Protective effects of colchicine on testicular torsion/detorsion-induced ischemia/reperfusion injury in rats
Vol. 17 No. 3 (2020),
16 May 2020
Purpose: To evaluate the short-term use of colchicine on preventing ischemia-reperfusion injury after surgery in an experimental animal model.
Materials and Methods: A total of 40 rats were divided into five groups (n = 8). Sham (Sh), ischemia-reperfusion (I/R), I/R and colchicine-treated for once per-operatively (I/Rc1), I/R and colchicine-treated for 5 days postoperatively (I/Rc5), and I/R and placebo given for 5 days (I/Rp) groups. Testicular torsion was created by rotating the testicle 720o in clockwise direction and held for 3 hours. In group I/Rc1 30 minutes before detorsion, p.o. 1 mg/kg mL infusion of colchicine was given only once. In group I/Rc5, colchicine continued p.o. once daily for five days. Tissue malonyldialdehite (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were measured for evaluating the oxidative stress. Apoptosis levels shown with Caspase-3 staining and mean seminiferous tubular diameter (MSTD), germinal epithelial cell thickness (GECT), and mean testicular biopsy score (MTBS) were used to evaluate the germ cell damage.
Results: Decreased protein MDA levels therewithal increased SOD, CAT and GPx levels achieved in I/Rc5 group when compared to I/R group and did not differ from the I/Rp group (p<0.05). MSTD, GECT, and JS were better in I/Rc5 than I/Rp which showed the natural course of I/R damage in testis (p<0.005). Caspase 3 positivity, as an apoptosis indicator, were significantly lower (p<0.05) in I/Rc5 group in comparison with I/R, I/Rc1, and I/Rp groups.
Conclusion: The usage of colchicine as a complementary treatment after definitive surgery reduce early-onset ischemia-reperfusion damage and diminishes apoptosis.
Karaguzel E, Kadihasanoglu M, Kutlu O. Mechanisms of testicular torsion and potential protective agents. Nat Rev Urol. 2014;11:391-9.
Pillai SB, Besner GE. Pediatric testicular problems. Pediatr Clin North Am. 1998;45:813-30.
Cuzzocrea S, Riley DP, Caputi AP, Salvemini D. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol Rev. 2001;53:135-59.
Oropesa Avila M, Fernandez Vega A, Garrido Maraver J, et al. Emerging roles of apoptotic microtubules during the execution phase of apoptosis. Cytoskeleton (Hoboken). 2015;72:435-46.
Choudhary GS, Al-Harbi S, Almasan A. Caspase-3 activation is a critical determinant of genotoxic stress-induced apoptosis. Methods Mol Biol. 2015;1219:1-9.
Slobodnick A, Shah B, Pillinger MH, Krasnokutsky S. Colchicine: old and new. Am J Med. 2015;128:461-70.
Leung YY, Yao Hui LL, Kraus VB. Colchicine--Update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum. 2015;45:341-50.
Kapoor S. Testicular torsion: a race against time. Int J Clin Pract. 2008;62:821-7.
Miklós Á, Bajor FZ. A review of main controversial aspects of acute testicular torsion. Journal of Acute Disease. 2016;5:1-8.
Figueroa V, Pippi Salle JL, Braga LH, et al. Comparative analysis of detorsion alone versus detorsion and tunica albuginea decompression (fasciotomy) with tunica vaginalis flap coverage in the surgical management of prolonged testicular ischemia. J Urol. 2012;188:1417-22.
Ustun H, Akgul KT, Ayyildiz A, et al. Effect of phospodiesterase 5 inhibitors on apoptosis and nitric oxide synthases in testis torsion: an experimental study. Pediatr Surg Int. 2008;24:205-11.
Erol B, Bozlu M, Hanci V, Tokgoz H, Bektas S, Mungan G. Coenzyme Q10 treatment reduces lipid peroxidation, inducible and endothelial nitric oxide synthases, and germ cell-specific apoptosis in a rat model of testicular ischemia/reperfusion injury. Fertil Steril.
Mitsui Y, Okamoto K, Martin DP, Schmelzer JD, Low PA. The expression of proinflammatory cytokine mRNA in the sciatic-tibial nerve of ischemia-reperfusion injury. Brain Res. 1999;844:192-5.
Chappey ON, Niel E, Wautier JL, et al. Colchicine disposition in human leukocytes after single and multiple oral administration. Clin Pharmacol Ther. 1993;54:360-7.
Bhattacharyya B, Panda D, Gupta S, Banerjee M. Anti-mitotic activity of colchicine and the structural basis for its interaction with tubulin. Med Res Rev. 2008;28:155-83.
Rao P, Falk LA, Dougherty SF, Sawada T, Pluznik DH. Colchicine down-regulates lipopolysaccharide-induced granulocyte-macrophage colony-stimulating factor production in murine macrophages. J Immunol. 1997;159:3531-9.
Li Z, Davis GS, Mohr C, Nain M, Gemsa D. Inhibition of LPS-induced tumor necrosis factor-alpha production by colchicine and other microtubule disrupting drugs. Immunobiology. 1996;195:624-39.
Sessions AE, Rabinowitz R, Hulbert WC, Goldstein MM, Mevorach RA. Testicular torsion: direction, degree, duration and disinformation. J Urol. 2003;169:663-5.
Sanada S, Komuro I, Kitakaze M. Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures. Am J Physiol Heart Circ Physiol. 2011;301:H1723-41.
Huang SH, Song JP, Qin J, Rong J, Wu ZK. Dynamics of interstitial calcium in rat myocardial ischemia reperfusion injury in vivo. J Huazhong Univ Sci Technolog Med Sci. 2014;34:37-41.
Korkmaz S, Erturan I, Naziroglu M, Uguz AC, Cig B, Ovey IS. Colchicine modulates oxidative stress in serum and neutrophil of patients with Behcet disease through regulation of Ca(2)(+) release and antioxidant system. J Membr Biol. 2011;244:113-20.
Spirlandeli AL, Deminice R, Jordao AA. Plasma malondialdehyde as biomarker of lipid peroxidation: effects of acute exercise. Int J Sports Med. 2014;35:14-8.
McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol. 2013;5:a008656.
Crompton M, Heid I. The cycling of calcium, sodium, and protons across the inner membrane of cardiac mitochondria. Eur J Biochem. 1978;91:599-608.
Crompton M. The mitochondrial permeability transition pore and its role in cell death. Biochem J. 1999;341 ( Pt 2):233-49.
Woo M, Hakem R, Soengas MS, et al. Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes. Genes Dev. 1998;12:806-19.
Ehrenfeld M, Levy M, Margalioth EJ, Eliakim M. The effects of long-term colchicine therapy on male fertility in patients with familial Mediterranean fever. Andrologia. 1986;18:420-6.
Lysiak JJ, Nguyen QA, Kirby JL, Turner TT. 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. 2003;69:202-10.
- Abstract Viewed: 430 times
- pdf/4918 Downloaded: 112 times