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  • Review Article
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Mechanisms of testicular torsion and potential protective agents

Subjects

Key Points

  • Testicular torsion is a urological emergency that requires urgent treatment

  • The main pathophysiology of testicular torsion is ischaemia–reperfusion injury of the testis

  • Activation of the inflammatory cascade and apoptosis are the most important pathological mechanisms in testicular torsion and detorsion

  • Several drugs have been successfully tested in animal models to reduce the dangerous effects of ischaemia–reperfusion in testicular torsion

  • The challenge is now to translate the results of animal studies to clinical trials and then clinical practice

Abstract

Testicular torsion is a urological emergency most commonly seen in adolescence, involving a decrease in blood flow in the testis resulting from torsion of the spermatic cord that can result in gonad injury or even loss if not treated in time. Testicular ischaemia–reperfusion injury represents the principle pathophysiology of testicular torsion, with ischaemia caused by twisting of the spermatic cord, and reperfusion on its subsequent release. Many cellular and molecular mechanisms are involved in ischaemia-reperfusion injury following testicular torsion. Studies have investigated the use of pharmacological agents as supportive therapy to surgical repair in order to prevent the adverse effects of testicular torsion. Numerous substances have been proposed as important in the prevention of post-ischaemia–reperfusion testicular injury. A range of chemicals and drugs has been successfully tested in animal models for the purpose of mitigating the dangerous effects of ischaemia-reperfusion in testis torsion.

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Figure 1: Pathophysiology of testicular torsion.

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References

  1. Ahmed, F. A., Whelan, J., Jequier, A. M. & Cummins, J. M. Torsion-induced injury in rat testes does not affect mitochondrial respiration or the accumulation of mitochondrial mutations. Int. J. Androl. 23, 347–356 (2000).

    CAS  PubMed  Google Scholar 

  2. Regadera, J., Nistal, M. & Paniagua, R. Testis, epididymis, and spermatic cord in elderly men. Correlation of angiographic and histologic studies with systemic arteriosclerosis. Arch. Pathol. Lab. Med. 109, 663–667 (1985).

    CAS  PubMed  Google Scholar 

  3. Ciftci, A. O., Senocak, M. E., Tanyel, F. C. & Buyukpamukcu, N. Clinical predictors for differential diagnosis of acute scrotum. Eur. J. Pediatr. Surg. 14, 333–338 (2004).

    CAS  PubMed  Google Scholar 

  4. McAndrew, H. F., Pemberton, R., Kikiros, C. S. & Gollow, I. The incidence and investigation of acute scrotal problems in children. Pediatr. Surg. Int. 18, 435–437 (2002).

    CAS  PubMed  Google Scholar 

  5. Makela, E., Lahdes-Vasama, T., Rajakorpi, H. & Wikstrom, S. A 19-year review of paediatric patients with acute scrotum. Scand. J. Surg. 96, 62–66 (2007).

    CAS  PubMed  Google Scholar 

  6. Barada, J. H., Weingarten, J. L. & Cromie, W. J. Testicular salvage and age-related delay in the presentation of testicular torsion. J. Urol. 142, 746–748 (1989).

    CAS  PubMed  Google Scholar 

  7. Ringdahl, E. & Teague, L. Testicular torsion. Am. Fam. Physician 74, 1739–1743 (2006).

    PubMed  Google Scholar 

  8. Williamson, R. C. N. Death in the scrotum: testicular torsion. N. Engl. J. Med. 296, 338 (1977).

    CAS  PubMed  Google Scholar 

  9. Akgür, F. M., Kilinç, K., Aktug, T. & Olguner, M. The effect of allopurinol pretreatment before detorting testicular torsion. J. Urol. 151, 1715–1717 (1994).

    PubMed  Google Scholar 

  10. Lysiak, J. J. et al. Essential role of neutrophils in germ cell-specific apoptosis following ischemia/reperfusion injury of the mouse testis. Biol. Reprod. 65, 718–725 (2001).

    CAS  PubMed  Google Scholar 

  11. Turner, T. T., Bang, H. J. & Lysiak, J. L. The molecular pathology of experimental testicular torsion suggests adjunct therapy to surgical repair. J. Urol. 172, 2574–2578 (2004).

    CAS  PubMed  Google Scholar 

  12. Cuzzocrea, S., Riley, D. P., Caputi, A. P. & Salvemini, D. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol. Rev. 53, 135–159 (2001).

    CAS  PubMed  Google Scholar 

  13. Reilly, P. M., Schiller, H. J. & Bulkley, G. B. Pharmacologic approach to tissue injury mediated by free radicals and other reactive oxygen metabolites. Am. J. Surg. 161, 488–503 (1991).

    CAS  PubMed  Google Scholar 

  14. Ustün, H. et al. Effect of phospodiesterase 5 inhibitors on apoptosis and nitric oxide synthases in testis torsion: an experimental study. Pediatr. Surg. Int. 24, 205–211 (2008).

