Degradation of Extracellular DNA by DNase1 Significantly Reduces Testicular Damage after Testicular Torsion in Rats
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Degradation of Extracellular DNA by DNase1 Significantly Reduces Testicular Damage after Testicular Torsion in Rats. / Boettcher, Michael; Meier, Dennis; Jiménez-Alcázar, Miguel; Eschenburg, Georg; Mietzsch, Stefan; Vincent, Deirdre; Klinke, Michaela; Trochimiuk, Magdalena; Appl, Birgit; Tiemann, Bastian; Bergholz, Robert; Reinshagen, Konrad; Fuchs, Tobias A.
In: UROLOGY, Vol. 109, 11.2017, p. 223.e1-223.e7.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Degradation of Extracellular DNA by DNase1 Significantly Reduces Testicular Damage after Testicular Torsion in Rats
AU - Boettcher, Michael
AU - Meier, Dennis
AU - Jiménez-Alcázar, Miguel
AU - Eschenburg, Georg
AU - Mietzsch, Stefan
AU - Vincent, Deirdre
AU - Klinke, Michaela
AU - Trochimiuk, Magdalena
AU - Appl, Birgit
AU - Tiemann, Bastian
AU - Bergholz, Robert
AU - Reinshagen, Konrad
AU - Fuchs, Tobias A
N1 - Copyright © 2017 Elsevier Inc. All rights reserved.
PY - 2017/11
Y1 - 2017/11
N2 - OBJECTIVE: To examine the effects of DNase1 treatment on testicular damage after TT aim of this study. It has been demonstrated that testicular torsion (TT) induces thrombus formation and that anticoagulation significantly reduces testicular damage after TT. It was hypothesized that these thrombi are dependent on neutrophil extracellular traps (NETs) and thus NETs disintegration would reduce testicular cell damage.METHODS: In 10 rats a sham operation was performed. 34 rats underwent induction of iatrogenic TT for 3 hours. After de-torsion and randomization, 24 rats received DNase1 or inactivated DNase1. The following parameters were assessed: testicular damage via Cosetino grading; spermatogenesis via Johnsen score; SCF and cKit, apoptosis via Bax, Bcl2, TUNEL assay and cleaved Caspase3 staining; oxidative stress via SOD, CAT, GPx and MDA; neutrophil recruitment via MPO and NE staining; and NET formation via cfDNA.RESULTS: 43 rats were included in the study. Subjects treated with DNase1 showed significantly less cellular damage, oxidative stress and apoptosis. Further, DNase1 treated rats demonstrated a significant improvement of spermatogenesis, compared to the controls.CONCLUSION: The results of the study indicate that thrombus formation during TT is quite likely NET-associated and that dissolution of cell-free DNA (including NETs) significantly improves testicular damage in rats. As treatment with DNase1 reduced apoptosis, oxidative stress, and inflammation, without adversely affecting coagulation, it might be a suitable treatment for (neonatal) TT and ought to be evaluated in humans.
AB - OBJECTIVE: To examine the effects of DNase1 treatment on testicular damage after TT aim of this study. It has been demonstrated that testicular torsion (TT) induces thrombus formation and that anticoagulation significantly reduces testicular damage after TT. It was hypothesized that these thrombi are dependent on neutrophil extracellular traps (NETs) and thus NETs disintegration would reduce testicular cell damage.METHODS: In 10 rats a sham operation was performed. 34 rats underwent induction of iatrogenic TT for 3 hours. After de-torsion and randomization, 24 rats received DNase1 or inactivated DNase1. The following parameters were assessed: testicular damage via Cosetino grading; spermatogenesis via Johnsen score; SCF and cKit, apoptosis via Bax, Bcl2, TUNEL assay and cleaved Caspase3 staining; oxidative stress via SOD, CAT, GPx and MDA; neutrophil recruitment via MPO and NE staining; and NET formation via cfDNA.RESULTS: 43 rats were included in the study. Subjects treated with DNase1 showed significantly less cellular damage, oxidative stress and apoptosis. Further, DNase1 treated rats demonstrated a significant improvement of spermatogenesis, compared to the controls.CONCLUSION: The results of the study indicate that thrombus formation during TT is quite likely NET-associated and that dissolution of cell-free DNA (including NETs) significantly improves testicular damage in rats. As treatment with DNase1 reduced apoptosis, oxidative stress, and inflammation, without adversely affecting coagulation, it might be a suitable treatment for (neonatal) TT and ought to be evaluated in humans.
KW - Journal Article
U2 - 10.1016/j.urology.2017.07.031
DO - 10.1016/j.urology.2017.07.031
M3 - SCORING: Journal article
C2 - 28774773
VL - 109
SP - 223.e1-223.e7
JO - UROLOGY
JF - UROLOGY
SN - 0090-4295
ER -