JAK Inhibition Prevents DNA Damage and Apoptosis in Testicular Ischemia-Reperfusion Injury via Modulation of the ATM/ATR/Chk Pathway.

Testicular ischemia reperfusion injury (tIRI) causes oxidative stress-induced DNA damage leading to germ cell apoptosis (GCA). The aim of the study is to establish a direct link between JAK2 activation and the DNA damage response (DDR) signaling pathways and their role in tIRI-induced GCA using AG490, a JAK2 specific inhibitor. Male Sprague Dawley rats ( = 36) were divided into three groups: sham, unilateral tIRI and tIRI + AG490 (40 mg/kg).

Inhibition of NADPH oxidase alleviates germ cell apoptosis and ER stress during testicular ischemia reperfusion injury.

Testicular torsion and detorsion (TTD) is a serious urological condition affecting young males that is underlined by an ischemia reperfusion injury (tIRI) to the testis as the pathophysiological mechanism. During tIRI, uncontrolled production of oxygen reactive species (ROS) causes DNA damage leading to germ cell apoptosis (GCA). The aim of the study is to explore whether inhibition of NADPH oxidase (NOX), a major source of intracellular ROS, will prevent tIRI-induced GCA and its association with endoplasmic reticulum (ER) stress.

JNK inhibition alleviates oxidative DNA damage, germ cell apoptosis, and mitochondrial dysfunction in testicular ischemia reperfusion injury.

The aim of this study is to determine whether the c-Jun N-terminal kinase (JNK) signaling is a regulator of oxidative DNA damage, germ cell apoptosis (GCA), and mitochondrial dysfunction during testicular ischemia reperfusion injury (tIRI) using the JNK inhibitor SP600125. Male Sprague Dawley rats (n = 36) were equally divided into three groups: sham, tIRI only, and tIRI + SP600125 (15 mg/kg). Testicular ischemia was induced for 1 h followed by 4 h of reperfusion prior to animal sacrifice.

The Thioredoxin System is Regulated by the ASK-1/JNK/p38/Survivin Pathway During Germ Cell Apoptosis.

The aim is to explore the mechanism of the apoptosis signal-regulating kinase-1 (ASK-1) signaling pathway and the involvement of the thioredoxin (Trx) system during testicular ischemia reperfusion injury (tIRI) by using ASK-1 specific inhibitor, NQDI-1. Male Sprague-Dawley rats (n = 36, 250-300 g) were equally divided into 3 groups: sham, tIRI, and tIRI + NQDI-1 (10 mg/kg, i.p, pre-reperfusion).