    PubMed  Google Scholar 

  15. Guidot, D. M., McCord, J. M., Wright, R. M. & Repine, J. E. Absence of electron transport (Rho 0 state) restores growth of a manganese-superoxide dismutase-deficient Saccharomyces cerevisiae in hyperoxia. Evidence for electron transport as a major source of superoxide generation in vivo. J. Biol. Chem. 268, 26699–26703 (1993).

    CAS  PubMed  Google Scholar 

  16. Jung, J. E. et al. Reperfusion and neurovascular dysfunction in stroke: from basic mechanisms to potential strategies for neuroprotection. Mol. Neurobiol. 41, 172–179 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Zini, A., O'Bryan, M. K., Magid, M. S. & Schlegel, P. N. Immunohistochemical localization of endothelial nitric oxide synthase in human testis, epididymis, and vas deferens suggests a possible role for nitric oxide in spermatogenesis, sperm maturation, and programmed cell death. Biol. Reprod. 55, 935–941 (1996).

    CAS  PubMed  Google Scholar 

  18. Shiraishi, K., Naito, K. & Yoshida, K. Nitric oxide promotes germ cell necrosis in the delayed phase after experimental testicular torsion of rat. Biol. Reprod. 65, 514–521 (2001).

    CAS  PubMed  Google Scholar 

  19. Doutheil, J., Althausen, S., Treiman, M. & Paschen, W. Effect of nitric oxide on endoplasmic reticulum calcium homeostasis, protein synthesis and energy metabolism. Cell Calcium 27, 107–115 (2000).

    CAS  PubMed  Google Scholar 

  20. Sinha Hikim, A. P. & Swerdloff, R. S. Hormonal and genetic control of germ cell apoptosis in the testis. Rev. Reprod. 4, 38–47 (1999).

    CAS  PubMed  Google Scholar 

  21. Lysiak, J. J., Turner, S. D. & Turner, T. T. Molecular pathway of germ cell apoptosis following ischemia/reperfusion of the rat testis. Biol. Reprod. 63, 1465–1472 (2000).

    CAS  PubMed  Google Scholar 

  22. Gute, D. C., Ishida, T., Yarimizu, K. & Korthuis, R. J. Inflammatory responses to ischemia and reperfusion in skeletal muscle. Mol. Cell. Biochem. 179, 169–187 (1998).

    CAS  PubMed  Google Scholar 

  23. Lefer, A. M. Role of the beta2-integrins and immunoglobulin superfamily members in myocardial ischemia-reperfusion. Ann. Thorac. Surg. 68, 1920–1923 (1999).

    CAS  PubMed  Google Scholar 

  24. Lysiak, J. J., Nguyen, Q. A., Kirby, J. L. & Turner, T. T. Ischemia-reperfusion of the murine testis stimulates the expression of proinflammatory cytokines and activation of c-jun N-terminal kinase in a pathway to E-selectin expression. Biol. Reprod. 69, 202–210 (2003).

    CAS  PubMed  Google Scholar 

  25. Lysiak, J. J., Bang, H. J., Nguyen, Q. A. & Turner, T. T. Activation of the nuclear factor kappa b pathway following ischemia-reperfusion of the murine testis. J. Androl. 26, 129–135 (2005).

    CAS  PubMed  Google Scholar 

  26. Moon, C. et al. Expression of CD44 adhesion molecule in rat testis with ischemia/reperfusion injury. J. Vet. Med. Sci. 68, 761–764 (2006).

    CAS  PubMed  Google Scholar 

  27. Weidemann, A. & Johnson, R. S. Biology of HIF-1alpha. Cell Death Differ. 15, 621–627 (2008).

    CAS  PubMed  Google Scholar 

  28. Palladino, M. A. et al. Myeloid cell leukemia-1 (Mc1–1) is a candidate target gene of hypoxia-inducible factor-1 (HIF-1) in the testis. Reprod. Biol. Endocrinol. 10, 104 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Piret, J. P., Mottet, D., Raes, M. & Michiels, C. Is HIF-1alpha a pro- or an anti-apoptotic protein? Biochem. Pharmacol. 64, 49–53 (2002).

    Google Scholar 

  30. Becker, E. J., Prillaman, H. M. & Turner, T. T. Microvascular blood flow is altered after repair of testicular torsion in the rat. J. Urol. 157, 1493–1498 (1997).

    CAS  PubMed  Google Scholar 

  31. Damber, J. E., Lindahl, O., Selstam, G. & Tenland, T. Testicular blood flow measured with a laser Doppler flowmeter: acute effects of catecholamines. Acta Physiol. Scand. 115, 209–215 (1982).

    CAS  PubMed  Google Scholar 

  32. Collin, O., Bergh, A., Damber, J. E. & Widmark, A. Control of testicular vasomotion by testosterone and tubular factors in rats. J. Reprod. Fertil. 97, 115–121 (1993).

    CAS  PubMed  Google Scholar 

  33. Turner, T. T., Caplis, L. & Miller, D. W. Testicular microvascular blood flow: alteration after Leydig cell eradication and ischemia but not experimental varicocele. J. Androl. 17, 239–248 (1996).

