidine Dithiocarbamate on Experimental Testicular Torsion and Detorsion Injury

  • Kabay, Sahin (Department of Urology, Faculty of Medicine, Dumlupınar University) ;
  • Ozden, Hilmi (Department of Anatomy, Faculty of Medicine, Eskisehir Osmangazi University) ;
  • Guven, Gul (Department of Anatomy, Faculty of Medicine, Eskisehir Osmangazi University) ;
  • Burukoglu, Dilek (Department of Histology and Embryology, Faculty of Medicine, Eskisehir Osmangazi University) ;
  • Ustuner, Mehmet Cengiz (Department of Medical Biology, Faculty of Medicine, Eskisehir Osmangazi University) ;
  • Topal, Fatma (Bilecik Seyh Edebali University, Vocational School Health Services) ;
  • Gunes, Hasan Veysi (Department of Medical Biology, Faculty of Medicine, Eskisehir Osmangazi University) ;
  • Ustuner, Derya (Eskisehir Osmangazi University, Vocational School Health Services) ;
  • Ozbayer, Cansu (Department of Medical Biology, Faculty of Medicine, Eskisehir Osmangazi University)
  • Received : 2014.03.17
  • Accepted : 2014.06.27
  • Published : 2014.08.30

Abstract

Testicular torsion results with the damage of the testis and it is a surgical emergency. Pyrrolidine dithiocarbamate (PDTC) is a low-molecular-weight antioxidant and potent inhibitor of nuclear factor kappa B (NF-${\kappa}B$) activation. In this study, we aimed to investigate the effects of PDTC to testicular torsion-detorsion (T/D) injury. Forty adult male Sprague-Dawley rats were separated into four groups. A sham operation was performed in group I. In group II, torsion is performed 2 hours by 720 degree extravaginally testis. In group III, 4 h reperfusion of the testis was performed after 2 h of testicular torsion. In group IV, after performing the same surgical procedures as in group III, PDTC (100 mg/kg, intravenous's) was administered before 30 min of detorsion. The testes tissue malondialdehyde (MDA), superoxide dismutase (SOD) catalase (CAT) level was evaluated. Histological evaluations were performed after hematoxylin and eosin staining. Testicular tissue MDA levels were the highest in the T/D groups compared with treatment group. Administration of PDTC prevented a further increase in MDA levels. Significant decrease occurred in CAT and SOD levels in treatment group compared with the control group. The rats in the treatment group had normal testicular architecture. The results suggest that PDTC can be a potential protective agent for preventing the biochemical and histological changes related to oxidative stress in testicular injury caused by testis torsion.

