N-acetylcysteine protects testicular tissue against ischemia/reperfusion injury via inhibiting endoplasmic reticulum stress and apoptosis.

BACKGROUND: In animal models, endoplasmic reticulum (ER) stress has been reported to play a vital role in mediating ischemia/reperfusion (I/R) injury in certain organs, such as brain, liver, and intestine. However, there are a limited number of studies examining the relationship between ER stress and torsion and detorsion (T/D)-induced testicular injury. OBJECTIVE: To investigate the effects of N-acetylcysteine (NAC) on ER-stress and apoptosis in an experimental testicular I/R injury model. DESIGN: A non-blinded experimental study with three arms. Rats were divided into three groups: control group, T/D group, and NAC group. In the pretreatment of the NAC group, 20 mg/kg NAC was given intraperitoneally 30 min before detorsion. Tissue 4-hydroxynonenal (4-HNE), 78-kDa glucose-regulated protein (GRP78), and activating transcription factor 6 (ATF6) levels were determined using enzyme-linked immunosorbent assay. The apoptosis levels were evaluated using terminal deoxynucleotide transferase-mediated dUTP nick-end label assay. RESULTS: In T/D group, tissue 4-HNE, GRP78, ATF6, and apoptotic index levels were significantly higher than control group. These increases were significantly reversed with NAC pretreatment. DISCUSSION: There are some potential drugs that have been shown to reduce ER stress in the experimental ischemia model, and it is questioned that these drug candidates can be used as a therapeutic agent in the treatment of ischemic diseases in the near future. This study was not without limitations. First, the authors applied NAC only 20 mg/kg. In a future study, a dose-dependent assay should be performed to assess the likelihood of an additional testicular protective effect. One limitation of this research is also that in vivo studies cannot be extrapolated to possible effect in clinics. More experiments therefore need to be conducted to extrapolate the study findings to humans. CONCLUSION: The study results showed that, after testicular torsion (TT), the ER stress-related apoptotic pathway plays a pivotal role in testicular injury. Further studies of other experimental models of TT may prove that NAC is a useful agent as an adjunctive treatment in surgical repair in human cases.

Antifibrogenic role of valproic acid in streptozotocin induced diabetic rat penis.

We investigated the therapeutic effects of valproic acid (VPA) on erectile dysfunction and reducing penile fibrosis in streptozocin (STZ)-induced diabetic rats. Eighteen male rats were divided into three experimental groups (Control, STZ-DM, STZ-DM plus VPA) and diabetes was induced by transperitoneal single dose STZ. Eight weeks after, VPA and placebo treatments were given according to groups for 15 days. All rats were anesthetised for the measurement of in vivo erectile response to cavernous nerve stimulation. Afterward penes were evaluated histologically in terms of immune labelling scores of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and transforming growth factor-ß1 (TGF-ß1). Slides were also evaluated in terms of collagen/smooth muscle ratio and penile apoptosis. After the treatment with VPA, erectile responses were found as improved when compared with STZ-DM rats but not statistically meaningful. eNOS and VEGF immune expressions diminished in penile corpora of STZ-DM rats and improved with VPA treatment. VPA led to decrease in TGF-ß1 expression and collagen content of diabetic rats' penes. Penile apoptosis was not diminished with VPA. In conclusion, VPA treatment seems to be effective for reducing penile fibrosis in diabetic rats and more prolonged treatment period may enhance erectile functions.