    CAS  PubMed  Google Scholar 

  34. Aalkjaer, C. & Nilsson, H. Vasomotion: cellular background for the oscillator and for the synchronization of smooth muscle cells. Br. J. Pharmacol. 144, 605–616 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Damber, J. E., Bergh, A. & Widmark, A. Testicular blood flow and microcirculation in rats after treatment with ethane dimethyl sulfonate. Biol. Reprod. 37, 1291–1296 (1987).

    CAS  PubMed  Google Scholar 

  36. Damber, J. E., Maddocks, S., Widmark, A. & Bergh, A. Testicular blood flow and vasomotion can be maintained by testosterone in Leydig cell-depleted rats. Int. J. Androl. 15, 385–393 (1992).

    CAS  PubMed  Google Scholar 

  37. Goldwasser, B., Weissenberg, R., Lunenfeld, B., Nativ, O. & Many, M. Semen quality and hormonal status of patients following testicular torsion. Andrologia 16, 239–243 (1984).

    CAS  PubMed  Google Scholar 

  38. Ryan, P. C., Whelan, C. A., Gaffney, E. F. & Fitzpatrick, J. M. The effect of unilateral experimental testicular torsion on spermatogenesis and fertility. Br. J. Urol. 62, 359–366 (1988).

    CAS  PubMed  Google Scholar 

  39. Chen, L. et al. Blood perfusion of the contralateral testis evaluated with contrast-enhanced ultrasound in rabbits with unilateral testicular torsion. Asian J. Androl. 11, 253–260 (2009).

    PubMed  PubMed Central  Google Scholar 

  40. Melikoglu, M., Guntekin, E., Erkilic, M. & Karaveli, S. Contralateral testicular blood flow in unilateral testicular torsion measured by the 133Xe clearance technique. Br. J. Urol. 69, 633–635 (1992).

    CAS  PubMed  Google Scholar 

  41. Tanyel, F. C., Buyukpamukcu, N. & Hicsonmez, A. Contralateral testicular blood flow during unilateral testicular torsion. Br. J. Urol. 63, 522–524 (1989).

    CAS  PubMed  Google Scholar 

  42. Minutoli, L. et al. Evidence for a role of mitogen-activated protein kinase 3/mitogen-activated protein kinase in the development of testicular ischemia-reperfusion injury. Biol. Reprod. 73, 730–736 (2005).

    CAS  PubMed  Google Scholar 

  43. Harrison, R. G., Lewis-Jones, D. I., Moreno de Marval, M. J. & Connolly, R. C. Mechanism of damage to the contralateral testis in rats with an ischaemic testis. Lancet 2, 723–725 (1981).

    CAS  PubMed  Google Scholar 

  44. Choi, H. et al. The alterations of cellular metabolism in the contralateral testis following spermatic cord torsion in rats. J. Urol. 150, 577–580 (1993).

    CAS  PubMed  Google Scholar 

  45. Sarica, K. et al. Influence of experimental spermatic cord torsion on the contralateral testis in rats. Evaluation of tissue free oxygen radical scavenger enzyme levels. Urol. Int. 58, 208–212 (1997).

    CAS  PubMed  Google Scholar 

  46. Puri, P., Barton, D. & O'Donnell, B. Prepubertal testicular torsion: subsequent fertility. J. Pediatr. Surg. 20, 598–601 (1985).

    CAS  PubMed  Google Scholar 

  47. Cosentino, M. J., Rabinowitz, R., Valvo, J. R. & Cockett, A. T. The effect of prepubertal spermatic cord torsion on subsequent fertility in rats. J. Androl. 5, 93–98 (1984).

    CAS  PubMed  Google Scholar 

  48. Anderson, J. B. & Williamson, R. C. Fertility after torsion of the spermatic cord. Br. J. Urol. 65, 225–230 (1990).

    CAS  PubMed  Google Scholar 

  49. Bartsch, G., Frank, S., Marberger, H. & Mikuz, G. Testicular torsion: late results with special regard to fertility and endocrine function. J. Urol. 124, 375–378 (1980).

    CAS  PubMed  Google Scholar 

  50. Jhunjhunwala, J. S., Desal, A. & Kropp, K. A. Torsion of the spermatic cord. An experimental study. Invest. Urol. 13, 318–320 (1976).

    CAS  PubMed  Google Scholar 

  51. Turner, T. T. Acute experimental testicular torsion. No effect on the contralateral testis. J. Androl. 6, 65–72 (1985).

    CAS  PubMed  Google Scholar 

  52. Hadziselimovic, F., Snyder, H., Duckett, J. & Howards, S. Testicular histology in children with unilateral testicular torsion. J. Urol. 136, 208–210 (1986).

    CAS  PubMed  Google Scholar 

  53. Anderson, J. B. & Williamson, R. C. The fate of the human testes following unilateral torsion of the spermatic cord. Br. J. Urol. 58, 698–704 (1986).

    CAS  PubMed  Google Scholar 

  54. Anderson, M. J., Dunn, J. K., Lipshultz, L. I. & Coburn, M. Semen quality and endocrine parameters after acute testicular torsion. J. Urol. 147, 1545–1550 (1992).