Keywords

References

  1. Donohue RE, Utley WL. Torsion of spermatic cord. Urology. 1978;11:33-36. https://doi.org/10.1016/0090-4295(78)90195-4
  2. Anderson JB, Williamson RC. Testicular torsion in Bristol: a 25-year review. Br J Surg. 1988;75:988-992. https://doi.org/10.1002/bjs.1800751015
  3. Ames BN. Endogenous oxidative DNA damage, aging, and cancer. Free Radic Res Commun. 1989;7:121-128. https://doi.org/10.3109/10715768909087933
  4. de Groot H, Rauen U. Ischemia-reperfusion injury: processes in pathogenetic networks: a review. Transplant Proc. 2007;39: 481-484. https://doi.org/10.1016/j.transproceed.2006.12.012
  5. Granger DN, Korthuis RJ. Physiologic mechanisms of postischemic tissue injury. Annu Rev Physiol. 1995;57:311-332. https://doi.org/10.1146/annurev.ph.57.030195.001523
  6. Yang S, Shih HJ, Chow YC, Tsai PS, Huang CJ. Hemin induced heme oxygenase-1 over expression involves nuclear factor-E2 related factor-2, nuclear factor-kappaB and extracellular regulated kinase: an experimental study in a testicular torsiondetorsion rodent model. J Urol. 2008;179:2456-2463. https://doi.org/10.1016/j.juro.2008.01.085
  7. Altavilla D, Romeo C, Squadrito F, Marini H, Morgia G, Antonuccio P, Minutoli L. Molecular pathways involved in the early and late damage induced by testis ischemia: evidence for a rational pharmacological modulation. Curr Med Chem. 2012; 19:1219-1224. https://doi.org/10.2174/092986712799320538
  8. Orrenius S, Nobel CS, van den Dobbelsteen DJ, Burkitt MJ, Slater AF. Dithiocarbamates and the redox regulation of cell death. Biochem Soc Trans. 1996;24:1032-1038. https://doi.org/10.1042/bst0241032
  9. Iseki A, Kambe F, Okumura K, Niwata S, Yamamoto R, Hayakawa T, Seo H. Pyrrolidine dithiocarbamate inhibits TNF-alpha-dependent activation of NF-kappaB by increasing intracellular copper level in human aortic smooth muscle cells. Biochem Biophys Res Commun. 2000;276:88-92. https://doi.org/10.1006/bbrc.2000.3452
  10. Liu SF, Ye X, Malik AB. Inhibition of NF-kappaB activation by pyrrolidine dithiocarbamate prevents In vivo expression of proinflammatory genes. Circulation. 1999;100:1330-1337. https://doi.org/10.1161/01.CIR.100.12.1330
  11. Bowie A, O'Neill LA. Oxidative stress and nuclear factorkappaB activation: a reassessment of the evidence in the light of recent discoveries. Biochem Pharmacol. 2000;59:13-23. https://doi.org/10.1016/S0006-2952(99)00296-8
  12. Schreck R, Meier B, Mannel DN, Droge W, Baeuerle PA. Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells. J Exp Med. 1992;175:1181-1194. https://doi.org/10.1084/jem.175.5.1181
  13. Borrello S, Demple B. NF kappa B-independent transcriptional induction of the human manganous superoxide dismutase gene. Arch Biochem Biophys. 1997;348:289-294. https://doi.org/10.1006/abbi.1997.0355
  14. Liu SF, Ye X, Malik AB. In vivo inhibition of nuclear factorkappa B activation prevents inducible nitric oxide synthase expression and systemic hypotension in a rat model of septic shock. J Immunol. 1997;159:3976-3983.
  15. Si X, McManus BM, Zhang J, Yuan J, Cheung C, Esfandiarei M, Suarez A, Morgan A, Luo H. Pyrrolidine dithiocarbamate reduces coxsackievirus B3 replication through inhibition of the ubiquitin-proteasome pathway. J Virol. 2005;79:8014-8023. https://doi.org/10.1128/JVI.79.13.8014-8023.2005
  16. Hartsfield CL, Alam J, Choi AM. Transcriptional regulation of the heme oxygenase 1 gene by pyrrolidine dithiocarbamate. FASEB J. 1998;12:1675-1682. https://doi.org/10.1096/fasebj.12.15.1675
  17. Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978;86:271-278. https://doi.org/10.1016/0003-2697(78)90342-1
  18. Goth L. A simple method for determination of serum catalase activity and revision of reference range. Clinica Chimica Acta. 1991;196:143-152. https://doi.org/10.1016/0009-8981(91)90067-M
