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 journalSCORING: Journal articleResearchpeer-review

Harvard

Boettcher, M, Meier, D, Jiménez-Alcázar, M, Eschenburg, G, Mietzsch, S, Vincent, D, Klinke, M, Trochimiuk, M, Appl, B, Tiemann, B, Bergholz, R, Reinshagen, K & Fuchs, TA 2017, 'Degradation of Extracellular DNA by DNase1 Significantly Reduces Testicular Damage after Testicular Torsion in Rats', UROLOGY, vol. 109, pp. 223.e1-223.e7. https://doi.org/10.1016/j.urology.2017.07.031

APA

Boettcher, M., Meier, D., Jiménez-Alcázar, M., Eschenburg, G., Mietzsch, S., Vincent, D., Klinke, M., Trochimiuk, M., Appl, B., Tiemann, B., Bergholz, R., Reinshagen, K., & Fuchs, T. A. (2017). Degradation of Extracellular DNA by DNase1 Significantly Reduces Testicular Damage after Testicular Torsion in Rats. UROLOGY, 109, 223.e1-223.e7. https://doi.org/10.1016/j.urology.2017.07.031

Vancouver

Boettcher M, Meier D, Jiménez-Alcázar M, Eschenburg G, Mietzsch S, Vincent D et al. Degradation of Extracellular DNA by DNase1 Significantly Reduces Testicular Damage after Testicular Torsion in Rats. UROLOGY. 2017 Nov;109:223.e1-223.e7. https://doi.org/10.1016/j.urology.2017.07.031

Bibtex

@article{e229a79a00bf4b0aa7dddfec3994fa37,
title = "Degradation of Extracellular DNA by DNase1 Significantly Reduces Testicular Damage after Testicular Torsion in Rats",
abstract = "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.",
keywords = "Journal Article",
author = "Michael Boettcher and Dennis Meier and Miguel Jim{\'e}nez-Alc{\'a}zar and Georg Eschenburg and Stefan Mietzsch and Deirdre Vincent and Michaela Klinke and Magdalena Trochimiuk and Birgit Appl and Bastian Tiemann and Robert Bergholz and Konrad Reinshagen and Fuchs, {Tobias A}",
note = "Copyright {\textcopyright} 2017 Elsevier Inc. All rights reserved.",
year = "2017",
month = nov,
doi = "10.1016/j.urology.2017.07.031",
language = "English",
volume = "109",
pages = "223.e1--223.e7",
journal = "UROLOGY",
issn = "0090-4295",
publisher = "Elsevier Inc.",

}

RIS

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 -