    CAS  PubMed  Google Scholar 

  55. Turner, T. T. & Brown, K. J. Spermatic cord torsion: loss of spermatogenesis despite return of blood flow. Biol. Reprod. 49, 401–407 (1993).

    CAS  PubMed  Google Scholar 

  56. Baker, L. A. & Turner, T. T. Leydig cell function after experimental testicular torsion despite loss of spermatogenesis. J. Androl. 16, 12–17 (1995).

    CAS  PubMed  Google Scholar 

  57. Kopera, I. A., Biliniska, B., Cheng, C. Y. & Mruk, D. D. Sertoli-germ cell junctions in the testis: a review of recent data. Philos. Trans. R. Soc. Lond. B Biol. Sci. 365, 1593–1605 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Steinberger, E. & Tjioe, D. Y. Spermatogenesis in rat testis after experimental ischemia. Fertil. Steril. 20, 639–649 (1969).

    CAS  PubMed  Google Scholar 

  59. Turner, T. T., Lysiak, J. J., Shannon, J. D., Nguyen, Q. A. & Bazemore-Walker, C. R. Testicular torsion alters the presence of specific proteins in the mouse testis as well as the phosphorylation status of specific proteins. J. Androl. 27, 285–293 (2006).

    CAS  PubMed  Google Scholar 

  60. Sahinkanat, T., Ozkan, K. U., Tolun, F. I., Ciralik, H. & Imrek, S. S. The protective effect of ischemic preconditioning on rat testis. Reprod. Biol. Endocrinol. 5, 47 (2007).

    PubMed  PubMed Central  Google Scholar 

  61. Erol, B. et al. Vardenafil reduces testicular damage following ischemia/reperfusion injury in rats. Kaohsiung J. Med. Sci. 25, 374–380 (2009).

    CAS  PubMed  Google Scholar 

  62. Romero, F. J. et al. Lipid peroxidation products and antioxidants in human disease. Environ. Health Perspect. 106, 1229–1234 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Istanbulluoglu, M. O. et al. Effects of vardenafil on testicular torsion/detorsion damage: an experimental study in pigs. Urol. Int. 86, 228–232 (2011).

    CAS  PubMed  Google Scholar 

  64. Yíldíz, H., Durmus, A. S., Simsek, H. & Yaman, M. Protective effect of sildenafil citrate on contralateral testis injury after unilateral testicular torsion/detorsion. Clinics (Sao Paulo) 66, 137–142 (2011).

    Google Scholar 

  65. Maresta, A. et al. Trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, reduces restenosis after percutaneous transluminal coronary angioplasty. Results of the randomized, double-blind STARC study. Studio Trapidil versus Aspirin nella Restenosi Coronarica. Circulation 90, 2710–2715 (1994).

    CAS  PubMed  Google Scholar 

  66. Bozlu, M., Acar, D., Cayan, S., Aktas, S. & Tunckiran, A. Protective effect of trapidil on long-term histologic damage in a rat model of testicular ischemia-reperfusion injury. World J. Urol. 27, 117–122 (2009).

    CAS  PubMed  Google Scholar 

  67. Karagüzel, E. et al. Comparison of the protective effect of dipyridamole and acetylsalicylic acid on long-term histologic damage in a rat model of testicular ischemia-reperfusion injury. J. Pediatr. Surg. 47, 1716–1723 (2012).

    PubMed  Google Scholar 

  68. Levine, M., Padayatty, S. J. & Espey, M. G. Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries. Adv. Nutr. 2, 78–88 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Azizollahi, S., Babaei, H., Derakhshanfar, A. & Oloumi, M. M. Effects of co-administration of dopamine and vitamin C on ischaemia-reperfusion injury after experimental testicular torsion-detorsion in rats. Andrologia 43, 100–105 (2011).

    CAS  PubMed  Google Scholar 

  70. Romeo, C. et al. Raxofelast, a hydrophilic vitamin E-like antioxidant, reduces testicular ischemia-reperfusion injury. Urol. Res. 32, 367–371 (2004).

    CAS  PubMed  Google Scholar 

  71. Antonuccio, P. et al. Lipid peroxidation activates mitogen-activated protein kinases in testicular ischemia-reperfusion injury. J. Urol. 176, 1666–1672 (2006).

    CAS  PubMed  Google Scholar 

  72. Slyshenkov, V. S., Dymkowska, D. & Wojtczak, L. Pantothenic acid and pantothenol increase biosynthesis of glutathione by boosting cell energetics. FEBS Lett. 569, 169–172 (2004).

    CAS  PubMed  Google Scholar 

  73. Etensel, B. et al. The protective effect of dexpanthenol on testicular atrophy at 60th day following experimental testicular torsion. Pediatr. Surg. Int. 23, 271–275 (2007).

    PubMed  Google Scholar 

  74. Packer, L., Tritschler, H. J. & Wessel, K. Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radic. Biol. Med. 22, 359–378 (1997).

    CAS  PubMed  Google Scholar 

  75. Ozbal, S. et al. The effects of α-lipoic acid against testicular ischemia-reperfusion injury in rats. ScientificWorldJournal 2012, 489248 (2012).