  19. Saba M, Morales CR, De Lamirande E, Gagnon C. Morphological and biochemical changes following acute unilateral testicular torsion in prepubertal rats. J Urol. 1997;157:1149-1154. https://doi.org/10.1016/S0022-5347(01)65158-9
  20. Nemeth ZH, Hasko G, Vizi ES. Pyrrolidine dithiocarbamate augments IL-10, inhibits TNF-alpha, MIP-1alpha, IL-12, and nitric oxide production and protects from the lethal effect of endotoxin. Shock. 1998;10:49-53. https://doi.org/10.1097/00024382-199807000-00009
  21. Sun Z, Andersson R. NF-kappaB activation and inhibition: a review. Shock. 2002;18:99-106. https://doi.org/10.1097/00024382-200208000-00001
  22. Frossard JL, Pastor CM, Hadengue A. Effect of hyperthermia on NF-kappaB binding activity in cerulein-induced acute pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2001;280: G1157-1162. https://doi.org/10.1152/ajpgi.2001.280.6.G1157
  23. Orfila C, Lepert JC, Alric L, Carrera G, Beraud M, Pipy B. Immunohistochemical distribution of activated nuclear factor kappaB and peroxisome proliferator-activated receptors in carbon tetrachloride-induced chronic liver injury in rats. Histochem Cell Biol. 2005;123:585-593. https://doi.org/10.1007/s00418-005-0785-2
  24. Tugcu V, Ozbek E, Tasci AI, Kemahli E, Somay A, Bas M, Karaca C, Altug T, Cekmen MB, Ozdogan HK. Selective nuclear factor kappa-B inhibitors, pyrolidium dithiocarbamate and sulfasalazine, prevent the nephrotoxicity induced by gentamicin. BJU Int. 2006;98:680-686. https://doi.org/10.1111/j.1464-410X.2006.06321.x
  25. Gu EY, Han HS, Park JS. Effect of minocycline on activation of glia and nuclear factor kappa B in an animal nerve injury model. Korean J Physiol Pharmacol. 2004;8:237-243.
  26. Hidaka S, Funakoshi T, Shimada H, Tsuruoka M, Kojima S. Protective effect of N-benzyl-D-glucamine dithiocarbamate against renal toxicity in rats during repeated cis-diamminedichloroplatinum administrations. Ren Fail. 1995;17:539-550. https://doi.org/10.3109/08860229509037618
  27. Kojima S, Sugimura Y, Ono H, Shimada H, Funakoshi T. N-benzyl-D-glucamine dithiocarbamate and N-p-isopropylbenzyl-D-glucamine dithiocarbamate improve the protective effect of diethyldithiocarbamate against cadmium-induced testicular toxicity in rats. Biol Pharm Bull. 1993;16:244-247. https://doi.org/10.1248/bpb.16.244
  28. Schwartz MD, Moore EE, Moore FA, Shenkar R, Moine P, Haenel JB, Abraham E. Nuclear factor-kappa B is activated in alveolar macrophages from patients with acute respiratory distress syndrome. Crit Care Med. 1996;24:1285-1292. https://doi.org/10.1097/00003246-199608000-00004
  29. Li C, Browder W, Kao RL. Early activation of transcription factor NF-kappaB during ischemia in perfused rat heart. Am J Physiol. 1999;276:H543-552.
  30. Muller DN, Dechend R, Mervaala EM, Park JK, Schmidt F, Fiebeler A, Theuer J, Breu V, Ganten D, Haller H, Luft FC. NF-kappaB inhibition ameliorates angiotensin II-induced inflammatory damage in rats. Hypertension. 2000;35:193-201. https://doi.org/10.1161/01.HYP.35.1.193
  31. Bach SP, Chinery R, O'Dwyer ST, Potten CS, Coffey RJ, Watson AJ. Pyrrolidinedithiocarbamate increases the therapeutic index of 5-fluorouracil in a mouse model. Gastroenterology. 2000;118:81-89. https://doi.org/10.1016/S0016-5085(00)70416-1
  32. Chen D, Peng F, Cui QC, Daniel KG, Orlu S, Liu J, Dou QP. Inhibition of prostate cancer cellular proteasome activity by a pyrrolidine dithiocarbamate-copper complex is associated with suppression of proliferation and induction of apoptosis. Front Biosci. 2005;10:2932-2939. https://doi.org/10.2741/1749
  33. Morais C, Pat B, Gobe G, Johnson DW, Healy H. Pyrrolidine dithiocarbamate exerts anti-proliferative and pro-apoptotic effects in renal cell carcinoma cell lines. Nephrol Dial Transplant. 2006;21:3377-3388. https://doi.org/10.1093/ndt/gfl543
