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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Molecular Pathways Involved in the Early and Late Damage Induced by Testis Ischemia: Evidence for a Rational Pharmacological Modulation

Author(s): L. Minutoli

Volume 19 , Issue 8 , 2012

Page: [1219 - 1224] Pages: 6

DOI: 10.2174/092986712799320538

Price: $65

Abstract

Testicular torsion or torsion of the spermatic cord is a surgical emergency in which misdiagnosis and inappropriate treatment can lead to male infertility. Events occurring during testicular torsion and detorsion are representative of an ischemia-reperfusion injury observed in other organs. The two most important factors determining testicular damage are the degree of twisting and the early onset of a surgical treatment to counter-rotate both testis and spermatic cord for inducing reperfusion.

The damage from reperfusion is more severe than that induced by ischemia and several mechanisms are implicated in the development of testicular damage following torsion and detorsion. However, these mechanisms have not yet been fully clarified and, as a consequence, there is still a strong need to identify specific pharmacological treatment to limit the damage triggered by the reperfusion procedures.

Ischemia and reperfusion of testis result in elevated production of reactive oxygen species (ROS), activate mitogen activated protein kinases (MAPKs) and PPARβ/δ receptor, induce transcription factors and growth factors including NF-κB and IL-1β . This pathological cascade is responsible for the testicular atrophy, decreased blood flow and impaired spermatogenesis. Several pharmacological approaches have been characterized as promising therapeutic agents for the management of testicular torsion and may be useful to ameliorate the sequel of this disease.

Keywords: Testicular torsion, spermatogenesis, MAPKs, VEGF, PPARβ/δ receptor, cytokines, apoptosis, melanocortin, ROS, infertility


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