    PubMed  PubMed Central  Google Scholar 

  76. Petersen Shay, K., Moreau, R. F., Smith, E. J. & Hagen, T. M. Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity. IUBMB Life 60, 362–367 (2008).

    Google Scholar 

  77. Ursini, F. & Bindoli, A. The role of selenium peroxidases in the protection against oxidative damage of membranes. Chem. Phys. Lipids 44, 255–276 (1987).

    CAS  PubMed  Google Scholar 

  78. Avlan, D. et al. The protective effect of selenium on ipsilateral and contralateral testes in testicular reperfusion injury. Pediatr. Surg. Int. 21, 274–278 (2005).

    PubMed  Google Scholar 

  79. Lacombe, C. & Mayeux, P. The molecular biology of erythropoietin. Nephrol. Dial. Transplant. 14, 22–28 (1999).

    CAS  PubMed  Google Scholar 

  80. Katavetin, P., Tungsanga, K., Eiam-Ong, S. & Nangaku, M. Antioxidative effects of erythropoietin. Kidney Int. 72, S10–S15 (2007).

    Google Scholar 

  81. Yazihan, N., Ataoglu, H., Koku, N., Erdemli, E. & Kose Sargin, A. Protective role of erythropoietin during testicular torsion of the rats. World J. Urol. 25, 531–536 (2007).

    CAS  PubMed  Google Scholar 

  82. Ghezzi, P. & Brines, M. Erythropoietin as an antiapoptotic, tissue-protective cytokine. Cell Death Differ. 11 (Suppl. 1), S37–S44 (2004).

    CAS  PubMed  Google Scholar 

  83. Chikuma, M., Masuda, S., Kobayashi, T., Nagao, M. & Sasaki, R. Tissue- specific regulation of erythropoietin production in the murine kidney, brain and uterus. Am. J. Physiol. Endocrinol. Metab. 279, E1242–E1248 (2000).

    CAS  PubMed  Google Scholar 

  84. Koksal, M. et al. Effects of melatonin on testis histology, oxidative stress and spermatogenesis after experimental testis ischemia-reperfusion in rats. Eur. Rev. Med. Pharmacol. Sci. 16, 582–588 (2012).

    CAS  PubMed  Google Scholar 

  85. Yapanoglu, T. et al. Antiapoptotic effects of dehydroepiandrosterone on testicular torsion/detorsion in rats. Andrologia 40, 38–43 (2008).

    CAS  PubMed  Google Scholar 

  86. Minutoli, L. et al. Melanocortin 4 receptor activation protects against testicular ischemia-reperfusion injury by triggering the cholinergic antiinflammatory pathway. Endocrinology 152, 3852–3861 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Lee, C. H. et al. Transcriptional repression of atherogenic inflammation: modulation by PPARdelta. Science 302, 453–457 (2003).

    CAS  PubMed  Google Scholar 

  88. Minutoli, L. et al. Peroxisome proliferator activated receptor beta/delta activation prevents extracellular regulated kinase 1/2 phosphorylation and protects the testis from ischemia and reperfusion injury. J. Urol. 181, 1913–1921 (2009).

    CAS  PubMed  Google Scholar 

  89. Lin, Y., Shi, R., Wang, X. & Shen, H. M. Luteolin, a flavonoid with potential for cancer prevention and therapy. Curr. Cancer Drug Targets 8, 634–646 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Diplock, A. T. et al. Functional food science and defence against reactive oxidative species. Br. J. Nutr. 80 (Suppl. 1), S77–S112 (1998).

    CAS  PubMed  Google Scholar 

  91. Jaganathan, S. K. & Mandal, M. Antiproliferative effects of honey and of its polyphenols: a review. J. Biomed. Biotechnol. 2009, 830616 (2009).

    PubMed  PubMed Central  Google Scholar 

  92. Korkmaz, A. & Kolankaya, D. Protective effect of rutin on the ischemia/reperfusion induced damage in rat kidney. J. Surg. Res. 164, 309–315 (2010).

    CAS  PubMed  Google Scholar 

  93. Guimarães, S. B. et al. Ternatin pretreatment attenuates testicular injury induced by torsion/detorsion in Wistar rats. Acta Cir. Bras. 26, 325–328 (2011).

    PubMed  Google Scholar 

  94. Aktoz, T., Kanter, M. & Aktas, C. Protective effects of quercetin on testicular torsion/ detorsion-induced ischaemia-reperfusion injury in rats. Andrologia 42, 376–383 (2010).

    CAS  PubMed  Google Scholar 

  95. Di Mascio, P., Kaiser, S. & Sies, H. Lycopene as the most efficient biological carotenoid singlet oxygen quencher. Arch. Biochem. Biophys. 274, 532–538 (1989).

    CAS  PubMed  Google Scholar 

  96. Hekimoglu, A. et al. Lycopene, an antioxidant carotenoid, attenuates testicular injury caused by ischemia/reperfusion in rats. Tohoku J. Exp. Med. 218, 141–147 (2009).

