How do agomelatine and selenium affect the experimental ischemia reperfusion injured rat testicular model?

Agomelatine is a melatonergic receptor analog that has been shown to be antioxidative, anti-inflammatory and anti-apoptotic in the literature, and myorelaxant effects on smooth muscles, although there are few studies demonstrating. Selenium is an important trace element for our organism, which has been proven to increase antioxidant enzyme activity for a very long time. Ischemia-Reperfusion (IR) injury can cause serious irreversible health problems at the tissue and organ level. The aim of this study is to investigate the possible effects of agomelatine alone and in combination with selenium against testicular IR injury. 40 male rats were randomly divided into 5 groups (n=8): Sham Operation (ShamOp), Agomelatine Control (AgoC), Ischemia-Reperfusion (IR), Agomelatine + Ischemia-Reperfusion (AgoIR), Agomelatine + Selenium + Ischemia-Reperfusion (AgoSeIR). ShamOp is healthy group; IR is injury group; AgoK is prophylactic treatment group; AgoIR and AgoSeIR are prophylactic treatment + injury groups. Agomelatine (20 mg/kg) and selenium (1.5 mg/kg) were dissolved in 1 milliliter (ml) of distilled water by mixing in the vortex and given to all treatment-containing groups by intraperitoneal (i.p.) injection for 14 consecutive days. IR injury was induced by intramuscular ketamine-xylazine (75 mg/kg-8 mg/kg) anesthesia under 720° surgical torsion (4 hours)/detrosion (24 hours). Histopathological examinations were performed with the Modified Johnsen Score using left-sided testicles. Physiological examinations were performed in an isolated organ bath system using right-sided testicles. According to the statistical analysis of our histopathological data, our groups have significant differences. Modified Johnsen scores were significantly higher in the AgoIR and AgoSeIR groups compared to the IR group (p<0.001). In addition, the AgoSeIR group had a significantly higher Johnsen score than the AgoIR group (p<0.05). The AgoC group had a statistically significantly higher Johnsen score than the AgoIR group (p<0.05). Similarly, the AgoC group had higher Johnsen scores than the AgoSeIR group, but the difference was not significant (p>0.05). The Johnsen score was higher in the ShamOp group than in the AgoIR and AgoSeIR groups. However, the difference was significant in the AgoIR group (p<0.05) but not in the AgoSeIR group (p>0.05). However, the ShamOp group did not differ significantly from the AgoC group (p>0.05). Finally, the AgoC and ShamOp groups had significant Johnsen scores compared to the IR group (p<0.001). No significant difference was found between our groups (p>0.05) based on the statistical analysis of our isolated organ bath data. However, when we analyzed the amplitude parameters over the within-group time values, we determined that there were significant decreases in the AgoC, IR and AgoIR groups (p<0.05). The ShamOp group had better contractile strength than the AgoC, IR and AgoIR groups, although not significantly (p>0.05). Agomelatine showed a significant therapeutic effect against surgical torsion/detorsion-induced testicular IR injury, possibly by reducing oxidative stress (p<0.001). When selenium is applied together with agomelatine, this curative effect increases significantly (p<0.05). Beyond that, we believe that our results should be strengthened with additional evidence from biochemical parameters in terms of the reliability of the data we have reached. It has been reported that the contractility in the smooth muscle-containing tunica albugine layer of the testis capsule is one of the forces that transmit the sperm from the seminiferous tubules to the epididymis, and a decrease in the contractility of the capsule may trigger infertility. The partial inhibitory effect of agomelatine on the testicular capsule needs to be supported by dose-dependent studies of the drug based on the analysis of our experimental data.