  34. Arima N, Arimura K, Tokito Y, Sakaki Y, Matsushita K, Orihara K, Akimoto M, Ozaki A, Kukita T, Hagiwara T, Hamada H, Tei C. HTLV-I Tax protein inhibits apoptosis induction but not G1 arrest by pyrrolidinedithiocarbamate, an anti-oxidant, in adult T cell leukemia cells. Exp Hematol. 2004; 32:195-201. https://doi.org/10.1016/j.exphem.2003.11.008
  35. Milacic V, Chen D, Giovagnini L, Diez A, Fregona D, Dou QP. Pyrrolidine dithiocarbamate-zinc(II) and -copper(II) complexes induce apoptosis in tumor cells by inhibiting the proteasomal activity. Toxicol Appl Pharmacol. 2008;231:24-33. https://doi.org/10.1016/j.taap.2008.03.009
  36. Chae HJ, Bae J, Chae SW. PDTC Inhibits TNF-${\alpha}$-Induced Apoptosis in MC3T3E1 Cells. Korean J Physiol Pharmacol. 2003;7:199-205.
  37. Zhang H, Wu JS, Peng F. Potent anticancer activity of pyrrolidine dithiocarbamate-copper complex against cisplatinresistant neuroblastoma cells. Anticancer Drugs. 2008;19:125-132. https://doi.org/10.1097/CAD.0b013e3282f2bdff
  38. Chatterjee PK, di Villa Bianca RD, Sivarajah A, McDonald MC, Cuzzocrea S, Thiemermann C. Pyrrolidine dithiocarbamate reduces renal dysfunction and injury caused by ischemia/ reperfusion of the rat kidney. Eur J Pharmacol. 2003;482: 271-280. https://doi.org/10.1016/j.ejphar.2003.09.071
  39. Li J, Sheng W, Feng C, Zuo Z. Pyrrolidine dithiocarbamate attenuates brain A${\beta}$ increase and improves long-term neurological outcome in rats after transient focal brain ischemia. Neurobiol Dis. 2012;45:564-572. https://doi.org/10.1016/j.nbd.2011.09.013
  40. Teke Z, Kabay B, Aytekin FO, Yenisey C, Demirkan NC, Sacar M, Erdem E, Ozden A. Pyrrolidine dithiocarbamate prevents 60 minutes of warm mesenteric ischemia/reperfusion injury in rats. Am J Surg. 2007;194:255-262. https://doi.org/10.1016/j.amjsurg.2006.06.054
  41. Teke Z, Aytekin FO, Kabay B, Yenisey C, Aydin C, Tekin K, Sacar M, Ozden A. Pyrrolidine dithiocarbamate prevents deleterious effects of remote ischemia/reperfusion injury on healing of colonic anastomoses in rats. World J Surg. 2007;31: 1835-1842. https://doi.org/10.1007/s00268-007-9106-3
  42. Mallick IH, Yang WX, Winslet MC, Seifalian AM. Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine. World J Gastroenterol. 2005;11:7308-7313. https://doi.org/10.3748/wjg.v11.i46.7308
  43. Tian XF, Yao JH, Li YH, Gao HF, Wang ZZ, Yang CM, Zheng SS. Protective effect of pyrrolidine dithiocarbamate on liver injury induced by intestinal ischemia-reperfusion in rats. Hepatobiliary Pancreat Dis Int. 2006;5:90-95.
  44. Kabay B, Teke Z, Aytekin FO, Yenisey C, Bir F, Sacar M, Erdem E, Ozden A. Pyrrolidine dithiocarbamate reduces lung injury caused by mesenteric ischemia/reperfusion in a rat model. World J Surg. 2007;31:1707-1715. https://doi.org/10.1007/s00268-007-9112-5
  45. El Eter E, Hagar HH, Al-Tuwaijiri A, Arafa M. Nuclear factor-kappaB inhibition by pyrrolidinedithiocarbamate attenuates gastric ischemia-reperfusion injury in rats. Can J Physiol Pharmacol. 2005;83:483-492. https://doi.org/10.1139/y05-034
  46. Ilbey YO, Ozbek E, Simsek A, Cekmen M, Otunctemur A, Somay A. Chemoprotective effect of a nuclear factor-kappaB inhibitor, pyrrolidine dithiocarbamate, against cisplatin-induced testicular damage in rats. J Androl. 2009;30:505-514. https://doi.org/10.2164/jandrol.108.006270

Cited by

  1. Protective effects of polydatin on experimental testicular torsion and detorsion injury in rats vol.29, pp.12, 2017, https://doi.org/10.1071/rd17046
  2. Comparison of Intraperitoneal and Intratesticular GYY4137 Therapy for the Treatment of Testicular Ischemia Reperfusion Injury in Rats vol.40, pp.2, 2020, https://doi.org/10.1007/s11596-020-2180-6