    CAS  PubMed  Google Scholar 

  97. Kim, Y. H., Kim, G. H., Shin, J. H., Kim, K. S. & Lim, J. S. Effect of korean red ginseng on testicular tissue injury after torsion and detorsion. Korean J. Urol. 51, 794–799 (2010).

    PubMed  PubMed Central  Google Scholar 

  98. Maffei Facino, R., Carini, M., Aldini, G., Berti, F. & Rossoni, G. Panax ginseng administration in the rat prevents myocardial ischemia-reperfusion damage induced by hyperbaric oxygen: evidence for an antioxidant intervention. Planta Med. 65, 614–619 (1999).

    CAS  PubMed  Google Scholar 

  99. Voces, J. et al. Effects of administration of the standardized Panax ginseng extract G115 on hepatic antioxidant function after exhaustive exercise. Comp. Biochem. Physiol. C Pharmacol. Toxicol. Endocrinol. 123, 175–184 (1999).

    CAS  PubMed  Google Scholar 

  100. Cabral de Oliveira, A. C., Perez, A. C., Merino, G., Prieto, J. G. & Alvarez, A. I. Protective effects of panax ginseng on muscle injury and inflammation after eccentric exercise. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 130, 369–377 (2001).

    CAS  PubMed  Google Scholar 

  101. Gökçe, A. et al. Protective effect of thymoquinone in experimental testicular torsion. Urol. Int. 85, 461–465 (2010).

    PubMed  Google Scholar 

  102. Ünsal, A. et al. Protective role of natural antioxidant supplementation on testicular tissue after testicular torsion and detorsion. Scand. J. Urol. Nephrol. 40, 17–22 (2006).

    PubMed  Google Scholar 

  103. Dokmeci, D. et al. Protective effect of L-carnitine on testicular ischaemia-reperfusion injury in rat. Cell Biochem. Funct. 25, 611–618 (2007).

    CAS  PubMed  Google Scholar 

  104. Akgül, T. et al. Ginkgo biloba (EGb 761) usage attenuates testicular injury induced by testicular ischemia/reperfusion in rats. Int. Urol. Nephrol. 40, 685–690 (2008).

    PubMed  Google Scholar 

  105. Borghi, C., Bacchelli, S., Degli Esposti, D. & Ambrosioni, E. A review of the angiotensin-converting enzyme inhibitor, zofenopril, in the treatment of cardiovascular diseases. Expert Opin. Pharmacother. 5, 1965–1977 (2004).

    CAS  PubMed  Google Scholar 

  106. Mak, I. T., Freedman, A. M., Dickens, B. F. & Weglicki, W. B. Protective effects of sulfhydryl-containing angiotensin converting enzyme inhibitors against free radical injury in endothelial cells. Biochem. Pharmacol. 40, 2169–2175 (1990).

    CAS  PubMed  Google Scholar 

  107. Altunoluk, B., Söylemez, H., Bakan, V., Ciralik, H. & Tolun, F. I. Protective effects of zofenopril on testicular torsion and detorsion injury in rats. Urol. J. 8, 313–319 (2011).

    PubMed  Google Scholar 

  108. Gokce, G., Karboga, H., Yildiz, E., Ayan, S. & Gultekin, Y. Effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on apoptotic changes in contralateral testis following unilateral testicular torsion. Int. Urol. Nephrol. 40, 989–995 (2008).

    CAS  PubMed  Google Scholar 

  109. Yancopoulos, G. D. et al. Vascular-specific growth factors and blood vessel formation. Nature 407, 242–248 (2000).

    CAS  PubMed  Google Scholar 

  110. Tunckiran, A. et al. Protective effect of vascular endothelial growth factor on histologic changes in testicular ischemia-reperfusion injury. Fertil. Steril. 84, 468–473 (2005).

    CAS  PubMed  Google Scholar 

  111. Hashimoto, H., Ishikawa, T., Yamaguchi, K., Shiotani, M. & Fujisawa, M. Experimental ischaemia-reperfusion injury induces vascular endothelial growth factor expression in the rat testis. Andrologia 41, 216–221 (2009).

    CAS  PubMed  Google Scholar 

  112. Minutoli, L. et al. Effects of polydeoxyribonucleotide on the histological damage and the altered spermatogenesis induced by testicular ischaemia and reperfusion in rats. Int. J. Androl. 35, 133–144 (2012).

    CAS  PubMed  Google Scholar 

  113. Shirazi, M. et al. Comparison of the protective effects of papaverine, lidocaine and verapamil on the sperm quality of the testis after induced torsion-detorsion in rats. Scand. J. Urol. Nephrol. 44, 133–137 (2010).

    CAS  PubMed  Google Scholar 

  114. Sarica, K. et al. Unilateral testicular torsion: protective effect of verapamil on contralateral testicular histology. Urol. Int. 62, 159–163 (1999).

    CAS  PubMed  Google Scholar 

  115. Oguzkurt, P., Okur, D. H., Tanyel, F. C., Buyukpamukcu, N. & Hicsonmez, A. The effects of vasodilatation and chemical sympathectomy on spermatogenesis after unilateral testicular torsion: a flow cytometric DNA analysis. Br. J. Urol. 82, 104–108 (1998).

