Please use this identifier to cite or link to this item:
Title: Does the Inhibition of NADPH Oxidase Prevent Germ Cell Apoptosis During Testicular Ischemia Reperfusion Injury?
Authors: Farah Saud Al-Saleh 
Supervisor: Dr. May Al-Maghrebi
Degree Awarded: Master's Degree in: Medical Biochemistry
Keywords: Testicular Ischemia Reperfusion Injury : NADPH Oxidase : Oxidative Stress : Apoptosis : ER Stress
Issue Date: 2019
Publisher:  Kuwait university - college of graduate studies
Abstract: Testicular torsion and detorsion (DTT) can seriously damage the testes and cause infertility if left untreated. It is represented experimentally as testicular ischemia reperfusion injury (tIRI) in animal models. During tIRI, excessive generation of reactive oxygen species (ROS) will induce DNA damage leading to germ cell apoptosis (GCA). This study explores the protective effect of inhibiting NADPH oxidase (NOX), a source of cellular ROS, on preventing the tIRI-induced cellular damages and whether endoplasmic reticulum (ER) stress is associated with tIRI-induced GCA. Thirty-six male Sprague-Dawley rats were divided into three groups: sham, tIRI only and tIRI treated with apocynin (a NOX inhibitor). The tIRI rats endured an ischemic injury for 1 hour followed by 4 hours of reperfusion. Spermatogenic damage was evaluated histologically, while oxidative stress and DNA damage were assessed using biochemical assays, apoptosis was detected by real time PCR and ELISA, and ER stress markers were detected by western blot and immunofluorescence staining. Disturbed spermatid differentiation was associated with increased lipid and protein peroxidation and decreased antioxidant activity of the enzyme superoxide dismutase (SOD) as a result of tIRI. Significant DNA damage induced by tIRI was demonstrated by increased double strand breaks and formation of 8-hydroxydeoxyguanosine associated with increased expression of the DNA damage response (DDR) phosphorylated (ph) proteins: ph-H2AX and ph-ATM. The ASK1/JNK apoptosis pathway was activated in response to tIRI. Finally, increased immuno-expression of the unfolded protein response (UPR) downstream markers like CHOP, GRP78, caspase 12 and ph-eIF2-alpha1 supported the occurrence of ER stress. Inhibition of NOX protected against GCA and ER stress. Based on the findings, NOX inhibition indeed had a positive impact on minimizing cellular damages induced by tIRI. Results also show an association between tIRI and ROS-induced ER stress and induction of GCA.
Appears in Programs:0540 Medical Biochemistry (M.Sc.)

Files in This Item:
File Description SizeFormat 
Farah Al-Saleh Thesis.pdf4,13 MBAdobe PDFView/Open    Request a copy
Show full item record

Page view(s)

checked on Dec 13, 2019

Google ScholarTM


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.