Journal Article

HMG-CoA reductase inhibition preserves testicular function after torsion/detorsion by modulating oxidative stress and AKT signaling

Keskin, İlknur, Kılıç, Ertuğrul, Yıldırım, Berna, Baygül, Oğuzhan, Balçıkanlı, Zeynep, Ateş, Nilay, Beker, Mustafa Çağlar, Şengün, Nursena, Üstündağ, Ünsal Veli

2025

Overview

Testicular torsion (TT) is a urological emergency that results in ischemia/reperfusion (I/R) injury, leading to oxidative stress, cellular apoptosis, and impaired spermatogenesis. This study investigated the protective effects of the HMG-CoA reductase inhibitor rosuvastatin on TT-induced I/R injury and explored the underlying mechanisms. Male Balb/C mice ( n  = 28) were subjected to 720° testicular torsion for two hours, followed by 24 h of detorsion. Rosuvastatin was administered either acutely (post-torsion) or prophylactically (prior to injury). Histopathological evaluation, assessment of oxidative stress parameters, sperm motility and morphology analysis, and Western blot examination of survival and stress related signaling proteins (pAKT, pJNK1/2, pERK1/2, and Bcl-xL) were performed. Rosuvastatin treatment significantly reduced tissue damage decreased oxidative stress (as indicated by increased TAS and reduced TOS/OSI), and improved sperm motility and morphology. Both acute and prophylactic treatment regimens enhanced cell survival by increasing pAKT and Bcl-xL levels, reducing pERK1/2 activation, and modulating stress responsive JNK1/2 signaling. These findings suggest that rosuvastatin mitigates I/R induced testicular damage primarily through modulation of key intracellular pathways, particularly PI3K/AKT, and support its therapeutic potential in acute testicular injuries and related degenerative conditions.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 1-Phosphatidylinositol 3-kinase / 631/80 / 692/1807 / 692/308 / 692/4017 / 692/4025 / 692/420 / 692/499 / 692/53 / AKT protein / Animals / Antioxidants / Apoptosis / Apoptosis - drug effects / Bcl-x protein / Cell signaling / Cell survival / Design of experiments / Disease Models, Animal / Drug dosages / Enzymes / Euthanasia / HMG-CoA reductase / HMG-CoA reductase inhibitors / Humanities and Social Sciences / Hydroxymethylglutaryl-CoA reductase / Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology / Ischemia / Ketamine / Kinases / Laboratory animals / Male / Medical research / Mice / Mice, Inbred BALB C / Morphology / Motility / multidisciplinary / Oxidative stress / Oxidative Stress - drug effects / PI3K/AKT pathway / Proto-Oncogene Proteins c-akt - metabolism / Reperfusion / Reperfusion Injury - drug therapy / Reperfusion Injury - metabolism / Reperfusion Injury - pathology / Reperfusion Injury - prevention & control / Rosuvastatin Calcium - pharmacology / Science / Science (multidisciplinary) / Signal Transduction - drug effects / Sperm / Sperm function / Sperm Motility - drug effects / Spermatic Cord Torsion - drug therapy / Spermatic Cord Torsion - metabolism / Spermatic Cord Torsion - pathology / Spermatogenesis / Statin / Statins / Testes / Testicular torsion / Testis - drug effects / Testis - metabolism / Testis - pathology