    CAS  PubMed  Google Scholar 

  116. Prillaman, H. M. & Turner, T. T. Rescue of testicular function after acute experimental torsion. J. Urol. 157, 340–345 (1997).

    CAS  PubMed  Google Scholar 

  117. Shin, I. W. et al. Propofol has delayed myocardial protective effects after a regional ischemia/reperfusion injury in an in vivo rat heart model. Korean J. Anesthesiol. 58, 378–382 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Wang, H. Y., Wang, G. L., Yu, Y. H. & Wang, Y. The role of phosphoinositide-3-kinase/Akt pathway in propofol-induced postconditioning against focal cerebral ischemia-reperfusion injury in rats. Brain Res. 1297, 177–184 (2009).

    CAS  PubMed  Google Scholar 

  119. Kidambi, S. et al. Propofol induces ERK-dependent expression of c-Fos and Egr-1 in neuronal cells. Neuroreport 20, 657–662 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Yagmurdur, H. et al. Propofol reduces nitric oxide-induced apoptosis in testicular ischemia-reperfusion injury by downregulating the expression of inducible nitric oxide synthase. Acta Anaesthesiol. Scand. 52, 350–357 (2008).

    CAS  PubMed  Google Scholar 

  121. Urt Filho, A. et al. Propofol effects on the morphology of rat testes subjected to testicular ischemia-reperfusion. Acta Cir. Bras. 27, 172–178 (2012).

    PubMed  Google Scholar 

  122. Almaas, R., Saugstad, O. D., Pleasure, D. & Rootwelt, T. Effect of barbiturates on hydroxyl radicals, lipid peroxidation, and hypoxic cell death in human NT2-N neurons. Anesthesiology 92, 764–774 (2000).

    CAS  PubMed  Google Scholar 

  123. Yagmurdur, H. et al. The preventive effects of thiopental and propofol on testicular ischemia-reperfusion injury. Acta Anaesthesiol. Scand. 50, 1238–1243 (2006).

    CAS  PubMed  Google Scholar 

  124. Yagmurdur, H. et al. Dexmedetomidine reduces the ischemia-reperfusion injury markers during upper extremity surgery with tourniquet. J. Hand. Surg. Am. 33, 941–947 (2008).

    PubMed  Google Scholar 

  125. Okada, H., Kurita, T., Mochizuki, T., Morita, K. & Sato, S. The cardioprotective effect of dexmedetomidine on global ischaemia in isolated rat hearts. Resuscitation 74, 538–545 (2007).

    CAS  PubMed  Google Scholar 

  126. Hanci, V. et al. Effect of dexmedetomidine on testicular torsion/detorsion damage in rats. Urol. Int. 84, 105–111 (2010).

    CAS  PubMed  Google Scholar 

  127. Dokmeci, D. et al. Protective effects of ibuprofen on testicular torsion/detorsion-induced ischemia/reperfusion injury in rats. Arch. Toxicol. 81, 655–663 (2007).

    CAS  PubMed  Google Scholar 

  128. Mogilner, J. G. et al. Effect of diclofenac on germ cell apoptosis following testicular ischemia-reperfusion injury in a rat. Pediatr. Surg. Int. 22, 99–105 (2006).

    PubMed  Google Scholar 

  129. Leitão, J. P. et al. L-alanyl-glutamine dipeptide pretreatment attenuates ischemia-reperfusion injury in rat testis. Acta Cir. Bras. 26, 21–25 (2011).

    PubMed  Google Scholar 

  130. Guimarães, S. B., Kimura, O. S. & Leitão de Vasconcelos, P. R. Dimethylsulfoxide attenuates ischemia-reperfusion injury in rat testis. Acta Cir. Bras. 25, 357–361 (2010).

    PubMed  Google Scholar 

  131. Bektasoglu, B., Esin Celik, S., Ozyurek, M., Guclu, K. & Apak, R. Novel hydroxyl radical scavenging antioxidant activity assay for water-soluble antioxidants using a modified CUPRAC method. Biochem. Biophys. Res. Commun. 345, 1194–1200 (2006).

    CAS  PubMed  Google Scholar 

  132. Sun, W. et al. Statins activate AMP-activated protein kinase in vitro and in vivo. Circulation 114, 2655–2662 (2006).

    CAS  PubMed  Google Scholar 

  133. Prinz, V. & Endres, M. Statins and stroke: prevention and beyond. Curr. Opin. Neurol. 24, 75–80 (2011).

    CAS  PubMed  Google Scholar 

  134. Karakaya, E., Ates, O., Akgür, F. M. & Olguner, M. Rosuvastatin protects tissue perfusion in the experimental testicular torsion model. Int. Urol. Nephrol. 42, 357–360 (2010).

    CAS  PubMed  Google Scholar 

  135. Wahl, C., Liptay, S., Adler, G. & Schmid, R. M. Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B. J. Clin. Invest. 101, 1163–1174 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Zhao, Y. G. et al. Sulfasalazine prevents apoptosis in spermatogenic cells after experimental testicular torsion/detorsion. Acta Pharmacol. Sin. 27, 603–608 (2006).

    CAS  PubMed  Google Scholar 

  137. Weinbroum, A. A., Rudick, V., Ben-Abraham, R. & Karchevski, E. N-acetyl-L-cysteine for preventing lung reperfusion injury after liver ischemia-reperfusion: a possible dual protective mechanism in a dose-response study. Transplantation 69, 853–859 (2000).

    CAS  PubMed  Google Scholar 

  138. Cay, A. et al. The effects of N-acetylcysteine on antioxidant enzyme activities in experimental testicular torsion. J. Surg. Res. 131, 199–203 (2006).

    CAS  PubMed  Google Scholar 

  139. Turkmen, S. et al. A comparison of the effects of N-acetylcysteine and ethyl pyruvate on experimental testicular ischemia-reperfusion injury. Fertil. Steril. 98, 626–631 (2012).

    CAS  PubMed  Google Scholar 

  140. Aktas, B. K. et al. The effects of N-acetylcysteine on testicular damage in experimental testicular ischemia/reperfusion injury. Pediatr. Surg. Int. 26, 293–298 (2010).

    PubMed  Google Scholar 

  141. Koc, A. et al. The protective role of erdosteine on testicular tissue after testicular torsion and detorsion. Mol. Cell. Biochem. 280, 193–199 (2005).

    CAS  PubMed  Google Scholar 

  142. Gezici, A., Ozturk, H., Buyukbayram, H., Ozturk, H. & Okur, H. Effects of gabexate mesilate on ischemia-reperfusion-induced testicular injury in rats. Pediatr. Surg. Int. 22, 435–441 (2006).

    PubMed  Google Scholar 

  143. Murry, C. E., Jennings, R. B. & Reimer, K. A. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74, 1124–1136 (1986).

    CAS  PubMed  Google Scholar 

  144. Shimizu, S. et al. Ischemic preconditioning and post-conditioning to decrease testicular torsion-detorsion injury. J. Urol. 182, 1637–1643 (2009).

    CAS  PubMed  Google Scholar 

  145. Shimizu, S. et al. Protective effect of ischaemic post-conditioning on ipsilateral and contralateral testes after unilateral testicular ischaemia-reperfusion injury. Int. J. Androl. 34, 268–275 (2011).

    CAS  PubMed  Google Scholar 

  146. Zhang, Y. et al. Hyperbaric oxygen therapy in rats attenuates ischemia-reperfusion testicular injury through blockade of oxidative stress, suppression of inflammation, and reduction of nitric oxide formation. Urology 82, 489.e9–489.e15 (2013).

    Google Scholar 

  147. Kolski, J. M. et al. Effect of hyperbaric oxygen therapy on testicular ischemia-reperfusion injury. J. Urol. 160, 601–604 (1998).

    CAS  PubMed  Google Scholar 

  148. Kalns, J. et al. Hyperbaric oxygen exposure temporarily reduces Mac-1 mediated functions of human neutrophils. Immunol. Lett. 83, 125–131 (2002).

    CAS  PubMed  Google Scholar 

  149. Labrouche, S., Javorschi, S., Leroy, D., Gbikpi-Benissan, G. & Freyburger, G. Influence of hyperbaric oxygen on leukocyte functions and haemostasis in normal volunteer divers. Thromb. Res. 96, 309–315 (1999).

    CAS  PubMed  Google Scholar 

  150. Thom, S. R. Leukocytes in carbon monoxide-mediated brain oxidative injury. Toxicol. Appl. Pharmacol. 123, 234–247 (1993).

    CAS  PubMed  Google Scholar 

  151. Zamboni, W. A. et al. Morphologic analysis of the microcirculation during reperfusion of ischemic skeletal muscle and the effect of hyperbaric oxygen. Plast. Reconstr. Surg. 91, 1110–1123 (1993).

    CAS  PubMed  Google Scholar 

  152. Fildissis, G. et al. Whole blood pro-inflammatory cytokines and adhesion molecules post-lipopolysaccharides exposure in hyperbaric conditions. Eur. Cytokine Netw. 15, 217–221 (2004).

    CAS  PubMed  Google Scholar 

  153. Dennog, C., Radermacher, P., Barnett, Y. A. & Speit, G. Antioxidant status in humans after exposure to hyperbaric oxygen. Mutat. Res. 428, 83–89 (1999).

    CAS  PubMed  Google Scholar 

  154. Rothfuss, A., Radermacher, P. & Speit, G. Involvement of heme oxygenase-1 (HO-1) in the adaptive protection of human lymphocytes after hyperbaric oxygen (HBO) treatment. Carcinogenesis 22, 1979–1985 (2001).

    CAS  PubMed  Google Scholar 

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E.K. and M.K. researched data for the article and contributed to discussion of the content and writing of the article. All authors contributed to review and editing of the manuscript before submission.

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Correspondence to Ersagun Karaguzel.

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Karaguzel, E., Kadihasanoglu, M. & Kutlu, O. Mechanisms of testicular torsion and potential protective agents. Nat Rev Urol 11, 391–399 (2014). https://doi.org/10.1038/nrurol.2014.135

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